Driving Results in

Inhaler Testing
METERED-DOSE INHALERS • DRY POWDER INHALERS
NEBULISERS • AQUEOUS DROPLET INHALERS • NASAL PRODUCTS

2021 EDITION
Inhaler Testing About Us

About Us
Copley: Driving Results for Over 75 Years

Founded in 1946 in Nottingham, UK, Copley remains family owned and managed.
We are recognised as the world’s leading manufacturer of inhaler test equipment, The
in addition to being a trusted provider of test instrumentation for other
pharmaceutical dosage forms. Copley
We continue to work closely with industry groups and These commitments are exemplified by our investment in the Promise
leading experts to bring relevant new products to ISO 9001:2015 Quality Management System for which we
market, with all equipment backed by expert training have certification to the latest standard for all aspects of our
and lifetime support. business, including equipment design. Innovative
Committed to excellence, we aim to deliver exemplary Copley customers benefit from: Innovative product design features ensure ease-of-use
service for an outstanding customer experience. and maximum productivity by streamlining workflows.
• High quality pharmaceutical testing equipment, designed,
We deliver pharmaceutical testing equipment with manufactured and tested in the UK
the necessary accuracy and reproducibility hard-
wired into its design by adopting the same Quality
• Product lifetime support from our friendly and experienced Compliant
technical support team
by Design (QbD) principles that our customers rely Products are certified to quality standards defined by global
on to control product performance. Continuous • First-class training and education pharmacopoeias and regulators, ensuring data integrity.
improvement is a core element of this approach and
we strive to exceed the expectations of the industry,
not only by enhancing equipment performance but Trusted
also through unrivalled service.
Robust design and manufacture from a company with over 75
years’ experience guarantees product reliability and longevity.
Copyright
This edition of the Copley Scientific Limited brochure Copley Scientific Limited does not assume any
is copyright 2021. All rights reserved. liability arising out of the application or use of any
product described herein. Neither does it convey any
No portion of this brochure may be reproduced
licence under its patent rights nor the rights of others.
without the permission of Copley Scientific Limited.
Copley Scientific Limited reserves the right to make Any third party documentation or organisation
changes without notice to any products herein to mentioned herein is referential only and implies no
improve reliability or design. company or product endorsement from, or affiliation
with, Copley Scientific Limited.

2 3
03
 Inhaler Testing Contents
Contents

Contents
Introduction 2 Delivered Dose Uniformity 18 Ancillaries 154 Special Applications 252

About Us 2 Background 18 Breathing Simulators 156 Abbreviated Impactor

ISO 9001: 2015 Quality Management DDU Over the Entire Contents 19 Breathing Simulator Model BRS 100i 158 Measurement (AIM) 253
System 2 Collection Devices for DDU Testing 20 Breathing Simulator Model BRS 200i 162 AIM in QC 253
The Copley Promise 3 Dose Uniformity Sampling Apparatus Breathing Simulator Model BRS 300i 167 AIM in R&D 254
(DUSA) 20 Flow Controllers 172 Fast Screen Andersen (FSA) 255
Table of Contents 4 DUSA for MDIs, BAIs, ADIs and Breath Actuation Controller BAC 100i 176 Reduced NGI (rNGI) 257
Nasal Aerosols 21 Fast Screening Impactor (FSI) 258
Critical Flow Controller TPK 100i 180
Orally Inhaled & Nasal Drug DUSA for DPIs and Nasal Powders 22 Generic Drug Development 260
Flow Meters 184
Products (OINDPs) 6 Waste Shot Collection Devices
Flow Meter DFM4 186 Fluticasone Propionate/Salmeterol
for DDU over the Entire Contents 24 Aerosols & Powders 261
Orally Inhaled Drug Products 7 Flow Meter DFM 2000 187
Waste Shot Collector: WSC2 24 Albuterol Inhalation Aerosols 264
Metered-Dose Inhalers (MDIs) 7 Vacuum Pumps 188
British Pharmacopoeia (BP) Content
Dry Powder Inhalers (DPIs) 8 LCP6 Low Capacity Pump 190
Uniformity Apparatus for MDIs 25
Nebulisers 9 HCP6 High Capacity Pump 191 Semi-Automation 266
Filter Holder for MDIs with Spacers/
Aqueous Droplet Inhalers (ADIs) 10 Valved Holding Chambers (VHCs) SCP6 Super Capacity Pump 192
Automated Shake, Fire and Flow
Nasal Drug Products 10 and for Nebulisers 25 NGI Cooler 194 Control for MDIs, Nasal Sprays
Applications of OINDPs 11 Nasal Spray Dose Collector Inhaler Testing Workstation (ITW) 196 and Aerosols 270
(NSDC) and Nasal Spray Waste Spare/Additional Tubing 199 Vertus II & Vertus Plus 272
Collector (NSWC) 26
Organisations and Their Roles 12 Quick-Release Connectors 199 DecaVertus II 278
USP Monographs 26
Glass Expansion Chambers 200 DUSA Shaker 282
Regulatory Bodies in the European Delivered Dose Uniformity Testing of:
Mouthpiece & Nosepiece Adapters 203 NGI Cup Coater 284
Union, China, Japan and USA 12 Metered Dose Inhalers (MDIs) 28
Gentle Rocker 287
International Regulation and MDIs with a Spacer/VHC 36
Inhalytix™ 206 Sample Preparation Unit SPU 200i 290
Harmonisation 14 Dry Powder Inhalers (DPIs) 42
NGI Assistant 294
Drug Safety, Quality and Efficacy – Nebulisers 48
The Pharmacopoeias 15 Improving IVIVCs 214 Impactor Cleaning System 298
Aqueous Droplet Inhalers (ADIs) 54
European Pharmacopoeia (Ph. Eur.) 15 Background 214
Nasal Sprays 60
United States Pharmacopeia (USP) 15 DDU and APSD Testing 218 Qualification/Servicing & Training 302
Nasal Aerosols 64
Chinese Pharmacopoeia (ChP) 16 Realistic Breathing Profiles 218
Nasal Powders 70 Qualification Services 304
Japanese Pharmacopoeia (JP) 16 Mixing Inlet 219
Impactor Qualification 304
Device Safety, Quality and Realistic Throat and Nasal Models 220
Aerodynamic Particle Size Distribution 76 Stage and Components Mensuration 304
Efficacy – International Standards
Alberta Idealised Throat (AIT) 220
Organisation (ISO) 16 Background 76 Data Interpretation 305
Alberta Idealised Nasal Inlet (AINI) 222
Expert Groups 16 An Introduction to Cascade Impaction 77 Impactor Performance Restoration 306
Improving IVIVCs: Example Test
European Pharmaceutical Aerosol How Does a Cascade Impactor Work? 80 In-House and On-Site Equipment
System for DDU Testing 223
Group (EPAG) 16 Servicing and Calibration 308
Types of Cascade Impactor 82 Improving IVIVCs: Example Test
International Pharmaceutical Next Generation Impactor (NGI) 82 Qualification Tools and Documents 309
System for APSD Measurement 225
Consortium on Regulation and IQ/OQ Documentation 309
Andersen Cascade Impactor (ACI) 88 Dissolution Testing 230
Science (IPAC-RS) 16
Multi-Stage Liquid Impinger (MSLI) 94 Qualification Tools 310
Product Quality Research Facemask Testing 236
Glass Twin Impinger (GTI) 98 Warranty 311
Institute (PQRI) 16 Face Models 237
Aerodynamic Particle Size Support 312
Organisational Chart: Guidelines Test Systems for Assessing
Measurement of: Facemask Performance 238 Design Support 312
and Regulations 17
Metered Dose Inhalers (MDIs) 102 Facemask Testing Apparatus Training Services 313
MDIs with a Spacer/VHC 109 (FMA) for MDIs with a Spacer/VHC 238
Dry Powder Inhalers (DPIs) 116 Facemask Testing Stand (FMS) Index 314
Nebulisers 122 For Nebulisers 242
Aqueous Droplet Inhalers (ADIs) 128 Morphology 246
Nasal Sprays 134 Cold Freon® Effect 247
Nasal Aerosols 141 Spray Force Tester SFT 1000 248
Nasal Powders 147 Plume Temperature Tester PTT 1000 250

4 5
 Inhaler Testing Orally Inhaled &
Nasal Drug Products

Orally Inhaled Drug Products

Metered-Dose Inhalers (MDIs)
MDIs use a propellant to deliver a fixed volume of liquid solution
or suspension to the patient in the form of an aerosol.
They are small, inexpensive, convenient for the user and suitable for a wide
range of drugs. However, the use of MDIs requires good coordination and
technique to actuate the device. The actuation force needed means they are
not always suitable for elderly or paediatric users. The use of breath-actuated
MDIs or add-on devices such as spacers or valved holding chambers (VHCs) can
help resolve these problems.

Conventional Pressurised Breath-Actuated

Orally Inhaled & Nasal

Comprises a pressurised canister Senses the patient’s
containing the medication and inhalation through the
propellant, together with a delivery actuator and synchronises

Drug Products (OINDPs)

device – normally a metering valve dose delivery with it.
linked to an actuator. Pressing
down on the canister releases
the drug in the form of an aerosol
cloud – this is then inhaled into
the lungs.
The range of OINDPs available
is broad, encompassing inhalers
(metered-dose, dry powder and
aqueous droplet), nebulisers (jet, Spacers/VHCs
ultrasonic and vibrating mesh) and Add-on devices such as
nasal sprays, aerosols and powders these reduce or eliminate
(aqueous-based, propellant-based a) the need for coordination
and dry powder). between actuation and
inhalation and b) the cold
Freon® effect (see page 247)
Metered-Dose Aqueous Droplet
F enhancing drug delivery.

Dry Powder Nasal Spray

Spacers/VHC: Coordinated v
Nebuliser F Nasal Powder Uncoordinated use
Performance is optimal and directly comparable
with a standard MDI if the patient inhales from the
spacer/VHC as the device is actuated. This is called
‘coordinated use’.
In contrast, the worst case scenario is if actuation
coincides with exhalation, i.e. ‘uncoordinated use’.

6 7
 Inhaler Testing Orally Inhaled &
Nasal Drug Products

Dry Powder Inhalers (DPIs) Nebulisers

As the name suggests, with a DPI the medication Nebulisers convert a liquid into aerosol droplets to produce a respirable cloud suitable for
comes in the form of a dry powder, rather than inhalation. They are widely used at home and in hospital and require little or no coordination
a liquid. for effective use. Nebulisers are normally loaded with the drug before each treatment and
usually operate continuously once loaded.
Typically, the active pharmaceutical ingredient(s) is mixed
with a coarser excipient, such as lactose, to which it The main advantage of nebulisers is that their use requires little or no coordination on the part of the patient.
attaches. During aerosolisation the active is stripped from However, they tend to be cumbersome and require either compressed air or an electrical supply. Expense,
the carrier and inhaled whilst the carrier particles impact inefficiency and inter-brand variability can also cause issues.
on the mouth and throat and are ingested.
However, their relatively high cost and reliance on
inhalation strength and duration are potential drawbacks.

Passive Ultrasonic Jet Mesh

The majority of DPIs are passive devices, that is to say drug delivery is driven solely by the inspiration of the
patient. There is no need to coordinate breathing with the actuation – the patient simply inhales deeply to
access the drug.

Pre-Metered Unit Dose Device-Metered Use electricity to vibrate a Use a compressed air supply Use ultrasonics to generate
piezoelectric crystal at high to atomise the liquid drug droplets which are then pushed
frequency. The resultant formulation to produce a fine through a static or vibrating
vibrations are transmitted to a mist using the Bernoulli principle. mesh or plate (either electro-
reservoir containing the liquid formed or laser drilled) to form a
Can be subdivided into three
drug formulation, creating a cloud prior to inhalation.
types depending on their output
series of waves from which
during exhalation. Some mesh nebulisers
liquid droplets separate to form
incorporate sensing devices to
an aerosol.
detect the patient’s inspiration
The dose is pre-measured The pre-measured dose in the The drug is contained in a
in order to provide breath-
during manufacture (for form of a gelatine capsule or reservoir within the device
enhanced, breath-activated or
example, blisters, capsules or blister is loaded by the patient which measures each dose
breath-integrated systems.
similar cavities). prior to use. on actuation.

TOP
TIP Some DPIs actively generate the aerosol, reducing dependence on patient inhalation, whilst simultaneously improving
Standard Breath-Enhanced Breath-Actuated
the accuracy and reproducibility of the delivered dose.

Such devices are normally termed ‘active’ DPIs and are particularly useful where the patient’s own inspiration capability Constant output throughout Continuous aerosolisation Aerosol produced only
is compromised. Assistance normally comes in the form of pressurised/compressed air or through vibrations generated the respiratory cycle. but provides higher output during inhalation.
by a piezoelectric transducer. during inhalation.

8 9
 Inhaler Testing Orally Inhaled &
Nasal Drug Products

Aqueous Droplet Inhalers (ADIs)

Both MDIs and DPIs suffer from the same two inherent problems: low
Applications of OINDPs
lung deposition (typically 5-20%) and dose variability (often due to Pulmonary and nasal delivery offers a number of advantages compared to traditional oral and parenteral
patient difficulties in coordination or inspiration). (subcutaneous injection) routes:

ADIs (often known as “Inhalation Metered Sprays’’ or “Soft Mist®” Inhalers) actively Directly targets the site of action Rapid onset of drug action Drugs effective in relatively low doses
aerosolise the liquid, forming a ‘soft mist’ to overcome these problems. These inhalers
generally deliver a higher fine particle fraction than MDIs or DPIs. However, as with any
multi-dose liquid system, microbial contamination can be a problem. Fewer side effects Avoids first pass metabolism Non-invasive administration

ADIs do not use a propellant to aerolise the liquid. Methods of aerosol generation include: Such drugs include treatments for diverse applications such as diabetes, erectile dysfunction, migraine,
(a) Forcing liquid through a nozzle (c) Thermal generation osteoporosis and for vaccine delivery.

(b) Electrospraying (d) Vibration mesh

As far as testing is concerned, most ADIs are treated as MDIs unless their particular
Orally Inhaled Drug Product Applications
design dictates otherwise. Orally inhaled drugs are becoming increasingly popular as a means of delivering local
or systemic therapy via the lungs.

Nasal Drug Products Local Treatment Systemic Treatment

Like inhalers, nasal products can be liquid-, propellant- or powder-based. They are commonly To treat lung diseases such Considerable research and
multi-dose although unit dose devices are popular for delivering vaccines and pain relief. as asthma and chronic development has been devoted
obstructive pulmonary disease to delivering new drugs into the
(COPD), and to deliver locally systemic circulation via the inhaled
acting drugs such as antibiotics route – no doubt attracted by the
and antivirals directly to the large surface area and easy air/
lungs to curb infection blood interface provided by the
Nasal Sprays Nasal Aerosols Nasal Powders
respiratory system.

Nasal Drug Product Applications

Traditionally, nasal preparations have been used for the local administration of antihistamines,
decongestants and steroids in order to alleviate cold or allergy symptoms and nasal congestion.

Mechanical metered-dose spray Nasal aerosols are propellant-based Available in both multi- and unit-dose More recently attention has focused on two other areas:
pumps are designed to deliver an and directly analogous to pressurised formats, powder-based devices offer
accurate and consistent dose to MDIs. An angled nosepiece or nozzle preservative-free delivery and can Systemic Circulation Central Nervous System
the user. facilitates insertion into the nostril. produce longer nasal retention times
than liquids. The potential rapid drug absorption The potential of the “Nose
Multi-dose spray pumps have
into the systemic circulation to Brain” entry to the central
dominated the nasal market and Powder-based nasal sprays are ideal
provided by the turbinates and nervous system presented
are widely available through a for peptides, hormones and antigens
(more stable) than liquid formulations
lymphoid tissues located at the by the olfactory region at the
number of device manufacturers.
and where high dose concentrations back of the nasal cavity. This is top of the nasal cavity for the
Unit-dose devices that deliver already in use in a number of treatment of, for example,
are required.
one or two shots (one per nostril),
areas, e.g. migraine and pain relief, diseases of aging such as
are usually based on the syringe
osteoporosis, vaccines. Alzheimer’s Disease.
principle.

10 11
 Inhaler Testing Organisations and their Roles

Organisations
and their Roles
The ultimate responsibility for the safety, quality and efficacy of medicines Additionally, the FDA has been focusing on further characterization. The goal of this initiative is to provide
and medical devices lies with the various national regulatory bodies designated strategies to support the development of generics, notably greater understanding of the complex interactions between
to safeguard public health. complex generics like OINDPs. The document “Alternative device, formulation, and patient factors, and eventually be
In Vitro Bioequivalence (BE) Pathways Which Can Reliably able to predict the therapeutic behaviour based on these in
Ensure In Vivo Bioequivalence of Product Performance vitro characteristics”.
Regulatory Bodies in the European Union, China, Japan and USA. with a Generic.” (Generic Drug User Fee Amendments
In April 2018, FDA published a new Draft Guidance for
At present, there are no worldwide standards that are (CDER) in respect of medicines and the Center for (GDUFA)) states, “Additional research is ongoing to explore
Industry for comment (Revision 1) entitled “Metered Dose
specifically applicable to OINDPs. Devices and Radiologic Health (CDRH) in respect of physicochemical API properties and device characteristics
Inhaler (MDI) and Dry Powder Inhaler (DPI) Products -
medical devices. to demonstrate structural similarities (Q3) between test
In Europe, the responsibility for the regulation of Quality Considerations”.
and reference Dry Powder Inhaler (DPI), Metered Dose
medicines and medical devices lies with the European The relevant current thinking from the FDA is reflected Inhaler (MDI), and nasal products. A series of projects are This guidance which covers both quality and performance
Medicines Agency (EMA) in the form of the Committee in the following regulatory Guidelines for Industry: exploring these Q3 characteristics, using Morphologically issues as well as CMC information is a revision of the
for Medicinal Products for Human Use (CHMP). Directed Raman Spectroscopy (MDRS) in conjunction previous 1998 Guidance “updated to reflect current
• CDER (1998), “Metered-Dose Inhaler (MDI) and
The EMA was set up in 1995 to harmonise the work of Dry Powder Inhaler (DPI) Drug Products”, Chemistry, with in vitro dissolution, more realistic Aerodynamic standards and requirements to enhance understanding of
existing national regulatory bodies in Europe. Manufacturing and Controls Documentation – Draft Particle Size Distribution (APSD) measurement under appropriate development approaches for these products
realistic in vitro testing conditions, and particle surface consistent with the quality by design (QbD) paradigm”.
The main guidance from the EMA relating to OINDPs is • CDER (2001), “Sterility Requirements for
contained in two guidelines: Aqueous-Based Drug Products for Oral Inhalation”,
Small Entity Compliance ICH Quality Guidelines
• CPMP (2006), “Guideline on the Pharmaceutical
Quality of Inhalation and Nasal Products” • CDER (2002), “Nasal Spray and Inhalation Solution,
Suspension and Spray Drug Products”, Chemistry, Q1A - Q1F Stability Q7 - Good Manufacturing Practice
• CPMP (2009), “Guideline on the requirements for
Manufacturing and Controls Documentation
clinical documentation for orally inhaled products
(OIP) including the requirements for demonstration • CDER (2003), “Integration of dose-counting Q2 - Analytical Validation Q8 - Pharmaceutical Development
of therapeutic equivalence between two inhaled mechanisms into MDI products”, Clinical Medical
products for use in the treatment of asthma and
• CDER (2003), “Bioavailability and bioequivalence Q3A - Q4B Impurities Q9 - Quality Risk Management
chronic obstructive pulmonary disease (COPD)
studies for nasal sprays for local action”,
in adults and for use in the treatment of asthma in
Biopharmaceutics – Draft
children and adolescents” Q4 - Q4B Pharmacopoeias Q10 - Pharmaceutical Quality System
Since December 2013, the FDA has issued a series
These guidelines give a comprehensive list of the
of product specific guidance relating to various
parameters that are critical to the safety, quality and Q5A - Q
 5E Quality of Q11 - D
 evelopment and Manufacture
active pharmaceutical ingredients (APIs) including
efficacy of the final product dependent on the specific Biotechnological Products of Drug Substances
Fluticasone Propionate (FP), Salmeterol, Tiotropium,
type of inhaled or nasal preparation concerned.
and Albuterol, amongst others, intended to help
Q6A - Q6B Specifications Q12 - Lifecycle Management
A similar regulatory function is provided by the generic manufacturers navigate the Abbreviated
Chinese FDA (CFDA) in China and the Ministry of New Drug Application (ANDA) process (see Special
Q13 - Continuous Manufacturing of
Health, Labour and Welfare (MHLW) in Japan. Applications, page 252). Drug Substances and Drug Q14 - Analytical Procedure Development
In the USA, the regulatory function is performed by Products

the Food and Drug Administration (FDA) through two

centres, the Center for Drug Evaluation and Research

12 13
 Inhaler Testing Organisations and their Roles

International Regulation and Harmonisation

The International Conference on Harmonisation of Technical Requirements for Registration of
Pharmaceuticals for Human Use (ICH) is a unique organisation consisting of representatives from
the EMA, MHLW and the FDA, and experts from the pharmaceutical industry in the associated
regions, in a single forum.
The purpose of the ICH is to promote greater The ICH Q8(R2) Annex describes the principles and gives
harmonisation in the way in which the individual regulatory examples of many of the essential concepts employed in
bodies regulate new drugs such that the medicine reaches QbD including Critical Quality Attributes (CQAs), Design
the patient economically and with the minimum delay Space and Control Strategy and its implementation
whilst maintaining the standards of safety, quality and through Process Analytical Technology (PAT) Tools.
efficacy necessary to safeguard public health. (Note: A
ICH Q9 describes the principles of quality risk management
similar organisation, the Global Harmonisation Task Force
and their application in a pharmaceutical environment.
(GHTF) exists for medical devices).
ICH Q10 provides a model PQS covering the different Drug Safety, Quality and Efficacy – The Pharmacopoeias
Whilst not OINDP-specific, over the past few years, the ICH
stages of a product life cycle and thus a link between The main role of the Pharmacopoeias is to define the standards with which medicines shall comply
has concentrated on the preparation of four new quality
pharmaceutical development and manufacturing. As a
related guidelines: and the methods by which compliance will be adjudged.
guideline, ICH Q10 is not enforceable – however, it is likely
that the regulators will consider it as standard As with the regulatory groups, the leading Pharmacopoeias tend to be those of the European Union,
• ICH Q8(R2) Pharmaceutical Development
best practice. USA, China and Japan.
• ICH Q9 Quality Risk Management
The practical implementation of the guidelines with respect
• ICH Q10 Pharmaceutical Quality System a) European Pharmacopoeia (Ph. Eur.) These chapters detail the test procedures relevant to each
to OINDPs is not easy because of (a) the complexities
• ICH Q11 Development and Manufacture of dosage form, divided between those relating to product
involved in manufacturing inhalation products, (b) the In the Ph.Eur., the initial information relating to the control
Drug Substances quality and those to product performance.
difficulties in applying real time test methods to them, and of OINDPs is contained in the monograph associated
(c) the lack of clear in vitro – in vivo correlations (IVIVCs) with the dosage form concerned, e.g. “Preparations for Product quality tests assess physical, chemical and
All of which have now been recommended for adoption for most formulations. This continues to be an area of Inhalation (0671)” with cross references to appropriate microbial attributes. Product performance tests assess
by the regulatory authorities concerned (EMA, FDA considerable discussion in pharmaceutical development, methods of testing, e.g. “2.9.18. Preparations for Inhalation: drug release from the dosage form concerned.
and MHLW). quality and regulatory circles. Aerodynamic Assessment of Fine Particles.”
In the case of “Inhalation and Nasal Drug Products”, the
Collectively, these provide the guidelines for a new ICH Q11 provides a Guideline to the “Development and The Ph.Eur. is also responsible for “Pharmeuropa”, a quality tests are described in Chapter <5> whereas the
Pharmaceutical Quality System (PQS) described in ICH Manufacture of Drug Substances” including the type bi-monthly publication available free online, which contains performance tests are described in Chapter <601>.
Q10. Based on International Standards Organisation and extent of information to be submitted in “Draft Monographs and General Texts for Comment” and
Both Ph.Eur. 2.9.44 and USP <1601> also now include
(ISO) quality concepts, the new system includes Good regulatory dossiers. “International Harmonisation”. This publication is a good
chapters on tests designed to characterise nebulisers.
Manufacturing Practice (GMP) regulations where applicable indicator of new and/or amended monographs, e.g. -
Mention should also be made of ICH Q12 which works
and complements ICH Q8 and ICH Q9. “Calibration and Mensuration Issues for the Standard In addition, the USP has introduced Chapter <1602> to
with ICH Q8-Q11 guidelines to provide a framework to
and Modified ACI” Vol.12.4, p.584-588 (2000) - “2.9.44 cover testing of the “Spacers and Valved Holding Chambers
One of the key features of the new PQS is the decision facilitate the management of the entire “Pharmaceutical
Preparations for Nebulisation: Characterisation” Vol. 18.2, (VHCs) used with Inhalation Aerosols” and a new “Chapter
to extend the system to include all parts of the product Product Lifecycle”
p.280-283 (2006). <1603> Cascade Impactor Practices”, which became official
lifecycle, namely: in December 2020, along with revisions to a new General
Finally, two further topics have been endorsed by the
b) United States Pharmacopeia (USP)
Assembly (ICH Q13 and ICH Q14) in June 2018. Chapter, “<1604> Data Interpretation of Aerodynamic
• Pharmaceutical Development Historically, the USP has adopted a similar approach to the Particle Size Distribution Measurements for Orally
ICH Q13, due to be adopted in November 2021, will outline
• Technology Transfer, e.g. from development Ph.Eur. but placed more emphasis on the Physical Tests Inhaled Products.”
Current Good Manufacturing Practices (CGMP) specific
to manufacturing and Determinations, e.g. “Aerosols, Nasal Sprays, Metered-
to the Continuous Manufacturing (CM). The guideline will The USP have also introduced a series of product-specific
Dose Inhalers and Dry Powder Inhalers <601>” than the type
• Manufacturing and also provide guidance to industry and regulatory agencies monographs intended to provide clarification of the testing
of dosage form, ”e.g. Pharmaceutical Dosage Forms <1151>”.
• Product Discontinuation regarding regulatory expectations on the development, of certain generics by methods not previously specified in
implementation, and assessment of CM technologies used However, in USP 38 the Pharmacopeia introduced a series the general chapters.
in the manufacture of drug substances and drug products. of new chapters, <1> through to <5>, which provide general
Like Ph.Eur., USP produce a bi-monthly publication which
information about the Critical Quality Attributes (CQAs)
This decision to extend the PQS to include Pharmaceutical The ICH Q14, due to be adopted in May 2022, will come contains discussion documents relating to new and/
applicable to various dosage forms based on their route
Development through the concept of Quality by Design with a revision to the ICH Q2(R1) Guideline on Validation of or amended chapters and monographs. “Pharmacopeial
of administration.
(QbD) is described in more detail in ICH Q8(R2) Part II Analytical Procedures, with a view to potentially combine Forum” features items relating to “In-Process Revision”,
Pharmaceutical Development – Annex. both documents into one, for simplification and clarity. “Harmonisation” and “Stimuli to the Revision Process.”

14 15
 Inhaler Testing Organisations and their Roles

c) Chinese Pharmacopoeia (ChP) Expert Groups Organisational Chart: Guidelines and Regulations
The ChP has four chapters contained within its Volume IV In addition to the above, there are a number
applicable to OINDPs, <0111>, <0112>, <0113> and <0951>, plus Metered-Dose Dry Powder Aqueous
of industry and quasi-industry expert groups Nasal Products Nebuliser
five drug specific monographs. Inhaler (MDI)* Inhaler (DPI) Droplet Inhaler
whose role is to assist the regulatory bodies in
Chapter <0111> relates to general requirements applicable establishing best practice in their thinking Regulatory
to MDIs, DPIs and nebulisers (incl. DDU) whilst <0951> and guidance.
describes those methods relating to APSD measurement Guideline on the Pharmaceutical Quality of Inhalation and Nasal Products (2006)
for OINDPs. European Pharmaceutical Aerosol Group (EPAG) EMA
Guideline on the Requirements for Clinical Documentation for Orally Inhaled Products (OIP) including the Requirements for
Guidelines
d) Japanese Pharmacopoeia (JP) Demonstration of Therapeutic Equivalence between Two Inhaled Products for use in the Treatment of Asthma and Chronic
A group of 28 member companies active in the OINDP Obstructive Pulmonary Disease (COPD) in Adults and for use in the Treatment of Asthma in Children and Adolescents (2009)
The JP has two chapters related to OIPs, “Chapter <6.14> on market within Europe, formed to establish scientifically
Metered-Dose Inhaler (MDI) & Dry Powder Inhaler (DPI)
Delivered Dose Uniformity” and “Chapter <6.15> on Particle based best practice, provide consensus comment to
Products (2018) - Quality Considerations
industry and government agencies on safety and quality FDA Draft
Size Distribution”. In addition to these, a General Chapter Guidance for
issues, and recommend harmonised standards and Nasal Aerosols and
“G6.4 General Information” is available and applicable Industry Nasal Sprays for Local
to OINDPs. methodology. Copley is an invited member of the cascade Action (2003)
impactor sub-team.
Nasal Spray, Inhalation
FDA Guidance Solution, Suspension
for Industry & Spray Drug Products
Device Safety, Quality and Efficacy – (2002)

International Standards Organisation Drug Efficacy

(ISO) International Pharmaceutical Consortium on Regulation European

Pharmacopoeia
Preparations for Inhalations (Dosage Forms 0671) Nasal Preparations
Preparations for
Nebulisation
and Science (IPAC-RS) Aerodynamic Assessment of Fine Particles (Chapter 2.9.18) (Dosage Forms 0676)
2021 (10.5) (Chapter 2.9.44)
Most OINDPs are unique dosage forms in so far as that
they comprise two components: A group of 21 international companies committed
Inhalation & Nasal Drug Products - General Information & Product Quality Tests <5>
(a) The drug formulation(s) to advancing consensus-based, scientifically driven Aerosols, Nasal Sprays, Metered-Dose Inhalers and Dry Powder Inhalers <601>
standards and regulations for OINDPs worldwide. Copley is Uniformity of Dosage Units <905> Products for
Cascade Impactor Practices <1603> Nebulization <1601>
(b) The medical device delivering that formulation an associate member. US Pharmacopeia Data Interpretation of Aerodynamic Particle Size Distribution Measurements for Orally Inhaled Products <1604>
to the patient 2020 (USP 43) Pharmaceutical Dosage Forms (Aerosols - Inhalations) <1151>

The responsibility of defining the standards relating to Spacers & VHCs

the medical device resides with the ISO. <1602>

The relevant standards are “ISO 20072 Aerosol drug Chinese

Inhalation Products - Metered-Dose, Dry Powder Inhalers and Nebulisers - Delivered Dose Uniformity <0111>
Pharmacopoeia
delivery device design verification – Requirements and Aerodynamic Particle Size Distribution (APSD) <0951>
2020
test methods” for inhalers and “ISO 27427 Anaesthetic Product Quality Research Institute (PQRI)
and respiratory equipment – Nebulising systems and PQRI is a collaborative, research organisation involving the
Japanese Delivered Dose Uniformity <6.14>
Pharmacopoeia Particle Size Distribution <6.15>
components” for nebulisers. FDA’s CDER, industry and academia. General Information <6.4>
(JP17)

It was formed to provide consensus advice on the Device Efficacy

scientific information to be submitted in a regulatory filing
International
to CDER and has been involved in a number of OINDP- Nebulizing Systems
Standards Aerosol Drug Delivery Devices - Requirements and test methods (ISO 20072: 2013)
(ISO 27427: 2013)
related products. Organisation

Expert Groups

European
EPAG
Pharmaceutical
European based industry expert group involved in orally inhaled and nasal drug products
Aerosol Group (EPAG)

International
Pharmaceutical
IPAC-RS
Consortium on
US based industry expert group involved in orally inhaled and nasal drug products
Regulation
& Science (IPAC-RS)

Product Quality
PQRI
Research Institute
A collaborative research organisation involving FDA’s CDER, industry and academia
(PQRI)

16 17
 Inhaler Testing Delivered Dose Uniformity

Delivered Dose
Uniformity (DDU)
One of the four Critical Quality Attributes (CQAs) that determine the DDU Over the Entire Contents
safety, quality and efficacy of orally inhaled and nasal drug products Both the European Pharmacopoeia (Ph. Eur.) and United States
(OINDPs) as discussed in the previous chapter, delivered dose is the total Pharmacopoeia (USP) state that DDU tests should be carried out on
amount of drug emitted from the drug device that is available to the user, all orally inhaled products (OIPs) and that in the case of multiple-dose
when the device is actuated correctly. devices* tests should be carried out throughout the life of the inhaler i.e.
The delivered dose is measured by firing the drug device into a sampling apparatus containing a dose uniformity over the entire contents.
filter. The dose is captured, dissolved in solvent and an aliquot is then analysed, normally using
In the case of Ph.Eur., for example, this involves the collection of 10 doses throughout the
high pressure liquid chromatography (HPLC).
life of each individual inhaler: three doses at the beginning, four in the middle and three
Each OINDP dose typically contains a mixture The uniformity of the delivered dose, or DDU of at the end (see below).
of one or more active pharmaceutical an OINDP must be ensured within and between
* In the case of Ph. Eur., for DPIs this only applies to reservoir type devices.
ingredients (API) together with excipients devices. A number of tests have been defined
designed to help with dose delivery to the by the various regulatory authorities, which are
patient. It is critical to assess that the API designed to demonstrate: Example: Ph. Eur. DDU Over the Entire Contents Requirements
dosage delivered is consistent, or ‘uniform’ with
Inhaler Life Beginning Middle End
each administration to ensure the correct drug
amount is delivered to the patient each time. No. required doses 3 shots 4 shots 3 shots

Dose no. 2, 3, 4 49, 50, 51, 52 98, 99, 100

100 labelled doses 90 shots to waste

Inter-batch dose Intra-dose consistency Dose no. 2, 3, 4 99, 100, 101, 102 198, 199, 200
consistency for multi-dose inhalers
throughout device life 200 labelled doses 190 shots to waste

Similar testing requirements exist for other pharmacopoeias and regulatory guidance (see
page 12). To obtain the required doses for analysis, the remaining contents of the inhaled
device must be wasted (and done so appropriately, i.e. reproducibly and safely).

   The number of deliveries In the case of dry powder

   are greater than or equal inhalers (DPIs), different flow
  
to the label claim rates specific to the patient
  
   population are considered

18 19
 Inhaler Testing Delivered Dose Uniformity

Collection Devices for DDU Testing DUSA for MDIs, BAIs, ADIs and Nasal Aerosols

Depending on the type of inhaler device under test, different apparatus set-ups are required.
The key collection devices are highlighted below. For further information about device-specific The DUSA for MDIs consists of a sample collection tube, a filter to capture the delivered dose and a connector to
connect the DUSA with the wider test set-up. It has been designed to enhance productivity and ensure ease-of-
testing, please proceed to the relevant sections within this chapter. use. The DUSA for MDIs can also be used to test BAIs, ADIs and nasal aerosols.

Schematic of DUSA for MDIs

Dose Uniformity Sampling Apparatus (DUSA)
Two types of DUSA are available for DDU testing - one for metered-dose inhalers (MDIs),
aqueous droplet inhalers (ADIs) and nasal aerosols and one for DPIs and nasal powders. Vacuum Sample
A
C
A E Quick-Release
Connector Collection Tube
Connectors
Typically, the device is connected to the DUSA via a is drawn into the DUSA using a vacuum pump (see supplied as
Mouthpiece D
mouthpiece or nosepiece adapter (see page 203). The page 188) connected to the outlet via a suitable B Rinsing Cap F standard
Adapter
drug-laden cloud released upon actuation of the device length of tubing. H
Filter
C G Rinsing Cap E
Support Cap

B
D Filter H MDI
During testing, air is drawn through the sampling apparatus F
to broadly simulate inhalation. Test conditions are therefore
dependent on device type.

Basic system set-up for DDU testing of MDIs

(according to Ph. Eur.) Component Parts:
G
DUSA for MDIs

Air Flow Direction

Vacuum Pump Tubing Filter DUSA Collection Mouthpiece Inhaler

Tube Adapter Dose Uniformity Sampling Apparatus (DUSA) for MDIs Spare Parts

Cat. No. Description Cat. No. Description

8201 Dosage Unit Sampling Apparatus for MDIs (Silicone Rubber Seals) 8202 Set of 3 Silicone Rubber Seals
8201A Dosage Unit Sampling Apparatus for MDIs (LDPE Seals) 8202A Set of 3 LDPE Seals
8203 Collection Tube
DDU testing of breath-actuated MDIs (BAIs)
8204 Filter Support Cap
Accessories 8205 Rinsing Cap (Silicone Rubber Seal)
8205A Rinsing Cap (LDPE Seal)
Air Flow Direction
8111 Stand (incl. Base Plate, Boss Head and Clamp) 8206 Flow Meter Cap (Silicone Rubber Seal)
8211 Stand for 10 Collection Tubes 8206A Flow Meter Cap (LDPE Seal)
Tubing Filter Inhaler 8207 Stainless Steel Filter Support Disc
8210 Pack of 500 Glass Fibre Filters
Note: Aluminium or 316 Stainless Steel DUSAs are available, if required

Vacuum Pump Breath Actuation DUSA Collection Mouthpiece

Controller Tube Adapter

20 21
 Inhaler Testing Delivered Dose Uniformity

DUSA for DPIs and Nasal Powders

The DUSA for DPIs is a larger version of the DUSA for MDIs and is designed specifically to sample at During testing, air is drawn through the sampling apparatus to broadly
flow rates up to 100 L/min. It is also used to characterise the flow resistance of DPIs. The pressure simulate inhalation. A critical flow controller is required to control air flow
tap (P1) in its wall is used to connect a critical flow controller to measure the pressure drop across supply to the inhaler and ensure critical (sonic) flow conditions during testing.
the device. The DUSA for DPIs can also be used to assess nasal powders.

Basic system set-up for DDU testing of DPIs

Schematic of DUSA for DPIs (according to Ph. Eur. and USP).

Vacuum Sample
A E
Connector Collection Tube Quick-Release
Air Flow Direction
A C Connectors
supplied as
B Rinsing Cap F Pressure Tap (P1) standard

Filter Mouthpiece D P1 Pressure

C G Port
Support Cap Adapter
E
D Filter H DPI
B

I Rinsing Cap
G

F
H

Vacuum Pump Tubing Critical Flow Controller Filter DUSA Collection Mouthpiece Inhaler
Tube Adapter

Dose Uniformity Sampling Apparatus (DUSA) for DPIs Spare Parts

Cat. No. Description Cat. No. Description

8601 Dosage Unit Sampling Apparatus for DPIs (Silicone Rubber Seals) 8602 Set of 3 Silicone Rubber Seals
8601A Dosage Unit Sampling Apparatus for DPIs (LDPE Seals) 8602A Set of 3 LDPE Seals
8603 Pack of 100 Glass Fibre Filters
8606 Filter Support Cap
8607 Rinsing Cap (Silicone Rubber Seal)
8607A Rinsing Cap (LDPE Seal)
Accessories 8608 Collection Tube with P1 Port
8608A Collection Tube without P1 Port
8111 Stand (incl. Base Plate, Boss Head and Clamp) 8609 Flow Meter Cap (Silicone Rubber Seal)
8604 Stand for 10 Collection Tubes 8609A Flow Meter Cap (LDPE Seal)
8610 Stainless Steel Filter Support Disc

Note: Aluminium or 316 Stainless Steel DUSAs are available, if required

Component Parts: DUSA for DPIs

22 23
 Inhaler Testing Delivered Dose Uniformity

Waste Shot Collection Devices British Pharmacopoeia (BP) Content

for DDU over the Entire Contents
Firing inhaled drug product shots to waste requires an
Uniformity Apparatus for MDIs
evacuation system, which captures the aerosol emitted In addition to the Ph.Eur. and USP specified DUSA, the BP has its own unique apparatus
from repeated actuations of the device. The system for determining the “Content of Active Ingredient delivered by actuation of the valve”,
must be capable of trapping large quantities of the drug likely retained for historical reasons. This comprises a stainless steel base plate having
for safe disposal. three legs and a central hole to accept the actuator stem in a small vessel (to which
solvent is added) suitable for shaking.
We offer both manual and automated fire-to-waste
Waste Shot Collector WSC2 systems. For our automated system, please see
page 278. BP Content Uniformity Apparatus for MDIs

Cat. No. Description

8212 BP Content Uniformity Apparatus for MDIs

Waste Shot Collector: WSC2

WSC2 mounted on the ITW
The Waste Shot Collector WSC2 is a compact vacuum
Filter Holder for MDIs with Spacers/Valved
with Switching Valve
filtration system ideal for use in both MDI and DPI
applications. It can be used in either standalone mode
or integrated into the Inhaler Testing Workstation Holding Chambers (VHCs) and for Nebulisers
(ITW, see page 196), via a switching valve, whereby
the vacuum pump used for the DUSA powers both The Filter Holder is designed for DDU testing for both contained within the holder, to capture the delivered
sampling and waste collection units. MDIs with spacers VHCs and for nebulisers. dose. The device under test is interfaced with the
filter holder using a suitable mouthpiece adapter. For
The external dimensions of the inlet of the WSC2 are The Filter Holder is designed for use together with
assessing the effects of a facemask for each device
identical to those of the DUSA. This means that: a breathing simulator, which is used to apply the
type, see page 236.
specific breathing profile required for representative
• the same mouthpiece adapter (and therefore inhaler)
device operating conditions (see page 156). A filter is
can be used with both pieces of equipment
• the two pieces of equipment are interchangeable
within a test set-up so all shots are collected or System set-up for DDU testing of Nebulisers Filter Holder with
discharged to waste under identical Angle Adapter

test conditions
Used to angle the device
Waste doses are captured in a disposable cartridge under test to a position
which collects and traps the contents in an integral representative of
HEPA filter, retaining 99.97% of particles over 0.3 in vivo usage

microns in diameter.

WSC2 with Disposable Cartridge

Breathing Simulator Filter and Filter Nebuliser

Waste Shot Collector WSC2 Holder

Cat. No. Description

5001 Waste Shot Collector WSC2 (including 1 Cartridge)
5002 Spare Filter Cartridge for Waste Shot Collector
8060 Flow Meter to Induction Port/WSC2 Adapter Filter Holder for MDIs with Spacers/VHCs and for Nebulisers
5238 Universal Flow Meter Adapter
5007 Waste Shot Tally Counter Cat. No. Description
9102 Filter Holder and Adapter for Breath Simulator BRS 100i
9102A Filter Holder and Adapter for Breath Simulator BRS 200i/300i
9103 Pack of 100 Filters for Filter Holder
9104 Angle Adapter for Breathing Simulator BRS 100i

24 25
 Inhaler Testing Delivered Dose Uniformity

Nasal Spray Dose Choose your Delivered Dose Collection Device

Collector (NSDC) and Nasal Spray
BP Content

Nasal Spray Waste

NSDC Uniformity USP
DUSA for MDIs DUSA for DPIs Filter Holder Dose Collector
Apparatus for Monographs
(NSDC)
MDIs

Collector (NSWC) MDI Y N N N Y Y

The NSDC is a specially designed apparatus for the
DDU testing of nasal sprays. The drug is sprayed into
an opening large enough to guarantee no drug hits the MDI with
N N Y N N N
Spacer/VHC
entrance but is small enough to greatly reduce the risk
of drug exiting after actuation. The ‘shark’s fin’ design
NSWC deflects the spray away from the centre point of the
DPI N Y N N N Y
nozzle in an aerodynamic fashion to minimise the risk
of any rebound. All points on the fin itself slope away
from the centre point thereby encouraging any drips
that form to run away from the centre. The NSDC has Nebuliser N N Y N N N

been designed to work together with the Vertus II/Plus

automated actuation systems (see page 270), but it
can also be used as a standalone device for the manual ADI Y N N N N N
dose collection of nasal sprays.
The NSWC is designed to collect high volumes of waste
doses with no splashback onto the nozzle, for safe and Nasal Spray N N N Y N N
convenient disposal of the waste drug. Designed for
use with the Vertus II/Plus, the NSWC streamlines nasal
NSDC component parts Nasal Spray Waste spray wasting in a reproducible and time-efficient way. Nasal Aerosol Y N N N N N
Collector (NSWC)
For further information about the Vertus range, see
page 270.
USP Monographs Nasal Powder N Y N N N N

The USP has product-specific monographs for a NSDC and NSWC

number of APIs including Albuterol (Salbutamol), and
Cat. No. Description
Fluticasone Propionate (FP)/Salmeterol combinations, 9735 Nasal Spray Dose Collector (NSDC)
which are used globally to treat asthma and COPD. Due 9737 Nasal Spray Holder for use with NSDC
to their widespread use and application, these active - Manual
ingredients are routine targets for generic development. 9736 Nasal Spray Waste Collector (NSWC)

These monographs cover both DDU testing and

Aerodynamic Particle Size Distribution (APSD)
measurement since these metrics are required for all
OIPs due to their defining influence on the success and
consistency of drug delivery.

We offer a range of test equipment that closely

replicates the original apparatus used in the
development of these reference labelled drugs (RLD),
enabling bioequivalence testing in accordance with
these monographs.
For more information about the various apparatus used,
Sample Collection Apparatus for FP/Salmeterol Aerosols
see page 260.

26 27
 Inhaler Testing Delivered Dose Uniformity

Regulations & Guidelines

The sampling procedure and acceptance criteria for the DDU of MDIs varies according to the
regulatory authority concerned.
Organisation Chapter(s)/Guidance Key DDU Tests

Pharmaceutical Development:
• DDU Through Container Life
• DDU Over Patient Flow Rate Range
Guideline on the Pharmaceutical Quality of
EMA Product Manufacture:
Inhalation and Nasal Products 2006
• Mean Delivered Dose
• Delivered Dose Uniformity
• Content Uniformity / Uniformity of Dosage Units

Uniformity of Delivered Dose

Ph. Eur. Chapter 0671
Number of Deliveries per Inhaler

MDI & DPI Products - Quality Considerations

FDA Delivered Dose Uniformity
Draft Guidance 2018

Delivered Dose Uniformity of Product

USP Chapter <601>
Dose Uniformity Over the Entire Unit Life

Ch.P. Chapter 0111 Delivered Dose Uniformity

Delivered Dose Uniformity JP Chapter 6.14 Delivered Dose Uniformity

Metered Dose
DDU Over the Entire Contents
1st Test Tier 1st Test Tier 2nd Test Tier 2nd Test Tier
Organisation
No. of Inhalers Criteria No. of Inhalers Criteria

Inhalers (MDIs) Ph.Eur

10 Inhalers/
1 prime
3 beginning of life
4 middle of life
9/10 doses to be
75-125% of Mean
All doses to be 65-135%
of Mean
20 Inhalers/ 1 dose
27/30 doses to be
75-125% of Mean Value
All doses to be 65-135%
of Mean Value
Mean Value to be
Mean to be 85-115% of LC*
MDI aerosol characteristics are relatively insensitive to changes in air flow rate because 3 end of life 85-115% of LC*

the aerosolisation and dispersion mechanisms are dependent on the force generated 10 Inhalers/
1 prime
by the propellant, rather than the patient’s inspiratory effort. Therefore, for MDIs, the USP
1 beginning of life
N/A N/A N/A

test flow rate is fixed at an arbitrary value of 28.3 L/min. 1 end of life

EMA As per Ph.Eur. As per Ph.Eur. As per Ph.Eur. As per Ph.Eur.

A vacuum pump is used to draw air through the Further information about the DDU testing of MDIs
assembled test set-up at this flow rate. with a spacer or VHC can be found on page 36. 54/60 doses to be
10 Inhalers/ 18/20 doses to be 80-120% 80-120% of TDD
20 Inhalers/
However, these test conditions are not applied for 1 beginning of life 20/20 to be 75-125% 60/60 to be 75-125%
FDA 1 beginning of life
DDU testing when the MDI is intended for use with 1 end of life of TDD** of TDD**
1 end of life
Mean to be 85-115% of TDD** Mean to be 85-115%
an add-on device such as a spacer or valved holding of TDD**
chamber (VHC).

1 Inhaler/10 doses 9/10 doses to be 75-125% 27/30 doses to be 75-125%

and all to be 65-135% of 2 inhalers/20 doses and all to be 65-135% of
Ch.P. (MDIs) and Multidose DPIs) Average Delivered Dose Average Delivered Dose
20 inhalers/1 dose of each
10 inhalers/1 dose of each Mean to be 80-120% of LC* Mean to be 80-120% of LC*

9/10 to be 75-125% 27/30 doses to be 75-125%

of Mean Value of Mean Value
JP 1 Inhaler/10 doses All to be 65-135% 2 inhalers/20 doses All to be 65-135%
of Mean Value of Mean Value
Mean to be 85-115% of LC* Mean to be 85-115% of LC*

* - Label Claim ** - Target Delivered Dose

28 29
 Inhaler Testing Delivered Dose Uniformity

DDU of MDIs: Manual Test System Set-Up DDU of MDIs: Manual Test System Component Parts

The minimum set-up for DDU testing as litres; this being the volume of air adjudged to be typical
of the average patient.
specified by the Ph. Eur. comprises a sample
collection tube, fitted at one end with a This additional criterion can be met by positioning
an electronically operated timer controlled two-way Dose Uniformity Sampling Apparatus
suitable mouthpiece adapter to accept the (DUSA) for MDIs
solenoid valve, such as that incorporated in the Breath
inhaler under test and connected at the Actuation Controller BAC 100i. See page 21
other end to a vacuum pump capable of
continuously drawing 28.3 L/min through DDU for MDIs: Test Specifications
the inhaler.
Flow Rate (Q) 28.3 L/min
In addition to the specifications laid down by the Ph.
Air Volume (Ph. Eur./EMA) Not defined In addition to the DUSA for MDIs, the following is needed to complete a fully-operational test set-up for the
Eur., the FDA recommends and the USP specifies that
delivered dose testing of MDIs:
the volume of air to be sampled should not exceed 2 Air Volume (USP/FDA) 2 litres

Vacuum Pump

A B C Designed for optimal operation at the low flow rates required for MDI
D testing, the Low Capacity LCP6 Vacuum Pump represents the latest in
high performance, low maintenance, vacuum pump technology. Our
E Vacuum Pump range is specifically designed for use in the testing of
OINDPs in accordance with pharmacopoeial requirements.

F See page 188 for further information about our Vacuum Pump range.

H
Breath Actuation Controller (BAC)
Ensuring that the volume of air sampled does not exceed
pharmacopoeial specifications, the Breath Actuation Controller
BAC 100i contains an electronically operated, timer-controlled
Breath Actuation Inhaler Testing
A Vacuum Pump B
Controller
C
Workstation (ITW)
D Flow Meter E Mouthpiece Adapter two-way solenoid valve and is positioned between the DUSA
and vacuum pump.
Waste Shot
F DUSA for MDIs G H Switching Valve
Collector See page 172 for further information about our Flow Controller range.

Related Accessories
TOP
TIP The BAC 100i can also be used for the testing of Breath-Actuated (or Breath-Operated) MDIs. In this case,
the BAC 100i is used to initiate the flow, simultaneously triggering the breath-actuated inhaler.

+ +
Flow Meter
Used for establishing accurate and consistent inlet flow rate
during testing, our range of Flow Meters measure and control
flow rates to the accuracy specified by the pharmacopoeias.
DUSA Collection Tube Stand Temperature and Relative Humidity Sensor MDI Actuation Sensor/Footswitch
Designed for the convenient transfer of Ideal for measuring environmental Suitable for most commercially available MDI canisters, See page 184 for further information about our range of
multiple DUSA for MDIs around test conditions. See page 179. the MDI Actuation Sensor connects directly to the
the laboratory. See page 21 Breath Actuation Controller BAC 100i to ensure precise Flow Meters.
synchronisation of MDI actuation. Alternatively, a Footswitch
can be attached to trigger actuation. See page 179.

30 31
 Inhaler Testing Delivered Dose Uniformity

DDU of MDIs: Manual Test System Component Parts DDU of MDIs:

Semi-Automated Test System Set-Up
Inhaler Testing Workstation (ITW) The Vertus automated shake, fire and shot waste range is made up of integrated turn-key
Designed to keep the sampling apparatus organised during testing and solutions for precise, controlled and reproducible MDI testing.
improve workflow efficiency, the Inhaler Testing Workstation ITW holds
the DUSA collection tube, vacuum connector, flow meter and waste shot Compatible with most MDIs, the Vertus systems Improve inhaler Increase productivity
collector (WSC2). offer analysts complete control over: testing accuracy and reduce hassle
and reproducibility
See page 196 for further information. • The speed, angle and duration of shaking,
ahead of actuation Replicate test Reduce handling errors
methods across and costly out-of-
• Firing force and the speed of application different sites specification results
and release of that force with ease
Waste Shot Collector and Switching Valve • The time delay between the end of shaking
A compact vacuum filtration system, the Waste Shot Collector WSC2 and device actuation
captures aerosols emitted from repeated actuations of the inhaler,
trapping large quantities of the drug for safe disposal. The Switching Valve
is used to re-direct air flow between the collection device and WSC2 for
quick and easy dose wasting.
Vertus II & Vertus Plus
See page 24 for further information about the WSC2. Alternatively,
Offering high productivity, walkaway MDI testing, the Vertus
automate labour-intensive MDI waste shot collection with the
II and Vertus Plus can collect doses at the start, middle and
Vertus and DecaVertus (see page 270).
end of product life (including shots to waste as required)
all without manual intervention. The Vertus Plus also offers
optional shot weight collection.

Mouthpiece Adapter
Moulded from high quality silicone rubber, our Mouthpiece Adapters
DecaVertus
guarantee an airtight seal between the inhaler and the test apparatus.
For a list of available Mouthpiece Adapters see page 203. Accepting up to 10 inhalers per run, the DecaVertus
is a high-throughput shake and fire-to-waste system, ideal
Custom Mouthpiece Adapters are available upon request. for alleviating the burden of tedious through-life testing.

Qualification Replaces the need for:

Good Manufacturing Practices (GMP) regulations require that Vacuum Pump Breath Actuation Controller Flow Meter

• The test methods used to monitor pharmaceuticals must meet proper standards of
accuracy and reliability
• Companies should establish procedures to ensure the fitness for use of instruments
that generate data supporting product testing
Inhaler Testing Workstation Waste Shot Collector
Copley provides a range of qualification documentation, services and tools to meet with Switching Valve
these requirements.
See page 270 for further information
See page 302 for further information. about the Vertus and Decavertus range.

32 33
 Inhaler Testing Delivered Dose Uniformity

Related Applications
We also offer a range of equipment for additional MDI testing application support:

For better in vitro-in vivo For cold Freon® effect testing For USP product-specific
correlation (IVIVC) testing See page 247 monograph testing
See page 214 See page 260

Semi-Automation Tools
Eliminate Increase
Improve efficiency Reduce variability
handling errors testing capacity

DUSA Shaker
Holding up to 21 MDI DUSA collection tubes, the DUSA
shaker automates the internal rinsing of the tubes to ensure
full, fast and repeatable drug dissolution and drug recovery
from internal surfaces.
See page 282 for further information.

Training, Servicing & Support

We offer a comprehensive range of services from bespoke product design to
installation, expert training and technical support, optimising all aspects of
pharmaceutical testing from start to finish.

Training Servicing Support Design

See page 313 See page 304 See page 312 See page 312

34 35
 Inhaler Testing Delivered Dose Uniformity

Add-on Device Schematic C

A Mouthpiece

B Spacer/VHC

C Inhaler

Regulation & Guidelines

The sampling procedure for the DDU testing of MDIs with a spacer/VHC varies according to the regulatory
Delivered Dose Uniformity authority concerned.

MDIs with Organisation Chapter(s)/Guidance Key DDU Tests

a Spacer/VHC FDA
MDI & DPI Products - Quality Considerations
Draft Guidance 2018
Effect of Flow Rate and Inhalation Delay
on MDIs with Spacers

Add-on devices such as spacers, VHCs and reverse VHCs reduce or eliminate the need
for coordination between actuation and inhalation and are widely used together with USP Chapter <1602>
Mass of drug delivered - fully coordinated
and fully uncoordinated
MDIs to overcome coordination issues.
When a patient uses an MDI without an add-on device, As the use of add-on devices has grown, the regulatory
the drug particles contained within the delivered dose authorities have become increasingly aware of the need
are inhaled almost instantaneously as the formulation to test with add-on devices as distinct from MDIs alone.
Table 1: Representative Tidal Breathing Patterns
is aerosolised. In contrast, when an add-on device such
The amount of drug received by the patient using an Paediatric Adult
as a spacer or VHC is used, the patient inhales the drug
add-on device with an MDI will be directly influenced
from a reservoir of aerosolised particles. Parameter Neonate Infant Child Normal 1 Normal 2
by the inhalation profile of the user concerned. For
The additional dead volume provided by this reservoir that reason, tests call for the application of specific Tidal Volume (mL) 25 50 155 770 500
allows aerosol expansion, but also an opportunity breathing profiles to reflect the physiology of the
Frequency (cycles/min) 40 30 25 12 13
for particle impaction, settling and/or electrostatic intended user, see Table 1.
deposition within the chamber itself, all of which can I/E Ratio 1:3 1:3 1:2 1:2 1:2

change the delivered dose. Minute Volume (mL) 1000 1500 3875 9240 6500

For DDU over the entire contents testing of MDIs with a spacer/VHC and a facemask, see page 238.

36 37
 Inhaler Testing Delivered Dose Uniformity

DDU of MDIs with a Spacer/VHC: DDU of MDIs with a Spacer/VHC: Test System Component Parts

Test System Set-Up

The standard sampling apparatus for MDIs with an add-on device consists of a breathing
Filter Holder (with Adapter for Breath Simulator
simulator to generate the specified breath profile, a filter holder containing the filter to capture
Model BRS 100i)
the delivered dose and a suitable mouthpiece adapter to connect the filter holder to the
See page 25
mouthpiece of the spacer/VHC concerned.

In the case of VHCs, tests are also carried out to compare the dose received when use is coordinated
or uncoordinated with device actuation, to assess the impact of valve operation.

In addition to the Filter Holder, the following is needed to complete a fully-operational test set-up for the
A B C delivered dose testing of MDIs with a spacer/VHC.

Breathing Simulator
Providing breathing profiles more representative of in vivo
behaviour than conventional systems offering a constant
flow rate, the Breathing Simulator Model BRS 100i is ideal for
assessing the effects of a spacer or VHC on the DDU of MDIs.
Alternatively, the higher capacity Breathing Simulator Model
BRS 100i
200i can be used to access expanded functionality including
the capability to apply user-defined profiles.
Find out more about our range of Breathing Simulators BRS 200i
A Breathing Simulator
on page 156.

B Filter Holder

C Mouthpiece Adapter
Mouthpiece Adapter
Moulded from high quality silicone rubber, our Mouthpiece Adapters
guarantee an airtight seal between the spacer/VHC and the test
apparatus. For a list of available Mouthpiece Adapters see page 203.
Related Accessories
TOP Custom Mouthpiece Adapters are available upon request.
TIP The constant 28.3 L/min air flow rate applied during the
testing of MDIs is replaced by a specific patient relevant
tidal breath profile more representative of the conditions
applied by the patient when using an add-on device.

MDI Actuation Sensor/Footswitch

Suitable for most commercially available MDI canisters, the MDI
Actuation Sensor connects directly to the Breath Actuation Controller
BAC 100i to ensure precise synchronisation of MDI actuation.
Alternatively, a Footswitch can be attached to trigger actuation.
See page 179.

38 39
 Inhaler Testing Delivered Dose Uniformity

Qualification
GMP regulations require that

• The test methods used to monitor pharmaceuticals must meet proper standards of
accuracy and reliability
• Companies should establish procedures to ensure the fitness for use of instruments
that generate data supporting product testing

Copley provides a range of qualification documentation, services and tools to meet

these requirements.
See page 302 for further information.

Related Applications
We also offer a range of equipment for additional MDIs with a spacer/VHC
testing application support:

For facemask testing

See page 236

Training, Servicing & Support

We offer a comprehensive range of services from bespoke product design to
installation, expert training and technical support, optimising all aspects of
pharmaceutical testing from start to finish.

Training Servicing Support Design

See page 313 See page 304 See page 312 See page 312

40 41
 Inhaler Testing Delivered Dose Uniformity

Regulations & Guidelines

The sampling procedure and acceptance criteria for the DDU testing of DPIs varies according
to the regulatory authority concerned.

Organisation Chapter(s)/Guidance Key DDU Tests

Pharmaceutical Development:
• DDU Through Container Life
• DDU Over Patient Flow Rate Range
Guideline on the Pharmaceutical Quality of
EMA Product Manufacture:
Inhalation and Nasal Products 2006
• Mean Delivered Dose
• Delivered Dose Uniformity
• Content Uniformity / Uniformity of Dosage Units

Uniformity of Delivered Dose

Ph. Eur. Chapter 0671
Number of Deliveries per Inhaler

MDI & DPI Products - Quality Considerations

FDA Delivered Dose Uniformity
Draft Guidance 2018

Delivered Dose Uniformity of Product

USP Chapter <601>
Dose Uniformity Over the Entire Unit Life

Ch.P. Chapter 0111 Delivered Dose Uniformity

Delivered Dose Uniformity JP Chapter 6.14 Delivered Dose Uniformity

Dry Powder DDU Over the Entire Contents

1st Test Tier 1st Test Tier 2nd Test Tier 2nd Test Tier

Inhalers (DPIs)
Organisation
No. of Inhalers Criteria No. of Inhalers Criteria

10 Inhalers/ 27/30 doses to be

9/10 doses to be
75-125% of Mean Value
1 prime 75-125% of Mean
All doses to be 65-135%
Ph.Eur 3 beginning of life All doses to be 65-135% 20 Inhalers/ 1 dose
of Mean Value
of Mean
For DPIs, the test regime is more complex Pressure difference between lungs and 4 middle of life
Mean to be 85-115% of LC*
Mean Value to be
3 end of life 85-115% of LC*
than for MDIs, since aerosolisation atmosphere when inhaling through a DPI
10 Inhalers/
depends on the strength and duration 1 prime
USP N/A N/A N/A
of a single inhalation by the user. 1 beginning of life
ΔP = 4 kPa 1 end of life
During a single, deep inhalation, a typical adult
produces a pressure drop over the device of
* � 100 kPa (atmosphere)
EMA As per Ph.Eur. As per Ph.Eur. As per Ph.Eur. As per Ph.Eur.

approximately 4 kPa. Depending on the device flow 54/60 doses to be

10 Inhalers/ 18/20 doses to be 80-120% 80-120% of TDD
resistance this will yield a flow rate, typical of the mean Pharynx
1 beginning of life
20 Inhalers/
20/20 to be 75-125% 60/60 to be 75-125%
patient inhalation flow rate, that is then used for all the FDA 1 beginning of life
1 end of life of TDD** of TDD**
1 end of life
required testing of that device. Trachea & primary bronchi Mean to be 85-115% of TDD** Mean to be 85-115%
of TDD**

Secondary bronchi
1 Inhaler/10 doses 9/10 doses to be 75-125% 27/30 doses to be 75-125%
and all to be 65-135% of 2 inhalers/20 doses and all to be 65-135% of
DDU for DPIs: Test Specifications Terminal bronchi Ch.P. (MDIs) and Multidose DPIs) Average Delivered Dose Average Delivered Dose
20 inhalers/1 dose of each
10 inhalers/1 dose of each Mean to be 80-120% of LC* Mean to be 80-120% of LC*
Flow Rate (Q) Device dependent (4 kPa)
Alveoli
� 96 kPa (lungs) 9/10 to be 75-125% 27/30 doses to be 75-125%
Air Volume (Ph. Eur./EMA) 4 litres
of Mean Value of Mean Value
JP 1 Inhaler/10 doses All to be 65-135% 2 inhalers/20 doses All to be 65-135%
Air Volume (USP/FDA) 2 litres of Mean Value of Mean Value
Mean to be 85-115% of LC* Mean to be 85-115% of LC*

* - Label Claim ** - Target Delivered Dose

42 43
 Inhaler Testing Delivered Dose Uniformity

DDU of DPIs: Test System Set-Up DDU of DPIs: Test System Component Parts

The basic requirements for DPI DDU testing are the same as for MDI testing, namely DUSA,
mouthpiece adapter, vacuum pump and flow meter. However, a critical flow controller (e.g.
Critical Flow Controller TPK 100i) to measure the pressure drop across the device and control Dose Uniformity Sampling Apparatus
the flow conditions during testing is also required. (DUSA) for DPIs

This is mandatory because most DPIs are passive varying degrees of flow resistance, i.e. some require more See page 22
breath-actuated devices which rely on the patient’s effort to inhale through than others.
inspiration rather than a propellant for dose
Find out more about critical flow control on page 172.
aerosolisation and delivery. The testing of DPIs is further
complicated by the fact that different inhalers provide In addition to the DUSA for DPIs, the following is needed to complete a fully-operational test set-up
for the delivered dose testing of DPIs:

A B C
D
Vacuum Pump
Ideal for the higher, sonic flow rate testing requirements of
E
DPIs, the High Capacity HCP6 and Super Capacity SCP6 Vacuum
Pumps represent the latest in high performance, low maintenance,
F vacuum pump technology. Our Vacuum Pump range is specifically
designed for use in the testing of OINDPs in accordance with
G pharmacopoeial requirements.
See page 188 for further information about our Vacuum Pump range.
H

Critical Flow Inhaler Testing

A Vacuum Pump B C D Flow Meter E Mouthpiece Adapter
Controller Workstation (ITW) Critical Flow Controller (TPK)

F DUSA for DPIs G

Waste Shot
H
Switching Simplify DPI test system set-up in accordance with pharmacopoeial
Collector Valve
recommendations with the Critical Flow Controller series. Positioned
between the DUSA and vacuum pump, the Critical Flow Controller
TPK 100i ensures critical (sonic) flow conditions during testing.
It measures and records all parameters required for testing and
Related Accessories controlling flow conditions.
See page 172 for further information about our Flow Controller Range.

+ +

Flow Meter
Used for establishing accurate and consistent inlet flow rate
during testing, our range of Flow Meters measure and control
DUSA Collection Tube Stand Temperature and Relative Humidity Sensor Footswitch flow rates to the accuracy specified by the pharmacopoeias.
Designed for the convenient transfer of Ideal for measuring environmental Connecting directly to the Critical Flow Controller
multiple DUSA for DPIs around test conditions. See page 183. TPK 100i, the Footswitch enables precise
See page 184 for further information about our range
the laboratory. See page 23. synchronisation of DPI device actuation with the of Flow Meters.
onset of flow. See page 183.

44 45
 Inhaler Testing Delivered Dose Uniformity

DDU of DPIs: Test System Component Parts Related Applications

We also offer a range of equipment for additional DPI testing application support:
Inhaler Testing Workstation (ITW)
Designed to keep the sampling apparatus organised during testing and
improve workflow efficiency, the Inhaler Testing Workstation ITW holds
the DUSA collection tube, vacuum connector, flow meter and waste
shot collector (WSC2).
See page 196 for further information.
For better in vitro-in vivo For USP product-specific
correlation (IVIVC) testing monograph testing
See page 214 See page 260
Waste Shot Collector and Switching Valve
A compact vacuum filtration system, the Waste Shot Collector WSC2
captures aerosols emitted from repeated actuations of the inhaler, trapping
large quantities of the drug for safe disposal. The Switching Valve is used
Semi-Automation Tools
to re-direct air flow between the collection device and WSC2 for quick and Eliminate Increase
Improve efficiency Reduce variability
easy dose wasting. Please note: only required for multi-dose devices. handling errors testing capacity

See page 24 for further information about the Waste Shot Collector WSC2.

DUSA Shaker

Mouthpiece Adapter Holding up to 12 DPI DUSA collection tubes, the DUSA shaker
automates the internal rinsing of the tubes to ensure full,
Moulded from high quality silicone rubber, our Mouthpiece Adapters
fast and repeatable drug dissolution and drug recovery from
guarantee an airtight seal between the inhaler under test and the test
internal surfaces.
apparatus. For a list of available Mouthpiece Adapters see page 203.
See page 282 for further information.
Custom Mouthpiece Adapters are available upon request.

DDU Over the Entire Contents Training, Servicing & Support

In the case of DPI reservoir type devices, tests should be carried out throughout the life of the inhaler i.e.
dose uniformity over the entire contents. For further information, see page 24.
We offer a comprehensive range of services from bespoke product design to
installation, expert training and technical support, optimising all aspects of
pharmaceutical testing from start to finish.
Qualification
GMP regulations require that
• The test methods used to monitor pharmaceuticals must meet proper standards of
accuracy and reliability
• Companies should establish procedures to ensure the fitness for use of instruments
that generate data supporting product testing Training Servicing Support Design
See page 313 See page 304 See page 312 See page 312
Copley provides a range of qualification documentation, services and tools to meet
these requirements.
See page 302 for further information.

46 47
 Inhaler
Inhaler
Testing
Testing Delivered Dose Uniformity

Regulations and Guidelines

The Filter Holder apparatus is used to perform those tests specified in the Pharmacopoeias relating to:
• Preparations for Nebulisation: Characterisation (Ph. Eur. 2.9.44)
• General Information: Products for Nebulization – Characterization Tests (USP <1601>)

Organisation Chapter(s)/Guidance Key DDU Tests listed

Guideline on the Pharmaceutical • Drug Delivery Rate

EMA
Quality of Inhalation and Nasal Products • Total Drug Delivered

Chapter 2.9.44. Preparations for Nebulisation: Ph. Eur. : Active Substance Delivery Rate
Ph. Eur.
Characterisation Total Active Substance Delivered

Guidance for Industry: Nasal Spray and

Inhalation Solution, Suspension and Spray
FDA Content Uniformity
Drug Products - Chemistry, Manufacturing and
Delivered Dose Uniformity Controls Documentation

Nebulisers
Chapter <1601> Products for Nebulization - Drug Substance Delivery Rate
USP
Characterization Tests Total Drug Substance Delivered

Ch.P. Chapter 0111 Delivered Dose Uniformity

The delivered dose testing of nebulisers is carried out to determine the total amount JP - -
of drug a patient might be expected to receive during a treatment period, rather than
through one inhalation.
Given the mode of operation of nebulisers, well-defined reliably achieved using breathing simulators
Table 2 : Breathing Simulator Specifications for Nebuliser Characterisation Tests
tidal breathing profiles for specific patient types are (see page 156).
specified for testing (see Table 2). These profiles can be Adult Neonatal Infant Child

Tatal Volume 500 ml 25 ml 50 ml 155 ml

Frequency 15 cycles/min 40cycles/min 30 cycles/min 25 cycles/min

Delivered Dose Testing Requirements for Nebulisers
Waveform Sinusoidal Sinusoidal Sinusoidal Sinusoidal
The delivered dose of a nebuliser is
I/E Ratio 1:1 1:3 1:3 1:2
quantified via two discrete metrics:
the active substance delivery rate and
the total active substance delivered. 1. Active Substance
Delivery Rate
(normally 60 seconds)
To measure active substance delivery rate the
Filter 1 60 Seconds 1.
output from the nebuliser is captured on a filter,
under appropriate test conditions, over a specified
time (typically 60 seconds). Replacing the
filter and continuing the test until nebulisation 2. Total Active
stops, because the reservoir is empty, enables Substance Delivered
(until exhaustion)
calculation of the second metric – total active Filter 2 Until 2. + 1.
exhaustion
substance delivered. This is the total mass
collected during steps 1 and 2 of the test.

48 49
 Inhaler Testing Delivered Dose Uniformity

DDU of Nebulisers: Test System Set-Up DDU of Nebulisers: Test System Component Parts

The sampling apparatus for nebulisers (mouthpiece-based products) consists of a

breathing simulator to generate the specified breathing profile, a filter holder containing
the filter to capture the delivered dose and a suitable mouthpiece adapter to connect the Filter Holder (with Angle Adapter and Adapter for
filter holder to the nebuliser under test. Breathing Simulator Model BRS 100i)
See page 25

A B C D

In addition to the Filter Holder, the following is needed to complete a fully-operational test set-up for the
delivered dose testing of nebulisers:

Breathing Simulator
Providing breathing profiles more representative of in vivo
behaviour than conventional systems offering a constant
flow rate, the Breathing Simulator Model BRS 100i is ideal
for assessing the DDU of nebulisers. Alternatively, the higher
BRS 100i
capacity Breathing Simulator Model BRS 200i can be used
to access expanded functionality including the capability to
apply user-defined profiles.
BRS 200i
Find out more about our range of Breathing Simulators on
A Breathing Simulator B Angle Adapter C Filter Holder D Mouthpiece Adapter page 156.

Mouthpiece Adapter
Moulded from high quality silicone rubber, our Mouthpiece
Adapters guarantee an airtight seal between the nebuliser and
the test apparatus. For a list of available Mouthpiece Adapters
See page 203.
Custom Mouthpiece Adapters are available upon request.

50 51
 Inhaler Testing Delivered Dose Uniformity

Qualification
GMP regulations require that

• The test methods used to monitor pharmaceuticals must meet proper standards of
accuracy and reliability
• Companies should establish procedures to ensure the fitness for use of instruments
that generate data supporting product testing

Copley provides a range of qualification documentation, services and tools to meet

these requirements.
See page 302 for further information.

Related Applications
We also offer a range of equipment for additional nebuliser testing application support:

For better in vitro-in vivo For facemask testing

correlation (IVIVC) testing See page 236
See page 214

Training, Servicing & Support

We offer a comprehensive range of services from bespoke product design to
installation, expert training and technical support, optimising all aspects of
pharmaceutical testing from start to finish.

Training Servicing Support Design

See page 313 See page 304 See page 312 See page 312

52 53
 Inhaler Testing Delivered Dose Uniformity

DDU of ADIs: Test System Set-Up

A B C
D

Delivered Dose Uniformity

Aqueous Droplet Inhalers (ADIs) Breath Actuation Inhaler Testing

A Vacuum Pump B C D Flow Meter E Mouthpiece Adapter
Controller Workstation (ITW)
Since they are active, aqueous-based devices, the DDU testing of ADIs is similar
to that of MDIs, with testing carried out at a constant flow rate of 28.3 L/min. F DUSA for MDIs G Waste Shot Collector H Switching Valve

Regulations and Guidelines

The sampling procedure and acceptance criteria for the DDU testing of ADIs varies according to the
regulatory authority concerned.
Related Accessories
Organisation Chapter(s)/Guidance Key DDU Tests

Guideline on the Pharmaceutical Quality of

EMA Delivered Dose Uniformaty
Inhalation and Nasal Products 2006
+ +

Ph. Eur. - -

Guidance for Industry: Nasal Spray and

Inhalation Solution, Suspension and Spray DUSA Collection Tube Stand Temperature and Relative Humidity Sensor Footswitch
FDA Content Uniformity
Drug Products - Chemistry, Manufacturing and
Designed for the convenient transfer of Ideal for measuring environmental Connecting directly to the Breath Actuation
Controls Documentation multiple DUSA for MDIs around test conditions. See page 179. Controller BAC 100i, the Footswitch enables
the laboratory. See page 21. precise synchronisation of ADI device
actuation with the onset of flow. See page 179.
USP - -

Ch.P. Chapter 0111 Delivered Dose Uniformity

JP - -

54 55
 Inhaler Testing Delivered Dose Uniformity

DDU of ADIs: Test System Component Parts

Inhaler Testing Workstation (ITW)

Dose Uniformity Sampling Apparatus Designed to keep the sampling apparatus organised during testing and
(DUSA) for MDIs improve workflow efficiency, the Inhaler Testing Workstation ITW holds
See page 21 the DUSA collection tube, vacuum connector, flow meter and waste shot
collector (WSC2).
See page 196 for further information.

In addition to the DUSA for MDIs, the following is needed to complete a fully-operational test set-up for the
delivered dose testing of ADIs:
Waste Shot Collector and Switching Valve
A compact vacuum filtration system, the Waste Shot Collector WSC2
Vacuum Pump captures aerosols emitted from repeated actuations of the inhaler, trapping
Designed for optimal operation at the low flow rates required for large quantities of the drug for safe disposal. The Switching Valve is used to
ADI testing, the Low Capacity LCP6 Pump represents the latest in re-direct air flow between the collection device and WSC2 for quick and easy
high performance, low maintenance, vacuum pump technology. Our dose wasting. Please note: only required for multi-dose devices.
Vacuum Pump range is specifically designed for use in the testing of
See page 24 for further information about the Waste Shot Collector WSC2.
OINDPs in accordance with pharmacopoeial requirements.
See page 188 for further information about our Vacuum Pump range.

Mouthpiece Adapter
Moulded from high quality silicone rubber, our Mouthpiece
Adapters guarantee an airtight seal between the inhaler under test
Breath Actuation Controller (BAC)
and the test apparatus. For a list of available Mouthpiece Adapters
Ensuring that the volume of air sampled does not exceed see page 203.
pharmacopoeial specifications, the Breath Actuation Controller BAC 100i
Custom Mouthpiece Adapters are available upon request.
contains an electronically operated, timer-controlled two-way solenoid
valve and is positioned between the DUSA and vacuum pump.
See page 172 for further information about our Flow Controller range.
DDU Over the Entire Contents
In the case of multiple dose devices, tests might need to be carried out throughout the life of the inhaler i.e.
dose uniformity over the entire contents. For further information, see page 24.

Flow Meter
Used for establishing accurate and consistent inlet flow rate Qualification
during testing, our range of Flow Meters measure and control
GMP regulations require that
flow rates to the accuracy specified by the pharmacopoeias.
• The test methods used to monitor pharmaceuticals must meet proper standards of
See page 184 for further information about our range
accuracy and reliability
of Flow Meters.
• Companies should establish procedures to ensure the fitness for use of instruments
that generate data supporting product testing

Copley provides a range of qualification documentation, services and tools to meet

these requirements.
See page 302 for further information.

56 57
 Inhaler Testing Delivered Dose Uniformity

Related Applications
We also offer a range of equipment for additional ADI testing application support:

For better in vitro-in vivo For USP product-specific

correlation (IVIVC) testing monograph testing
See page 214 See page 260

Semi-Automation Tools
Eliminate Increase
Improve efficiency Reduce variability
handling errors testing capacity

DUSA Shaker
Holding up to 21 MDI DUSA collection tubes, the DUSA shaker
automates the internal rinsing of the tubes to ensure full, fast and
repeatable drug dissolution and drug recovery from internal surfaces.
See page 282 for further information.

Training, Servicing & Support

We offer a comprehensive range of services from bespoke product design to
installation, expert training and technical support, optimising all aspects of
pharmaceutical testing from start to finish.

Training Servicing Support Design

See page 313 See page 304 See page 312 See page 312

58 59
 Inhaler Testing Delivered Dose Uniformity

DDU of Nasal Sprays:

Semi-Automated Test System Set-Up

Delivered Dose Uniformity

Nasal Sprays NSDC component parts Nasal Spray Waste

Collector (NSWC)

B
According to regulatory guidance, for the DDU testing of nasal sprays, the test unit
should be actuated in a vertical or near-vertical, valve-up position with adequate
controls over the critical mechanical actuation parameters, such as actuation force,
speed and rest periods.

Regulations and Guidelines

The sampling procedure and acceptance criteria for the DDU testing of nasal sprays varies according to the
regulatory authority concerned. A Vertus Plus with Balance B Nasal Spray Dose
and Printer Collector (NSDC)

Organisation Chapter(s)/Guidance Key DDU Tests

Guideline on the Pharmaceutical Quality of Compatible with most nasal sprays, the Vertus Improve nasal spray Increase productivity
EMA Delivered Dose Uniformity Through Container Life testing accuracy and reduce hassle
Inhalation and Nasal Products systems offer analysts complete control over:
and reproducibility
• The speed, angle and duration of shaking,
Ph. Eur. - - ahead of actuation Replicate test Reduce handling errors
methods across and costly out-of-
• Firing force and the speed of application different sites specification results
Guidance for Industry: Nasal Spray and
Inhalation Solution, Suspension and Spray
and release of that force with ease
FDA Content Uniformity
Drug Products - Chemistry, Manufacturing and • The time delay between the end of shaking
Controls Documentation and device actuation
Chapter <601> Inhalation and Nasal Drug
USP Products: Aerosols, Sprays, and Powders - Delivered Dose Uniformity of Product
For more information about the NSDC and NSWC see page 26.
Performance Quality Tests
To find out more about our range of Automated Shake & Fire systems, see page 270.
Ch.P. Chapter 0111 Delivered Dose Uniformity

JP - -

60 61
 Inhaler Testing Delivered Dose Uniformity

DDU of Nasal Sprays:

Qualification
Manual Test System Set-Up GMP regulations require that

• The test methods used to monitor pharmaceuticals must meet proper standards of
accuracy and reliability
• Companies should establish procedures to ensure the fitness for use of instruments
Used together with its manual holder, the NSDC that generate data supporting product testing
is a compact dose collection system designed
for manual DDU sampling of nasal sprays. This Copley provides a range of qualification documentation, services and tools to meet
convenient system is ideal for quick, hassle-free these requirements.
DDU testing.
See page 302 for further information.
For ordering information, see page 26.

Related Applications
We also offer a range of equipment for additional MDI testing application support:

DDU Over the Entire Contents

In the case of multiple dose devices, tests might need to be carried out throughout the life of the inhaler i.e. For cold Freon® effect testing
dose uniformity over the entire contents. For further information, see page 24. See page 247

Training, Servicing & Support

We offer a comprehensive range of services from bespoke product design to
installation, expert training and technical support, optimising all aspects of
pharmaceutical testing from start to finish.

Training Servicing Support Design

See page 313 See page 304 See page 312 See page 312

62 63
 Inhaler Testing Delivered Dose Uniformity

DDU of Nasal Aerosols: Test System Set-Up

A B C

Delivered Dose Uniformity F

Nasal Aerosols
G

DDU testing of nasal aerosols follows a similar process to that of MDIs (page 28), since
both use a propellant to deliver a specified volume of active ingredient(s) upon actuation
of a metered valve system. Testing is typically conducted at a fixed flow rate of 28.3 L/
min using a DUSA for MDIs for sample collection. A Vacuum Pump B Breath Actuation C Inhaler Testing D Flow Meter E Nosepiece Adapter
Controller Workstation (ITW)

F DUSA for MDIs G Waste Shot Collector H Switching Valve

Regulations and Guidelines

The sampling procedure and acceptance criteria for the DDU of nasal aerosols varies according to the
regulatory authority concerned.
Related Accessories
Organisation Chapter(s)/Guidance Key DDU Tests

Guideline on the Pharmaceutical Quality of

EMA Delivered Dose Uniformity Through Container Life
Inhalation and Nasal Products

+ +
Ph. Eur. - -

Guidance for Industry: Metered Dose Inhaler

FDA (MDI) and Dry Powder Inhaler (DPI) Content Uniformity
Drug Products
DUSA Collection Tube Stand Temperature and Relative Humidity Sensor Footswitch
Chapter <601> Inhalation and Nasal Drug Designed for the convenient transfer of Ideal for measuring environmental Connecting directly to the Breath Actuation
multiple DUSA for MDIs around test conditions. See page 179. Controller BAC 100i, the Footswitch enables
USP Products: Aerosols, Sprays, and Powders - Delivered Dose Uniformity of Product
the laboratory. See page 21. precise synchronisation of nasal aerosol device
Performance Quality Tests actuation with the onset of flow.
See page 179.
Ch.P. Chapter 0111 Delivered Dose Uniformity

JP - -

70
64 65
71
 Inhaler Testing Delivered Dose Uniformity

DDU of Nasal Aerosols: Test System Component Parts

Inhaler Testing Workstation (ITW)

Dose Uniformity Sampling Apparatus Designed to keep the sampling apparatus organised during testing and
(DUSA) for MDIs improve workflow efficiency, the Inhaler Testing Workstation ITW holds
See page 21 the DUSA collection tube, vacuum connector, flow meter and WSC2.
See page 196 for further information.

Waste Shot Collector and Switching Valve

In addition to the DUSA for MDIs, the following is needed to complete a fully-operational test set-up for the
delivered dose testing of nasal aerosols: A compact vacuum filtration system, the Waste Shot Collector WSC2
captures aerosols emitted from repeated actuations of the inhaler, trapping
large quantities of the drug for safe disposal. The Switching Valve is used to
Vacuum Pump re-direct air flow between the collection device and WSC2 for quick and easy
Designed for optimal operation at the low flow rates required for nasal dose wasting. Please note: only required for multi-dose devices.
aerosol testing, the Low Capacity LCP6 Pump represents the latest in
See page 24 for further information about the Waste Shot Collector WSC2.
high performance, low maintenance, vacuum pump technology. Our
Vacuum Pump range is specifically designed for use in the testing of
OINDPs in accordance with pharmacopoeial requirements.
See page 188 for further information about our Vacuum Pump range.
Nosepiece Adapter
Special nosepiece adapters are available to accommodate the nasal
aerosol device and interface it with the test set-up.

Breath Actuation Controller (BAC) See page 203 for further information.

Ensuring that the volume of air sampled does not exceed

pharmacopoeial specifications, the Breath Actuation Controller BAC
100i contains an electronically operated, timer-controlled two-way
solenoid valve and is positioned between the DUSA and DDU Over the Entire Contents
vacuum pump.
In the case of multiple dose devices, tests might need to be carried out throughout the life of the inhaler i.e.
See page 172 for further information about our Flow Controller range. dose uniformity over the entire contents. For further information, see page 24.

Qualification
Flow Meter GMP regulations require that
Used for establishing accurate and consistent inlet flow rate • The test methods used to monitor pharmaceuticals must meet proper standards of
during testing, our range of Flow Meters measure and control accuracy and reliability
flow rates to the accuracy specified by the pharmacopoeias.
• Companies should establish procedures to ensure the fitness for use of instruments
See page 184 for further information about our range that generate data supporting product testing
of Flow Meters.
Copley provides a range of qualification documentation, services and tools to meet
these requirements.
See page 302 for further information.

66 67
 Inhaler Testing Delivered Dose Uniformity

Semi-Automation Tools
Eliminate Increase
Improve efficiency Reduce variability
handling errors testing capacity

DUSA Shaker
Holding up to 21 MDI DUSA collection tubes, the DUSA shaker
automates the internal rinsing of the tubes to ensure full, fast
and repeatable drug dissolution and drug recovery from
internal surfaces.
See page 282 for further information.

Training, Servicing & Support

We offer a comprehensive range of services from bespoke product design to
installation, expert training and technical support, optimising all aspects of
pharmaceutical testing from start to finish.

Training Servicing Support Design

See page 313 See page 304 See page 312 See page 312

68 69
 Inhaler Testing Delivered Dose Uniformity

DDU of Nasal Powders: Test System Set-Up

A B C

Delivered Dose Uniformity E

Nasal Powders F

The minimum requirements for nasal powder delivered dose testing are the same as H

for DPI testing (see page 42), namely DUSA, nosepiece adapter, vacuum pump and
flow meter, plus a critical flow controller to measure the pressure drop across the
device and control flow conditions during testing. A B
Critical Flow
C
Inhaler Testing
D Flow Meter
Vacuum Pump
Controller Workstation (ITW)

Nosepiece Waste Shot

Regulations and Guidelines

E F DUSA for DPIs G H Switching Valve
Adapter Collector

The sampling procedure and acceptance criteria for the DDU testing of nasal powders varies according
to the regulatory authority concerned.

Organisation Chapter(s)/Guidance Key DDU Tests Related Accessories

Guideline on the Pharmaceutical Quality of
EMA Delivered Dose Uniformity Through Container Life
Inhalation and Nasal Products

Ph. Eur. - - + +

Guidance for Industry: Metered Dose Inhaler

FDA (MDI) and Dry Powder Inhaler (DPI) Drug Content Uniformity
Products
DUSA Collection Tube Stand Temperature and Relative Humidity Sensor Footswitch
Chapter <601> Inhalation and Nasal Drug
Designed for the convenient transfer of Ideal for measuring environmental Connecting directly to the Critical Flow
USP Products: Aerosols, Sprays, and Powders - Delivered Dose Uniformity of Product multiple DUSA for DPIs around test conditions. See page 183. Controller TPK 100i, the Footswitch enables
Performance Quality Tests the laboratory. See page 23. precise synchronisation of nasal powder device
actuation with the onset of flow.
See page 183.
Ch.P. Chapter 0111 Delivered Dose Uniformity

JP - -

70 71
 Inhaler Testing Delivered Dose Uniformity

DDU of Nasal Powders: Test System Component Parts

Inhaler Testing Workstation (ITW)

Designed to keep the sampling apparatus organised during testing and
Dose Uniformity Sampling Apparatus
improve workflow efficiency, the Inhaler Testing Workstation ITW holds
(DUSA) for DPIs the DUSA collection tube, vacuum connector, flow meter and waste shot
See page 22 collector (WSC2).
See page 196 for further information.

In addition to the DUSA for DPIs, the following is needed to complete a fully-operational test set-up for the Waste Shot Collector and Switching Valve
delivered dose testing nasal powders: A compact vacuum filtration system, the Waste Shot Collector WSC2
captures aerosols emitted from repeated actuations of the inhaler, trapping
large quantities of the drug for safe disposal. The Switching Valve is used to
Vacuum Pump re-direct air flow between the collection device and WSC2 for quick and easy
Ideal for the higher, sonic flow rate testing requirements of nasal dose wasting. Please note: only required for multi-dose devices.
powders, the High Capacity HCP6 Pump represents the latest in high See page 24 for further information about the Waste Shot Collector WSC2.
performance, low maintenance, vacuum pump technology. Our Vacuum
Pump range is specifically designed for use in the testing of OINDPs in
accordance with pharmacopoeial requirements.
See page 188 for further information about our Vacuum Pump range.
Nosepiece Adapter
Special nosepiece adapters are available to accommodate the nasal
powder device and interface it with the test set-up.

Critical Flow Controller (TPK) See page 203 for further information.
Simplify nasal powder test system set-up in accordance with
pharmacopoeial recommendations with the Critical Flow Controller
series. Positioned between the DUSA and vacuum pump, the Critical
Flow Controller TPK 100i ensures critical (sonic) flow conditions during DDU Over the Entire Contents
testing. It measures and records all required parameters required for In the case of multiple dose devices, tests might need to be carried out throughout the life of the inhaler i.e.
testing and for controlling flow conditions. dose uniformity over the entire contents. For further information, see page 24.
See page 172 for further information about our Flow Controller range.

Qualification
GMP regulations require that
• The test methods used to monitor pharmaceuticals must meet proper standards of
Flow Meter accuracy and reliability
Used for establishing accurate and consistent inlet flow rate
• Companies should establish procedures to ensure the fitness for use of instruments
during testing, our range of Flow Meters measure and control
that generate data supporting product testing
flow rates to the accuracy specified by the pharmacopoeias.
See page 184 for further information about our range Copley provides a range of qualification documentation, services and tools to meet
of Flow Meters. these requirements.
See page 302 for further information.

72 73
 Inhaler Testing Delivered Dose Uniformity

Semi-Automation Tools
Eliminate Increase
Improve efficiency Reduce variability
handling errors testing capacity

DUSA Shaker
Holding up to 12 DPI DUSA collection tubes, the DUSA shaker
automates the internal rinsing of the tubes to ensure full, fast
and repeatable drug dissolution and drug recovery from
internal surfaces.
See page 282 for further information.

Training, Servicing & Support

We offer a comprehensive range of services from bespoke product design to
installation, expert training and technical support, optimising all aspects of
pharmaceutical testing from start to finish.

Training Servicing Support Design

See page 313 See page 304 See page 312 See page 312

74 75
 Inhaler Testing Aerodynamic Particle
Size Distribution

Aerodynamic Particle
Size Distribution An Introduction to
Together with delivered dose, aerodynamic particle size distribution (APSD) Cascade Impaction
is typically identified as a Critical Quality Attribute (CQA) for orally inhaled
and nasal drug products (OINDPs) making it a primary focus for in vitro The cascade impactor is the instrument of choice for both regulators and
characterisation. The APSD of an OINDP defines how particles behave in a pharmacopoeias when measuring the APSD of inhaled drug products due
moving air stream. It is intuitively relevant to the understanding of likely lung to some unique features. Cascade impactors separate a sample on the
deposition and hence potential drug efficacy. basis of particle inertia (which is a function of velocity and aerodynamic
particle size) without the need to know either particle density or shape.
To be therapeutically effective, inhaled drug entrained in the air stream and be exhaled.
particles should ideally be in the range of 1 to The mass of dose delivered at a particle size
5 microns to deposit in the lungs. Particles below 5 microns is normally described as the
more than 5 microns will generally impact in fine particle mass (FPM) or dose (FPD) and is Next Generation Impactor (NGI)
the oropharynx and be swallowed, whereas an important metric for OIPs.
below 1 micron particles will likely remain

Broad characterisation of particle

deposition within respiratory system

Pharynx Particle D > 10 microns (Mouth/Throat)

Particle D = 5 - 10 microns (Upper Respiratory Tract)

Trachea & primary bronchi Particle D = 1 - 5 microns (Deep Lungs)

Secondary bronchi Particles D = 1 micron (Exhaled)

Terminal bronchi

Andersen Cascade Impactor (ACI)

Alveoli

TOP TOP
TIP TIP
The term “impactor” is generally used for an instrument where the particles “impact”
Aerodynamic diameter (Dae) D = Dp ½ f(S) on a dry impaction plate or cup. The term “impinger” is used to describe instruments
is the diameter of a sphere of where the particles impinge into a liquid or onto a moist collection surface.
unit density whose behaviour D = Geometric diameter
in an air-stream is the same as p = Particle density
the drug particle. S = Shape factor
D = 3 µm D = 1 µm
D = 3 µm D = 3 µm

76 77
 Inhaler Testing Aerodynamic Particle
Size Distribution

Cascade impactors have three unique features which make them the ideal tool for particle size assessment
of inhaled products.
Cascade Impactor NGI Cooler Vacuum Pump

1. Cascade impactors measure 2. Cascade impactors deliver active 3. Cascade impactors capture
aerodynamic particle size data pharmaceutical ingredient (API) the entire dose Example particle sizing
specific measurements system set-up for
Cascade impactors measure Cascade impactors, unlike other
nebulisers
aerodynamic particle size which is Cascade impactors provide a direct sizing techniques, which just
a function of particle density, as means of recovering and quantifying provide a snapshot of part of the
well as the physical dimensions API contained in the aerosol cloud. dose, capture the entire dose
and shape of the particles The aerosol clouds generated by allowing complete characterisation
concerned. This is a more relevant pharmaceutical inhalers typically of the aerosol under test.
parameter when studying how comprise a combination of API(s) and
particles behave in a moving air other excipients or components, but it
stream (as exemplified by the is the size distribution of the API that
respiratory tract) rather than influences efficacy. Cascade impaction
simple “geometric” size. generates an APSD specifically for the
API to meet this informational need.

TOP
Glass Expansion TIP
The pharmacopoeias recommend a number of commercially available impactors for the routine testing of
Chamber A cascade impactor, contrary
OINDPs including the Next Generation Impactor (NGI) and the Andersen Cascade Impactor (ACI), both of which
to common understanding, is
are used globally for the testing of metered-dose inhalers (MDIs), dry powder inhalers (DPIs) and ADIs (Aqueous not a lung simulator. The lung
Droplet Inhalers). Cascade Impactor is a complex organ, with high
humidity, decreasing velocity with
each bifurcation and complex
Induction Port Mouthpiece Adapter Vacuum Pump deposition mechanisms (diffusion and sedimentation,
Vacuum as well as impaction). A cascade impactor is a
For most inhaler-related applications, The inhaler is connected to the Once discharged from the inhaler, the Pump highly discriminatory, reproducible measure of
the inlet to the impactor is fitted induction port by means of a aerosol cloud is drawn through the relative product difference and is therefore ideally
with a right-angled induction port mouthpiece adapter which provides impactor by means of a vacuum pump suited to quality control and in-vitro bioequivalence
designed to act as a simplified throat. an airtight seal between the induction connected to the outlet of the impactor applications. Enhancements to improve the clinical
The dimensions of this induction port port and the device under test. by a suitable length of tubing. realism of testing, in-line with improving in vitro-in
are standardised between the various vivo correlations (IVIVCs), can found on page 214.
pharmacopoeias and serve to ensure
that the aerosol cloud produced by Example particle sizing system set-up for nasal products
the inhaler is sampled in a
Example particle sizing
reproducible manner.
system set-up for MDIs
Example particle sizing system for DPIs
Cascade Impactor
Consists of one or more stages
Cascade Impactor Critical Flow Controller Vacuum Pump
normally arranged in the form of
a ‘stack’, which can be vertical or
horizontal. These separate the particles
entrained in the aerosol stream, into a
series of size bands or fractions in the
respirable range, broadly corresponding
to their likely deposition sites in the
respiratory tract.

78 79
 Inhaler Testing Aerodynamic Particle
Size Distribution

How Does a Cascade Impactor Work? Other Considerations

Airborne particles are directed towards the surface of the
collection plate for a particular stage
Cascade Impactor Impactor Mensuration
Each stage of the cascade Stage mensuration replaces the need for repetitive calibration using standardised aerosols
impactor is made up of nozzles and ensures that only impactors conforming to specification are used in testing. It involves
through which a fixed volumetric individually inspecting every jet on every stage of the impactor to ensure compliance.
flow of air is drawn
All cascade impactors (including induction ports and preseparators), supplied by Copley, are
checked at every stage of manufacture using the very latest in metrology equipment and
are provided with a mensuration certificate prior to release.
Aerosol Flow
To find out more about our Servicing options, please see page 304.

Impactor Leak Testing

The ability of a cascade impactor to accurately size separate particles relies on maintaining
a fixed volumetric flow rate of air through it. Leaks between impactor stages that allow air
Collection Plate Nozzle to become entrained into the impactor from the outside can modify this flow rate and
cause incorrect particle sizing. Performing a leak test prior to each test is recommended to
Particle separation and sizing is ensure data integrity.
achieved by accelerating the flow To find out more about our Impactor Leak Testing Kit, please see page 304.
Particles contained within
(and hence particles) through
precisely defined size
progressively small nozzle areas at
fractions are deposited on
each stage and directing it toward a
the collection plates for
collection surface below the nozzles
Impactor Cleaning
subsequent chemical analysis Cascade impactors are precision instruments and should be treated with care. Regular
and perpendicular to the flow.
cleaning and drying is an essential element of good impactor practice and ensures that the
Cascade Impaction: At each stage, as the flow turns instrument is free of product residue and debris prior to testing and that the unit remains in
Priniciple of Operation through a right-angle, particles break optimum condition throughout its life.
Vacuum Source
free of the air stream and impact
See page 298 for more information about our Impactor Cleaning System.
on collection plates, in order of
The smallest particles are trapped by a final filter decreasing aerodynamic size.

Data Analysis Software: Inhalytix™

At the end of the test, the particle mass on each stage collection plate is recovered using a
suitable solvent and then analysed, usually using High Pressure Liquid Chromatography (HPLC)
to determine the amount of drug present.
By analysing the amount of drug deposited on the
stages, it is possible to calculate a range of metrics To find out more about our data
including the Fine Particle Dose (FPD) and Fine Particle analysis software Inhalytix™,
Fraction (FPF) and, following further manipulation, please see page 206.
the Mass Median Aerodynamic Diameter (MMAD) and
Geometric Standard Deviation (GSD).

80 81
 Inhaler Testing Aerodynamic Particle
Size Distribution

NGI: Key Features

7 stages (plus Micro Easy-clean system with
Orifice Collector [MOC]) quick-locking handle

NGI with Preseparator

and Induction Port

Types of TOP
TIP

Cascade Impactor The NGI+ is an alternative to the nickel-

plated aluminum seal body of the
standard NGI. Supporting the use of
Operation between
15 and 100 L/min
A Quick-Release Connector
is supplied as standard

harsher chemical solvents, the stainless

steel seal body of the NGI+ makes it ideal Removable seal body
for a wider range of testing applications. (containing all nozzle pieces)
for easy impactor cleaning

Next Generation Impactor (NGI)

The NGI is a high performance, precision cascade impactor suitable for the APSD
characterisation of all types of OINDPs. Ideal for testing at all flow rates specified NGI (open)

in the relevant pharmacopoeias, the highly flexible NGI is the cascade impactor
of choice for many laboratories throughout the world.

Meets and Low inter-stage Seven stages; five with cut-

exceeds all wall losses for good offs between 0.54 and 6.12
Ph.Eur. and USP drug recovery (mass microns at flow rates from
specifications balance) 30 to 100 L/min

Electrically Excellent stage User friendly design for

conductive; efficiency (GSD maximum throughput Removable cup tray A horizontal planar Low inter-stage losses and
- just lift and remove layout for ease minimal particle carry-over
unaffected by <1.2), accuracy and and easy automation
complete set of of operation and mean that only the cups
static reproducibility collection cups automation and trays need changing
between tests

82 83
 Inhaler Testing Aerodynamic Particle
Size Distribution

The sample-laden air flow passes through the NGI in a saw-tooth pattern across stages arranged in a NGI: Component Parts
horizontal plane.
A number of supporting component parts are required in addition to the NGI itself:
Stage 2 Stage 4 Stage 6 MOC Stage 1 nozzle Inter-stage passageway
6 holes 52 holes 396 holes 4032 holes
Removable
impaction cups

Bottom frame with

cup tray in place
Lid with seal NGI Induction Port
body attached
MOC Manufactured from 316 stainless steel, the tapered and hardened
outlet of the NGI Induction Port provides an airtight seal with the
Location pin
inlet to Stage 1 and the mouthpiece adapter.
Stage 1 Stage 3 Stage 5 Stage 7
1hole 24 holes 152 holes 630 holes

NGI Principle of Operation Schematic of Seal Body Showing Orientation of the Various Stages

NGI Preseparator
The NGI requires the use of a preseparator when used with DPIs in order
Interstage passageway Interstage passageway
The cut-off diameters
to next stage from previous stage to catch any powder boluses and large non-inhalable particles. Offering
for the relevant stages
high capacity, high efficiency, two-stage separation, the NGI Preseparator
at volumetric flow rates
Lid provides a sharp and reproducible cut-point of between 10 and 15
of 15, 30, 60 and 100 L/
microns depending on flow rate.
min are shown in the
Seal body
Air Flow table below.
Cup tray

Bottom frame

Filter Holder
Collection cup Multi-nozzle stage
In most cases, the MOC eliminates the need for a final paper
filter, having an 80% collection efficiency of 0.3 micron
NGI Inter-Stage Airflow
particles at 30 L/min. If ultra-fine particles are present and at
flow rates below 30 L/min, then an internal or external filter
holder can be used.
NGI Cut-Off Diameters
15 30 60 100 L/min TOP
TIP
Stage 1 14.10 11.72 8.06 6.12 microns Automation: The 3-part
construction of the NGI Sample Collection Cups
Stage 2 8.61 6.40 4.46 3.42 microns makes it ideal for semi-
Four special types of sample collection cups are available in
automation.
Stage 3 5.39 3.99 2.82 2.18 microns addition to those supplied as standard with the NGI:
See page 266 for further
Stage 4 3.30 2.30 1.66 1.31 microns information on our semi- Gravimetric Cup - for APSD determinations based on sample weight
automation solutions.
Stage 5 2.08 1.36 0.94 0.72 microns Deep Cup - to bypass a stage, obviating impaction

Stage 6 1.36 0.83 0.55 0.40 microns

Exhaust Cup - to bypass a downstream portion of the impactor
Glass Disc Cup - for Malvern Panalytical Morphologi system
Stage 7 0.98 0.54 0.34 0.24 microns

84 85
 Inhaler Testing Aerodynamic Particle
Size Distribution

NGI: Accessories NGI: Technical Specifications

Flow Rate Range 15 – 100 L/min

Particle Size Range 0.24 – 14.1 microns (dependent on flow rate)

Number of Stages 7
NGI Cup Rack
Operation Method Impaction
For the convenient storage of a full set of NGI Cups, protecting the
critical surfaces from inadvertent damage and dust collection when Inter-Stage Losses Low (<5%)
not in use.
Chemical analysis
- HPLC
Method of Drug Assay
- Ultra Performance Liquid Chromatography (UPLC)
- Infrared Spectroscopy (IR)

Material(s) of Construction Nickel Plated Aluminium or 316 Stainless Steel

NGI Carrying/Wash Rack

Next Generation Impactor (NGI)
For transporting the NGI system components around the
laboratory and storing them, protecting the critical surfaces
from damage and scratches. The rack is also designed to Impactors Accessories
hold the components in place when using our Impactor
Cat. No. Description Cat. No. Description
Cleaning System.
5201 Next Generation Impactor (NGI) 5222 NGI Collection Cup Rack
See page 298. 5201A NGI+ Next Generation Impactor 5205 NGI Carrying/Wash Rack
5202 NGI+ Next Generation Impactor Upgrade 5265 Set of 2 Silicone Rubber Rinsing Caps
for NGI Induction Port
5266 Set of 2 Silicone Rubber Rinsing Caps
Component Parts
for NGI Preseparator
5227 Set of 2 Stainless Steel Rinsing Caps
Induction Ports
for NGI Induction Port
5203 NGI Induction Port
Rinsing Caps 8060 Flow Meter to Induction Port/WSC2 Adapter
5228 Set of 2 Stainless Steel Rinsing Caps
for NGI Preseparator
Silicone Rubber and 316 Stainless Steel Rinsing Caps are available 5238 Universal Flow Meter Adapter
5232 Set of 2 Silicone Rubber Stoppers
for capping off the open ends of the NGI Induction Port and the NGI Preseparators for testing DPIs
for NGI I.P./Preseparator
Preseparator during manual and semi-automated drug recovery. 5254 NGI Transportation Case
5204 NGI Preseparator (Nickel Plated Aluminium)
5204A NGI Preseparator with Stainless Steel Insert
NGI Cooler
Filter Holders
5206 Internal Filter Holder 5009 NGI Cooler
5210 External Filter Holder 5011 NGI Cooler Qualification Documentation
5240 Box of 100 Filters (for Internal/External Filter Holder) 5012 NGI Cooler Qualification Tools
TOP 5013 Re-calibration of NGI Cooler Qualification Tools
TIP
Sample Collection Cups
All NGIs supplied by Copley are machined to the same precision tolerances to guarantee reproducibility between
5243A Deep Cup, Small (to bypass a stage,
impactors. Each NGI is supplied with a full stage mensuration report (system suitability).
obviating impaction) Spare Parts
5242A Malvern Glass Disc Cup, Small (for Malvern
Recommended annually, NGI stage mensuration replaces the need for repetitive, difficult and typically 5208 Collection Cup Tray
Panalytical Morphologi system)
unreliable calibration and ensures that only impactors conforming to specification are used in testing. 5209 Set of 8 Collection Cups (2 Large, 6 Small)
5243 Exhaust Cup, Small (to bypass downstream stages
For more information on our Servicing options, see page 304. 5245 Welded Cup Tray Manifold
of impactor)
5211 Set of 18 Seals for the Next Generation Impactor
5241 Gravimetric Cup Small (for APSD determinations
Further details regarding the design and archival calibration of the NGI can be found in the Journal of Aerosol 5246 Set of 10 Seals for the NGI Preseparator
based on weight)
Medicine Volume 16(3), 2003 and Volume 17(4), 2004. 5247 Set of 10 Seals for the NGI Internal Filter Holder
5241A Pack of 100 Filters for Small and Large Gravimetric Cup
5248 Set of 10 Seals for the NGI External Filter Holder
5244 Gravimetric Cup Large (for APSD determinations
5249 NGI Outlet Diameter Reducing Adapter
based on weight)

86 87
 Inhaler Testing Aerodynamic Particle
Size Distribution

ACI: Key Features

Available in a range of construction

materials to ensure durability against
different drug recovery solvents

Each Collection Plate

contains the batch number
for traceability

Leak-free inter-stage sealing

Andersen
Cascade Impactor (ACI) ACI with Induction Port A Quick-Release
Connector is supplied
as standard
Well-established and readily accepted by the regulatory authorities, the ACI
has been used for the APSD characterisation of OINDPs for over 30 years. A vertical planar layout
with a small unit footprint

Meets and Low flow resistance 60 and 90 L/min

exceeds all at high flow rates Conversion Kits available
Ph.Eur. and USP when Stages 6 & 7 for high flow rate testing,
ACI: Materials of Construction
specifications are removed whilst retaining the 28.3 316 Stainless Steel Titanium Aluminium
L/min cut-off diameters Superior corrosion resistance and Lightweight handling, superior Lightweight, lower cost, where
durability to extend impactor life corrosion resistance corrosion resistance is not an issue
Electrically Reduced stack option
conductive; for work with nasal
unaffected by aerosols and sprays
TOP
static TIP When used at calibration flow rates, cascade
impactors can be operated at different angles,
which may be useful when testing device
performance at different positions.

88 89
 Inhaler Testing Aerodynamic Particle
Size Distribution

Aerosol Particles

First Stage Nozzle(s)

ACI: Component Parts
First Stage Nozzle(s) A number of supporting component parts are required in addition to the ACI itself:
Stage 0
Seal Collection Plate
Collection Plate

Second Stage Nozzle(s)

Stage 1
Collection Plate
USP Induction Port
Provides an airtight seal achieved between the ACI inlet
Collection Plate
and the mouthpiece adapter.
Intervening Stages Stage 2

Stage 3

Stage 4
Last Stage Nozzle(s) Stage 5
Stage 6
Collection Plate

Collection Plate

Filter Stage 7 Collection Plate ACI Preseparator

Filter Stage with Filter Designed to collect the large mass of non-inhalable powder boluses emitted
from powder-based inhalers prior to their entry into the impactor, the ACI
Base Preseparator is ideal for DPI testing applications. Preseparators are available for
Vacuum
testing at 28.3, 60 and 90 L/min.
Principle of Operation ACI: Exploded View

Unlike the NGI, the stages of the ACI are arranged vertically. The aerosol flow passes first through the stage at the
top of the impactor, through to the last stage and a final filter at the bottom of the impactor arrangement.

ACI: Accessories
ACI: Modified Configurations
The standard ACI is designed for use at 28.3 L/min. In change in cut-points that would occur for each stage
some cases (particularly with low resistance DPIs), it is with any change to the flow rate. We offer two modified
necessary to operate at flow rates greater than 28.3 L/ configurations of the ACI for operation at calibrated
min, if a pressure drop over the inhaler of 4 kPa is to flow rates of 60 and 90 L/min to help address this. ACI Quick Clamp
be achieved. However, it is important to consider the Constructed from stainless steel, the ACI Quick Clamp enables
quick and efficient adjustment of the ACI plate stack.

28.3 L/min Version 60 L/min Version 90 L/min Version

Stages Plates ECD* Stages Plates ECD* Stages Plates ECD*

o = with hole
0 0 9.0 -1 0 8.6 -2A 0 8.0
x = without a hole
1 0 5.8 -0 0 6.5 -1A 0 6.5
* Effective Cut-Off Diameter
2 x 4.7 1 0 4.4 -0 0 5.2
3 x 3.3 2 x 3.2 1 0 3.5
4 x 2.1 3 x 1.9 2 x 2.6
5 x 1.1 4 x 1.2 3 x 1.7 ACI Collection Plate Rack
6 x 0.7 5 x 0.6 4 x 1.0
For the convenient storage of the ACI collection plates,
7 x 0.4 6 x 0.3 5 x 0.2
protecting the critical collection surfaces from inadvertent
F 0.0 F 0.0 F 0.0
scratches and dents when not in use.
Modified ACI Configurations

90 91
 Inhaler Testing Aerodynamic Particle
Size Distribution

ACI: Accessories ACI: Technical Specifications

28.3 L/Min
Flow Rate Range
Modified configurations: Conversion kits for 60 L/Min and 90 L/Min available
ACI Carrying/Wash Rack 0.4 - 9.0 microns (28.3 L/Min)
Constructed from heavy duty polypropylene and fitted with Particle Size Range 0.3 - 8.6 microns (60 L/Min)
0.2 - 8.0 microns (90 L/Min)
neoprene cushions, the ACI Carrying/Wash Rack is ideal for
transporting the ACI system components around the laboratory Number of Stages 8
and storing them, protecting the critical surfaces from damage and
Operation Method Impaction
scratches. The rack is also designed to hold the components in place
when used with our Impactor Cleaning System. Inter-Stage Losses Low to High (depending on product)

Chemical analysis
See page 298.
- HPLC
Method of Drug Assay
- UPLC
- IR

Material(s) of Construction Aluminium, 316 Stainless Steel or Titanium

Rinsing Caps Andersen Cascade Impactor (ACI)

Silicone Rubber Rinsing Caps are available for capping off
the open ends of the ACI Induction Port during manual and Impactors Accessories
semi-automated drug recovery.
Cat. No. Description Cat. No. Description
8301 28.3 L/Min Andersen Cascade Impactor*
Rinsing Caps
8301-60 60 L/Min Andersen Cascade Impactor*
8504 Set of 2 Silicone Rubber Rinsing Caps
8301-90 90 L/Min Andersen Cascade Impactor*
for ACI Induction Port

TOP Conversion Kits for the standard 28.3 L/min ACI Spare Parts
TIP 8318 Conversion Kit for 60 L/min operation* 8307 Complete Set of 13 ACI Silicone Rubber O-Rings
All ACIs supplied by Copley are machined to the same precision tolerances in order to guarantee reproducibility 8314 Set of 8 Stainless Steel Collection Plates (28.3 L/min)
8319 Conversion Kit for 90 L/min operation*
between impactors. Each ACI is supplied with a full stage mensuration report (system suitability). 8314-60 Set of 8 Stainless Steel Collection Plates (60 L/min)
8314-90 Set of 8 Stainless Steel Collection Plates (90 L/min)
Component Parts 8316 Box of 100 Glass Fibre Filters
8306 Set of 6 O-Rings for Spring Clamp
Induction Ports 8308 Set of 3 Spring Clamps
8501 USP Induction Port* 8309 Set of 3 PVC End Caps for Spring Clamps
8510 USP Induction Port (One-piece 316 Stainless Steel) 8403 Set of 4 O-Rings for Preseparator
8060 Flow Meter to Induction Port/WSC2 Adapter 8395 ACI Carrying Case
5238 Universal Flow Meter Adapter 8351 Inlet Cone*
8352 Stage -2A*
Preseparators for testing DPIs 8353 Stage -1A (for 90 L/min operation)*
8401 28.3 L/min Preseparator* 8354 Stage -1 (for 60 L/min operation)*
8420 60 L/min Preseparator* 8355 Stage -0*
8420-90 90 L/min Preseparator* 8356 Stage 0*
8357 Stage 1*
8358 Stage 2*
Accessories 8359 Stage 3*
8360 Stage 4*
Cat. No. Description 8361 Stage 5*
8362 Stage 6*
5212 ‘Quick Clamp’ for Andersen Cascade Impactor
8363 Stage 7*
8111 Stand (incl. Base Plate, Boss Head and Clamp)
8364 Stage F (Filter)*
5441 ACI Collection Plate Rack
8365 Base (including Hose Fitting)*
5401 ACI Carrying/Wash Rack
*Please specify Aluminium (A), 316 Stainless Steel (S) or Titanium (T)
when placing your order.

92 93
 Inhaler Testing Aerodynamic Particle
Size Distribution

MSLI: Key Features

PTFE seals as standard

for leak-free testing?

Bungs for easy solvent

dispensing and sample
collection access
A vertical planar layout
with a small unit footprint

MSLI with Induction Port

Multi-Stage Liquid Impinger (MSLI) A Quick-Release

Connector is supplied
as standard
A traditional apparatus for routine testing and research applications in industry
and academia, the MSLI comprises four impaction stages and a final filter stage.
Whilst it does not offer the number of stages of the ACI or NGI, it has virtually
no inter-stage losses.
Also, unlike the ACI and NGI, the collection stages of the MSLI are kept moist, which eliminates
the problem of particle bounce associated with conventional impactors.
MSLI: Materials of Construction

316 Stainless Steel Titanium Aluminium

Superior corrosion resistance and Lightweight handling, superior Lightweight, lower cost, where
Ph.Eur. Chapter Eliminates particle Choice of construction
durability to extend impactor life corrosion resistance corrosion resistance is not an issue
2.9.18 compliant for bounce and materials to suit all
MDIs and DPIs re-entrainment budgets and needs
problems
TOP
TIP A stage mensuration certificate and leak test certificate are included
Quick and easy Virtually no with each MSLI as standard. During the mensuration, the sintered glass
impingement stages are positioned using calibrated gauge blocks to
to mensurate inter-stage losses
ensure that the correct jet-to-plate distance is maintained.

94 95
 Inhaler Testing Aerodynamic Particle
Size Distribution

Aerosol Inlet The aerosol stream is drawn into the top of the
MSLI, passing first through Stage 1 which acts as a
preseparator. Particles with sufficient inertia will impact
on the moist surface of the sintered glass disc. Those
Stage 1
with insufficient inertia will pass through to Stage 2. The
same process of impaction and particle selection takes
place until the final filter stage (Stage 5), which captures
Stage 2 any remaining fine particles.

The cut-off diameters for the relevant stages at a

volumetric flow rate of 60 L/min are shown in the
Stage 3 table below.

MSLI Cut-Off Diameters

Stage 4 60 L/Min

Stage 1 13.0 microns

Stage 5 (Filter)
Stage 2 6.8 microns
Vacuum Source Stage 3 3.1 microns

Stage 4 1.7 microns

Stage 5 (Filter) < 1.7 microns

MSLI: Technical Specifications

Flow Rate Range Between 30 and 100 L/min

Particle Size Range 1.7 - 13.0 microns (dependent on flow rate)

No. of Stages 4

Operation Method Impingement

Inter-Stage Losses Zero

Chemical Analysis
- HPLC
Method of Drug Assay
- UPLC
- IR

Material(s) of Construction Aluminium, 316 Stainless Steel or Titanium

Multi-Stage Liquid Impinger (MSLI)

Cat. No. Description Spare Parts

8801 Multi-Stage Liquid Impinger (MSLI)*
8501 USP Induction Port* 8805 Set of 3 O-Rings
8510 USP Induction Port (One-piece 316 Stainless Steel) 8807 Set of 8 Inter-Stage PTFE Gaskets (Code M)
8060 Flow Meter to Induction Port/WSC2 Adapter 8814 Filter Support Plate (Code S)
5238 Universal Flow Meter Adapter 8834 Pack of 10 Silicone Rubber Stoppers
8839 Pack of 100 Glass Fibre Filters
8840 Ground Glass Cylinder (Code E)
Options
8844 Set of 4 Sintered Glass Discs (Code D)
8111 Stand (incl. Base Plate, Boss Head and Clamp)
* Please specify Aluminium (A), 316 Stainless Steel (S) or Titanium
8851 Torque Adjuster for MSLI
(T) when placing your order.

96 97
 Inhaler Testing Aerodynamic Particle
Size Distribution

GTI Key Features:

Corrosion resistant

A special modification for the

measurement of the particle size
of nasal sprays according to the Small unit footprint
Aaiche and Beyssac method is
also available as an option.

Throat Aerosol The GTI operates on the principle of liquid

Flow
impingement to divide the dose emitted from the

Glass Twin Impinger (GTI) inhaler into respirable and non-respirable portions.
Prior to testing, 7 mL of solvent is typically
Retained as Apparatus A in Ph.Eur. 2.9.18 due to its value as a simple and inexpensive Upper Chamber dispensed into the upper impingement chamber
and 30 mL to the lower impingement chamber.
routine quality control tool, the two-stage GTI is ideal for use where batch-to-batch Upper
variability in FPD is required and a coarser test may be acceptable. Impingement The upper impingement chamber (stage 1) is
Chamber
designed such that at a flow rate of 60 L/ min
Its usage is typically restricted to the assessment of nebulisers, MDIs, nasal sprays and DPIs where it can through the impinger, the particle cut-off is 6.4
Liquid
be demonstrated that a flow rate of 60 (+/- 5) L/min is suitable. microns. Particles smaller than 6.4 microns pass into
Vacuum
Source the lower impingement chamber (stage 2).
After the test is complete, the active drug collected
Ph.Eur. 2.9.18 compliant Regular mensuration Lower in the lower impingement chamber is assayed and
Impingement
(Apparatus A) is not required Chamber expressed as a respirable fraction (or percentage) of
the delivered dose.

Liquid GTI Schematic

No inter-stage losses Ideal for routine quality Lower Chamber

control applications

98 99
 Inhaler Testing Aerodynamic Particle
Size Distribution

GTI: Technical Specifications Choose your Impactor

Flow Rate Range 60 L/Min

Particle Size Range 6.4 microns only

Number of Stages 1

Operation Method Impingement

Device Type NGI ACI MSLI GTI Pharmacopoeia
Inter-Stage Losses Zero
Y Y Y Y Ph. Eur./EMA
Chemical Analysis
- HPLC Y Y N N USP/FDA
Method of Drug Assay MDI
- UPLC
- IR Y Y N Y ChP

Material(s) of Construction Glass

Y Y Y N JP

Y Y Y Y Ph. Eur./EMA

Glass Twin Impinger (GTI) MDI with a Spacer/ Y Y N N USP/FDA

Valved Holding
Cat. No. Description Chamber (VHC) Y Y N Y ChP
Spare Parts
8901 Glass Twin Impinger
8906 Coupling Tube (Ph.Eur. Code E) Y Y N N JP
8999 Modification for Nasal Sprays (acc. to Aaiche & Beyssac)
8907 Screwthread Side-Arm Adapter (Ph.Eur. Code F)
Y Y Y Y Ph. Eur./EMA
8912 Lower Jet Assembly (Ph.Eur. Code G)
Spare Parts 8908 Lower Impingement Chamber (Ph.Eur. Code H)
Y Y Y N USP/FDA
8909 Throat Flow Meter Adapter (Ph.Eur. Code I)
8903 Throat (Ph.Eur. Code B) DPI
8910 Vacuum Pump Adapter (Ph.Eur. Code J)
Y Y N Y ChP
8904 Neck (Ph.Eur. Code C) 8913 Set of 2 Conical Joint Clips (Yellow)
8905 Upper Impingement Chamber (Ph.Eur. Code D) 8914 Set of 4 Conical Joint Clips (Green) Y Y Y N JP
8916 Spare Set of Glassware (incl. clips and Lower
Jet Assembly) Y N N N Ph. Eur./EMA

Y N N N USP/FDA

Technical Specifications: Comparison Summary Nebuliser

Y N N N ChP

Y N N N JP

Y Y N N Ph. Eur./EMA

Y Y N N USP/FDA
ADI
NGI ACI MSLI GTI Y Y N N ChP

28.3 L/min Y Y N N JP
Flow Rate Range 15 – 100 L/min 60 L/min 30 – 100 L/min 60 L/min
90 L/min Y Y N N Ph. Eur./EMA

Particle Size Range 0.24 – 11.7 microns 0.4 – 9.0 microns 1.7 – 13.0 microns 6.4 microns Nasal Y Y N N USP/FDA
Products
Number of Stages 7 8 4 1 Y Y N N ChP

Operation Method Impaction Impaction Impingement Impingement Y Y N N JP

Method of Drug Assay Chemical Analysis (HPLC, UPLC, IR)

100 101
 Inhaler Testing Aerodynamic Particle
Size Distribution

APSD of MDIs: Manual Test System Set-Up

A B C D E F

Aerodynamic Particle Size Distribution

Metered Dose Inhalers (MDIs)

The APSD testing of MDIs is typically performed at a flow rate of 28.3 L/min when
using an ACI or 30 L/min when using an NGI. For Breath Actuated MDIs (BAIs) a Breath
A
Mouthpiece
B
Induction
Alternative Impactors/Impingers
Actuation Controller may also be used to generate a time delay. Adapter Port

There is no requirement for a preseparator in MDI achieve analytical sensitivity.

C
Next Generation
D
Breath Actuation Andersen Multi-Stage Glass Twin
measurement. Plate and/or cup coating may be used Impactor (NGI) Controller
For further information on the APSD testing of MDIs Cascade Impactor Liquid Impinger Impinger
to prevent particle bounce and re-entrainment, but (ACI) (MSLI) (GTI)
with a Spacer or Valved Holding Chamber (VHC), see
is generally not required if the formulation includes Flow Vacuum
page 109. E F
a surfactant. Multiple doses are typically required to Meter Pump

Regulations and Guidelines

Organisation Chapter/Guidance
Ph. Eur. / EMA 2.9.18 App E

USP / FDA <601> App 6

NGI ChP <0951> App 3

JP 6.15.5 App 3

Organisation Chapter/Guidance
Ph. Eur. / EMA 2.9.18 App D

USP / FDA <601> App 1

Related Accessories
ChP <0951> App 2

ACI JP 6.15.5 App 2

Organisation Chapter/Guidance
Ph. Eur. / EMA 2.9.18 App C
+
USP / FDA <601> App 1

ChP -

MSLI JP 6.15.5 App 1

Organisation Chapter/Guidance
Temperature and Relative Humidity Sensor MDI Actuation Sensor/Footswitch
Ph. Eur. / EMA 2.9.18 App A
Ideal for measuring environmental Suitable for most commercially available MDI canisters,
USP / FDA - test conditions. See page 179. the MDI Actuation Sensor connects directly to the
Breath Actuation Controller BAC 200i to ensure precise
ChP <0951>/App 1 synchronisation of MDI actuation. Alternatively, a
Footswitch can be attached to trigger actuation.
GTI JP - See page 179.

102 103
 Inhaler Testing Aerodynamic Particle
Size Distribution

APSD of MDIs: Manual Test System Component Parts

Next Generation Impactor (NGI) Flow Meter

The recommended test set-up is with an NGI, but an ACI Used for establishing accurate and consistent inlet flow rate during
may also be used. Impactors with 7 or 8 stages are preferred testing, our range of Flow Meters measure and control flow rates to the
by regulators, as they provide good APSD resolution. accuracy specified by the pharmacopoeias. See page 184 for further
However, for some established methods the MSLI or GTI may information about our range of Flow Meters.
be acceptable.
Required for:

Inhaler Testing Workstation (ITW)

In addition to the above, the following is needed to complete a fully-operational test Designed to keep the apparatus organised during testing and improve workflow
set-up for APSD measurement of MDIs: efficiency, the ITW holds the casacde impactor and flow meter in position
throughout the testing process.
See page 196 for further information.
Vacuum Pump
Designed for optimal operation at the flow rates required for MDI Recommended for:
testing, the Low Capacity LCP6 Vacuum Pump represents the latest in
high performance, low maintenance, vacuum pump technology. Our
Vacuum Pump range is specifically designed for use in the testing of
OINDPs in accordance with pharmacopoeial requirements.
See page 188 for further information about our Vacuum Pump range. Mouthpiece Adapter
Moulded from high quality silicone rubber, our Mouthpiece Adapters
Required for: guarantee an airtight seal between the inhaler under test and the test
apparatus. For a list of available Mouthpiece Adapters see page 203.
Custom Mouthpiece Adapters are available upon request.

Breath Actuation Controller (BAC) Required for:

Ensuring that the volume of air sampled does not exceed the
pharmacopoeial specifications, the Breath Actuation Controller BAC
100i contains an electronically operated, timer-controlled two-way
solenoid valve and is positioned between the impactor and Vacuum
Pump to control air flow through the inhaler. Qualification
See page 172 for further information about our Flow Controller range.
GMP regulations require that
• The test methods used to monitor pharmaceuticals must meet proper standards of
accuracy and reliability
Recommended for:
• Companies should establish procedures to ensure the fitness for use of instruments
that generate data supporting product testing

TOP Copley provides a range of qualification documentation, services and tools to meet
TIP The BAC 100i can also be used for the testing of Breath-Actuated (or Breath-Operated) MDIs. In this case, the BAC 100i these requirements.
is used to initiate the flow, simultaneously triggering the breath-actuated inhaler.
See page 302 for further information.

104 105
 Inhaler Testing Aerodynamic Particle
Size Distribution

APSD of MDIs: Data Analysis Software: Inhalytix™

Semi-Automated Test System Set-Up A flexible and fully validated solution for the entry, analysis and reporting
of APSD data for all inhaled products.
The Vertus automated shake, fire and shot waste range is made up of integrated
turn-key solutions for precise, controlled and reproducible MDI testing. User-configurable, the software will accept See page 206 for further information about
data from standard and customised cascade Inhalytix™.
impactors and impingers, including the NGI,
Compatible with most MDIs, the Vertus systems Improve inhaler Increase productivity ACI, MSLI and GTI.
offer analysts complete control over: testing accuracy and reduce hassle
and reproducibility
• The speed, angle and duration of shaking,
ahead of actuation Replicate test Reduce handling errors
• Firing force and the speed of application
and release of that force
methods across
different sites
and costly out-of-
specification results Semi-Automation Tools
with ease
• The time delay between the end of shaking Eliminate Increase
Improve efficiency Reduce variability
and device actuation handling errors testing capacity

Gentle Rocker
Agitates the NGI Collection Cup Tray in a controlled, repeatable manner to
Vertus II & Vertus Plus ensure complete dissolution of the active drug prior to analysis. See page 287.
Offering high productivity, walkaway
Recommended for:
MDI testing, the Vertus II and Vertus
Plus can be used for APSD sampling
directly with an NGI, ACI or GTI and
Sample Preparation Unit SPU 200i
all without manual intervention. The
Vertus Plus also offers optional shot Simplifies and automates the drug recovery process from induction ports
weight collection. and preseparators. See page 290.

Recommended for:

NGI Assistant
Replaces the need for:
A complete system for drug recovery from the NGI Collection Cup Tray,
Vacuum Pump Breath Actuation Controller Flow Meter Induction Port and Preseparator, boosting analytical throughput. See page 294.

Recommended for:

Impactor Cleaning System

Standardises cleaning and drying procedures to help ensure the NGI and ACI
Inhaler Testing Workstation
remain in optimum condition throughout their life. See page 298.

See page 270 for further information about the Vertus range. Recommended for:

106 107
 Inhaler Testing Aerodynamic Particle
Size Distribution

Related Applications
We also offer a range of equipment for additional MDI testing application support:

For better in vitro-in vivo For cold Freon® effect testing For USP product-specific monographs
correlation (IVIVC) testing See page 247 See page 260
Aerodynamic Particle Size Distribution
See page 214
MDIs with a Spacers/VHC
Training, Servicing & Support Due to the potential opportunity for particle expansion, impaction and deposition within
the chamber of add-on devices such as spacers or VHCs, the APSD characteristics may be
We offer a comprehensive range of services from bespoke product design to substantially altered from what is emitted when the MDI is used alone. This potential for change
installation, expert training and technical support, optimising all aspects of must be appropriately assessed.
pharmaceutical testing from start to finish.
Regulations and Guidelines
Organisation Chapter/Guidance
Ph. Eur. / EMA -

USP / FDA <1602> App 6

NGI ChP -
Training Servicing Support Design
See page 313 See page 304 See page 312 See page 312 JP -

Organisation Chapter/Guidance
Ph. Eur. / EMA -

USP / FDA <1602> App 1

ChP -

ACI JP -

In Section 3 of USP Chapter <1602> Spacers and Valved Holding Chambers used with Inhalation Aerosols, two tests
are specified relating to the APSD characterisation of add-on devices used with the MDIs:

Test 3.1 Test 3.2

Designed to measure the APSD from the For testing VHCs only and designed to measure the
spacer/VHC when used under optimal APSD from the VHC when used under “worst case”
conditions, that is, with no delay following conditions, i.e. with a delay of 2 or more seconds
actuation of the inhaler. Direct comparisons between inhaler actuation and patient inspiration..
can then be made between the APSD
The delay can be simulated by placing a timer
produced by the MDI both with and without
controlled two-way solenoid valve such as the Breath
the add-on device.
Actuation Controller BAC 100i between the impactor
and the pump.

108 109
 Inhaler Testing Aerodynamic Particle
Size Distribution

APSD of MDIs with a Spacer/VHC: APSD of MDIs with a Spacer/VHC: Test System Component Parts

Test System Set-Up Andersen Cascade Impactor (ACI)

D E
If the spacer/VHC is intended for adults, then the standard ACI or NGI
A B C should be used with a suitable vacuum pump capable of producing
28.3 or 30 L/min respectively. If the add-on device is intended for
neonates, infants or small children, then only the NGI should be used
as this can be used at the lower flow rate of 15 L/min.

In addition to the above, the following is needed to complete a fully-operational test

set-up for the APSD measurement of MDIs with a spacer or VHC:

Vacuum Breath Actuation Inhaler Testing Mouthpiece

A
Pump
B
Controller
C
Workstation (ITW)
D
Adapter
E Flow Meter Vacuum Pump
Designed for optimal operation at the low flow rates required for MDI
Andersen Cascade
F Induction
Port
G
Impactor (ACI) Alternative Impactors testing, the Low Capacity LCP6 Vacuum Pump represents the latest in
high performance, low maintenance, vacuum pump technology. Our
Next Generation Impactor (NGI)
Vacuum Pump range is specifically designed for use in the testing of
OINDPs in accordance with pharmacopoeial requirements.
See page 188 for further information about our Vacuum Pump range.

Required for:

Breath Actuation Controller (BAC)

Related Accessories
Ensuring that the volume of air sampled does not exceed the
pharmacopoeial specifications, the Breath Actuation Controller BAC 100i
contains an electronically operated, timer-controlled two-way solenoid
valve and is positioned between the impactor and Vacuum Pump to
control air flow supply to the inhaler.
+
See page 172 for further information about our Flow Controller range.

Recommended for:
Temperature and Relative Humidity Sensor MDI Actuation Sensor/Footswitch
Ideal for measuring environmental Suitable for most commercially available MDI canisters, the MDI
test conditions. See page 179. Actuation Sensor connects directly to the Breath Actuation Controller
BAC 100i to ensure precise synchronisation of MDI actuation.
Alternatively, a Footswitch can be attached to trigger actuation.
See page 179.

110 111
 Inhaler Testing Aerodynamic Particle
Size Distribution

Flow Meter
Data Analysis Software: Inhalytix™
Used for establishing accurate and consistent inlet flow rate during A flexible and fully validated solution for the entry, analysis and reporting of APSD
testing, our range of Flow Meters measure and control flow rates to the
data for all inhaled products.
accuracy specified by the pharmacopoeias.
User-configurable, the software will accept See page 206 for further information about
See page 184 for further information about our range of Flow Meters.
data from standard and customised cascade Inhalytix™.
impactors and impingers, including the NGI,
Required for: ACI, MSLI and GTI.

Inhaler Testing Workstation (ITW)

Semi-Automation Tools
Designed to keep the apparatus organised during testing and improve Eliminate Increase
Improve efficiency Reduce variability
workflow efficiency, the ITW keeps the cascade impactor and flow meter handling errors testing capacity
in position throughout the testing process.
See page 196 for further information.
Gentle Rocker
Agitates the NGI Collection Cup Tray in a controlled, repeatable manner to
Recommended for:
ensure complete dissolution of the active drug prior to analysis. See page 287.

Recommended for:

Mouthpiece Adapter
Moulded from high quality silicone rubber, our Mouthpiece Adapters Sample Preparation Unit SPU 200i
guarantee an airtight seal between the inhaler/add-on device Simplifies and automates the drug recovery process from induction ports
combination under test and the test apparatus. For a list of available and preseparators. See page 290.
Mouthpiece Adapters see page 203.
Recommended for:
Custom Mouthpiece Adapters are available upon request.

Required for:

NGI Assistant
A complete system for drug recovery from the NGI Collection Cup Tray,
Induction Port and Preseparator, boosting analytical throughput. See page 294.

Recommended for:
Qualification
GMP regulations require that
• The test methods used to monitor pharmaceuticals must meet proper standards of Impactor Cleaning System
accuracy and reliability
Standardises cleaning and drying procedures to help ensure the NGI and ACI
• Companies should establish procedures to ensure the fitness for use of instruments remain in optimum condition throughout their life. See page 298.
that generate data supporting product testing
Recommended for:
Copley provides a range of qualification documentation, services and tools to meet
these requirements.
See page 302 for further information.

112 113
 Inhaler Testing Aerodynamic Particle
Size Distribution

Related Applications
We also offer a range of equipment for additional application testing support:

For facemask testing

See page 236

Training, Servicing & Support

We offer a comprehensive range of services from bespoke product design to
installation, expert training and technical support, optimising all aspects of
pharmaceutical testing from start to finish.

Training Servicing Support Design

See page 313 See page 304 See page 312 See page 312

114 115
 Inhaler Testing Aerodynamic Particle
Size Distribution

APSD of DPIs: Test System Set-Up

A B C D E F G

Aerodynamic Particle Size Distribution

Dry Powder Inhalers (DPIs)

The APSD measurement of DPIs is typically performed under the same conditions
as DDU testing. However there are some differences.
A preseparator is typically interposed between device, to approximate the mean patient inhalation
the induction port and stage 0 of cascade impactor to flow rate achieved during clinical use.
capture the large, non-inhalable carrier particles,
A
Mouthpiece
Adapter
B
Induction
Port
Alternative Impactors/Impingers
Cup-coating should be considered and validated
to prevent impactor over-loading. as part of method development to reduce particle
Next Generation
C Preseparator D Andersen
As for delivered dose testing of DPIs, test flow rate is bounce and re-entrainment. Impactor (NGI) Multi-Stage Glass Twin
set on the basis of a 4 kPa pressure drop across the Cascade Liquid Impinger Impinger
Critical Flow Flow Impactor (ACI) (MSLI) (GTI)
E F
Controller Meter

Regulations and Guidelines G Vacuum Pump

Organisation Chapter/Guidance
Ph. Eur. / EMA 2.9.18 App. E

USP / FDA 601 App. 5

NGI ChP <0951> App. 3

JP 6.15.5 App 3

Organisation Chapter/Guidance
Ph. Eur. / EMA 2.9.18 App. D

USP / FDA 601 App. 2

ChP <0951> App. 2

ACI JP 6.15.5 App 2 Related Accessories
Organisation Chapter/Guidance
Ph. Eur. / EMA 2.9.18 App. C

USP / FDA 601 App. C

+
ChP -
MSLI JP 6.15.5 App 1

Organisation Chapter/Guidance
Ph. Eur. / EMA 2.9.18 App. A
Temperature and Relative Humidity Sensor Footswitch
USP / FDA -
Ideal for measuring environmental Connecting directly to the Critical Flow Controller TPK
ChP <0951> App. 1 test conditions. See page 183. 100i, the Footswitch enables precise synchronisation of
DPI actuation with the onset of flow. See page 183.
GTI JP -

116 117
 Inhaler Testing Aerodynamic Particle
Size Distribution

APSD of DPIs: Test System Component Parts

Critical Flow Controller (TPK)

Next Generation Impactor (NGI)
Simplify DPI test system set-up in accordance with pharmacopoeial
The recommended test set-up is with an NGI, but an ACI may also be
recommendations with the Critical Flow Controller series. Positioned
used. Impactors with 7 or 8 stages are preferred by the regulators, as
between the impactor and vacuum pump, the Critical Flow Controller
they provide good APSD resolution. However, for some established
TPK 100i ensures critical (sonic) flow conditions during testing. It
methods the MSLI or GTI may be acceptable.
measures and records all parameters required for testing and for
controlling flow conditions.
See page 172 for further information about our Flow Controller range.

DON’T
FORGET Required for:
Preseparator
For the collection of large mass, non-inhalable powder boluses
typically emitted from a DPI, prior to entry into the impactor. Flow Meter
Different preseparators are available for the NGI and ACI.
Used for establishing accurate and consistent inlet flow rate during
See pages 85 and 91 respectively. testing, our range of Flow Meters measure and control flow rates to the
Note: Preseparators are not required for APSD testing of DPIs accuracy specified by the pharmacopoeias.
using an MSLI or GTI. See page 184 for further information about our range of Flow Meters.

Required for:
Required for:

In addition to the above, the following is needed to complete a fully-operational test

set-up for the APSD measurement of DPIs: Inhaler Testing Workstation (ITW)
Designed to keep the apparatus organised during testing and improve workflow
Vacuum Pump efficiency, the ITW keeps the cascade impactor and flow meter in position
Ideal for the higher, sonic flow rate testing requirements of throughout the testing process.
DPIs, the High Capacity HCP6 and Super Capacity SCP6 Vacuum See page 196 for further information.
Pumps represent the latest in high performance, low maintenance,
vacuum pump technology. Our Vacuum Pump range is specifically Recommended for:
designed for use in the testing of OINDPs in accordance with
pharmacopoeial requirements.
See page 188 for further information about our Vacuum Pump range.
Mouthpiece Adapter
Required for:
Moulded from high quality silicone rubber, our Mouthpiece Adapters
guarantee an airtight seal between the inhaler under test and the test
apparatus. For a list of available Mouthpiece Adapters see page 203.
TOP Custom Mouthpiece Adapters are available upon request.
TIP
Induction Port P1 Measurement Adapter
Used together with the Critical Flow Controller, the Induction Port P1 Measurement Adapter Required for:
can be placed between the inhaler and the NGI induction port to measure the pressure drop
(P1) over the inhaler under test in the absence of a DUSA for DPIs. Cat No: 8502.

118 119
 Inhaler Testing Aerodynamic Particle
Size Distribution

Qualification NGI Assistant

GMP regulations require that A complete system for drug recovery from the NGI Collection Cup Tray,
Induction Port and Preseparator, boosting analytical throughput. See page 294.
• The test methods used to monitor pharmaceuticals must meet proper standards of
accuracy and reliability Recommended for:
• Companies should establish procedures to ensure the fitness for use of instruments
that generate data supporting product testing

Copley provides a range of qualification documentation, services and tools to meet Impactor Cleaning System
these requirements. Standardises cleaning and drying procedures to help ensure the NGI and ACI
See page 302 for further information. remain in optimum condition throughout their life. See page 298.

Recommended for:

Data Analysis Software: Inhalytix™

A flexible and fully validated solution for the entry, analysis and reporting of APSD
data for all inhaled products. Related Applications
User-configurable, the software will accept See page 206 for further information about We also offer a range of equipment for additional DPI testing application support:
data from standard and customised cascade Inhalytix™.
impactors and impingers, including the NGI,
ACI, MSLI and GTI.

Semi-Automation Tools
Eliminate Increase For better in vitro-in vivo For USP product-specific
Improve efficiency Reduce variability
handling errors testing capacity correlation (IVIVC) testing monographs
See page 214 See page 260

NGI Cup Coater

Standardises the NGI Collection Cup coating application process and guarantees
uniformity of the surface coating substance across cups. See page 284.
Training, Servicing & Support
Recommended for: We offer a comprehensive range of services from bespoke product design to
installation, expert training and technical support, optimising all aspects of
pharmaceutical testing from start to finish.
Gentle Rocker
Agitates the NGI Collection Cup Tray in a controlled, repeatable manner to
ensure complete dissolution of the active drug prior to analysis. See page 287.

Recommended for:

Sample Preparation Unit SPU 200i Training Servicing Support Design

See page 313 See page 304 See page 312 See page 312
Simplifies and automates the drug recovery process from the Induction
Ports and Preseparators. See page 290.

Recommended for:

120 121
 Inhaler Testing Aerodynamic Particle
Size Distribution

APSD of Nebulisers: Test System Set-Up

A B C D E F G

Aerodynamic Particle Size Distribution

Nebulisers A Mouthpiece Adapter B Induction Port TOP

TIP Determine sampling time (To) by balancing the risk of impactor
Next Generation overload with the requirement for analytical sensitivity. Time
For devices such as nebulisers, the evaporation of droplets exacerbated by the C
Impactor (NGI)
D NGI Cooler
chosen should be sufficient to ensure an adequate sample is
thermal mass of the impactor can be a problem, especially for drugs in solution. Breath Actuation collected for analysis without overloading the collection cups,
E F Flow Meter
Controller which causes liquid streaking.
Loss of solvent reduces droplet size, producing The recommended flow rate of 15 L/min employed
artificially low APSD measurements, compromising the in the APSD testing of nebulisers is lower than that G Vacuum Pump

integrity of the resulting data. Cooling the impactor to of other OINDPs in order to better represent the tidal
approximately 5°C is the recommended method for breathing conditions employed in their use.
overcoming this problem.
Related Accessories
Regulations and Guidelines
Organisation Chapter/Guidance
+
Ph. Eur. / EMA 0671 App. E

USP / FDA <1601> App. 6

NGI ChP 0951 App. 3

JP -
Temperature and Relative Humidity Sensor Footswitch
Ideal for measuring environmental Connecting directly to the Breath Actuation
test conditions. See page 179. Controller BAC 100i, the Footswitch enables precise
synchronisation of nebuliser device actuation with the
onset of flow. See page 179.

122 123
 Inhaler Testing Aerodynamic Particle
Size Distribution

APSD of Nebulisers: Test System Component Parts

NGI Cooler
Next Generation Impactor (NGI) Accommodating the NGI both open and closed, the NGI Cooler
The APSD characterisation of a nebuliser should be conducted using an allows the NGI to be operated in a temperature controlled
NGI. This is because the NGI is calibrated for use at 15 L/min and has environment. Additional space allows for cooling of extra sets
collection cups well suited to retaining liquid droplets. of Collection Cups, so multiple tests can be undertaken in
quick succession.
See page 194 for further information about the NGI Cooler.

In addition to the above, the following is needed to complete a fully-operational test

set-up for the APSD measurement of nebulisers:
Mouthpiece Adapter
Moulded from high quality silicone rubber, our Mouthpiece Adapters
Vacuum Pump guarantee an airtight seal between the inhaler under test and the test
Designed for optimal operation at low flow rates required for nebuliser apparatus. For a list of available Mouthpiece Adapters see page 203.
testing, the Low Capacity LCP6 Vacuum Pump represents the latest in Custom Mouthpiece Adapters are available upon request.
high performance, low maintenance, vacuum pump technology. Our
Vacuum Pump range is specifically designed for use in the testing of
OINDPs in accordance with pharmacopoeial requirements.
See page 188 for further information about our Vacuum Pump range.

Qualification
GMP regulations require that
• The test methods used to monitor pharmaceuticals must meet proper standards of
accuracy and reliability
Breath Actuation Controller (BAC)
• Companies should establish procedures to ensure the fitness for use of instruments
Ensuring that the volume of air sampled does not exceed the
that generate data supporting product testing
pharmacopoeial specifications, the Breath Actuation Controller model
BAC 100i contains an electronically operated, timer-controlled two-
Copley provides a range of qualification documentation, services and tools to meet
way solenoid valve and is positioned between the impactor and
these requirements.
Vacuum Pump to control air flow supply to the nebuliser.
See page 302 for further information.
See page 172 for further information about our Flow Controller range.

Flow Meter
Used for establishing accurate and consistent inlet flow rate during
testing, our range of Flow Meters measure and control flow rates to the
accuracy specified by the pharmacopoeias. See page 184 for further
information about our range of Flow Meters.

124 125
 Inhaler Testing Aerodynamic Particle
Size Distribution

Data Analysis Software: Inhalytix™ Related Applications

A flexible and fully validated solution for the entry, analysis and reporting We also offer a range of equipment for additional nebuliser testing application support:
of APSD data for all inhaled products.
User-configurable, the software will accept See page 206 for further information about
data from standard and customised cascade Inhalytix™.
impactors and impingers, including the NGI,
ACI, MSLI and GTI.

Semi-Automation Tools For facemask testing

See page 236
For better in vitro-in vivo
correlation (IVIVC) testing
Eliminate Increase
See page 214
Improve efficiency Reduce variability
handling errors testing capacity

Gentle Rocker
Training, Servicing & Support
Agitates the NGI Collection Cup Tray in a controlled, repeatable manner to We offer a comprehensive range of services from bespoke product design to
ensure complete dissolution of the active drug prior to analysis. See page 287. installation, expert training and technical support, optimising all aspects of
Recommended for: pharmaceutical testing from start to finish.

Sample Preparation Unit SPU 200i

Simplifies and automates the drug recovery process from induction ports
and preseparators. See page 290.

Recommended for: Training Servicing Support Design

See page 313 See page 304 See page 312 See page 312

NGI Assistant
A complete system for drug recovery from the NGI Collection Cup Tray,
Induction Port and Preseparator, boosting analytical throughput. See page 294.

Recommended for:

Impactor Cleaning System

Standardises cleaning and drying procedures to help ensure the NGI and ACI
remain in optimum condition throughout their life. See page 298.

Recommended for:

126 127
 Inhaler Testing Aerodynamic Particle
Size Distribution

APSD of ADIs: Test System Set-Up

A B C D E F G

Aerodynamic Particle Size Distribution A

Mouthpiece
Adapter
B
Induction
Port
Alternative Impactors/Impingers

Aqueous Droplet Inhalers (ADIs) C

Next Generation
Impactor (NGI)
D NGI Cooler
Andersen
Cascade TOP
E
Breath Actuation
Controller
F
Flow
Meter
Impactor (ACI) TIP
Historically, ADIs have
For ADIs as for nebulisers, the evaporation of droplets exacerbated by the thermal been tested using the ACI.
Vacuum
mass of the impactor can be a problem. G
Pump The NGI Cooler can also
be used with the ACI if
Loss of solvent reduces droplet size, producing Classified as active devices, the recommended flow rate required to control the test
artificially low APSD measurements, compromising the for ADI testing is 28.3 L/min for the ACI or 30 L/min for environment.
integrity of the resulting data. Cooling the impactor to the NGI.
approximately 5°C is the recommended method for
overcoming this problem.

Regulations and Guidelines

Whilst there is no current pharmacopoeial or regulatory aerosol droplet generation of nebulisers. Testing, and Related Accessories
guidance for ADIs, they are considered to combine the the equipment that features in this section, reflects this
metered-dose technology of MDIs with the aqueous combined technology.

Organisation Chapter/Guidance +

Ph. Eur. / EMA 0671 App. E

USP / FDA <1601> App. 6

NGI ChP 0951 App. 3

JP - Temperature and Relative Humidity Sensor Footswitch

Ideal for measuring environmental Connecting directly to the Breath Actuation Controller BAC 100i,
test conditions. See page 179. the Footswitch enables precise synchronisation of ADI device
actuation with the onset of flow. See page 179.

128 129
 Inhaler Testing Aerodynamic Particle
Size Distribution

APSD of ADIs: Test System Component Parts

Flow Meter
Next Generation Impactor (NGI)
Used for establishing accurate and consistent inlet flow rate during
The recommended test set-up is with an NGI. An ACI can also be used
testing, our range of Flow Meters measure and control flow rates to the
for the assessment of ADIs.
accuracy specified by the pharmacopoeias. See page 184 for further
information about our range of Flow Meters.

Required for:

In addition to the above, the following is needed to complete a fully-operational test

set-up for the APSD measurement of ADIs:
NGI Cooler
Accommodating the NGI both open and closed, the NGI Cooler
allows the NGI to be operated in a temperature controlled
Vacuum Pump environment. Additional space allows for cooling of extra sets of
Designed for optimal operation at low flow rates required for ADI collection cups, so multiple tests can be undertaken in
testing, the Low Capacity LCP6 Vacuum Pump represents the latest in quick succession.
high performance, low maintenance, vacuum pump technology. Our See page 194 for further information about the NGI Cooler.
Vacuum Pump range is specifically designed for use in the testing of
OINDPs in accordance with pharmacopoeial requirements.
Required for:
See page 188 for further information about our Vacuum Pump range.

Mouthpiece Adapter
Required for:
Moulded from high quality silicone rubber, our Mouthpiece Adapters
guarantee an airtight seal between the inhaler under test and the test
apparatus. For a list of available Mouthpiece Adapters see page 203.
Custom Mouthpiece Adapters are available upon request.
Breath Actuation Controller (BAC)
Ensuring that the volume of air sampled does not exceed the Required for:
pharmacopoeial specifications, the Breath Actuation Controller BAC
100i contains an electronically operated, timer-controlled two-way
solenoid valve and is positioned between the impactor and Vacuum
Pump to control air flow supply to the inhaler.
Qualification
See page 172 for further information about our Flow Controller range.
GMP regulations require that
• The test methods used to monitor pharmaceuticals must meet proper standards of
Recommended for:
accuracy and reliability
• Companies should establish procedures to ensure the fitness for use of instruments
that generate data supporting product testing

Copley provides a range of qualification documentation, services and tools to meet

these requirements.
See page 302 for further information.

130 131
 Inhaler Testing Aerodynamic Particle
Size Distribution

Data Analysis Software: Inhalytix™ Related Applications

A flexible and fully validated solution for the entry, analysis and reporting We also offer a range of equipment for additional ADI testing application support:
of APSD data for all inhaled products.
User-configurable, the software will accept See page 206 for further information about
data from standard and customised cascade Inhalytix™.
impactors and impingers, including the NGI,
ACI, MSLI and GTI.

For better in vitro-in vivo For cold Freon® effect testing For USP product-specific
correlation (IVIVC) testing See page 247 monographs
Semi-Automation Tools See page 214 See page 260

Eliminate Increase
Improve efficiency Reduce variability

Training, Servicing & Support

handling errors testing capacity

Gentle Rocker We offer a comprehensive range of services from bespoke product design to
Agitates the NGI Collection Cup Tray in a controlled, repeatable manner to
installation, expert training and technical support, optimising all aspects of
ensure complete dissolution of the active drug prior to analysis. See page 287. pharmaceutical testing from start to finish.

Recommended for:

Sample Preparation Unit SPU 200i

Simplifies and automates the drug recovery process from induction ports
and preseparators. See page 290. Training Servicing Support Design
See page 313 See page 304 See page 312 See page 312
Recommended for:

NGI Assistant
A complete system for drug recovery from the NGI Collection Cup Tray,
Induction Port and Preseparator, boosting analytical throughput. See page 294.

Recommended for:

Impactor Cleaning System

Standardises cleaning and drying procedures to help ensure the NGI and ACI
remain in optimum condition throughout their life. See page 298.

Recommended for:

132 133
 Inhaler Testing Aerodynamic Particle
Size Distribution

APSD of Nasal Sprays:

Manual Test System Set-Up
A B

C D

Aerodynamic Particle Size Distribution

F

Nasal Sprays
Nasal sprays typically produce droplets in the range 20-200 microns, which is outside G

the effective range of cascade impactors. However, most sprays deliver a proportion
(typically <5%) of fine droplets in the <10 micron range.
It is important to quantify the amount of droplets Regulators recommend the use of a cascade impactor A Vacuum Pump B
Glass Expansion
Chamber
Alternative Impactors/Impingers
in this range since it is the amount of dose that can in conjunction with a high volume expansion chamber
Adapter and
penetrate beyond the nasal tract and into the lower to quantify the amount of drug in the <10 micron C
Clamp for ACI
D Flow Meter Fast Screening Glass Twin
respiratory tract or lungs, which may range, to assess the potential risk of deposition Andersen Impinger
be undesirable. in the lungs. E
Nosepiece
F
Andersen Cascade (FSA) (GTI)
Adapter Impactor (ACI)

Inhaler Testing
G
Workstation (ITW)

Regulations and Guidelines Next Generation

Impactor
(NGI)
Organisation Chapter/Guidance
Ph. Eur. / EMA -
Nasal Spray and Inhalation Solution, Suspension, and Spray Drug Products —
USP / FDA Chemistry, Manufacturing, and Controls Documentation

NGI ChP -

JP -

Organisation. Chapter/Guidance
Ph. Eur / EMA -
Nasal Spray and Inhalation Solution, Suspension, and Spray Drug Products —
USP / FDA Chemistry, Manufacturing, and Controls Documentation

ChP -
ACI
JP -
Organisation Chapter/Guidance
Ph. Eur. / EMA -

USP / FDA -

ChP -

GTI JP -

134 135
 Inhaler Testing Aerodynamic Particle
Size Distribution

APSD of Nasal Sprays: Manual Test System Component Parts

Andersen Cascade Impactor (ACI)

Inhaler Testing Workstation (ITW)
The ACI is particularly suitable for nasal spray APSD measurements as
Designed to keep the apparatus organised during testing and improve workflow
stages can easily be removed where no deposition occurs. An NGI may
efficiency, the ITW keeps the cascade impactor and flow meter in position
also be used.
throughout the testing process.
Impactors with 7 or 8 stages are preferred by regulators, as they provide
good APSD resolution. The FSA, a reduced stack plus filter version of the Recommended for:
ACI, is also suitable, for analogous reasons; little deposition is expected
in the lower stages of the impactor. See page 255 for further information
about the FSA.
For some established methods a GTI can also be used to assess the
Glass Expansion Chamber
APSD of nasal sprays. A special modification for the measurement of the
Glass expansion chambers are available for the quantification of nasal
particle size of nasal sprays according to Aaiche and Beyssac method is
drug product present in the form of particles or droplets that are less
available as an option.
than 10 microns.
We offer two sizes:
2 L chamber: to maximise aerosolisation and impactor deposition for
regular nasal sprays
5 L chamber: for powerful nasal sprays where increased volume is required
In addition to the above, the following is needed to complete a fully-operational test to allow a full aerosol plume to generate.

set-up for the APSD measurement of nasal sprays: See page 200 for further information.

Required for:
Vacuum Pump
Designed for optimal operation at the low flow rates required for nasal
spray testing, the Low Capacity LCP6 Vacuum Pump represents the latest
in high performance, low maintenance, vacuum pump technology. Our Adapter and Clamp
Vacuum Pump range is specifically designed for use in the testing of Adapters are available to connect the outlet port of the Glass Expansion
OINDPs in accordance with pharmacopoeial requirements. Chamber to the inlet of the NGI, Inlet Cone of the ACI and the inlet of
the MSLI. Each adapter is supplied with a clamp which allows the Glass
See page 188 for further information about our Vacuum Pump range.
Expansion Chamber to be removed easily from the impactor for assay.

Required for: See page 200 for further information.

Required for:

Flow Meter
Used for establishing accurate and consistent inlet flow rate during Nosepiece Adapter
testing, our range of Flow Meters measure and control flow rates to the
Special Nosepiece Adapters are available to accommodate the nasal
accuracy specified by the pharmacopoeias.
spray device and interface it with the test set-up.
See page 184 for further information about our range of Flow Meters.
See page 203 for further information.

Required for:
Required for:

136 137
 Inhaler
Index Testing Aerodynamic Particle
Size Distribution

Qualification Data Analysis Software: Inhalytix™

GMP regulations require that
A flexible and fully validated solution for the entry, analysis and reporting
• The test methods used to monitor pharmaceuticals must meet proper standards of of APSD data for all inhaled products.
accuracy and reliability
User-configurable, the software will accept See page 206 for further information about
• Companies should establish procedures to ensure the fitness for use of instruments
data from standard and customised cascade Inhalytix™.
that generate data supporting product testing
impactors and impingers, including the NGI,
Copley provides a range of qualification documentation, services and tools to meet ACI, MSLI and GTI.
these requirements.
See page 302 for further information.

APSD of Nasal Sprays: Semi-Automation Tools

Semi-Automated Test System Set-Up Improve efficiency Reduce variability
Eliminate
handling errors
Increase
testing capacity

The Vertus automated shake, fire and shot waste range is made up of integrated
turn-key solutions for precise, controlled and reproducible nasal spray testing.
Gentle Rocker
Compatible with most nasal sprays, the Vertus II or Improve nasal spray Increase productivity
Agitates the NGI Collection Cup Tray in a controlled, repeatable manner to
Vertus Plus offers analysts complete control over: testing accuracy and reduce hassle
and reproducibility ensure complete dissolution of the active drug prior to analysis. See page 287.
• The speed, angle and duration of shaking, ahead
of actuation Replicate test Reduce handling errors Recommended for:
methods across and costly out-of-
• Firing force and the speed of application and
different sites specification results
release of that force with ease
• The time delay between the end of shaking
and device actuation NGI Assistant
A complete system for drug recovery from the NGI Collection Cup Tray,
Induction Port and Preseparator, boosting analytical throughput. See page 294.

Vertus II & Vertus Plus Recommended for:

Offering high productivity, walkaway nasal
spray testing, the Vertus II and Vertus Plus
are ideal for automating aerodynamic
particle size distribution testing, boosting
Impactor Cleaning System
testing efficiency. The Vertus Plus also
offers optional shot weight collection. Standardises cleaning and drying procedures to help ensure the NGI and ACI
remain in optimum condition throughout their life. See page 298.

Recommended for:
Replaces the need for:
Flow Meter Vacuum Pump Inhaler Testing Workstation

See page 270 for further information about the Vertus range.

138 139
 Inhaler
Index Testing Aerodynamic Particle
Size Distribution

Related Applications
We also offer a range of equipment for additional nasal spray testing application support:

For better in vitro-in vivo

correlation (IVIVC) testing
See page 214

Training, Servicing & Support

We offer a comprehensive range of services from bespoke product design to
installation, expert training and technical support, optimising all aspects of Aerodynamic Particle Size Distribution
pharmaceutical testing from start to finish.
Nasal Aerosols
Like nasal sprays, nasal aerosols typically produce droplets in the range 20-200 microns,
which is outside the effective range of cascade impactors. However, nasal aerosols
deliver a proportion (typically <5%) of fine droplets in the <10 micron range. Unlike nasal
Training Servicing Support Design sprays, nasal aerosols are propellant-driven.
See page 313 See page 304 See page 312 See page 312
It is important to quantify this FPD since it can in conjunction with a high volume expansion
penetrate beyond the nasal tract and into the lower chamber to quantify the amount of drug in the <10
respiratory tract or lungs, which may be undesirable. micron range, to assess the potential risk of deposition
Regulators recommend the use of a cascade impactor in the lungs.

Regulations and Guidelines

Organisation Chapter/Guidance
Ph. Eur. / EMA -
Nasal Spray and Inhalation Solution, Suspension, and Spray Drug Products —
USP / FDA Chemistry, Manufacturing, and Controls Documentation

NGI ChP -

JP -

Organisation Chapter/Guidance
Ph. Eur. / EMA -
Nasal Spray and Inhalation Solution, Suspension, and Spray Drug Products —
USP / FDA Chemistry, Manufacturing, and Controls Documentation

ChP -
ACI JP -

140 141
 Inhaler
Index Testing Aerodynamic Particle
Size Distribution

APSD of Nasal Aerosols: Test System Set-Up APSD of Nasal Aerosols: Test System Component Parts

Andersen Cascade Impactor (ACI)

The ACI is particularly suitable for nasal aerosol APSD measurements as
A B stages can easily be removed where no deposition occurs. An NGI may
also be used.

D
Impactors with 7 or 8 stages are preferred by regulators, as they provide
good APSD resolution. The FSA, a reduced stack plus filter version of the
C
ACI, is also suitable, for analogous reasons; little deposition is expected
E in the lower stages of the impactor.
See page 255 for further information about the FSA.
F

In addition to the above, the following is needed to complete a fully-operational test

set-up for the APSD measurement of nasal aerosols:

A Vacuum Pump B
Glass Expansion
Chamber
Alternative Impactors/Impingers
C
Adapter and
D Flow Meter
Vacuum Pump
Clamp for ACI Next Generation Fast Screening
Designed for optimal operation at low flow rates required for nasal
Impactor Andersen
E
Nosepiece
F
Andersen Cascade
(NGI) (FSA)
aerosol testing, the Low Capacity LCP6 Vacuum Pump represents the
Adapter Impactor (ACI)
latest in high performance, low maintenance, vacuum pump technology.
G
Inhaler Testing Our Vacuum Pump range is specifically designed for use in the testing
Workstation (ITW)
of OINDPs in accordance with pharmacopoeial requirements.
See page 188 for further information about our Vacuum Pump range.

Required for:

Flow Meter
Used for establishing accurate and consistent inlet flow rate during
testing, our range of Flow Meters measure and control flow rates to the
accuracy specified by the pharmacopoeias.
See page 184 for further information about our range of Flow Meters.

Required for:

142 143
 Inhaler Testing Aerodynamic Particle
Size Distribution

Inhaler Testing Workstation (ITW)

Qualification
Designed to keep the apparatus organised during testing and improve workflow
GMP regulations require that
efficiency, the ITW keeps the cascade impactor and flow meter in position throughout
the testing process. • The test methods used to monitor pharmaceuticals must meet proper standards of
See page 196 for further information. accuracy and reliability
• Companies should establish procedures to ensure the fitness for use of instruments
Recommended for: that generate data supporting product testing

Copley provides a range of qualification documentation, services and tools to meet

these requirements.
See page 302 for further information.
Glass Expansion Chamber
Glass Expansion Chambers are available for the quantification of nasal
drug product present in the form of particles or droplets that are less
than 10 microns. Data Analysis Software: Inhalytix™
We offer one size ideal for the APSD characterisation of nasal aerosols: A flexible and fully validated solution for the entry, analysis and reporting
1 L chamber: to maximise drug deposition below the top stage of APSD data for all inhaled products.
of the impactor. User-configurable, the software will accept See page 206 for further information about
See page 200 for further information. data from standard and customised cascade Inhalytix™.
impactors and impingers, including the NGI,
ACI, MSLI and GTI.
Required for:

Semi-Automation Tools
Eliminate Increase
Improve efficiency Reduce variability
handling errors testing capacity

Adapter and Clamp

Gentle Rocker
Adapters are available to connect the outlet port of the Glass Expansion
Agitates the NGI Collection Cup Tray in a controlled, repeatable manner to
Chamber to the inlet of the NGI, Inlet Cone of the ACI and the inlet of
ensure complete dissolution of the active drug prior to analysis. See page 287.
the MSLI. Each adapter is supplied with a clamp which allows the Glass
Expansion Chamber to be removed easily from the impactor for assay. Recommended for:
See page 200 for further information.

Required for: NGI Assistant

A complete system for drug recovery from the NGI Collection Cup Tray,
Induction Port and Preseparator, boosting analytical throughput. See page 294.

Recommended for:

Nosepiece Adapter
Special Nosepiece Adapters are available to accommodate Impactor Cleaning System
the nasal aerosol device and interface it with the test set-up.
Standardises cleaning and drying procedures to help ensure the NGI and ACI
See page 203 for further information. remain in optimum condition throughout their life. See page 298.

Required for: Recommended for:

144 145
 Inhaler Testing Aerodynamic Particle
Size Distribution

Related Applications
We also offer a range of equipment for additional nasal aerosol testing application support:

For better in vitro-in vivo

correlation (IVIVC) testing
See page 214

Training, Servicing & Support Aerodynamic Particle Size Distribution

We offer a comprehensive range of services from bespoke product design to
installation, expert training and technical support, optimising all aspects of Nasal Powders
pharmaceutical testing from start to finish.
Like nasal sprays and aerosols, nasal powders typically produce droplets in
the range 20-200 microns, which is outside the effective range of cascade
impactors. However, nasal powders deliver a proportion (typically <5%) of fine
droplets in the <10 micron range.
It is important to quantify this FPD since it can The APSD measurement of nasal powders is
Training Servicing Support Design penetrate beyond the nasal tract and into the lower typically performed under similar conditions as the
See page 313 See page 304 See page 312 See page 312 respiratory tract or lungs, which may be undesirable. APSD measurement of DPIs. However a preseparator
Regulators recommend the use of a cascade impactor is not required.
in conjunction with a high volume expansion chamber
to quantify the amount of drug in the <10 micron range,
to assess the potential risk of deposition in the lungs.

Regulations and Guidelines

Organisation Chapter/Guidance
Ph. Eur. / EMA -
Nasal Spray and Inhalation Solution, Suspension, and Spray Drug Products —
USP / FDA Chemistry, Manufacturing, and Controls Documentation

NGI ChP -

JP -

Organisation Chapter/Guidance
Ph. Eur. / EMA -
Nasal Spray and Inhalation Solution, Suspension, and Spray Drug Products —
USP / FDA Chemistry, Manufacturing, and Controls Documentation

ChP -
ACI JP -

146 147
 Inhaler Testing Aerodynamic Particle
Size Distribution

APSD of Nasal Powders: Test System Set-Up APSD of Nasal Powders: Test System Component Parts

Next Generation Impactor (NGI)

A B C D E F The test set-up is shown with an NGI but an ACI is equally suitable for
the assessment of nasal powders. The Fast Screening Andersen (FSA)
impactor is a reduced stack plus filter version of the ACI. As little deposition
is expected in the lower stages, the FSA may be used to assess the APSD
characteristics of nasal powders.
See page 255 for further information about the FSA.

In addition to the above, the following is needed to complete a fully-operational test

set-up for the APSD measurement of nasal powders:

Vacuum Pump
A
Nosepiece
Adapter
B
Induction
Port
Alternative Impactors/Impingers Ideal for the higher, sonic flow rate testing requirements of nasal powders,
the High Capacity HCP6 and Super Capacity SCP6 Vacuum Pumps
Next Generation Critical Flow
C
Impactor (NGI)
D
Controller Fast Screening Andersen represent the latest in high performance, low maintenance, vacuum pump
Andersen Cascade technology. Our Vacuum Pump range is specifically designed for use in the
E Flow Meter F Vacuum Pump (FSA) Impactor (ACI) testing of OINDPs in accordance with pharmacopoeial requirements.
See page 188 for further information about our Vacuum Pump range.

Required for:

Critical Flow Controller (TPK)

Simplify nasal powder test system set-up in accordance with
pharmacopoeial recommendations with the Critical Flow Controller
series. Positioned between the impactor and vacuum pump, the Critical
Flow Controller TPK 100i ensures critical (sonic) flow conditions during
testing. It measures and records all parameters required for testing and
for controlling flow conditions.
Related Accessories See page 172 for further information about our Flow Controller range.
TOP
TIP
Required for:

The angle of the impactor can be

+ adjusted to replicate the angle
that the nasal powder device
may be used at, to investigate
Flow Meter
device performance under Used for establishing accurate and consistent inlet flow rate during
representative conditions. The testing, our range of Flow Meters measure and control flow rates to the
APSD measurement is unaffected
Temperature and Relative Humidity Sensor Footswitch accuracy specified by the pharmacopoeias.
by gravimetric forces.
Ideal for measuring environmental Connecting directly to the Critical Flow Controller
test conditions. See page 183. TPK 100i, the Footswitch enables the precise See page 184 for further information about our range of Flow Meters.
synchronisation of nasal powder device actuation
with the onset of flow. See page 183.
Required for:

148 149
 Inhaler Testing Aerodynamic Particle
Size Distribution

Inhaler Testing Workstation (ITW)

Semi-Automation Tools
Designed to keep the apparatus organised during testing and improve Eliminate Increase
Improve efficiency Reduce variability
workflow efficiency, the ITW keeps the cascade impactor and flow meter in handling errors testing capacity

position throughout the testing process.

See page 196 for further information.
NGI Cup Coater
Recommended for: Standardises the NGI Collection Cup coating application process and
guarantees uniformity of the surface coating substance across cups.
See page 284.

Recommended for:

Nosepiece Adapter
Special Nosepiece Adapters are available to accommodate the nasal
Gentle Rocker
powder device and interface it with the test set-up.
Agitates the collection cup tray in a controlled, repeatable manner to ensure
See page 203 for further information.
complete dissolution of the active drug prior to analysis. See page 287.

Required for: Recommended for:

Sample Preparation Unit SPU 200i

Simplifies and automates the drug recovery process from the Induction
Ports and Preseparators. See page 290.
Qualification
GMP regulations require that Recommended for:

• The test methods used to monitor pharmaceuticals must meet proper standards of
accuracy and reliability
• Companies should establish procedures to ensure the fitness for use of instruments NGI Assistant
that generate data supporting product testing A complete system for the drug recovery process from the NGI Collection
Cup Tray, Induction Ports and Preseparators, boosting analytical throughput.
Copley provides a range of qualification documentation, services and tools to meet See page 294.
these requirements.
Recommended for:
See page 302 for further information.

Impactor Cleaning System

Data Analysis Software: Inhalytix™ Standardises cleaning and drying procedures to help ensure the NGI and ACI
remain in optimum condition throughout their life. See page 298.
A flexible and fully validated solution for the entry, analysis and reporting
of APSD data for all inhaled products. Recommended for:

User-configurable, the software will accept See page 206 for further information about
data from standard and customised cascade Inhalytix™.
impactors and impingers, including the NGI,
ACI, MSLI and GTI.

150 151
 Inhaler Testing Aerodynamic Particle
Size Distribution

Related Applications
We also offer a range of equipment for additional nasal powder testing application support:

For better in vitro-in vivo

correlation (IVIVC) testing
See page 214

Training, Servicing & Support

We offer a comprehensive range of services from bespoke product design to
installation, expert training and technical support, optimising all aspects of
pharmaceutical testing from start to finish.

Training Servicing Support Design

See page 313 See page 304 See page 312 See page 312

152 153
 Inhaler Testing Ancillaries

Ancillaries
This chapter describes the ancillaries required in addition to the Vacuum Pumps
Dosage Unit Sampling Apparatus (DUSA) and cascade impactor to Driving most inhaler testing systems is the vacuum pump.
make up a fully-operational test set-up for determining the Delivered We offer a choice of three Vacuum Pumps dependent on
Dose Uniformity (DDU) and Aerodynamic Particle Size Distribution the system set-up and the capacity required.

(APSD) of orally inhaled and nasal drug products (OINDPs). See page 188

Breathing Simulators
NGI Cooler
Used to apply a more clinically representative breathing profile
(relative to a constant flow rate) during testing, our range of Breathing Designed to maintain the integrity of the APSD data of aerolised
Simulators cover the variety of breathing patterns found in neonatal, droplets by eliminating evaporation induced by the thermal mass
infant, child and adult physiologies. of the impactor, the NGI Cooler provides a temperature-controlled
environment for testing.
See page 156
See page 194

Inhaler Testing Workstation (ITW)

Flow Controllers
Providing an ‘extra pair of hands’, the ITW holds key test equipment
Our Breath Actuation Controller is an electrically-operated, timer in place during testing. Available with attachments to support both
controlled, two-way valve specifically designed for testing MDIs, DDU and APSD testing, the versatile ITW is the ideal benchtop
BAIs, MDIs with add-on devices (spacers and valved holding companion for busy analysts.
chambers (VHCs), nebulisers, ADIs, nasal sprays and aerosols.
See page 196
Designed to generate a standardised square-wave breath profile,
our Critical Flow Controller is ideal for the routine testing of ‘passive’
devices such as DPIs, where the drug aerosolisation is dependent
on the strength and duration of the patient’s inspiration. Glass Expansion Chambers
See page 172 Ideal for maximising the aerolisation of nasal drug products in the
assessment of fine particles by cascade impaction, Glass Expansion
Chambers are available for a wide range of nasal drug product applications.
See page 200

Flow Meters Mouthpiece & Nosepiece Adapters

Flow rate is a critical parameter in the in vitro testing of OINDPs. Our high quality silicone Mouthpiece and Nosepiece adapters are
We offer two Flow Meters with the required range and accuracy available for the most common devices on the market. A custom
to ensure accurate and consistent inlet flow rate during testing; design service is also available for other devices.
one based on differential pressure, the other on thermal mass
See page 203
measurement. Both units will give similar readings provided they
are calibrated and operated correctly.
See page 184

154 155
 Inhaler Testing Ancillaries

Choose your Breathing Simulator

From the generation of simple sinusoidal patterns stated in USP and Ph.Eur. for testing of nebulisers and MDIs with
a spacer/VHC to complex user-generated profiles for improving in-vitro in-vivo correlations (IVIVCs), our range of
versatile Breathing Simulators can be used for a variety of testing applications.

BRS 100i BRS 200i BRS 300i

Relevant Applications Relevant Applications Relevant Applications

Testing nebulisers Testing nebulisers Limited testing of nebulisers

Ancillaries Testing MDIs with a spacer/VHC Testing MDIs with a spacer/VHC Testing MDIs with a spacer/VHC

Breathing Simulators Improving IVIVCs for MDIs with a

spacer/VHC and nebulisers:
With Filter Holder and Adapter (DDU)
Improving IVIVCs for MDIs and DPIs:
With DUSA for MDI/DPI (DDU)
With Impactor and Mixing Inlet (APSD)

Our range of Breathing Simulators are designed to generate an inhalation and/ With Impactor and Mixing Inlet (APSD)

or exhalation profile that mimics that of a human subject for more clinically Improving IVIVCs for nasal products Improving IVIVCs for nasal products

representative testing.
Volume Volume Volume
Replacing the fixed flow rate normally used for breathing simulators to measure the effects of different 0 to 800 mL 0 - 155 mL 0 - 900 mL 0 to 5000 mL
regulatory testing with a breathing profile has become breathing profiles, flow rates and breathing techniques
Patient Profile Suitability Patient Profile Suitability Patient Profile Suitability
routine in orally inhaled product (OIP) assessment, during product development.
Neonate/Infant ✓ Neonate/Infant ✓ Neonate/Infant ✗
with more and more laboratories turning to the use of
Child ✓ Child ✓ Child ✗
Adult ✓ Adult ✓ Adult ✓
Their use has two major applications:
21 CFR Part 11 Compliant 21 CFR Part 11 Compliant 21 CFR Part 11 Compliant
✗ ✓ ✓

Improving in vitro-in vivo Frequency Frequency Frequency

Pharmacopoeial 12 - 40 bpm 6 - 60 bpm 6 - 60 bpm
correlations (IVIVCs)
I:E Ratio I:E Ratio I:E Ratio
To assess the DDU of: To apply more clinically representative conditions 1:1, 1:2 or 1:3 Variable Variable
1. Nebulisers as per Ph. Eur. 2.9.44 and USP during in vitro testing so as to generate data that
are more relevant to in vivo behaviour. Waveforms Waveforms Waveforms
chapter <1601>
Sinusoidal ✓ Sinusoidal ✓ Sinusoidal ✓
2. MDIs when used together with spacers and Square ✗ Square ✓ Square ✓
valved holding chambers, as per USP <1602> Triangular ✗ Triangular ✓ Triangular ✓
User-defined ✗ User-defined ✓ (flow vs time) User-defined ✓ (flow vs time)

Profiles Profiles Profiles

Inhalation ✓ Inhalation ✓ Inhalation ✓
Exhalation ✓ Exhalation ✓ Exhalation ✓

TOP Control: Start Control: Start Control: Start

TIP The use of breathing simulators is supported by the Quality by Design (QbD) strategy outlined in ICH Q8, which relies on
On inhalation ✓ On inhalation ✓ On inhalation ✓
scoping the potential impact of any variability that may arise from, for example, difference in patient physiology or technique.
On exhalation ✓ On exhalation ✓ On exhalation ✓
User-defined ✗ User-defined ✓ User-defined ✓

156 157
 Inhaler Testing Ancillaries

Key Features:

Piston/cylinder arrangement Compatible with MDI Actuation

driven by motor with accurate Sensor and Footswitch for
speed and position control coordinated testing

Breathing Simulator
BRS 100i

Ph. Eur. 2.9.44 USP <1601> and ISO 27427:2013

compliant <1602> compliant compliant

MDI Actuation Selectable start

Touchscreen Sensor/ Footswitch position (inhalation
user interface remote start or exhalation) for
capability spacers/VHCs
In-line arrangement Intuitive touchscreen control
for convenient test with icon-based menu
set-up structure simplifies operation
and clearly displays test
Extensive data parameters throughout run
output options
Inlet/outlet port for
direct connection to the
dose filter holder and
nebuliser, spacer or VHC

158 159
 Inhaler Testing Ancillaries

BRS 100i: User Interface

TOP
TIP
The BRS 100i can also be used in place of
a standard vacuum pump with a cascade
impactor such as the NGI or ACI and a Mixing
Inlet to form a simple and inexpensive
system for APSD studies utilising more
representative patient profiles for MDIs with
and without a spacer/VHC.
Setting a test parameter Set v Actual test parameters Set v Actual test parameters
(before test run) (during test run, with test progress
bar and enhanced visualisation of
breath status)

BRS 100i Accessories

Angle Adapter
Used to angle the device to a position representative of in vivo usage.

Settings menu BRS 100i connectivity options

Reporting Qualification & Maintenance

BRS 100i: Technical Specifications Extensive data output options are available as • Calibration certificate of compliance to
standard, including direct reporting to a printer or PC. Ph. Eur./USP provided as standard
Volume 0 to 800 mL (manually adjust)
• Comprehensive IQ/OQ/PQ documentation
Reported parameters
Frequency 12 - 40 bpm packages and toolkits available
• Start with: Inhalation/Exhalation • Qualification Kit available
I:E Ratio 1:1, 1:2 or 1:3
• I:E Ratio RS-232
Cycle Number 1 - 9,999 breaths
• Extended Warranty available
• Breath frequency (bpm)
Waveforms Sinusoidal • Number of breaths
• Set
Start Select start on inhalation or exhalation stroke
• Actual
Breathing Simulator BRS 100i
USB A

User Interface 5 inch, resistive colour touchscreen Cat. No. Description

9231 Breathing Simulator Model BRS 100i
Dimensions 460 x 385 x 290 mm (w x d x h)
1014 BRS 100i Extended Warranty - 1 year
RS-232 1015 BRS 100i Extended Warranty - 2 years
USB B
RUN - IN - for MDI Actuation Sensor or Footswitch
Connectivity Accessories
USB A (for connection with a USB printer)
8797 MDI Actuation Sensor
USB B (for connection with a PC)
8791 Footswitch
9110 Printer
BRS Qualification Kit
9117 IQ/OQ Documentation for BRS 100i/200i/300i
9105 Qualification Kit for BRS 100i/200i/300i
9107 Re-calibration of BRS 100i/200i/300i Qualification Kit
9108 BRS 100i Re-calibration Certificate
9122 Angle Adapter

160 161
 Inhaler Testing Ancillaries

Key Features:

Compatible with Temperature

and Relative Humidity Sensor for
measurement of environmental
test conditions

2 x piston/cylinder Compatible with MDI Quick-Release

arrangement driven Actuation Sensor Connectors
by motor with and Footswitch for included as
accurate speed and coordinated testing standard
position control

Breathing Simulator
BRS 200i

Ph. Eur. 2.9.44 USP <1601> and ISO 27427:2013

compliant <1602> compliant compliant

21 CFR Part 11 Stores and recalls Touchscreen user

compliant methods interface

For inhalation-only Inlet/outlet port for Intuitive 10.1 inch Easily import/export
Improved accuracy for profiles, the exhaust connection to the touchscreen control with methods and reports
Extensive data port diverts air directly DUSA, Filter Holder and icon-based menu structure
output options infant and neonate out of the exhaust, Mixing Inlet simplifies operation
profile volume instead of back through and clearly displays test
the device parameters throughout run
requirements

TOP
TIP For VHCs, simulate uncoordinated product use by starting the breathing profile
on the exhalation portion of the profile

162 163
 Inhaler Testing Ancillaries

BRS 200i: User Management

The user management feature of the BRS 200i helps ensure data remains compliant with 21 CFR
BRS 200i: User Interface
Part 11. Take control of your data and grant appropriate levels of access to users:

Access Level Permissions

1 Run approved methods

2 Run methods pending approval, and approved methods

3 Configure methods, run approved and pending methods

4 Approve methods
Main run test screen Main run test screen
5 Assign user roles, modify system administration settings
(ready to test) (test in progress)
6 Unrestricted access to all functions

With password-protected
user logins, each test run is
date and time stamped and
attributable to that user,
providing a clear audit trail.

User login screen Assigning user access level Volume/piston selection Settings menu

BRS 200i: Method Management BRS 200i: Technical Specifications

The BRS 200i offers users a number of different ways to define their chosen breathing patterns:
Volume 2 cylinders, 2 volumes: 0 - 155 mL, 0 - 900 mL

Choose from one of the Import a defined breath pattern Frequency 6 - 60 bpm
pre-set methods Configure their own from an external source
I:E Ratio Variable

Waveforms Sinusoidal, square, triangular, user-defined (flow vs time)

Profiles Inhalation and/or exhalation

Start Start on inhalation or exhalation stroke

User Interface 10.1 inch, capacitive colour touchscreen

RS-232
3 x USB A (for import/export of methods and connection with a USB keyboard or mouse)
Ethernet - for computer networking
Connectivity Temperature/Humidity Sensor port
RUN IN - for MDI Actuation Sensor or Footswitch
RUN OUT - to trigger activation of other connected electronic devices

164 165
 Inhaler Testing Ancillaries

BRS 200i Accessories

NGI Cooler Stand

The NGI Cooler Stand supports interfacing of the NGI Cooler
with the BRS 200i, whilst saving precious benchtop space.
See page 195 for further information.

Real-Time Breath Verification Chamber

Enabling measurement and recording of the breathing profile generated
through the inhaler during the actual test itself, using the Flow Certifier
available in the Qualification Kit. For use with the USP Induction Port only.

Reporting Breathing Simulator

Extensive data output options are available as
standard, including direct reporting to a PC and 3 x USB A 2 x Ethernet BRS 300i
export to a USB memory stick.

3 standard reports are available; Method Report, Run Qualification & Maintenance Ph. Eur. 2.9.44 USP <1601> and ISO 27427:2013
Report and Audit Report.
• Calibration certificate of compliance to Ph. Eur./USP compliant <1602> compliant compliant
1) Method Report and 2) Run Report both report the
provided as standard
following parameters:
• Comprehensive IQ/OQ/PQ documentation packages
• Waveform • Cycles
and toolkits available
• Volume (mL) • Cycle Duration (s)
• Frequency (bpm) • Test Duration (s) • Qualification Kit available 21 CFR Part 11 Extensive data Touchscreen user
• I:E Ratio • Max. Flow (L/Min) • Extended Warranty available compliant output options interface
• Start Delay (s) • Max. Acceleration (L/Min/Min)
• Inhalation Duration (s) • Cylinder Size (mL)
Breathing Simulator: BRS 200i
• Inhalation Delay (s) • Method creation information
• Exhalation Duration (s) (e.g. Status, Last Modified By) - Cat. No. Description Powerful drive system for
• Exhalation Delay (s) Method Report only Stores and
9176 Breathing Simulator Model BRS 200i generating challenging
• Start with: Inhalation/ • Last Run by (e.g. User, Last Run 1016 BRS 200i/300i Extended Warranty - 1 year recalls methods
profiles
Exhalation Date) - Run Report only 1017 BRS 200i/300i Extended Warranty - 2 years

3) Audit report Accessories

All data changes reported with a date and 8976 Temperature and Relative Humidity Sensor
time stamp attributable per user. 8797 MDI Actuation Sensor
8791 Footswitch
9117 IQ/OQ Documentation for BRS 100i/200i/300i
9115 Qualification Kit for BRS 100i/200i/300i
9107 Re-calibration of BRS 100i/200i/300i Qualification Kit
9109 Real-Time Breath Profile Verification Chamber

166 167
 Inhaler Testing Ancillaries

Key Features: BRS 300i: User Management

The user management feature of the BRS 300i helps ensure data remains compliant
with 21 CFR Part 11. Take control of your data and grant appropriate levels of access to users:

Compatible with Temperature Access Level Permissions

and Relative Humidity
Sensor for measurement of 1 Run approved methods
environmental test conditions
2 Run methods pending approval, and approved methods

3 Configure methods, run approved and pending methods

4 Approve methods

5 Assign user roles, modify system administration settings

6 Unrestricted access to all functions

Piston/cylinder Compatible with MDI Quick-Release
arrangement driven by Actuation Sensor Connectors
motor with accurate and Footswitch for included as
speed and position coordinated testing standard
With password-protected
control
user logins, each test run is
date and time stamped and
attributable to that user,
providing a clear audit trail.

User login screen Assigning user access level

BRS 300i: Method Management

The BRS 300i offers users a number of different ways to define their chosen breathing patterns:

Choose from one of the Import a defined breath pattern

Configure their own
pre-set methods from an external source

For inhalation-only profiles, the Inlet/outlet port for Intuitive 10.1 inch Easily import/export
exhaust port diverts air directly connection to the DUSA touchscreen control with methods and reports
out of the exhaust, instead of or Mixing Inlet icon-based menu structure
back through the device simplifies operation
and clearly displays test
parameters throughout run

TOP
TIP
For VHCs, simulate uncoordinated product use by starting the breathing profile
on the exhalation portion of the profile.

168 169
 Inhaler Testing Ancillaries

BRS 300i: User Interface BRS 300i Accessories

Real-Time Breath Verification Chamber

Providing measurement and recording of the breathing profile generated
through the inhaler during the actual test itself, using the Flow Certifier
available in the Qualification Kit. For use with the USP Induction Port only.

Main run test screen Main run test screen Settings menu
(ready to test) (test in progress)

Reporting
BRS 300i: Technical Specifications
Extensive data output options are available as 3 x USB A 2 x Ethernet
standard, including direct reporting to a PC and
Volume 0 - 5000mL (500 - 5000 mL certified)
export to a USB memory stick.
Frequency 6 - 60 bpm Qualification & Maintenance
3 standard reports are available; Method Report, Run
I:E Ratio Variable Report and Audit Report. • Calibration certificate provided as standard

1) Method Report and 2) Run Report both report the • Comprehensive IQ/OQ/PQ documentation packages
Waveforms Sinusoidal, square, triangular, user-defined (flow vs time)
following parameters: and toolkits available
Profiles Inhalation and/or exhalation • Qualification Kit available
• Waveform • Cycles
Start Start on inhalation or exhalation stroke • Extended Warranty available
• Volume (mL) • Cycle Duration (s)
• Frequency (bpm) • Test Duration (s)
User Interface 10.1 inch, capacitive colour touchscreen
• I:E Ratio • Max. Flow (L/Min)
• Start Delay (s) • Max. Acceleration (L/Min/Min) Breathing Simulator BRS 300i
RS-232 • Inhalation Duration (s) • Cylinder Size (mL)
3 x USB A (for import/export of methods and connection with a USB keyboard or mouse) • Inhalation Delay (s) • Method creation information Cat. No. Description
Ethernet - for computer networking
• Exhalation Duration (s) (e.g. Status, Last Modified By) - 9186 Breathing Simulator Model BRS 300i
Connectivity Temperature/Humidity Sensor port 1016 BRS 200i/300i Extended Warranty - 1 year
• Exhalation Delay (s) Method Report only
RUN IN - for MDI Actuation Sensor or Footswitch 1017 BRS 200i/300i Extended Warranty - 2 years
• Start with: Inhalation/ • Last Run by (e.g. User, Last Run
RUN OUT - to trigger activation of other connected electronic devices
Exhalation Date) - Run Report only
Accessories
3) Audit report
8976 Temperature and Relative Humidity Sensor
All data changes reported with a date and 8797 MDI Actuation Sensor
time stamp attributable per user. 8791 Footswitch
9109 Real-Time Breath Profile Verification Chamber
9117 IQ/OQ Documentation for BRS 100i/200i/300i
9105 Qualification Kit for BRS 100i/200i/300i
9107 Re-calibration of BRS 100i/200i/300i Qualification Kit
9109 Real-Time Breath Profile Verification Chamber

170 171
 Inhaler Testing Ancillaries

Schematic of DDU Testing System for MDIs (with Breath Actuation

Contoller to restrict volume of sampled air to no more than 2 litres)

Timer

2 port / 2 way solenoid valve

Vacuum Pump Tubing Breath Actuation Filter DUSA Collection Mouthpiece

Controller Tube Adapter

DPIs
In the case of DPIs, flow control is particularly The testing of DPIs is further complicated by the fact
important. Since most DPIs are classified as “passive” that devices vary in terms of their resistance to flow i.e.
devices (i.e. they rely solely on the patient’s inspiration some require more effort to inhale through than others.
to operate), variations in flow rate can significantly
Setting the flow rate for the testing of DPIs is more
affect device performance. It is therefore a regulatory
complex than for other types of OINDP. There are three
requirement that critical flow conditions are applied
Ancillaries during testing.
variables which need to be established to determine
the breath profile for DPI testing:

Flow Controllers Flow Rate (Q) Inspiration Volume Critical Flow Control

Flow rate and volume of air control are crucial when it comes to the DDU testing and 1. Flow Rate (Q)
APSD measurement of OINDPs. The use of an appropriate flow controller is vital to The in vivo strength and duration of the user’s Using a flow control valve, it is then a simple matter
comply with the regulatory requirements and streamline the testing, and when creating inspiration is broadly replicated by the flow rate to adjust the flow rate from the vacuum pump to
used and the duration of testing. produce the required pressure drop of 4 kPa and
specific methods which are easy to follow and transfer as required. then, by replacing the inhaler with a suitable flow
To establish the correct flow rate the flow rate meter, to measure the flow rate, Q, required to
The Ph. Eur. and USP require that test flow rate is controlled to within +/-5% of the specified value. This requirement required must first be established to produce a
can be met by selecting an appropriate flow control ancillary. produce this pressure drop.
pressure drop comparable with that found at the
mouth of the user in vivo when using the particular
inhaler being studied.
MDIs, MDIs with a Spacer/VHC, BAIs, Nebulisers, ADIs, Nasal Sprays
Both the Ph.Eur. and USP suggest a pressure drop Flow
& Nasal Aerosols over the inhaler of 4 kPa as broadly representative
Regulatory requirements for these OINDPs call for the control of: of the pressure drop generated during inhalation by
patients using DPIs.
- air flow rate - to a defined constant flow rate or to apply defined breathing profiles. See 156.
- total air volume The pressure drop created by drawing air through
ΔP = 4 kPa
- delay/synchronisation to begin sampling at a defined time. an inhaler can be determined by measuring the
absolute pressure downstream of the inhaler
mouthpiece and comparing this directly with
* � 100 kPa (atmosphere)

atmospheric pressure. � 96 kPa (lungs)

It is this Flow Rate Q, that the pharmacopoeias state should be used for DDU testing and APSD measurement.
The only exception to this criterion is that if the flow required to produce a 4 kPa pressure drop is >100 L/min, as for example in the case
of particularly low resistance inhalers, then 100 L/min should be used.

172 173
 Inhaler Testing Ancillaries

Conforming to the Ph. Eur. and USP specifications for section), our Flow Controllers have become the
2. Inspiration Volume a system that controls the key variables impacting the industry-standard for both DDU and APSD applications.
TOP
Once the flow rate (Q) has been established, it is now necessary TIP test conditions for DPIs (as described in the previous
to control the volume of air drawn through the inhaler during testing
By using a timer to control the time
to the 2 or 4 litres per simulated inhalation required by
that the solenoid valve is open, it is
the pharmacopoeias/regulators.

This is to simulate the in vivo inspiration volume of the patient and is

possible to control the volume of air
drawn through the inhaler to achieve Choose your Flow Controller
the volume specified.
achieved by introducing a timer-controlled, fast-acting solenoid valve
between the test device and the vacuum pump.

TOP
TIP 4 litres is considered to be the normal forced inhalation capacity of an average sized male weighing approx. 70kg. In
practice, it is not uncommon to widen the scope of the test parameters to cover a broader target patient population,
such as geriatrics and paediatrics, as well as those already suffering from pulmonary problems, including typical use and
unintentional misuse conditions.

Device Type BAC 100i/-R TPK 100i/-R

The relationship between flow rate and test time for DPI testing.
Example Calculation
4 L at 100 L/min
Volume: 4 litres (Ph. Eur) 150 MDI Y Y
4 L at 60 L/min
Flow Rate (Q): 100 L/min
Flow rate (L/min)

Time = Volume * 60/Flow rate

100
= 2.4 seconds
MDI with
Y Y
Spacer/VHC
Volume: 4 litres (Ph. Eur) 50
Flow Rate (Q): 60 L/min
Time = Volume * 60/Flow rate Time
0 Breath-Actuated MDI Y Y
= 4 seconds 0 1 2 3 4 (seconds)

DPI N Y
3. Critical Flow Control
Once the parameters to control the strength and An easy way to validate flow rate stability is to
duration of the simulated breathing cycle have been ensure that critical (sonic) flow occurs in the flow
Nebuliser Y Y
established, there is one final issue to be considered control valve. This can be confirmed by simply
– flow rate stability. measuring the absolute pressure at a point on either
side of the valve.
Ensuring stable flow throughout the test is critical ADI Y Y
to the testing of DPIs, since, as passive devices, they Providing that the pressure downstream of the valve
can be sensitive to small changes in flow rate. is less than half of the upstream pressure i.e. that the
ratio P3/P2 ≤ 0.5 then critical (sonic) flow is assured Nasal Spray Y Y
and the flow rate can be assumed to be stable.

Schematic of APSD Measurement System for DPIs

Nasal Aerosol Y Y

Nasal Powder N Y

DUSA
Vacuum Pump Critical Flow Collection Vacuum Pump Critical Flow Cascade
Controller Tube Controller Impactor

174 175
 Inhaler Testing Ancillaries

Key Features:

Quick-Release Automatic calculation of

Connectors included test duration from volume
as standard and flow rate

Interfaces
with DFM4

Breath Actuation Controller and DFM

2000 Flow
Meters. See
BAC 100i page 184

Ph. Eur. and Simplified workflow Integrated timer for

USP compliant with user-guided control of solenoid
test set-up valve
USB printer port Intuitive touchscreen Compact unit Hot-pluggable
interface for report user interface footprint
output
Fully automated
Extensive data Intuitive touchscreen
In situ impactor
output options control
leak testing
TOP
TIP BAC 100i v BAC 100i-R

Two versions of the unit are available.

Spacer/VHC
Inlet/In-line flow Atmospheric pressure The BAC 100i-R (Reversed) is functionally
testing delay identical to the BAC 100i but the position
meter modes measurement
function of the pneumatic connections are reversed
to improve connectivity with other inhaler
testing equipment .

BAC 100i-R and BAC 100i

176 177
 Inhaler Testing Ancillaries

BAC 100i: User Interface BAC 100i Accessories

MDI Actuation Sensor

Enabling precise synchronisation of the MDI actuation with the onset of flow,
the MDI Actuation Sensor simply clips on to most commercially available MDI
canisters and connects directly to the BAC 100i.
Alternatively, a Footswitch can be used to synchronise the actuation of MDIs,
nebulisers, ADIs and nasal aerosols with the onset of flow.
Guided test set up process Target v Actual test parameters Settings menu
(before test run) The MDI Actuation Sensor can also be used for the testing of MDIs with a spacer/
VHC in accordance with the specifications laid down in USP Chapter <1602>.

Temperature and Relative Humidity Sensor

The Temperature and Relative Humidity Sensor is designed to provide
analysts with accurate data about environmental conditions.
Leak test screen Flow method screen Easy setting of delay time

BAC 100i: Technical Specifications

User Interface Resistive touchscreen Printer
Connect a compatible printer via the USB connection in the
Flow Setting Manual
BAC 100i unit for instant test run reports.
Temperature/Relative Humidity
Yes (see page 179)
Measurement Capabilities

MDI Actuation Sensor

Auto-Trigger
Footswitch
Reporting Breath Actuation Controller BAC 100i
Critical Flow Control No Extensive data output options are available as
Cat. No. Description
Solenoid Valve Opening/Closing Time 25/25 ms standard, including direct reporting to a printer or PC.
8975 Breath Actuation Controller Model BAC 100i
Timer Range 0-600.0s resolution 0.1s 8975-R Breath Actuation Controller Model BAC 100i-R (Inlet
Available reports: Outlet Reversed)
Dimensions 415 x 315 x 250 mm (w x d x h)
• Run test 1020 BAC 100i/R Extended Warranty - 1 year
1021 BAC 100i/R Extended Warranty - 2 years
• Test setup RS-232 USB A
• Leak test
• Calibration Accessories
8976 Temperature and Relative Humidity Sensor
USB B 8797 MDI Actuation Sensor
8791 Footswitch
8766 Printer
Qualification & Maintenance 8983 BAC 100i Re-calibration Certificate
8752 Flow Time Verification Kit
• Certificate of compliance to Ph. Eur./USP provided 8753 Re-calibration of Flow Time Verification Kit
as standard.
• Comprehensive IQ/OQ/PQ documentation
packages and toolkits available.
• Extended warranty available

178 179
 Inhaler Testing Ancillaries

Key Features:
TOP
TIP
The TPK can also be used as a Breath Actuation Controller
(BAC) for testing MDIs with a spacer/VHC and BAIs in
accordance with Ph.Eur. 0671 and USP Chapter <1602>.

Quick-Release Automatic calculation of

Connectors included test duration from volume
as standard and flow rate

Critical Flow Controller Interfaces

TPK 100i with DFM4

and DFM
2000 Flow
Meters. See
page 184

Ph. Eur. and Simplified workflow User warned if sonic flow

USP compliant with user-guided conditions are not met
test set-up
USB printer port interface Intuitive touchscreen Compact unit Hot-pluggable
for report output user interface footprint

Fully automated Extensive data ‘Fly-by-wire’ flow control

In situ impactor output options valve – operation can be
leak testing automated for more efficient
TOP
TIP
and reproducible data
TPK 100i v TPK 100i-R
Two versions of the unit are available. The TPK 100i-R
(Reversed) is functionally identical to the TPK 100i
In-line flow Intuitive touchscreen but the position of the pneumatic connections are
reversed to improve connectivity between the TPK
measurement control
and other inhaler testing equipment.
accommodated

TPK 100i-R and TPK 100i

180 181
 Inhaler Testing Ancillaries

TPK 100i: User Interface TPK 100i Accessories

Temperature and Relative Humidity Sensor

The Temperature and Relative Humidity Sensor is designed to provide
analysts with accurate data about environmental conditions.

Guided test set up process Test set-up report Target v Actual test parameters
(before test run)

Footswitch
Enabling precise synchronisation of device actuation with the onset
of flow, the Footswitch connects directly to the TPK 100i.
Alternatively, an MDI Actuation Sensor can be used for
Leak test screen Device resistance measurement Settings menu synchronisation of MDI actuation and the onset of flow.

Printer
Connect a compatible printer via the USB connection in the BAC 100i
unit for instant test run reports.
Guided calibration process Flow method screen Test settings

TPK 100i: Technical Specifications

Reporting Critical Flow Controller TPK 100i
User Interface Resistive touchscreen
Extensive data output options are available as
Cat. No. Description
Flow Setting Manual and Automated standard, including direct reporting to a printer or PC.
8970 Critical Flow Controller Model TPK 100i
Temperature/Relative Humidity 8970-R Critical Flow Controller Model TPK 100i-R
Yes (see page 183) Available reports: (Inlet/Outlet Reversed)
Measurement Capabilities
• Run test 1018 TPK 100i/R Extended Warranty - 1 year
Auto-Trigger Footswitch | MDI Actuation Sensor 1019 TPK 100i/R Extended Warranty - 2 years
• Test setup RS-232 USB A
Critical Flow Control Yes
• Leak test
Solenoid Valve Opening/Closing Time 25 ms / 25 ms • Flow resistance Accessories
• Calibration 8976 Temperature and Relative Humidity Sensor
Timer Range 0-600.0s resolution 0.1s
USB B
8791 Footswitch
Dimensions 415 x 315 x 250 mm (w x d x h) 8797 MDI Actuation Sensor
8766 Printer

Qualification & Maintenance 8973 TPK 100i Re-calibration Certificate

8752 Flow Time Verification Kit
• Certificate of compliance to Ph. Eur./USP provided 8753 Re-calibration of Flow Time Verification Kit
as standard.
• Comprehensive IQ/OQ/PQ documentation
packages and toolkits available.
• Extended warranty available

182 183
 Inhaler Testing Ancillaries

Determining Test Flow Rate

Although patient inspiration subjects inhalers to varying flow rates, DDU testing and APSD measurement require
a constant volumetric air flow. Within this constraint, flow rates are specified, as far as possible, to reflect the
conditions of use. Because of the link between air flow rate and cascade impactor performance, flow meters
for OINDP testing must:

1. Be capable of measuring volumetric flow (L/min) TOP

2. Be calibrated for exit flow as opposed to inlet flow TIP
The pharmacopoeias specify that
We offer two flow meters that meet these criteria. test flow rate should lie within +/-
5% of the specified value.

Choose your Flow Meter

Ancillaries

Flow Meters
Air flow control is critical in the DDU and APSD testing of OINDPs. For many inhaled Application DFM4 DFM 2000
products, air flow triggers or drives aerosolisation of the formulation and it can therefore
have a significant effect on both delivered dose and APSD. Equally importantly, air flow Pharmacopoeial Y Y
impacts the performance of the test apparatus, notably cascade impactors which are
designed to function at a constant air flow rate.
IVIVC N Y
In addition, for some devices, especially DPIs, the air flow through the device provides the motive force for dose
delivery; indeed, some breath-actuated/operated devices trigger only when the flow rate through them exceeds
a certain value.

DDU Testing APSD Measurement Inlet Flow Y Y

A constant, repeatable flow rate is required throughout Air flow rate has a direct influence on the
testing to ensure conformance with the regulatory aerodynamic performance of cascade impactors.
requirements and pharmacopoeial specifications. The jet-to-plate distances on most commonly used In-line Flow N Y
impactors are fixed. Therefore, as long as the nozzle
diameters remain within defined tolerances and there
are no leaks in the system, the cutoff diameter of
any given stage is directly related to the volumetric
flow rate of air passing through it. A change in flow
rate results in a change in the aerodynamic particle
size characteristics of the stage or stages concerned
altering the measured APSD.

184 185
 Inhaler Testing Ancillaries

Flow Meter DFM4 Flow Meter DFM 2000

Key Features: Key Features:
Robust design High accuracy

Volumetric Mode:
Calculation of flow
Low flow resistance
rate based on live T/P
conditions

Calibration kit Portable, Portable,

available for user
hand-held device hand-held device
calibrations

Standard Mode:
Direct measurement of Calculation of flow rate
Clear digital display Can also be Data connectivity
volumetric flow used in-line based on preset T/P
conditions

DFM 2000 in Holder Universal Flow

of Inhaler Testing Meter Adapter
Workstation (ITW)

Clear digital No inlet filter Data connectivity

display required

Technical Specifications Qualification & Maintenance Technical Specifications Qualification & Maintenance
Operation Principle Differential Pressure (Venturi)
• Calibration certificate of compliance Operation Principle Hot Wire Mass Flow
• Calibration certificate of compliance
to Ph. Eur./USP provided as standard to Ph. Eur./USP provided as standard
Flow Rate Range 10 – 105 L/min Flow Rate Range 0 – 200 L/min

Resolution 0.1 L/min Resolution 0.1 L/min between 90 and 200 L/min
Flow Meter DFM4 Flow Meter DFM 2000
Accuracy +/- 2% of reading or 0.7 L/min (whichever greater) Accuracy +/- 2% of reading
Cat. No. Description Cat. No. Description
Flow Resistance Low flow resistance (1.0 kPa @ 100 L/min) 8004 Flow Meter Model DFM4 8764 Flow Meter Model DFM 2000
Accurate calculation from in-built
Volumetric Flow Calculation
T & P sensors
Volumetric Flow Calculation Direct measurement of volumetric flow Accessories Accessories
Inlet Filter No inlet filter required Inlet filter required in un-filtered
5238 Universal Flow Meter Adapter Inlet Filter 5238 Universal Flow Meter Adapter
laboratory environment
8061 Re-calibration Certificate for DFM4 8765 Re-calibration Certificate for DFM 2000
Interface to external devices, such as
8005 Calibration Kit for DFM4
Connectivity - Breath Actuation Controller BAC 100i Interface to external devices, such as
8006 Re-calibration of DFM4 Calibration Kit
- Critical Flow Controller TPK 100i Connectivity - Breath Actuation Controller BAC 100i
- Critical Flow Controller TPK 100i
Reporting Flow rate and calibrate date via RS-232
Reporting Flow rate & calibrate date via RS-232
Calibrations Calibration kit available for user calibrations
Calibrations Factory calibrations only

186 187
 Inhaler Testing Ancillaries

Choose your Vacuum Pump

Low Capacity High Capacity Super Capacity

Application 2 x HCP6
Pump LCP6 Pump HCP6 Pump SCP6

MDI Y Y Y Y
Ancillaries

Vacuum Pumps MDI with

Spacer/VHC
Y Y Y Y

We offer vacuum pumps specifically designed for use in the testing of MDIs, DPIs, DPI sonic flow with
N N Y Y
nebulisers and nasal products in accordance with the specifications laid down NGI @ > 80 L/Min

in the Ph. Eur. and USP.

DPI sonic flow with
N Y Y Y
NGI @ < 80 L/Min

Nebuliser Y Y Y Y

ADI Y Y Y Y

Nasal Spray Y Y Y Y

Nasal Aerosol Y Y Y Y

Nasal Powder N Y Y Y

188 189
 Inhaler Testing Ancillaries

LCP6 Low Capacity Pump HCP6 High Capacity Pump

Key Features: Key Features:
Low
maintenance
Advanced
Advanced cooling
cooling
Low Advanced Oil-free
Advanced sound maintenance sound
insulation insulation
Quick-Release
Self-sealing compound carbon
Connector
Quick-Release included as vanes continually adjust so
Connector standard that the pump effectively
included as Oil-free performs with “as new” efficiency
standard
throughout its service life.

Self-sealing compound Left and right vacuum

inlets - choose where to
carbon vanes continually place pump in system
adjust so that the pump
effectively performs
with “as new” efficiency TOP
throughout its service life. TIP Boost performance
Where the flow rate produced by the HCP6 is
still not adequate, it is possible to connect a
Flow rate easily Small benchtop second HCP6 to the primary pump to give a
adjusted with dial footprint
maximum unregulated flow rate of up to 833 L/
Left and right vacuum Flow rate Anti-vibration Small benchtop
min, for example when testing DPIs under sonic
inlets - choose where easily adjusted feet footprint
Left and right regulated and flow conditions with the NGI, at high flow rates.
to place pump in with dial
unregulated inlets
system Appropriate hose fittings are supplied with all HCP6
units to allow them to be operated in this way.

Technical Specifications Qualification & Maintenance Technical Specifications Qualification & Maintenance
Type Rotary Vane • Included in IQ/OQ Documentation for 1 x HCP6 2 x HCP6 • Included in IQ/OQ Documentation for
Inhaler Testing Systems - see page 309 Inhaler Testing Systems - see page 309
Lubrication Type Dry Type Rotary Vane Rotary Vane
• Extended Warranty available • Extended Warranty available
Max. Flow in L/min (unrestricted) 133 Lubrication Type Dry Dry

Max. Sonic Flow through NGI N/A Max. Flow in L/min (unrestricted) 416 833
LCP6 Low Capacity Pump HCP6 High Capacity Pump
Max. Vacuum Level <15 kPa Max. Sonic Flow through NGI 80 100
Cat. No. Description Cat. No. Description
Applications: Nasal Yes Max. Vacuum Level <15 kPa <15 kPa
7923 Low Capacity Pump Model LCP6 7921 High Capacity Pump Model HCP6
Nebulisers Yes 1022 LCP6 Pump Extended Warranty - 1 year Applications: Nasal Yes Yes 1024 HCP6 Pump Extended Warranty - 1 year
1023 LCP6 Pump Extended Warranty - 2 years 1025 HCP6 Pump Extended Warranty - 2 years
MDIs Yes Nebulisers Yes Yes
DPIs No MDIs Yes Yes Accessories
Accessories
Routine Maintenance None DPIs Yes No
7905 Overhaul Kit for HCP6
Dimensions (w x d x h) 270 x 335 x 280 mm 7904 Overhaul Kit for LCP6 Routine Maintenance None None

Weight (kg) 18.4 kg Dimensions (w x d x h) 322 x 580 x 390 mm 750 x 580 x 390 mm

Weight (kg) 45 90

190 191
 Inhaler Testing Ancillaries

SCP6 Super Capacity Pump

Key Features:
Low
maintenance

Advanced
cooling Advanced sound
insulation

Quick-Rrelease
Connector
Oil lubricated
included as rotary vane
standard

Dual filtration process,

ensures that there is
virtually no oil vapour in
Left and right vacuum
the exhaust air, making
inlets - choose where it suitable for use in a
to place pump in laboratory environment
system

Flow rate easily

adjusted with dial
DON’T
FORGET
Purchase replacement lubricant to keep your
Left and right regulated vacuum pump in optimum working condition.
and unregulated inlets Buy it together with your pump from us today!

Technical Specifications Qualification & Maintenance

Type Rotary Vane • Included in IQ/OQ Documentation for
Inhaler Testing Systems - see page 309
Lubrication Type Oil
• Extended Warranty available
Max. Flow in L/min (unrestricted) 683

Max. Sonic Flow through NGI 100

SCP6 Super Capacity Pump
Max. Vacuum Level <0.1 kPa
Cat. No. Description
Applications: Nasal Yes 7928 Super Capacity Pump Model SCP6
Nebulisers Yes 1026 SCP6 Pump Extended Warranty - 1 year
1027 SCP6 Pump Extended Warranty - 2 years
MDIs Yes

DPIs Yes Accessories

Routine Maintenance Oil/Filter Change
7909 Maintenance Kit for SCP6
Dimensions (w x d x h) 423 x 653 x 455 mm 7913 Replacement Lubricant (5 Litres) and
Funnel for SCP5
Weight (kg) 71

192 193
 Inhaler Testing Ancillaries

Key Features:
Built-in light for Easy access via
high visibility large front and
rear doors

Twin side
access ports for
the nebuliser
(and mixing
inlet if used)

Double-glazed
panels ensure
high energy
efficiency

Comfortably
accommodates
NGI in open or
closed position

Additional space
for cooling of other
components, such as
collection cups meaning
Ancillaries Benchtop unit multiple test can occur

NGI Cooler
in quick succession

Exacerbated evaporation caused by the thermal mass of the NGI may be an NGI Cooler Accessories Qualification & Maintenance
issue for devices such as nebulisers that deliver the drug as an aerolised solution. • Comprehensive IQ/OQ/PQ documentation
Loss of solvent reduces droplet size, producing artificially low particle size NGI Cooler Stand
packages and toolkits available
measurements and compromises the integrity of APSD data. Saving precious benchtop space, • Extended Warranty available
the NGI Cooler Stand raises the
The NGI Cooler is designed to support testing in a temperature-controlled environment, NGI Cooler to eye level making
cooling the impactor to 5°C to overcome the issue of droplet size change due to evaporation. operation convenient for the user, NGI Cooler
creating an area underneath to
Cat. No. Description
place any additional ancillaries
5009 NGI Cooler
and components. 1046 NGI Cooler Extended Warranty - 1 year
Ph. Eur. and Quiet
1047 NGI Cooler Extended Warranty - 2 years
USP compliant operation

Accessories
NGI Cooler: Technical Specifications
9114 NGI Cooler Stand for BRS 200i
Ph. Eur. 2.9.44 5011 NGI Cooler Qualification Documentation
Precise temperature
5012 NGI Cooler Qualification Tools
Pharmacopoeial Compliance USP <1601>
control 5013 Re-calibration of NGI Cooler
EPAG recommended
Qualification Tools
Temperature Range 0 °C and ambient (typically 5 °C to 10 °C)

Temperature Accuracy ± 1.5 °C

Dimensions (w x d x h) 1000 x 500 x 575 mm

194 195
 Inhaler Testing Ancillaries

ITW: DDU Testing

The ITW keeps the DUSA collection tube, vacuum connection, flow meter
and waste shot collector (WSC2) in place during the testing process.

DFM 2000 Flow

Meter Holder

Rotatable DUSA holder

enables easy manipulation

Ancillaries of the sampling apparatus

Holder for MDI DUSA

Inhaler Testing
Workstation (ITW)
WSC2: Waste Shot Collector Mount

The hub of an inhaler testing system, the ITW is a modular workstation designed Quick-release
to aid handling and manipulation of the various pieces of test apparatus and connectors ITW for WSC2 with Switching Valve

accessories, improving workflow.

ITW attachments for DDU testing
The ITW offers analysts the flexibility to pick and choose the attachments necessary for their
test set-up needs. Simply connect the required attachments and start testing with greater ease.

Suitable for DDU Quick-slide Suitable for both

testing and APSD attachments for rapid right- and left-handed
measurement method change configurations
applications

Flexible configurations Stable and secure Supplied with quick-

to suit different platform for test release connectors for Holder for DUSA DFM4 Flow Meter Tubing attachments
Filter Holder in Holder ensure the workstation
testing requirements components easy interfacing
remains organised

196 197
 Inhaler Testing Ancillaries

ITW: APSD Measurement Spare/Additional Tubing Quick-Release Connectors

The ITW provides a stable support for the impactor during testing,
together with the flow meter.

DFM 2000 Flow Meter Holder A variety of tubing is available to provide connections Quick-Release Connectors are provided as standard
between the various components making up the inhaler with various pieces of equipment. Additional connectors
Holder for USP Induction Port
testing system. The 3 mm tubing is designed to provide can be purchased if required in two sizes, 13 mm and 16
the connection between the DUSA for DPIs and Critical mm designed for use with 10 mm i.d. and 16 mm i.d.
Flow Controller. tubing respectively.
ITW attachments for
APSD measurement
Tubing Quick-Release Connectors

Cat. No. Description Cat. No. Description

5015 10 mm i.d. PVC Tubing (per metre) 5026 13mm Quick-Release Connector - 3/8” threaded QR Male
5016 16 mm i.d. Wire Reinforced PVC Tubing (per metre) 5027 13mm Quick-Release Connector - 1/2” threaded QR Male
5017 3 mm i.d. PVC Tubing (per metre) 5028 16mm Quick-Release Connector - 3/8” threaded QR Male
5029 16mm Quick-Release Connector - 1/2” threaded QR Male
DFM4 Flow
Meter Holder

Holder for ACI Base

Also compatible with: Inhaler Testing Workstation (ITW)

Cat. No. Description

8120 Inhaler Testing Workstation - Baseplate and Upright
8125 Inhaler Testing Workstation for WSC2 with Switching Valve
8136 ITW Holder for ACI Base
8135 ITW Holder for DFM 2000
8134 ITW Holder for DFM4
8132 ITW Holder for DPI DUSA
8131 ITW Holder for MDI DUSA
8133 ITW Holder for MDI/DPI Filter Support Cap
8137 ITW Holder for USP Induction Port
8130 ITW QR Tube Holder
Fast Screening
Andersen (FSA)

Multi-Stage Liquid
Impinger (MSLI)

198 199
 Inhaler Testing Ancillaries

FDA compliant 3 chamber sizes available

Special nosepiece adapters are available

Certified volume for the entry port to accommodate the
different types of nasal devices

Ancillaries
Key Features:
Glass Expansion Chambers
The majority of nasal products are designed to generate droplets/particles with a mass
median aerodynamic diameter (MMAD) of greater than 10 to 20 microns. This is to increase
nasal deposition and minimise deposition in the lungs.
However, most sprays deliver a proportion (typically Cascade impactors are designed to capture particles in
<5%) of fine droplets in the <10 micron range. It is the range 0 to 10 microns and are widely used for
important to quantify this Fine Particle Dose (FPD) this application. Representative testing: entry
since it can penetrate beyond the nasal tract and port at 30° to outlet port for
insertion of nasal device
into the lower respiratory tract or lungs, which may
be undesirable.
ACI and NGI adapters
available for airtight
connection between outlet
Broad characterisation of nasal drug particle deposition within respiratory system port of expansion chamber TOP
and impactor TIP After validation, it may be
appropriate to use a reduced
impactor stack (e.g. Stage 0
Particle D > 10 microns (Internal Passageways) = >9 microns, Stage 2 = 4.7 to
Nasal cavity 9 microns, Stage F = 0.0 – 4.7
microns of an ACI at 28.3
Mouth
L/min).
Particle D = 5 - 10 microns (Upper Respiratory Tract)
Pharynx

Trachea & primary bronchi

Secondary bronchi ACI with Glass Expansion Chamber

Particle D = < 5 microns (Deep Lungs)

Terminal bronchi
We offers three sizes:
Alveoli

1 L chamber: 2 L chamber: 5 L chamber:

to maximise drug to maximise for powerful nasal sprays
deposition below the top aerosolisation and where increased space is
The use of a cascade impactor in conjunction with a high volume expansion chamber is used to measure the
stage of the impactor (i.e. impactor deposition required to generate full plume
amount of drug in small particles or droplets in respect of nasal sprays and aerosols.
for nasal aerosols) (i.e. for nasal sprays)
In accordance with the draft guidance, we offer a range of glass expansion chambers to meet these requirements.

200 201
 Inhaler Testing Ancillaries

Glass Expansion Chamber Accessories

Benchtop Holder for Glass Expansion Chamber

For keeping benchtops tidy and glass expansion chambers safe.

Expansion Chamber to Flow Meter Adapter

For ensuring a proper interface between the Glass Expansion Chamber
and flow meter when setting flow rate.

Glass Expansion Chambers

Cat. No. Description Ancillaries

Mouthpiece &
8950 1000 mL Glass Expansion Chamber
8951 2000 mL Glass Expansion Chamber
8952 5000 mL Glass Expansion Chamber
8953 Volume Verification Certificate for Expansion Chamber
8954
5217
8961
5212
Adapter & Clamp for ACI/FSA*
Adapter & Clamp for NGI/FSI*
Set of 10 O-Rings for Expansion Chamber Adapter
‘Quick Clamp’ for ACI
Nosepiece Adapters
8955 Benchtop Holder for Glass Expansion Chamber Ensure a proper seal is maintained between the device under test and the sampling
apparatus with our range of Mouthpiece and Nosepiece Adapters.
* Please specify Aluminium (A), 316 Stainless Steel (S) or Titanium (T) when placing your order.
Specially moulded from high quality silicone rubber to The adapters are generally transferable between
ensure superior performance, adapters are available for different product test systems, however, there are
the more common devices on the market, or can be cases where the inlet diameters may differ between
custom-made for your specific device type. apparatus. Please specify the intended testing system
when ordering to ensure the correct size adapter
is supplied.

202 203
 Inhaler Testing Ancillaries

Mouthpiece Adapters
Suffix the letter below to the Cat. No. for listed Mouthpiece Adapters, e.g. 5003C Mouthpiece Adapters
C Easyhaler® D Cyclohaler® E Handihaler® F Diskus® Cat. No. Description
G Novolizer® H Rotahaler® I Turbuhaler® J Diskhaler® 5003 Custom Mouthpiece Adapter for Induction Port, DUSA, WSC2, Filter Holder and Child Alberta Idealised Throat
5004 Tooling Charge for Custom Mouthpiece Adapter
K Respimat® L Evohaler® M Pari LC Plus® N Trudell AeroChamber® 5237 Custom Mouthpiece Adapter for Glass Twin Impinger and FP Induction Port
8515 Custom Mouthpiece Adapter for Adult Alberta Idealised Throat and Albuterol SCA
O Tobi Podhaler® P Ellipta® Q Rapihaler® R Nexthaler®
9013 Custom Mouthpiece Adapter for PTT 1000
S Qvar® Autohaler® T K-haler® U Airomir® Inhaler V PowdAir Plus®
Accessories

Cat. No. Description

Bespoke Design Available
xx 5003X Inhaler Support Accessory
For any device types not listed above, we offer a custom 5003Y Mouthpiece Adapter Engraving (per Mouthpiece Adapter)
mouthpiece adapter design service. Simply supply a sample 5004 Tooling Charge for Custom Mouthpiece Adpater
5005 Mouthpiece Adapter Rack
of the inhaler to be tested so that a ‘cast’ can be taken. This
5022 Certificate of Conformance for Mouthpiece
is used to create a moulding tool, which is used to make the
Adapter Material
mouthpiece adapter.
The tool is then supplied along with the mouthpiece adapter(s)
to the user so that it can be reused should any additional
mouthpiece adapters be required of that design, in the future.
Nosepiece Adapters
We offer nosepiece adapters that create
TOP a perfect fit between a nasal device and
TIP
Standard adapter colour is light blue, but other a Glass Expansion Chamber (page 200).
colours are available on request
A custom nosepiece adapter design service is available
for all nasal product device types. Simply supply
a sample of the nasal device and we will create a
moulding tool to make the nosepiece adapter. The tool
Mouthpiece Adapter Accessories can be re-used if additional nosepiece adapters of that
design are required.

Inhaler Support Accessory Nasal Adapters

For devices that require extra support, the Inhaler Support Accessory
Cat. No. Description
holds the device under test in the correct position throughout testing.
8957 Nasal Aerosol Nosepiece Adapter for Expansion
Chamber Inlet
8958 Tooling Charge (per nasal aerosol device)
8959 Nasal Spray Nosepiece Adapter for Expansion
Chamber Inlet
8960 Tooling Charge (per nasal spray device)
8956 Expansion Chamber to Flow Meter Adapter
Mouthpiece Adapter Rack 5022 Certificate of Conformance for Noisepiece
Adapter Material
To keep benchtops tidy and mouthpiece adapters organised.

204 205
 Inhaler Testing AerodynamicSoftware
Particle
Size Distribution

Inhalytix™
USP Chapter <601> and Ph.Eur. Chapter 2.9.18 and draft USP Chapter <1604> System Characteristics
specify various types of multi-stage cascade impactor that can be used for Quick and easy to install, Inhalytix™ is 21 CFR
measuring the drug-specific aerodynamic particle size distribution (APSD) of part 11 compliant, enabling the creation of users,
orally inhaled and nasal drug products (OINDPs). assignment of multiple roles (typically admin,
supervisor and analyst) and access to audit logs,
This process involves quantitative recovery and metrics can be derived that are used to characterise assisting in data monitoring and ensuring data
chemical analysis of the size-fractionated aerosol, the APSD, in accordance with pharmacopoeial integrity. The software will operate on Windows 7, 8
typically by High Pressure Liquid Chromatography specifications and various FDA and EMA guidance. and 10 operating systems.
(HPLC). From the resulting assay a number of important

System Operation (Configure > Test > Report)

Dashboard: On entering the software
the user is presented with a dashboard
providing useful information about how
the software is being used. This contains
information such as the number of
analysts and supervisors set up on the
system, as well as the total number of
tests prepared, executed and completed.
It also summarises the number of tests,
equipment and report configurations, as
well as details of the equipment inventory,
databased by type.

Inhalytix™ data analysis software is a flexible and fully the software will accept data from standard and Equipment Types
validated solution for the entry, analysis and reporting customised cascade impactors, including the Andersen
The software is pre-populated with the most
of the APSD of drug output from all OINDPs. It also Cascade Impactor (ACI), Next Generation Impactor (NGI),
commonly used impactor types for immediate
serves as a database for laboratory-based cascade Fast Screening Impactor (FSI), Fast Screening Andersen
use. However, it is not uncommon for custom
impactor inventory and provides for the setting up and (FSA), Glass Twin Impinger (GTI)
versions of cascade impactors to be used in
running of detailed test methods. User-configurable, and Multi-Stage Liquid Impinger (MSLI).
some laboratories. In these circumstances,
users can generate bespoke impactor types
that can then be stored and recalled for use
later. This function may, for example, allow a
Licensing user to add or remove certain stages from an
Inhalytix™ is available as a thee user licence software package, based on named impactor or add special components to the
users that can be added or removed by the system administrator. The software software, such as modified induction ports.
is available via PC, server and cloud-based installations, with digital licence keys
supplied by email. Additional packages of three users are available and can be
added to the system at any time.

206 207
 Inhaler Testing AerodynamicSoftware
Particle
Size Distribution

Equipment Inventory
Keeping track of equipment inventory and associating The software allows a high degree
it with the corresponding inhaler testing data can be a of customisation, including both
burden. For this reason, the Inhalytix™ equipment asset a “Summary” or “Detailed” report
library allows users to keep their equipment databased template and toggles to turn on or
and include equipment-specific data in their testing off the reporting of a broad range
reports. Not only does this allow users to keep track of metrics. Company logos can be
of equipment, it ensures full traceability by keeping added to the report header
comprehensive records of which specific pieces of if required.
equipment were used for each test. Furthermore, the
software provides the user with the option to enter
impactor-specific mensuration data, allowing the
precise calculation of stage cut-off diameters, thereby
enhancing the precision and accuracy of test results.
The software will also notify users if an impactor is due
for stage mensuration.

2. Equipment
Configuration The equipment configuration screen
Testing of different drug products requires different methods to be allows users to generate specific
in place, different equipment to be used and different metrics to be combinations of impactor/impinger
calculated. This configuration takes place in three easy steps: and components to match the
equipment configuration described
Reports • Equipment • Methods in the testing protocol. Users simply
drag and drop the impactor and
components of their choice into the
equipment configurator. This, for
1. Reports
example, could see the combination
The Reports configuration screen allows users to create tailored report of an NGI, with external filter holder,
templates, which are then stored and can be paired with different test NGI preseparator, NGI induction port,
methods, allowing data to be reported as required. mouthpiece adapter and inhaler.
The software automatically sorts
the components into the correct
order and ensures that only viable
combinations can be created.

208 209
 Inhaler Testing AerodynamicSoftware
Particle
Size Distribution

1. Prepare
3. Methods To prepare for a test, users are required to recall the test method relating to the product to be tested. During this step,
users will have the opportunity to enter test specific information, including the number of runs to be performed.

Creating a test method allows the user to combine delivered dose (when testing MDIs, DPIs, ADIs
detailed product information, such as drug etc.) or drug substance delivery rate (when testing
components and device details, with equipment and nebulisers) is recorded. Configuring the product
report configurations. Users have the opportunity to specific method is the final step before a user can
define for example stage groupings and fine particle run a test and analyse their results.
dose (FPD) specifications and to select whether

Tests
Once the necessary report, equipment and
test method configurations are in place,
the user is ready to enter the data and
complete the analysis. This function can
be found under the ‘Tests’ tab. Tests are
completed in three steps:
2. Execute
Prepare • Execute • Analyse
The user then executes the test
All tests are databased and their current by entering the number of doses
status can be monitored to see if they are actuated and drug deposition values
at the prepared stage, whether results have for each stage of the impactor, as
been entered or whether they are complete. well as any additional components
included in the equipment
configuration. This process is
then repeated for all additional
runs. Alternatively, data can be
automatically imported from a CSV
or XLSX file.
All values are easily displayed in a
scrollable table and can be edited
at any point prior to analysis, for
example when importing data from
HPLC software or exporting data for
report writing.

210 211
 Inhaler Testing AerodynamicSoftware
Particle
Size Distribution

Download a free demo from our website at

www.copleyscientific.com

3. Analyse
Once all data has been entered or imported the • Graphs – allows viewing of log-probit plot, drug
software analyses the data and presents it to the user deposition (by impactor stage/component) and
in the form of: cumulative drug distribution for each run. Also allows
• Results Summary – provides all the key metrics for all the comparison of up to 3 runs from the same
test runs in a scrollable table for immediate review. test or other tests, so long as the same equipment
configuration and data analysis specifications have
• Groups Results (where used) - displays the drug
been set previously.
fractions for each stage or size grouping defined in
the method. • Reports – allows viewing and printing of standard and
customised reports.

Inhalytix
Summary of Key Features
• Standardised approach to the analysis of impactor data Cat. No. Description
8260C Inhalytix Data Analysis Software
• Ph. Eur. 2.9.18 and draft USP <1604> compliant
(3 user licences) - Cloud
• 21 CFR Part 11 compliant 8260P Inhalytix Data Analysis Software
• Fully validated with in-built auto-validation protocols (1 user licence) - PC
8260S Inhalytix Data Analysis Software
• Supports PC, server and cloud-based installations
(3 user licences) - Server
• Equipment inventory and test-related database 8261 Additional 3 User Licences for Inhalytix
• Impactor-specific mensuration data log (Cloud & Server)

• Bespoke configurations, methods and reports 8263 Annual Support and Upgrade
Package (per user)
• Data import and export capability for use with HPLC software
• Quick 3-step results analysis: Prepare - Execute - Analyse
• Runs and/or Tests comparison capabilities

212 213
 Inhaler Testing Aerodynamic
ImprovingParticle
IVIVCs
Size Distribution

Improving IVIVCs Assessing Drug Efficacy

Predicting the pharmacokinetic and pharmacodynamic (PK/PD) properties The core in vitro tests for OINDPs, for DDU testing and APSD measurement are highly
repeatable and validated methods relied upon for product QC. However, in R&D, the
of orally inhaled and nasal drug products (OINDPs) using methods such
requirement is to understand product behaviour better and optimise performance
as in vitro lung deposition modelling and in silico PK modelling can be to deliver targeted in vivo drug deposition.
problematic, given the dynamic nature and complex geometry of the lungs,
not to mention the need to consider different lung deposition mechanisms
(diffusion, sedimentation, impaction etc.) and patient-to-patient variability.

Making a relatively small investment in systems that enhance the clinical realism of standard
Patient
pharmacopoeial in-vitro test set-ups for the delivered dose uniformity (DDU) testing and Flow Rate & Volume
aerodynamic particle size distribution (APSD) measurement may help bridge the gap between data
collected during quality control (QC) testing and in vivo performance helping to accelerate and
improve research and development (R&D).

Dissolution
USP/PH.Eur. Methods Testing
Clinic (PK/PD)

Efficacy Compliance
DDU
Realistic
FPD*
Breathing
Profiles Morphology
Particle
Improving Dispersion

IVIVCs
Formulation Device
Resistance
Realistic Throat
& Nasal Models Facemask
IVIVCs - Bridging the gap Testing
*Fine Particle Dose

Cold Freon® In this environment, accuracy and sensitivity alone do not maximise the utility of in
Effect
vitro testing. Due to the complex interactions between formulation and device and
the impact of patient-to-patient variability, identifying robust relationships between
product characteristics and clinical efficacy can be challenging - very few good IVIVCs
exist for OINDPs.

214 215
 Inhaler Testing Aerodynamic
ImprovingParticle
IVIVCs
Size Distribution

Demonstrating Bioequivalence (BE) Methods for Improving IVIVCs

One way to assess in vivo performance is to compare Not only this, but this ‘sameness’ method provides a
the characteristics of a test (T) OINDP, typically a deeper understanding of the performance between DDU and APSD Testing
generic, relative to those of a reference (R) product. different formulations under test. With this additional Realistic Breathing Profiles
Demonstrating bioequivalence between T and R data, the most promising candidates can be put Most OINDPs are routinely assessed using constant air flow rate conditions, which are
reduces the need for clinical testing providing the forward for clinical trials, potentially reducing the risk not representative of the inhalation/exhalation profiles of human subjects. Different
in vitro tests capture variability in in vivo behaviour. of clinical trial failure. patients exhibit different breathing profiles, which may affect the efficiency of drug
Better IVIVCs are therefore important for the robust delivery especially for passive devices such as dry powder inhalers (DPIs).
demonstration of BE, a prerequisite for regulatory Regulatory Guidance See page 218
submissions for generics.
Enhancing the clinical relevance requirements of Realistic Throat and Nasal Models
In a similar way better IVIVCs also support Quality by in vitro testing safeguards data quality, patient safety The standard Ph.Eur./USP Induction Port is known to poorly represent aerosol
Design (QbD) which calls for the systemic identification and clinical efficacy. transport through the upper respiratory tract. Using more realistic throat and nasal
and control of all parameters that have an impact on
Despite the slow uptake of a QbD approach to OINDP models enables a more representative assessment of drug delivery to the target site.
the clinical efficacy of a drug product. In vitro methods
are therefore far more useful in QbD studies if they development, regulators are now beginning to take a See page 220
accurately reflect in vivo behaviour. more defined position regarding its implementation.

For OINDPs it is possible to identify Critical Quality Improving the clinical relevance of in vitro tests and in Dissolution Testing
attributes (CQAs) relating to the Patient, Device silico models is an important area of focus for both the
In vitro dissolution testing is becoming more widely used for optimising efficacy
and Formulation. The impact of variability in all of industry and for regulators, largely because of demand
during drug development, ensuring batch-to-batch consistency and in some cases
these parameters is necessarily a focus in product for generic OINDPs. This is reflected in the recent
to predict bioavailability in vivo and and help demonstrate BE.
development and more easily studied if the clinical investments made by the FDA for the identification,
development and validation of clinically relevant in vitro See page 230
realism of in vitro test methods is improved.
testing methods.

Facemask Testing
Beclomethasone Dipropionate Inhalation In situations where the user lacks the capability of using a mouthpiece (e.g. small
Aerosol Draft Guidance (2019) children, the elderly), it is commonplace to use a facemask for inhaled drug
The FDA has released product specific draft delivery. The amount of inhaled drug available to the patient is dependent upon
Throat Geometry Throat Geometry
Breath Profile Breath Profile
guidance highlighting the use of novel in vitro testing the interface between the facemask and the patient and must be rigorously
Patient Delivered Dose = Delivered Dose
Aerodynamic Particle Aerodynamic Particle approaches for the assessment of Beclomethasone quantified under representative conditions.
CQAs Size Distribution Size Distribution
Dipropionate aerosol as an alternate to a comparative See page 236
clinical endpoint BE study.
Flow Resistance Flow Resistance
Dose delivery method Dose delivery method
The guidance lists additional supportive in vitro
Device (e.g. blister) = (e.g. blister)

CQAs
Formulation dispersion
method (CFD)
Formulation dispersion
method (CFD)
studies that can be conducted to support and Morphology
enhance clinical realism and improve IVIVCs.
Profiling the morphological properties e.g. particle size and shape of an inhaled
These studies include the use of representative
drug formulation may be useful for comparative assessment against a reference
Dose Dose mouth-throat models and breathing profiles; the
Formulation Dissolution rate
=
Dissolution rate
characterisation of aerosol velocity profiles and
drug product notably to assess aerosolisation performance and the extent of
Morphology/particle Morphology/particle
CQAs interaction interaction
evaporation rate; drug dissolution testing; and a full deagglomeration. See page 246
assessment of particle morphology.

T R Cold Freon® Effect

Designed to bridge the knowledge gap between in vitro Users of MDIs and nasal sprays may well be familiar with the “cold Freon®” effect -
By Grouping the Critical Quality Attributes (CQAs) and in vivo OINDP performance, our range of IVIVC test the inadvertent reaction, such as a cough, to the chilling sensation at the back of the
based on ‘Patient’, ‘Device’ and ‘Formulation’, a greater equipment provides analysts with the tools required throat following actuation of the device. Caused by impaction of the delivered dose
understanding of the relative difference between to assess test products under conditions that more and the rapid evaporation of any remaining propellant, the cold Freon® effect strongly
the Test (T) and Reference (R) formulations can be closely replicate in vivo performance for the most influences the efficiency of drug delivery.
ascertained, accelerating the commercialisation of representative testing. There are a number of ways
to adapt the existing regulatory standard systems to See page 247
efficacious products and in the case of generics, a
more reliable demonstration of bioequivalence. improve clinical realism for all inhaled drug types, as
shown opposite.

216 217
 Inhaler Testing Improving
Ancillaries
IVIVCs

TOP
TIP Using data acquired from the clinical use of spirometers, breathing simulators are used to generate representative
breathing profiles, offering the chance to more closely assess how factors such as the strength of inhalation and lung
capacity can affect the performance for passive devices such as DPIs.

See page 156 for more information about our range of Breathing Simulators.

Mixing Inlet
Applying more representative breathing profiles using a breathing simulator during APSD measurement is
complicated by two key issues:

Improving IVIVCs

DDU and APSD Testing

1 the impactors used to measure APSD must operate at a constant flow rate

2 the test flow rate applied to the inhaler may need to be lower than the minimum calibrated flow rate
of the impactor. For example in paediatric studies a representative flow rate may be 10 L/min but the
Two factors that have been identified as being critical to improving the clinical impactor may have a minimum calibrated operating flow rate of 28.3 L/min.
relevance of DDU testing and APSD measurement are:

Our Mixing Inlets are designed to allow the cascade impactor to operate
Realistic Breathing Profiles Realistic Throat and Nasal Models
at a constant flow rate, whilst permitting a lower fixed or variable rate
Replacing the existing constant In the case of APSD measurement, to pass through the inhaler. Positioned between the induction port/
air flow rate conditions used in replacing the existing Ph.Eur./USP throat/nasal inlet and cascade impactor, Mixing Inlets decouple the flow
testing with breathing profiles Induction Port with an age-appropriate rate through the device from the air flow drawn through the impactor,
more representative of the mouth/throat or nasal model with a enabling more representative testing.
conditions applied by specific more realistic human-like geometry.
patient populations.
Mixing Inlet (NGI), Mixing Inlet (ACI)
Mixing Inlet

Realistic Breathing Profiles Cat. No.

8328A
Description
Mixing Inlet for ACI, FSA and MSLI (316 Stainless Steel)
8326 ACI to NGI Outlet Adapter
Human beings do not breathe at a constant flow rate. Rather the breathing cycles generated by patients produce 8327 NGI to ACI Outlet Adapter
a continually varying flow rate - very different to the fixed, steady-state flow rates used during in vitro testing. 8329A Mixing Inlet for NGI and FSI (316 Stainless Steel)
Applying more representative breathing profiles can therefore help to achieve better IVIVCs. 8324 Set of 2 O-Rings for ACI Mixing Inlet
9160 Compressed Air Flow Controller for Mixing Inlet
Whilst the use of breathing simulators is currently 9164 Air Compressor for Mixing Inlet
Patient representative
only specified by regulators for the dose uniformity 9165 Compressed Air Flow Controller Re-Calibration Certificate
120
Standard pharmacopoeial assessment of MDIs with spacers/VHCs and also for 9166 Maintenance Kit for Air Compressor
100 testing square profile
nebulisers, they can be applied to the assessment
80 of other OINDPs in order to improve clinical realism
Flow Rate (L/min)

60 of the impactor-sized mass obtained during Breathing Simulator Qualification Tools

APSD measurement.
40
We offer an extensive range of qualification tools for our range of
20
Furthermore, the dose delivery and aerosol generation/ Real-Time Profile Breath Verification Chamber
Breathing Simulators, including a Real-Time Breath Profile Verification
dispersion characteristics of many inhaled products Chamber to measure and record the breathing profile generated.
0
(especially passive devices) are known to be sensitive to See page 156 further information.
0 1 2 3 4
Time (s) flow rate properties, such as acceleration, peak flow and
inhaled volume creating an additional incentive for use.

218 219
 Inhaler Testing Improving
Ancillaries
IVIVCs

Realistic Throat and Nasal Models Key Features:

The drug mass sized by the cascade impactor (impactor dose captured in the throat or nasal airway is essential
sized mass) should ideally be representative of the dose to understand the dosage delivery characteristics of Idealised geometry Smooth, uniform internal Quick-release clips
represents a range of geometry to allow for coating make internal coating
that would actually enter the lungs. To achieve this, the a given OINDP. In many cases, the portion of the dose patient groups and to ensure inter-throat and drug recovery
induction port or other accessory used to interface the collected in the throat or nasal airway represents a uniformity quick and simple
device to the impactor must capture a representative significant proportion of the delivered dose.
fraction of the dose. Knowledge of the portion of the

The throats and nasal models we offer were developed from extensive research into typical patient populations including information
provided by CT and MRI scans, direct observation of living subjects and data in the archival literature. Each has a standardised internal
geometry more representative of in vivo physiology than a standard induction port and suitable for a range of patient profiles. More
information and references are available on request.

Mouthpiece adapter
interface at inlet

Alberta Idealised Throat (AIT) Adult AIT (Open)

For orally inhaled products (OIPs), the AIT provides

analysts with data more representative of measured Chemically compatible Child AIT (Open)
Oral Cavity with a wide range of
in vivo behaviour, by ensuring that the ISM corresponds
drug recovery solvents
Pharynx with the portion of the aerosol that would likely enter
the lungs.
With a standardised, highly reproducible, human-
Epiglottis
like geometry, the AIT offers robust performance
independent of flow rate and is designed to make Adult Alberta Idealised Throat (AIT)
drug recovery quick and simple.
Larynx
Cat. No. Description
Schematic of the
8511 Adult Alberta Idealised Throat (AIT) in Aluminium
regions represented
by the AIT Two versions of the AIT are available:
Accessories
8512 Alberta Idealised Throat to ACI/FSA Adapter
8513 Alberta Idealised Throat to NGI/FSI Adapter
8514 Flow Meter to Adult Alberta Idealised Throat Adapter
8516 Spare silicone seal for Adult AIT
8518 Leak test Inlet cap and outlet adapter for Adult AIT

Child Alberta Idealised Throat (AIT)

Adult Child (6-14 years) 8530 Child Alberta Idealised Throat (AIT) in Aluminium

Both come complete with mensuration and leak

Accessories
test certificates.
8512 Alberta Idealised Throat to ACI/FSA Adapter
8513 Alberta Idealised Throat to NGI/FSI Adapter Different outlet adapters are available for a
8531 Flow Meter to Child Alberta Idealised Throat Adapter range of applications
8532 Spare Silicone Seal for Alberta Idealised Throat (Child)
8533 Leak Test Inlet Cap and Outlet Adapter for Child AIT

220 221
 Inhaler Testing Improving
Ancillaries
IVIVCs

Alberta Idealised Nasal Inlet (AINI)

Understanding and optimising regional deposition is
Olfactory region essential to maximise the fraction of drug absorbed
via the target pathway and to minimise drug transit
Turbinates
to the lungs. For nasally inhaled products, the AINI
enables representative testing of the deposition of
Vestibule (Nostril) drug within the nasal airways
Made up of 4 separate parts: vestibule (nostril),
Nasopharynx turbinates, olfactory region and nasopharynx, the AINI
enables representative testing of drug deposition
within the nasal airways. The AINI accurately mimics

Schematic of the regions

represented by the AINI
deposition behaviour in each region, allowing
the collection of drug samples that reflect the
Improving IVIVCs:
corresponding fraction of the dose for analysis.
The AINI is easily separated into its component parts
Example Test System for DDU Testing
to enable drug recovery and assay for each individual
area. The AINI comes complete with mensuration and E
A B C D
test certificates.

Key Features:
Quick-release clips Idealised geometry Smooth, uniform internal geometry
make internal coating representing a range for more representative testing
and drug recovery of patient groups to allow for coating and to ensure
quick and simple inter-nasal passageway uniformity F

Olfactory region

AINI (Closed) AINI (Open)

Turbinates
Seals ensure
leak-free testing

Nasopharynx

Vestibule
(Nostril)
Chemically Manufactured from aluminium
compatible for durability and to ensure
with a range of dimensional reproducibility
solvents
IVIVC System for DDU Testing of MDIs

Alberta
Alberta Idealised
Idealised Nasal
Nasal Inlet (Open)Inlet (AINI) A
Dose Uniformity Sampling
B Inhaler Testing C Mouthpiece Adapter
Apparatus (DUSA) for MDIs workstation (ITW)
DUSA Holder
Cat. No. Description
D E Alternative dose F Alternative dose collection
8540 Alberta Idealised Nasal Inlet (AINI) for NGI/FSI Breathing Simulator
collection device: device: Filter Holder
8541 Alberta Idealised Nasal Inlet (AINI) for ACI/FSA DUSA for DPIs
8326 ACI to NGI Outlet Adapter
Different outlet adapters are available for a
8327 NGI to ACI Outlet Adapter range of applications
8543 Alberta Idealised Nasal Inlet Leak Test Cap and Inlet Adapter

222 223
 Inhaler Testing Improving
Ancillaries
IVIVCs

Improving IVIVCs - DDU Testing System Components: Improving IVIVCs:

Breathing Simulator Example Test System for APSD Measurement
With an intuitive touchscreen interface for easy operation, our range
of Breathing Simulators are designed to produce breath profiles across
A B C D E F G H I J K
a range of ages (paediatric to geriatric) and patient conditions (mild to
severe lung impairment).
For further information about the range, see page 156.

Required for: AINI for Nasal Drug Testing

In addition to the Breathing Simulator, the following is needed to complete a fully-operational

IVIVC test system for DDU testing:

Dose Collection Device

DUSA for MDIs, ADIs and Nasal Aerosols. See page 21.

Required for:
IVIVC System for APSD Measurement of DPIs
DUSA for DPIs and Nasal Powders. See page 22.
Compressed Air Compressed Air Alberta Idealised Mouthpiece F Preseparator
A B C D E Mixing Inlet
Source Flow Controller Throat Adapter
Required for:
Cascade Breathing Critical Flow Flow
G H I J K Vacuum Pump
Impactor Simulator Controller Meter
Filter Holder for MDIs with Spacers/VHCs and Nebulisers. See page 25.

Required for:
A B C D E F G H I J K

Mouthpiece Adapters
Moulded from high quality silicone rubber, our Mouthpiece Adapters
guarantee an airtight seal between the inhaler under test and the
test apparatus.

Required for:

Nosepiece Adapters
Our Nosepiece Adapters interface the nasal device with the test system.

Required for:
IVIVC System for APSD Measurement of Nebulisers
See page 203 for further information
Breathing Compressed Mouthpiece
A B C D Induction Port E Mixing Inlet F Cascade Impactor
Simulator Air Source Adapter

NGI Cooler Compressed Air Critical Flow

G NGI Cooler H I J K Vacuum Pump
Stand Flow Controller Controller
MDI MDI with DPI Nebuliser ADI Nasal Nasal Nasal
Spacer/VHC Spray Aerosol Powder

224 225
 Inhaler Testing Improving
Ancillaries
IVIVCs

Improving IVIVCs - APSD Measurement Test System Components: In addition to the Breathing Simulator, Mixing Inlet and a realistic throat/nasal model, the
following is needed to complete a fully-operational IVIVC test system for APSD measurement:

Breathing Simulator
Cascade Impactor
With an intuitive touchscreen interface for easy operation, our range
Forming the basis of most systems used to measure APSD, a choice of
of Breathing Simulators are designed to produce breath profiles across
cascade impactors is available depending on device type and application.
a range of ages (paediatric to geriatric) and patient conditions (mild to
See page 82 for further information about our range of Cascade Impactors.
severe lung impairment).
For further information about the range, see page 156. Required for:

Required for:
Vacuum Pump
Our Vacuum Pump range represents the latest in high performance,
low maintenance, technology and is specifically designed for use in
Mixing Inlet the testing of OINDPs. See page 188 for further information about our
Vacuum Pump range.
Decoupling the flow rate through the device from the air flow drawn
through the impactor, the Mixing Inlets are needed to enable the Required for:
cascade impactor to continue to operate at a constant flow rate, whilst
allowing a lower fixed or variable rate to pass through the inhaler.

Critical Flow Controller

Required for:
Positioned between the cascade impactor and vacuum pump, the Critical
Flow Controller TPK 100i ensures critical (sonic) flow conditions during
IVIVC testing. This ensures changes to balancing flow from the compressed
air supply do not affect the cascade impactor flow rate. See page 172 for
Alberta Idealised Throat (AIT) further information about our Flow Controller range.
With a standardised, highly reproducible, human-like geometry, the AIT offers
robust performance independent of flow rate and is designed to make drug Required for:
recovery quick and simple. Adult and child (6-14 years) versions are available.

Flow Meter
Required for:
Used for establishing accurate and consistent inlet flow rate during
testing, our range of Flow Meters measure and control flow within
method specification. See page 184 for further information about our
Alberta Idealised Nasal Inlet (AINI)
range of Flow Meters.
Mimicking nasal drug deposition behaviour in the nostril, turbinates,
olfacrtory region and nasopharynx, the AINI helps users to identify the Required for:
fraction of the drug absorbed via the target pathway and realistically
evaluate any unintended drug transit to the lungs.

NGI Cooler
Required for: Accommodating the NGI both open and closed, the NGI Cooler
maintains a temperature-controlled environment throughout testing.
Additional space allows for the cooling of extra sets of collection
cups, so that multiple tests can be undertaken in quick succession.
See page 194 for further information.

MDI MDI with DPI Nebuliser ADI Nasal Nasal Nasal

Spacer/VHC Spray Aerosol Powder Required for:

226 227
 Inhaler Testing Improving
Ancillaries
IVIVCs

NGI Cooler Stand Qualification

Saving precious benchtop space, the NGI Cooler Stand raises the GMP regulations require that
NGI Cooler to eye level making operation convenient for the user
and creates an area underneath the unit to place any additional • The test methods used to monitor pharmaceuticals must meet proper standards of
ancillaries and components. accuracy and reliability

See page 195 for further information. • Companies should establish procedures to ensure the fitness for use of instruments
that generate data supporting product testing
Required for:
Copley provides a range of qualification documentation, services and tools to meet
these requirements.
See page 302 for further information.
Compressed Air Flow Controller
Designed to balance the steady state flow rate entering the impactor,
the Compressed Air Flow Controller ensures that the flow rate at the
inlet to the induction port is zero prior to starting the test. TOP
TIP
Vertus System interface with Breathing Simulator
Required for:
For the IVIVC testing of MDIs, nasal sprays and
nasal aerosols, interfacing the VertusII/Plus (see
page 270) with the Breathing Simulator Model BRS
300i enables full control of the device actuation
parameters (e.g. shaking, actuation force) allowing
Air Compressor for Mixing Inlet the fully automated application of patient
representative profiles. Users can create test
To provide supplementary air to the inlet port of the Mixing Inlet via the
methods that fully describe the patient population
Compressed Air Controller. the product is intended for and thus, create a
realistic testing method according to their needs.

Required for:

Improving IVIVCs
Mouthpiece Adapters
Cat. No. Description
Moulded from high quality silicone rubber, our Mouthpiece Adapters 8328A Mixing Inlet for ACI, FSA and MSLI (316 Stainless Steel)
guarantee an airtight seal between the inhaler under test and the 8326 ACI to NGI Outlet Adapter
test apparatus. 8327 NGI to ACI Inlet Adapter
8329A Mixing Inlet for NGI and FSI (316 Stainless Steel)
Required for: 8324 Set of 2 O-Rings for ACI Mixing Inlet
9160 Compressed Air Flow Controller for Mixing Inlet
9161 Compressed Air Inlet Manifold for Mixing Inlet
Nosepiece Adapters 9162 Compressed Air Inlet Manifold for Mixing Inlet & BRS 100i
9163 Compressed Air Inlet Manifold for Mixing Inlet & BRS 200i/300i
Our Nosepiece Adapters interface the nasal device with the test system. 9164 Air Compressor for Mixing Inlet
9165 Re-calibration of Compressed Air Flow Controller
9166 Maintenance Kit for Air Compressor
Required for:

See page 203 for further information

228 229
 Inhaler Testing Improving
Ancillaries
IVIVCs

We offer a range of equipment designed for particle selection, dose collection and dissolution testing, to help
analysts identify, segregate and assess the dissolution characteristics of inhaled drug products.

1. Particle Selection

or

Next Generation Impactor (NGI) Anderson Cascade Impactor

2. Dose Collection

or

Improving IVIVCs Watchglass/PTFE Assembly

Dissolution Testing
NGI Dissolution Cups

3. Dissolution Testing
Due to the small size of inhaled drug particles and their typically highly soluble nature,
dissolution has always assumed to be very rapid at the site of action. However, the
dissolution of inhaled drugs is complicated by a number of issues and is becoming an
area of increasing interest for regulators. For example, there is concern that variability
between patient groups in the amount and composition of lung and nasal fluid may
affect drug uptake. It is important to highlight the value of inhaled dissolution as a BE
tool, with the potential to discriminate between formulations of the same drug(s).
Designing a standardised dissolution test method One of the main problems facing the developers Standard USP Dissolution Tester
relevant to the lungs is not easy because of the small of such methods is the identification and segregation of
amount of aqueous fluid involved and the presence that part of the total emitted dose actually reaching the
of endogenous surfactants. Currently, there are no target site (as opposed to the whole dose) in a
official dissolution test methods specifically for form readily adaptable to conventional dissolution
inhaled products. testing techniques.

The small amount of aqueous fluid and surfactant found in the lung make it extremely difficult to mimic inhaled dissolution
testing in vitro. Marques, Loebenberg and Almukainzi (2011) list five of the most simulated lung fluids in Table 11 of their article
‘Simulated Biological Fluids with Possible Application in Dissolution Testing’. Read it to find out more.

230 231
 Inhaler Testing Improving
Ancillaries
IVIVCs

1 & 2. Particle Selection & Dose Collection Andersen Cascade Impactor (ACI)
Following a similar technique to that used for the NGI,
with the ACI the drug is instead captured directly onto
Next Generation Impactor (NGI) the membrane prior to analysis.
A modification of the standard NGI Collection Cup, the
1 A 76 mm polycarbonate membrane is applied to the
NGI Dissolution Cup and Membrane Holder enables collection plate prior to particle sizing
size-fractionated particles from an aerosol cloud to
2 Particle sizing is carried out in the conventional manner
be collected and tested using a conventional tablet
dissolution tester. 3 The membrane is inverted and sandwiched between the
glass and PTFE surfaces of the Watchglass/PTFE Assembly
NGI Dissolution Cups (traditionally used for transdermal patches). Watchglass/PTFE Assembly for use with ACI

The NGI Dissolution Cup differs from the standard

cup in that it has a 50 mm removable insert in the
impaction area.

1 Particle sizing is carried out in the conventional manner. NGI Dissolution Cups ACI with Membrane

2 Following collection, the insert is carefully removed from Cat. No. Description Cat. No. Description
the cup. 6001 NGI Dissolution Cup and Membrane Holder (each) 6003 Watchglass/PTFE Assembly for use with ACI (each)
3 The insert is covered with a pre-punched 55 mm 6002 55 mm Punch 6004 Pack of 100 Polycarbonate Filters
diameter polycarbonate membrane and secured in 6004 Pack of 100 Polycarbonate Filters (0.1 micron x 76 mm diameter)
position in a Membrane Holder, using a ring, to form a (0.1 micron x 76 mm diameter)
sealed “disc” or “sandwich”. NGI Dissolution Cup and Membrane Holder 6005 Spare Set of O-Rings

4 The Membrane Holder is then placed in a conventional

Dissolution Tester, such as Copley’s DIS 800i and tested
in a manner similar to the ‘Paddle Over Disc’ method
described in the Pharmacopoeias.

3. Dissolution Testing
We offer USP Method 2 dissolution testers for use with
the NGI and ACI Membrane Holders.
Further details about our range of dissolution testers
can be found in our sister brochure
“Driving Results in Pharmaceutical Testing”.

232 233
 Inhaler Testing Improving
Ancillaries
IVIVCs

The following is needed to complete a fully-operational test system for

inhaled dissolution dose collection:

Mouthpiece Adapters
Cascade Impactor
Moulded from high quality silicone rubber, our Mouthpiece Adapters
Use of a cascade impactor allows size fractionated particles guarantee an airtight seal between the inhaler under test and the
from an aerosol cloud to be collected for testing. test apparatus.
For further information about our range of Cascade
Required for:
Impactors, please see page 82.

Nosepiece Adapters
Our Nosepiece Adapters interface the nasal device with the test system.

Required for:
Vacuum Pump
See page 203 for further information
Our Vacuum pump range represents the latest in high
performance, low maintenance technology and is,
specifically designed for use in the testing of OINDPs.
See page 188 for further information about our Qualification
Vacuum Pump range.
GMP regulations require that
• The test methods used to monitor pharmaceuticals must meet proper standards of
accuracy and reliability
• Companies should establish procedures to ensure the fitness for use of instruments
that generate data supporting product testing
Flow Controller
Copley provides a range of qualification documentation, services and tools to meet
Suitable for controlling air flow rate across the range required for
these requirements.
OINDP testing reproducibility and the ease of method transfer,
reducing potential sources of data variability. See page 302 for further information.
See page 172 for further information about our Flow Controller range.

Flow Meter
Used for establishing accurate and consistent inlet air flow
rate during testing, our range of Flow Meters measures and
controls flow within method specification.
See page 184 for further information about our range of
Flow Meters.

234 235
 Inhaler Testing Improving
Ancillaries
IVIVCs

Face Models
A critical component of the test apparatus
used for facemask testing is the face model.
This should be appropriate to the age group
for which the product is intended, e.g. infant,
child or adult. Face models should:

Achieve realistic dead space Have physiologically accurate Provide a means of mounting
within the mask and at the soft facial tissue to simulate in the spacer/VHC or nebuliser
same time ensure the absence vivo conditions. such that the facemask is in
Improving IVIVCs of leaks between the mask correct alignment with the face
and model model as in “real-life” conditions.

Facemask Testing We offer a range of facemask testing systems for to allow users to utilise their own validated models, if
different devices, which seek to address the above desired. All models are fitted with replaceable face skins.
In many cases, inhaled drug products may be administered using a facemask instead of
requirements, whilst also providing sufficient flexibility
a mouthpiece. This is often the case for infants and small children and in other situations
where the user lacks the capability to use a mouthpiece.
A key factor in determining the amount of inhaled drug Due to the important role that a facemask has in
available to the patient is the interface between the transporting the drug aerosol from the device Face Model Products
facemask and the patient. A properly sized mask, firmly to the patient, further assessment is required in
Cat. No. Description
placed against the face, for example, will provide the addition to the standard DDU testing and APSD
9142 FMA/FMS Filter Holder and Adapter for BRS 100i
user with far more drug than a poorly fitting equivalent measurement methods routinely applied.
9143 FMA/FMS Filter Holder and Adapter for BRS 200i/300i
where much of the drug is lost to the environment 9103 Pack of 100 Filters for Filter Holder
through leakage. 9144 Adult Head and Adapter for FMA/FMS
9145 Child Head and Adapter for FMA/FMS
9146 Infant Head and Adapter for FMA/FMS
Relevant for two types of devices: 9149 Replacement Face Skins for Adult Head (Pack of 6)
9150 Replacement Face Skins for Child Head (Pack of 6)
9151 Replacement Face Skins for Infant Head (Pack of 6)

MDIs used with a spacer/VHC Nebulisers used with

and a facemask a facemask
Filter Holder and Adapter located in a cavity
behind the face model’s lips

236 237
 Inhaler Testing Improving
Ancillaries
IVIVCs

FMA: DDU Testing

A B C D

A Breathing Simulator

Filter Holder and

B
Adapter

C Face Model

Test Systems for Assessing D

Facemask Apparatus
(FMA)

Facemask Performance
Products Featured in this System
Two types of apparatus are available, each providing standardised test methods to
quantify the effect of using a facemask on drug delivery from the device under test.
Facemask Testing Apparatus

1. Facemask Testing Apparatus (FMA) The FMA is designed to meet all the critical requirements for assessing
the impact of facemasks on performance of MDIs with a spacer/VHC.

for MDIs with a Spacer/VHC

Device Securing Fixture: Secures the Digital gauge measures the force In addition to the above, the following is needed to complete a fully-operational DDU test system for assessing
spacer/VHC and its associated facemask applied to the face model in N or the impact of facemasks on the performance of MDIs with a Spacer/VHC:
into position prior to testing kg (Range 0-2.5 kg)

Face Model
Models are available for all age groups - adult, child and infant. All
models are fitted with replaceable face skins which provide flexibility
and elasticity similar to real life tissue.

Position adjustable in
both axes
Filter Holder & Adapter
FMA with example valved holding Positioned in the cavity behind the lips of the face model, the holder
chamber (VHC), Face Model and
contains a filter to capture the active drug from the device under test.
MDI (face model not included
with FMA) See page 25 for further information.

Face Model Support accepts Handwheel adjusts Device Securing

three different models: infant, Fixture to accommodate spacer/
child and adult VHCs of various sizes
Breathing Simulator
Providing breathing profiles that are more clinically representative
Face Model Products than a constant flow rate, the Breathing Simulator BRS 100i is ideal
for assessing the impact of a facemask on the DDU of MDIs with a
Cat. No. Description
spacer/VHC.
9141 Facemask Test Apparatus for Spacers & VHCs Model FMA
9142 FMA/FMS Filter Holder and Adapter for BRS 100i Find out more about our range of Breathing Simulators on page 156.
9143 FMA/FMS Filter Holder and Adapter for BRS 200i/300i

238 239
 Inhaler Testing Improving
Ancillaries
IVIVCs

FMA: APSD Measurement Filter Holder & Adapter

Positioned in the cavity behind the lips of the face model, the holder
contains a filter to capture the active drug from the device under test.
A B C D E F See page 25 for further information.

Next Generation Impactor (NGI)

The APSD characterisation of facemask performance should be
conducted using an NGI.
See page 82 for further information.

FMA to NGI Interface A Facemask B Face Model C Induction Port

Accessory Apparatus FMA to NGI Interface Accessory
Please note – (FMA)
the FMA to NGI Interface Provides a direct connection between the FMA and Face Model which
Accessory is a combination Cascade Breath Actuation is mounted onto the inlet of the NGI Induction Port.
D E F Vacuum Pump
of the base attachment Impactor Controller
(red line) and the white
attachment interface shown
in the pop-out bubble

Flow Controller
Suitable for setting flow rate and sampling time delays, as well as controlling
inhaled volume, our range of Flow Controllers improve testing reproducibility
Products Featured in this System
and the ease of method transfer, reducing potential sources of data variability.
See page 172 for further information about our Flow Controller Range.

Facemask Testing Apparatus (FMA)

The FMA is designed to meet all the critical requirements for assessing
the impact of facemasks on the performance MDIs with a spacer/VHC. Flow Meter
Used for establishing accurate and consistent inlet flow rate during
testing, our range of Flow Meters measure and control flow within
method specification.
In addition to the above, the following is needed to complete a fully-operational APSD measurement See page 184 for further information about our range of Flow Meters.
set-up for testing the performance of MDIs with a Spacer/VHC when used with a facemask.

Vacuum Pump
Face Model Our Vacuum Pump range represents the latest in high performance,
Models are available for all age groups - adult, child and infant. All low maintenance, technology, and is specifically designed for use in
models are fitted with replaceable face skins which provide flexibility the testing of OINDPs.
and elasticity similar to real life tissue.
See page 188 for further information about our Vacuum Pump range.

240 241
 Inhaler Testing Improving
Ancillaries
IVIVCs

Qualification FMS: DDU Testing

A B C
GMP regulations require that

• The test methods used to monitor pharmaceuticals must meet proper standards of
accuracy and reliability
A Breathing Simulator
• Companies should establish procedures to ensure the fitness for use of instruments
that generate data supporting product testing Face Model
B

Copley provides a range of qualification documentation, services and tools to meet

C Facemask Stand (FMS)
these requirements.
See page 302 for further information.

Products Featured in this System

2. Facemask Testing Stand (FMS) for Nebulisers
Facemask Stand (FMS)
The FMS is designed to meet all the critical requirements for assessing
the effect of facemasks on the use of nebulisers.

In addition to the above, the following is needed to complete a fully-operational DDU test system for assessing
the impact of facemasks on nebuliser performance:

Face Model
Models are available for all age groups - adult, child and infant. All models
Position adjustable
in both axes are fitted with replaceable face skins which provide flexibility and elasticity
Device Securing Fixture:
Secures the nebuliser and similar to real life tissue.
its associated facemask in
position prior to testing
Face Model Support accepts
three different models: infant, Filter Holder & Adapter
child and adult
Positioned in the cavity behind the lips of the face model, the holder
contains a filter to capture the active drug from the device under test.
FMS with example nebuliser See page 25 for further information.
(face model not included)

Breathing Simulator
Providing breathing profiles that are more clinically representative than a
Facemask Testing Stand (FMS) constant flow rate, the Breathing Simulator BRS 100i is ideal for assessing the
impact of a facemask on the DDU of nebulisers.
Cat. No. Description
BRS
9156 Facemask Stand for Nebulisers Model FMS Alternatively, the higher capacity Breathing Simulator Model BRS 200i can 100i
9142 FMA/FMS Filter Holder and Adapter for BRS 100i be used to access expanded functionality including the capability to apply
9143 FMA/FMS Filter Holder and Adapter for BRS 200i/300i user-defined profiles. BRS
200i
Find out more about our range of Breathing Simulators on page 156.

242 243
 Inhaler Testing Improving
Ancillaries
IVIVCs

FMS: APSD Measurement Next Generation Impactor (NGI)

A B C D E F
The APSD characterisation of a nebuliser should be conducted using an NGI,
because it has calibrated performance at the 15 L/min test rate specified
for nebulisers.

FMS to NGI Interface Accessory

Provides a direct connection between the FMS and Face Model that is
mounted onto the inlet of the NGI Induction Port.

Flow Meter
Used for establishing accurate and consistent inlet flow rate during
FMA to NGI Interface Facemask Stand Face Model Inducton Port
Accessory
A B C testing, our range of Flow Meters measure and control flow within
(FMS)
Please note – method specification.
the FMA to NGI Interface
D Cascade Impactor E Vacuum Pump E Flow Meter
Accessory is a combination See page 184 for further information.
of the base attachment (red
line) and the white interface
attachment shown in the
pop-out bubble
Vacuum Pump
Our Vacuum Pump range represents the latest in high performance,
Products Featured in this System low maintenance, technology, and is specifically designed for use in
the testing of OINDPs.
See page 188 for further information about our Vacuum Pump range.
Facemask Stand (FMS)
The FMS is designed to meet all the critical requirements for assessing
the effect of facemasks on the use of nebulisers. TOP
TIP The NGI Cooler can only be used for nebulisers with mouthpieces. For nebulisers with facemasks
the NGI will need to be removed from the NGI Cooler for testing, once the required temperature has
been reached.

In addition to the above, the following is needed to complete a fully-operational APSD measurement system for
assessing the impact of facemasks on nebuliser performance:

Qualification
Face Model
Models are available for all age groups - adult, child and infant. All models GMP regulations require that
are fitted with replaceable face skins which provide flexibility and elasticity • The test methods used to monitor pharmaceuticals must meet proper standards of
similar to real life tissue. accuracy and reliability
• Companies should establish procedures to ensure the fitness for use of instruments
that generate data supporting product testing
Filter Holder & Adapter
Positioned in the cavity behind the lips of the face model, the holder Copley provides a range of qualification documentation, services and tools to meet
contains a filter to capture the active drug from the device under test. these requirements.

See page 25 for further information. See page 302 for further information.

244 245
 Inhaler Testing Improving
Ancillaries
IVIVCs

Morphology
Cascade impactors separate the delivered dose from an inhaled product on the basis
of particle inertia, producing sized fractions which are then subject to chemical assay
Cold Freon® Effect
to produce an APSD for the active drug. The cold Freon®effect is the inadvertent reaction to the chilling sensation at the
back of the throat or nasal passages following the actuation of MDIs or nasal sprays
Whilst this process provides a useful indication of where even when APSDs are equivalent. This can be
respectively, and it can significantly influence the efficiency of drug delivery.
inhaled drug particles are likely to deposit within the particularly useful in generic development when trying
respiratory tract, it does not profile the morphological to replicate the performance of a reference product. The For example, the effect may cause the patient to cough, or abort the inhalation
properties of these particles. Generating component Malvern Glass Disc Cup, allows for collection of particles manoeuvre, resulting in inconsistent dose delivery.
specific particle geometric size and shape data may on a quartz glass disk, which can then be transferred
Spray pattern and plume geometry are common measurement techniques employed by the pharmaceutical
be helpful in understanding differences between to a Malvern Panalytical Morphologi 4-ID or equivalent
industry to characterise the emitted spray from MDIs and nasal sprays. However, the reaction of the user to the
formulations and hence their potential bioavailability, system for morphological analysis.
impaction force of the spray on the throat or nasal passageways is also of much concern.

TOP TOP
TIP The ‘cold Freon®’ effect is a function TIP Cold Freon® effect assessment is important in
of aerosol spray force and plume switching propellants for MDIs. For example,
Morphology Sampling Apparatus temperature reformulation of CFC to HFA 134a and HFA 152a

Cat. No. Description

Novel Inhaled Formulations Generic Inhaled Formulations
5242A Malvern Glass Disc Cup, Small
(for Morphologi 4-ID system) Assessing the cold Freon® effect of a new MDI or nasal An assessment of the cold Freon® effect of generic
formulation is valuable in evaluating and minimising the formulations can also provide useful supportive
potential for any unintended reaction by the patient evidence for the demonstration of BE. Comparative
which may impede drug delivery. Assessing the spray measures of impaction force and temperature are
force and plume temperature of a given formulation a good indicator of local delivery equivalence, or
when actuated as per the manufacturer’s instructions otherwise, and help to confirm that in clinical use the
can give a good indication of whether either of these generic will be interchangeable with the reference
parameters may induce an adverse reaction by the product. Since velocity is directly related to the
patient when used in real life. impaction force and temperature, the latter should be
a good indicator of local delivery equivalence for an
inhaled drug.

Copley offers two types of test apparatus

to assess cold Freon®. Drug A
Drug A and Drug
Drug B? B demonstrate
bioequivalence
in vitro, however,
differences in
their cold Freon®
characteristics may
Drug B? cause differences in
in vivo performance
Spray Force Tester Plume Temperature Tester

246 247
 Inhaler Testing Improving
Ancillaries
IVIVCs

Key Features:
Circular impaction plate – Quick-release device
Clear load cell display clamp ensures rigid
easily removed for cleaning
inhaler support

Compact footprint

Special rubber feet Precision slider for

eliminate vibration positioning of inhaler relative
transmission to load cell to impaction plate

Spray Force Tester SFT 1000 A sample of the inhaler to be tested is required at the time of placing an order so that a customised
clamp can be made.

Offering high precision impaction force testing for

MDIs and nasal sprays, the Spray Force Tester SFT 1000 SFT 1000: Technical Specifications
provides analysts with a simple and reliable way of
Flow Rate Range 0 to 2500 mN
assessing the effects of cold Freon® on the throat and
nasal cavity over the duration of the spray plume. Accuracy +/- 2.5 mN

The distance of the device relative to the impaction plate can be adjusted between 0 and
Adjustable Distance
200 mm +/- 0.03 mm using the precision digital gauge.

Power Battery or mains powered

High sensitivity Pass/Fail alarms for user- Dimesions (L x W x H) 580 mm x 200 mm x 80 mm

digital load cell programmable limits (for QC)
Reporting RS232 output to computer or printer

Supplied complete with calibration certificates for load cell and gauge
Memory capability for Load cell calibration
up to 100 spray force verification easily
measurements performed by user SFT 1000

Cat. No. Description Cat. No. Description

9000 Spray Force Tester Model SFT 1000 9005 Digital Mini Processor (Statistical Printer)
9001 Additional Device Clamp 9006 IQ/OQ Documentation for SFT 1000
9002 Re-calibration of Spray Force Load Cell 9007 Qualification Tools for SFT 1000
9003 Re-calibration of Digital Gauge 9008 Re-calibration of SFT 1000 Qualification Tools
9004 Spare Impaction Plate

248 249
 Inhaler Testing Improving
Ancillaries
IVIVCs

Plume Temperature Tester PTT 1000 Flow Meter

Used for establishing accurate and consistent inlet flow rate during
Providing analysts with a quick and easy method for assessing aerosol plume temperature, testing, our range of Flow Meters measure and control flow within
the PTT 1000 is ideal for the sensitive profiling of MDIs. method specification.

The outlet of the PTT 1000 is normally connected to however, easily be connected directly to a DUSA See page 184 for further information about our range of Flow Meters.
a waste shot collector and vacuum pump to capture collection tube or Induction Port if preferred, since the
the measured doses at the relevant flow rate. It can, outside diameter of all three accessories are identical.
Waste Shot Collector WSC2
A compact vacuum filtration system, the Waste Shot Collector WSC2 safely
A B C D E F G captures aerosols emitted from repeated actuations of the inhaler.
See page 24 for further information.

Mouthpiece Adapters
Moulded from high quality silicone rubber, our Mouthpiece Adapters
guarantee an airtight seal between the inhaler under test and the
test apparatus.

See page 203 for further information.

Vacuum PTT 1000 Data Waste Shot Sampling Mouthpiece PTT 1000
A B C D E F G Flow Meter
Pump Acquisition Model Collector Manifold Adapter Software
Qualification
GMP regulations require that

• The test methods used to monitor pharmaceuticals must meet proper standards of
Products Featured in this System
accuracy and reliability
• Companies should establish procedures to ensure the fitness for use of instruments
that generate data supporting product testing
Plume Temperature Tester PTT 1000
The PTT 1000 is supplied together with the data acquisition assembly, Copley provides a range of qualification documentation, services and tools to meet
sampling manifold assembly, flow meter adapter and software. these requirements.
See page 302 for further information.

In addition to the above, the following is needed to complete a fully-operational plume temperature test system
for MDIs: Plume Temperature Tester: PTT 1000

Cat. No. Description

Vacuum Pump 9010 Plume Temperature Tester Model PTT 1000 (incl. Software)
5001 Waste Shot Collector WSC2
Our Vacuum Pump range represents the latest in high performance,
9013 Shortened mouthpeice adapter
low maintenance, technology, and is specifically designed for use in 9011 IQ/OQ Documentation for PTT 1000
the testing of OINDPs. 9012 Re-calibration of 4 Thermocouples

See page 188 for further information about our Vacuum Pump range.

250 251
 Inhaler Testing Aerodynamic
Special Applications
Particle
Size Distribution

Special Applications Abbreviated Impactor

We offer a range of specialised test equipment for specific applications
relating to the performance assessment of orally inhaled and nasal
Method (AIM)
drug products (OINDPs). Background
Due to the unique nature of their part device/part formulation,
the practical application of QbD principles to OINDPs is not easy.
The preferred and current instrument of methods may not only be time-consuming
choice for measuring the aerodynamic but also require a high degree of skill and
particle size distribution (APSD) of OIPs for consistency on the part of the analyst if
both regulators and pharmacopoeias is error is to be avoided.
the cascade impactor (see page 76). Whilst
For these reasons and with the adoption
providing a detailed size classification
of QbD potentially increasing demands for
of the aerosol cloud concerned, recent
analytical data, attention has turned to
QbD initiatives have highlighted that full
the concept of AIM.
resolution multi-stage cascade impaction

AIM in QC
For OIP product batch release testing purpose once a full APSD profile has been
and QC applications, it is possible to established using a full-resolution cascade
use simpler but highly sensitive metrics impactor. This is known as Efficient Data
to determine if the product is fit for Analysis (EDA).

Typically, the APSDs of inhaled products exhibit a Normal (or Gaussian) Distribution centred around the
Mass Median Aerodynamic Diameter (MMAD). It is therefore possible to determine even subtle changes
in the APSD by measuring the following:

Abbreviated Impactor Measurement (AIM) Generic Drug Development 1. Impactor Sized Mass (ISM): the sum
of the drug mass deposited on the filter LPM/SPM sensitive to shift in APSD
The drive for greater efficiency is stimulating There is growing interest in the development and all impactor stages except the
debate as to whether full-resolution, multiple- of generic orally inhaled products (OIPs) as uppermost. This metric indicates any
stage cascade impaction can be supplemented the patents on the original products expire. shift in the amplitude of the APSD.

Drug Mass (µm)

with AIM as part of a Quality by Design This has led to the reintroduction into the
2. Ratio of Large Particle Mass to
(QbD) process. pharmacopoeias of some of the test methods
Small Particle Mass (LPM/SPM):
employed in the development of the original
Once the full APSD profile of a product has determined by splitting the ISM into
drug products. two fractions on either side of the
been established, AIM may be useful as a rapid
MMAD: LPM greater than the MMAD
screening tool in R&D and, with the use of See page 260 for further information.
and SPM smaller than the MMAD. This
appropriate metrics, in QC applications also.
ratio indicates any shift in the central
See page 253 for further information. tendency of the APSD.

TOP
TIP Although EDA can be applied to full-resolution impactor testing, its true value comes from combining
it with AIM, which uses only a reduced number of impactor stages, speeding up throughput and
further reducing analytical error. Full-resolution impactor testing is then reserved for out-of-
specification (OOS) investigations.

252 253
 Inhaler Testing Aerodynamic
Special Applications
Particle
Size Distribution

In this diagram, the AIM-QC model shows how abbreviating AIM - The Future
the ACI to just 2 stages and a filter, with the central stage
To meet these various demands and to provide a basis If validated and implemented, these impactors could
(Stage X) selected to have a cut-off diameter close to the
for the proof-of-concept work necessary to validate help to speed up formulation screening, prior to full
product MMAD allows the EDA metrics of ISM and LPM/SPM
to be easily determined. them, Copley has introduced a number of different resolution impactor studies being performed on the
versions of abbreviated impactor for use in both QC most promising candidates and then subsequent
The table on page 90 indicates which stage can be used for
(QC Models) and R&D (HRT Models). These are based used for product release in QC.
Stage X.
on stage versions of the popular Andersen Cascade
Adapted from: Mitchell, J.P. et al. Relative Precision of Inhaler Aerodynamic Impactor (ACI) and Next Generation Impactor (NGI).
Particle Size Distributon (APSD) Metrics by Full Resolution and Abbreviated
Andersen Cascade Impactors (ACIs): Part 1., AAPS PharmSciTechnol., 2010,
11(2): 843-851

Fast Screening Andersen (FSA)

FSA is an AIM version of the standard ACI suitably modified to provide a reduced stack plus filter (F) suitable
for either:

AIM in R&D Quality Control (FSA-QC)

AIM has also been suggested as a useful tool This is not easy; as has been mentioned before, a Stages 0 (or -1, or -2A) and F are used in conjunction with a Stage X,
in R&D for the fast screening of new formulations cascade impactor is not analogous to the lung. The with a cut-off diameter as close as possible to the MMAD of the aerosol,
in product development. lung is a complex organ, with high humidity, decreasing as determined during full resolution cascade impactor testing.
velocity with each bifurcation and complex deposition
An important aim is to establish how to generate
mechanisms (diffusion and sedimentation, as well as
clinically representative data to reduce the
impaction). This makes correlation between in vitro
dependence on time-consuming and expensive
cascade impactor measurements and deposition in the
clinical trials.
Human Respiratory Tract (HRT) highly complex.

Product Development (FSA-HRT) with Realist Throat and Nasal Models

There is some evidence to suggest that abbreviated versions
of full stack cascade impactors can be used to broadly indicate Stages with cut-off diameters are available at 5.0 and 1.0 microns for metered-
in vivo lung deposition based on two or three size bands dose inhaler (MDI) applications at 28.3 L/min. Also, for this and higher flow rates
(or fractions): (60 and 90 L/min) stages having traditional ACI cut points of 4.7 and 1.1 microns
are available, primarily for dry powder inhaler (DPI) applications.
1. Coarse Particle Mass (CPM) – That portion of the aerosol
considered to be too large to be inhaled (usually considered to be Find out more about the our Realistic Throat and Nasal products on page 220.
>5 microns)

2. Fine Particle Mass (FPM) – That portion between 5 and 1

micron, usually considered likely to deposit deep into the lung
and hence be therapeutically effective

3. Extra-fine Particle Mass (EPM) – That portion below 1 micron,

usually considered to be too small to deposit in the lung and
potentially exhaled.

Adapted from: Mitchell, J.P. et al. Relative Precision of Inhaler

Aerodynamic Particle Size Distributon (APSD) Metrics by Full Resolution
and Abbreviated Andersen Cascade Impactors (ACIs): Part 1., AAPS
PharmSciTechnol., 2010, 11(2): 843-851

254 255
 Inhaler Testing Aerodynamic
Special Applications
Particle
Size Distribution

In addition to the FSA, the following ancillaries are required to complete a fully operational test set-up for
determining the CPM, FPM, EPM, or LPM/SPM ratio Reduced NGI (rNGI)
The individual stages of the NGI are fixed within the seal body, such that they cannot be
removed. However, the NGI can be used in an abbreviated form, the rNGI, for both AIM-QC and
AIM-HRT applications.

As with the FSA, and depending as normal in the collection cups of

on the flow rate to be used, a those stages upstream.
stage between 2 and 4 (see blue
Vacuum Pump Critical Flow Controller Flow Meter Mouthpiece Adapter Note: when using the rNGI
highlights in the table below) of the
Filter Holder Assembly, it is not Split Ring
See page 188 For DPI testing only See page 184 See page 203 NGI can be selected with a cut-off
possible to have a second stage
See page 172 diameter close to the product’s
representing the Extra-fine Particle
MMAD (AIM-QC application) or
Mass (EPM).
close to 5 microns (in the case of
an AIM-HRT application). The flow resistance and the Filter
FSA-QC with Stage X cut-off diameter close to product MMAD total volume of the NGI are not
The rNGI Filter Holder Assembly is
appreciably affected by the
Cat. No. Description placed in the stage immediately
presence of the rNGI Filter Holder
8341 FSA-QC - 28.3 L/min (Stages 0, X and F)* after the cut-off stage selected.
Assembly and therefore with Filter Support
8342 FSA-QC - 60.0 L/min (Stages -1, X and F)*
8343 FSA-QC - 90.0 L/min (Stages -2A, X and F)* It consists of a filter support mesh careful selection of a suitable
which is placed on top of the stage filter this approach can be useful
FSA-HRT with cut-off diameters of 5.0 and 1.0 or 4.7 and 1.1 microns nozzles and a split ring used to for AIM studies of DPIs, when
hold the filter in position on top of equivalence between NGI and rNGI
8344 FSA-HRT - 28.3 L/min (Spacer, Stages 5.0 and 1.0 micron, and F)* the filter support mesh. data is desirable, but where start- NGI Stage 3
8345 FSA-HRT - 28.3 L/min (Spacer, Stages 2, 5 and F)*
up kinetics issues may otherwise
8346 FSA-HRT - 60.0 L/min (Spacer, Stages 1, 4 and F)* When operating the rNGI, particles
be significant.
8347 FSA-HRT - 90.0 L/min (Spacer, Stages -0, 3 and F)* smaller than the cut-off diameter
of the stage preceding the rNGI
Induction Ports Filter Holder Assembly will be
captured on the paper filter of the
8501 USP Induction Port* rNGI
rNGI, whilst particles larger than
8510 USP Induction Port (One-piece 316 Stainless Steel)
the cut-off diameter will impact 5259 rNGI Filter Holder Assembly
8060 Flow Meter to Induction Port/WSC2 Adapter
5259A Pack of 100 Filters
5238 Mouthpiece Adapter (UIP to DFM2000)

Preseparators for testing DPIs

Stage Cut-off Diameters for the NGI at Different Flow Rates
8401 28.3 L/min Preseparator*
8420 60 L/min Preseparator* Flow Rate (L/min)
8420-90 90 L/min Preseparator*
Stage 15 30 40 50 60 70 80 90 100

1 14.10 11.72 10.03 8.89 8.06 7.42 6.90 6.48 6.12

Spare Parts
2 8.61 6.40 5.51 4.90 4.46 4.12 3.84 3.61 3.42
8367-I Stage 5.0 micron cut-off @ 28.3 L/min*
8368 Stage 1.0 micron cut-off @ 28.3 L/min* 3 5.39 3.99 3.45 3.09 2.82 2.61 2.44 2.30 2.18
8371 FSA Spacer Stage*
4 3.30 2.30 2.01 1.81 1.66 1.54 1.45 1.37 1.31
8334 Complete Set of 7 Silicone Rubber O-Rings
8335 Set of 2 Stainless Steel Collection Plates (28.3 L/min) 5 2.08 1.36 1.17 1.04 0.94 0.87 0.81 0.76 0.72
8336 Set of 2 Stainless Steel Collection Plates (60 or 90 L/min)
6 1.36 0.83 0.70 0.61 0.55 0.50 0.46 0.43 0.40
8316 Box of 100 Glass Fibre Filters
8308A Set of 3 Shortened Spring Clamps - 4 Stage 7 0.98 0.54 0.45 0.38 0.34 0.31 0.28 0.26 0.24
8308B Set of 3 Shortened Spring Clamps - 3 Stage

*Please specify Aluminium (A), 316 Stainless Steel (S) or Titanium (T) when placing your order.

256 257
 Inhaler Testing Aerodynamic
Special Applications
Particle
Size Distribution

Fast Screening Impactor (FSI) In addition to the FSI, the following ancillaries are required to complete a fully operational test set-up for
determining the CPM, FPM, or LPM/SPM ratio:

Based on proven NGI Preseparator technology, the FSI represents a purpose-made approach
to AIM that separates the dose into CPM and FPM making it suitable for AIM-HRT applications
(i.e. FSI-HRT) for MDIs, DPIs and nasal sprays.
A range of inserts are available, to generate a 5 micron An additional insert is available for generating a 10
cut-off diameter within the flow rate range of 30-100 micron cut-off diameter at 30 L/min. When used
L/min at 5 L/min intervals. This makes the FSI ideal with a Glass Expansion Chamber (see page 200) this
for DPIs tested at a flow rate that equates to a 4 kPa makes the FSI ideal for the fast screening of nasal Vacuum Pump Critical Flow Controller Flow Meter
pressure drop over the inhaler. aerosols and sprays. Bespoke inserts are also available See page 188 For DPI testing only See page 184
on request with a range of cut-off diameter/flow rate See page 172
The FSI uses the same induction port as the NGI. It combinations, allowing for an FSI-QC version, with a
employs a two-stage separation process in which first cut-off diameter close to the product MMAD.
large non-inhalable boluses are captured in a liquid trap
followed by a fine-cut impaction stage at 5 microns.
This gives unparalleled accuracy, high capacity, low
internal losses and low carryover. The fine particle dose
is collected on a glass fibre filter located in an external
filter holder with quick-release catches for easy access.

Mouthpiece Adapter Glass Expansion Chamber

See page 203 For Nasal Spray testing only. See page 200

Fast Screening Impactor (FSI) complete

Cat. No. Description

5260 FSI complete with one insert (please specify flow rate – see below)
5261 Additional Inserts – 5 microns @ 30, 35, 40, 45, 50, 55, 60,
Filter Holder 65, 70, 75, 80, 85, 90, 95 or 100 L/min for MDIs or DPIs
(please specify flow rate)
5240 Box of 100 Filters (for Fine Fraction Collector)

Fine Fraction Collector for users that already have NGI Preseparator
5262 Fine Fraction Collector only
Note: For a complete system, users must also purchase an insert (see 5261) to replace the existing insert in their preseparator

Interchangeable Inserts
Accessories for MDIs and DPIs
5203 NGI Induction Port
8060 Flow Meter to Induction Port/WSC2 Adapter
5238 Universal Flow Meter Adapter
5204 NGI Preseparator

Accessories for MDIs and DPIs

Fast Screening Impactor (FSI) 5263 Additional Insert – 10 microns @ 30 L/min for Nasal Sprays

258 259
 Inhaler Testing Aerodynamic
Special Applications
Particle
Size Distribution

Fluticasone Propionate/Salmeterol
Aerosols & Powders
The inhalation powder monographs require that DDU According to the monographs, the 28.3 L/min version
measurements be conducted for a duration consistent of the ACI (Stages 0 to 7 plus filter stage) should be
with the withdrawal of 2 litres of air. This volume is used to measure APSD for both aerosols and powders
generally considered to be representative of a typical despite the fact that the powder method specifies
patient with asthma or COPD. testing at 60 L/min.
The duration of testing for APSD measurements is
APSD measurement is conducted using a standard adjusted to give the volumetric equivalent of 3 litres
ACI equipped with a specially modified induction port of air. This is likely due to the need to achieve adequate
common to both aerosols and powders and a specially volume changes in the ACI.
modified inlet cone and preseparator for aerosols and
powders respectively.
Special Applications

Generic Drug Development FP/Salmeterol Aerosols

Apparatus requirements:

Delivered Dose Uniformity Aerodynamic Particle Size Distribution

The success of a generic drug formulation submission relies on the robust demonstration of
bioequivalence (BE) to a reference labelled drug (RLD). This normally involves the provision of in
vitro data to demonstrate that the generic will perform in a clinically identical way to the RLD.

The FDA has recently issued product-specific guidance A further monograph for Albuterol Inhalation Aerosol
for several active pharmaceutical ingredients (APIs) products has been approved.
that are used globally for the treatment of asthma and
In August 2020, the USP made a general announcement
COPD and are consequently routine targets for generic
for a draft guidance New Inhalation Product
development. The USP has also introduced product-
Monographs: Proposed Approach for Performance Tests
specific monographs for Fluticasone Propionate (FP)
Employing Non-standard Apparatus. This covers the use
and Salmeterol.
of current drug-specific monographs and outlines an
These product-specific monographs call for the use of approach for future monographs.
test equipment based on methods used in the original
The product-specific monographs concerned cover
development of these products.
both DDU testing and APSD measurements. DDU and
The USP list four such monographs for FP and FP/ APSD are required performance metrics for all OIPs
Salmeterol combination products: because of their defining influence on the success and Sample Collection Apparatus for Andersen Cascade Impactor (ACI)
consistency of drug delivery. FP/Salmeterol Aerosols
• Two relate to the use of the APIs as aerosols delivered
by an MDI
_ FP/Salmeterol Induction Port
• Two are for APIs prepared as inhalation powders for
delivery by a DPI
_ ACI Inlet Cone for FP/Salmeterol Aerosols

260 261
 Inhaler Testing Aerodynamic
Special Applications
Particle
Size Distribution

FP/Salmeterol Powders
Apparatus requirements:

Delivered Dose Uniformity Aerodynamic Particle Size Distribution Apparatus for DDU testing of FP/Salmeterol Products

Cat. No. Description

8646 Sample Collection Apparatus for FP/Salmeterol Aerosols
8640 Sample Collection Apparatus for FP/Salmeterol Powders

Spare Parts for Sample Collection Apparatus for Aerosols

8649 Pack of 500 Cotton Wool Balls
8647 Separating Flask
8648 Flow Meter Adapter
8650 Vacuum Pump Adapter

Spare Parts for Sample Collection Apparatus for Powders

8641 Pack of 100 Glass Fibre Filters 70 mm
8903 Throat
8642 Upper Chamber
8643 Lower Chamber
8610 Stainless Steel Filter Support Disc
Sample Collection Apparatus for Andersen Cascade Impactor (ACI) 8645 Clamp Assembly
FP/Salmeterol Powders 8909 Flow Meter Adapter
8910 Vacuum Pump Adapter
_ FP/Salmeterol Induction Port 8644 Spare Set of Glassware (complete)

_ ACI Preseparator for FP/Salmeterol Powders Apparatus for APSD testing of FP/Salmeterol Products

_ ACI Inlet Cone for FP/Salmeterol Aerosols 8372 ACI Inlet Cone for FP/Salmeterol Aerosols*
8405 ACI Preseparator for FP/Salmeterol Powders*
8406 Set of 2 O-rings for FP/Salmeterol ACI Preseparator (Spare)
8505 FP/Salmeterol Induction Port*
In addition to the above and previous page, the following are recommended to complete a fully-operational 8505SW FP/Salmeterol Induction Port (One-piece 316 Stainless Steel)
8506 Flow Meter Adapter for FP/S Induction Port
test set-up for the DDU testing and APSD measurement of FP/Salmeterol Aerosols & Powders.
5401A FP/Salmeterol ACI Carrying/Wash Rack

* Please specify Aluminium (A) or 316 Stainless Steel (S) when placing your order.

Other
8503 Set of 2 Silicone Rubber Rinsing Caps for FP Induction Port

Vacuum Pump Critical Flow Controller Flow Meter Mouthpiece Adapter

See page 188 For DPI testing only See page 184 See page 203
See page 172

262 263
 Inhaler Testing Aerodynamic
Special Applications
Particle
Size Distribution

Albuterol Inhalation Aerosols

The draft monograph for Albuterol Inhalation Aerosols (Albuterol Inhalation Aerosol In-Process In addition to the above, the following are recommended to complete a fully-operational test
Revision 44(1)) specifies a special glass Sample Collection Apparatus to be used for DDU set-up for the DDU testing and APSD measurement of Albuterol Inhalation Aerosols.

testing (see below).

Albuterol Induction Albuterol Induction

Port with sleeve Port without sleeve Vacuum Pump Critical Flow Controller Flow Meter Mouthpiece Adapter
See page 188 For DPI testing only See page 184 See page 203
See page 172

The apparatus uses a solid plastic firing APSD measurement is conducted using a standard ACI
adapter, instead of a mouthpiece adapter, to equipped with a specially modified induction port. A special
Apparatus for DDU testing of Albuterol Aerosol Products
accept an inhaler with a circular mouthpiece Inlet Sleeve is available that slips over the induction port
of corresponding dimensions. Alternatively, a inlet, to enable the induction port to be used with regular Cat. No. Description
silicone Mouthpiece Adapter (page 203) can mouthpiece adapters used on USP/NGI induction ports. 8520 Sample Collection Apparatus for Albuterol Aerosol
also be used. 8524 Glass Wool (1m length)
8521 Firing Adapter
8522 Flow Meter Adapter
Delivered Dose Uniformity Aerodynamic Particle Size Distribution

Spare Parts for Sample Collection Apparatus for Albuterol Aerosol

8523 Glassware for Albuterol Aerosol Sample Collection Apparatus

Apparatus for APSD testing of Albuterol Aerosol Products

8509 Albuterol Induction Port*
8509SW Albuterol Induction Port (One-piece stainless steel)
8519 Albuterol Induction Port Inlet Sleeve*
8060 Flow Meter to Induction Port/WSC2 Adapter

* Please specify Aluminium (A) or 316 Stainless Steel (S) when placing your order.

Sample Collection Apparatus for Andersen Cascade Impactor (ACI)

Albuterol Aerosol

Firing Adapter Albuterol Induction Port

_ Albuterol Induction Port Inlet Sleeve (optional)

264 265
 Inhaler Testing Aerodynamic
Semi-Automation
Particle
Size Distribution

Automated Shake, Fire & Flow

Control for MDIs, Nasal Sprays
and Nasal Aerosols
The Vertus Series
Compatible with multiple collection devices

Semi-Automation
including the NGI, ACI, GTI, DUSA and waste shot
collector, the Vertus II and Vertus Plus are fully
automated benchtop shake and fire systems for
precise, controlled and reproducible MDI, nasal
spray and nasal aerosol testing.
Delivering up to a four-fold increase in throughput, semi-automation
reduces manual handling and operator input, delivering enhanced Suitable for:
reproducibility, lowering the risk of repetitive strain injury (RSI) and reducing
See page 270
overall testing costs.
We supply a broad range of semi-automation solutions supporting both
sampling and recovery for delivered dose uniformity (DDU) testing and Automated 10-Way Shake
aerodynamic particle size distribution (APSD) measurement. Our off-the- and Fire to Waste for MDIs
shelf solutions streamline validation and product testing methods and
DecaVertus II
boost test accuracy and productivity in both R&D and QC.
A high-throughput 10-way shake and fire to
waste system for highly reproducible, controlled
MDI testing.

Suitable for:

Improve Reduce Eliminate handling Increase testing See page 270

efficiency variability errors capacity

Automated Drug
Recovery for DDU Testing
DUSA Shaker
Automates the internal rinsing of both MDI
and DPI DUSA collection tubes for complete,
reproducible drug recovery.

Suitable for:

See page 282

266 267
 Inhaler Testing Aerodynamic
Semi-Automation
Particle
Size Distribution

Automated Cascade
Impactor Preparation
NGI Cup Coater NGI Assistant
Standardises the NGI Collection Cup coating process A complete system for drug recovery from the
guaranteeing uniform distribution of the surface NGI Collection Cup Tray, Induction Ports and
coating substance across the cups. Preseparators, boosting analytical throughput.

Recommended for: Recommended for:

See page 284 See page 294

Automated Drug Recovery Impactor Cleaning System

for APSD Measurement Standardises cleaning and drying
procedures to help maintain the NGI
Gentle Rocker and ACI in optimum condition.
Agitates the NGI Collection Cup Tray in a
controlled, repeatable manner to ensure complete Recommended for:
dissolution of the active drug prior to analysis.
See Page 298
Recommended for:

See page 287

Sample Preparation Unit SPU 200i

Simplifies and automates the drug recovery process
from the Induction Ports and Preseparators.

Recommended for:

See page 290

268 269
 Inhaler Testing Aerodynamic
Semi-Automation
Particle
Size Distribution

Identifying issues within the test method and limiting enable precise, controlled, reproducible testing while at
variability between analysts can be challenging, but the same time boosting productivity. Our Vertus and
inadequate control may lead to erroneous data and DecaVertus range offers extensive parameter control
consequently substantial costs to the company. and monitoring, allowing:
- Precise and easy method validation
Automated shake and fire systems enhance the
- Streamlined routine testing
sensitivity of OINDP testing and, more broadly, boost
- Cause of variation identification
data integrity by eliminating firing errors, controlling air
- Enhanced data integrity and accuracy
flow speed and automating leak testing. Such systems

Semi-Automation Choose your Automated Shake & Fire System

Automated Shake, Fire and
Flow Control for MDIs, Nasal
Sprays and Aerosols Vertus II Vertus Plus DecaVertus
Due to the nature of metered spray pump technology and propellant-based aerosols, the
testing of MDIs, nasal sprays and nasal aerosols is inherently susceptible to variability Max. Number of
Devices Supported 1 1 10
from a number of different sources. per Run

Fire to Sample ✓ ✓ ✗
Shaking Leaks

Fire to Waste ✓ ✓ ✓

Speed Angle Duration NGI ACI Sample Weighing ✗ ✓ ✗

Sources of
Testing
Variability Devices supported

Firing Delay Air Flow Speed

Between Through MDIs ✓ ✓ ✓

Shake and Fire Collection Device
Firing Forces
Nasal Sprays ✓ ✓ ✗

Nasal Aerosols ✓ ✓ ✓ (canister only)

Speed of Actuation Duration of Fire Down Time Speed of Release

270 271
 Inhaler Testing Semi-Automation

Key Features:

Remote support
module available

Modern intuitive
touchscreen interface
used to control all method
parameters and reporting

Reporting available via

USB and Local Area
Network

Vertus II & Vertus Plus Robust safety systems

including easy access-
stops and safety guarding
The Vertus II and Vertus Plus are fully automated shake TOP
TIP
and fire benchtop systems for precision-controlled, highly The Vertus Plus has the
repeatable MDI, nasal spray and nasal aerosol testing. additional capability of
measuring shot weight
Compatible with most device types and a wide range of dose using an integrated
collection devices, they allow complete control over the test analytical balance

technique, while offering the flexibility to apply any industry

standard test method.

Ph. Eur. and 21 CFR Part 11 Ideal for both

USP compliant compliant R&D and QC
testing

Analytical balance provides Interchangeable plates make it External printing

Precise control In situ impactor leak Easy to use
automatic shot weight calculation easy to switch between DUSA option available
over all test testing capability touchscreen measurable to 5 decimal places Stack, NGI, ACI and GTI
interface (Vertus Plus only)
parameters

The Vertus II and Vertus Plus series provides analysts with absolute control
Suitable for both Improves reproducibility over a wide range of specific parameters including:
DDU and APSD and frees up analyst time
• Shaking profile (including • Time between • Firing profile (including force, pause, • Air flow through
testing
speed, angle and duration shake and fire fire down, rise and release time) the system

272 273
 Inhaler Testing Aerodynamic
Semi-Automation
Particle
Size Distribution

Vertus II & Vertus Plus: Test Interfaces TOP

TIP The Vertus II and Vertus Plus
interfaces are identical and
can be interchanged easily
ACI Interface Plate between systems Nasal Spray Dose Collector (NSDC)

NSDC component parts Nasal Spray Waste

Collector (NSWC)

NGI with Alberta Idealised Nasal Inlet (AINI)

NGI Interface Plate Shown here: NGI with Alberta Idealised Nasal Inlet (AINI)

DUSA Stack Interface Plate ACI with Glass Expansion Chamber

with Waste Shot Collector Shown here: ACI with Glass Expansion Chamber

Additional test interfaces are available, please contact us for more details.

274 275
 Inhaler Testing Aerodynamic
Semi-Automation
Particle
Size Distribution

Vertus II & Vertus Plus: Technical Specifications Vertus II & Vertus Plus

Pharmacopoeial Compliance Ph. Eur., USP, Ch. P. and JP Cat. No. Description Cat. No. Description
9701 Vertus II Shake and Fire System 9720 Vertus Plus Shake and Fire System
21 CFR Part 11 Compliant ✓ 1040 Vertus II Extended Warranty - 1 year 1042 Vertus Plus Extended Warranty - 1 year
1041 Vertus II Extended Warranty - 2 years 1043 Vertus Plus Extended Warranty - 2 years

Shaking Parameter Control

Accessories Nasal
Type of Shake ✓ Speed ✓
9702 Temperature and Humidity Sensor 9746 Nasal Spray Holder for use with Expansion Chamber
Starting Angle ✓ Duration ✓ 9703 LAN Data Storage for ER/ES Compliance 9747 Nasal Spray Holder for use with Alberta Nasal (AINI)
9704 Direct Thermal Printer for Vertus/DecaVertus 9748 Nasal Spray Holder for use with GTI
Angle of Rotation ✓ 9730 Vertus/DecaVertus Qualification Kit 9738 Nasal Spray Holder for use with NSDC and NSWC - Vertus II
9728 IQ/OQ Documentation for Vertus II/Vertus Plus 9740 Universal NGI Interface plate for Nasal products
9729 Vertus II to Vertus Plus upgrade 9741 ACI Interface plate for use with Expansion Chamber
Firing Parameter Control 9742 ACI Interface plate for use with Alberta Nasal
9744 Universal FFC Interface plate for Nasal products
Force Rise Time ✓ Pause before fire ✓ MDIs 9745 GTI Interface Plate for Nasal Products

Fire Down Time ✓ Pause after fire ✓ 9705 9705 MDI Holder (per inhaler design)
9706 ACI Interface Plate with Induction Port Support Spares
Force Release Time ✓ Maximum force ✓ 9707 NGI Interface Plate
9708 NGI Interface Plate with Waste Shot Collector 9719 Thermal Transfer Printer Labels (12 Rolls of 475 each)
9715 GTI Interface Plate 9716 Direct Thermal Printer Labels (12 Rolls of 475 each)
User Interface Colour touchscreen 9710 DUSA (x4) Interface Plate with Waste Shot Collector 9712 Spare Filter Cartridge for Waste Shot Collector
9711 Waste Shot Collector with Interface Plate
Dimensions (w x d x h) 1011 x 593 x 369 mm 9718 Thermal Transfer Printer for Vertus/DecaVertus
9725 Thermal Transfer Printer Ribbon (6 Cartridges)
USB A x 2
9705L Evohaler MDI Holder
Ethernet LAN
Connectivity 9705Q Symbicort MDI Holder
Thermal transfer printer
9705T Flutiform MDI Holder
Temperature and Relative Humidity Probe
9705U Airomir MDI Holder
9901 Mouthpiece Adapter Mould (per inhaler/inlet design)
9902 Mouthpiece Adapter for ACI/NGI Induction Port and DUSA

Vertus II & Vertus Plus: Reporting Qualification & Maintenance 9903

9714
Mouthpiece Adapter for Other Inlets (each)
Compressor
Extensive data output options are available • Comprehensive IQ/OQ documentation packages
as standard: and toolkits available
• Qualification Kit
• Extended Warranty available

USB A ETHERNET PRINTER • Remote support

Reported Parameters:
• User information and method ID used

• All method parameters (inc. shake and fire variables)

• Shots fired during and before run

• Air flow before shot

• Distance can moved during fire and insertion

• Time to fire

• Leak test results

276 277
 Inhaler Testing Semi-Automation

Key Features:

Remote support Hold either can-only Hold up to 10 Multiple safety features

module available or can in-actuator inhalers at any including emergency stop
one time and safety shield with
magnetic switch

DecaVertus II
DDU testing for MDIs requires sampling throughout the TOP
TIP
life of the product and the associated firing-to-waste of
intermediate shots. The regulatory expectation is that firing The USP specifies the testing Independent airflow control Reporting available via Modern intuitive
of 10 inhalers for DDU (for to ensure each inhaler USB and Local Area touchscreen interface
to waste is carried out under representative conditions, a is tested in the same Network used to control all
testing over the entire unit
repetitive, labour-intensive process. life), with the collection of two
environment methods parameters
and reporting
samples, one at the beginning
The DecaVertus II is a state-of-the-art, fully automated, high throughput and one at the end of product
10-way shake and fire-to-waste system for MDI testing. Designed to life. In the case of a 100-dose
accommodate the entire inhaler, as used by a patient (in-actuator), it is inhaler this could mean firing
98 shots to waste, for each
equally suitable for traditional canister-only wasting.
of 10 inhalers, to complete
Automating the firing-to-waste is highly advantageous from the perspective the test.
of conserving analyst time, eliminating the risk of RSI, and maximising
the repeatability of test data; firing-to-waste under well-defined, closely TOP
TIP
controlled conditions eliminates a potential source of variability in testing. Each inhaler is tested within an identical environment; each has dedicated air flow control, dedicated firing mechanism and
a separate waste channel. This design significantly reduces the risk of inconsistent firing force or air flow, at the same time
minimising cleaning requirements and the likelihood of channel blockage.

Ph. Eur. and 21 CFR Part 11 Improves reproducibility

USP compliant compliant and frees up analyst The Vertus II and Vertus Plus series provides analysts with absolute control
time over a wide range of specific parameters including:

• Shaking profile (including • Time between • Firing profile (including force, pause, • Air flow through
speed, angle and duration shake and fire fire down, rise and release time) the system

Fire-to-waste under Reduces risk Fully compatible with

closely controlled of RSI the Vertus series for TOP
conditions easy method transfer TIP Since DecaVertus is fully compatible with Vertus II, methods can be easily transferred between systems as the product
proceeds to commercialisation, with DecaVertus often used in production to alleviate the increased burden of through-
life testing.

278 279
 Inhaler Testing Aerodynamic
Semi-Automation
Particle
Size Distribution

DecaVertus II: Reporting Qualification & Maintenance

Extensive data output options are available • Comprehensive IQ/OQ documentation packages
as standard: and toolkits available
• Qualification Kit
• Extended Warranty available

USB A ETHERNET PRINTER • Remote support

Loading MDIs into carriage Waste shot collector array

Reported Parameters:
• User information and method ID used

• All method parameters (inc. shake and fire variables)

• Shots fired during and before run

• Air flow before shot

• Distance can moved during fire and insertion

DecaVertus II: Technical Specifications • Time to fire

• Leak test results

Pharmacopoeial Compliance Ph. Eur., USP, Ch. P. and JP

21 CFR Part 11 Compliant ✓

DecaVertus Waste Shot Collection for MDIs

Shaking Parameter Control Cat. No. Description

9801 DecaVertus II Shake and Fire to Waste System
Type of Shake ✓ Speed ✓
1044 DecaVertus II Extended Warranty - 1 year
1045 DecaVertus II Extended Warranty - 2 years
Starting Angle ✓ Duration ✓

Angle of Rotation ✓
Accessories (MDIs only) Spare Parts

Firing Parameter Control 9803 LAN Data Storage for ER/ES Compliance 9820 Pack of 10 Spare Waste Filter Cartridges
9704 Direct Thermal Printer for Vertus/DecaVertus 9821 Pack of 100 O-rings
Insert Force ✓ Fire down time ✓ 9716 Direct Thermal Printer Labels (12 Rolls of 475 each) 9719 Thermal Transfer Printer Labels (12 Rolls of 475 each)
9718 Thermal Transfer Printer for Vertus/DecaVertus 9725 Thermal Transfer Printer Ribbon (6 Cartridges)
Fire Force ✓ Force release time ✓ 9805L Evohaler Carriage
9805Q Symbicort pMDI Carriage
Force Rise Time ✓ Pause before fire ✓ 9805T Flutiform Carriage
9805U Airomir Carriage
9805 Carriage for MDI (per inhaler design)
User Interface Colour touchscreen 9808 Carriage for MDI Canister Only (any size)
9714 Compressor
Dimensions (w x d x h) 921 x 490 x 758 mm 9730 Vertus/DecaVertus Qualification Kit
9810 IQ/OQ Documentation for DecaVertus
USB A x 2
Connectivity Ethernet LAN
Thermal transfer printer

280 281
 Inhaler Testing Aerodynamic
Semi-Automation
Particle
Size Distribution

Key Features:
Rinsing action achieved by a combination Add/remove collection
of lateral shaking and simultaneous rolling tubes at any time
of the sealed collection tubes

DUSA Shaker Rubber coated rollers specifically

designed to grip the collection tubes – Low noise

Ensuring full, fast and repeatable drug recovery from all internal surfaces of both MDI and no need for clamps or other fixtures

DPI DUSA collection tubes, the DUSA Shaker eliminates a time-consuming and highly variable
manual drug recovery processes. To allow rotation, the DUSA Shaker is only compatible available as Collection Tube without P1 Port
with DPI Collection Tubes that have the P1 port blanking (Cat. No. 8608A).
The automated rinsing action of the DUSA Shaker action ensures that all internal surfaces are wetted and
plug fitted. DPI Collection Tubes without the P1 port are
is achieved by a combination of lateral (side-to- that agitation is performed with a consistent, smooth
side) shaking and simultaneous rolling of the sealed but vigorous action.
collection tubes. The resultant multi-directional mixing DUSA Shaker: Technical Specifications Qualification & Maintenance
• Comprehensive IQ/OQ/PQ documentation
Shake Speed: 0 and 200 shakes per minute
packages and toolkits available
Flexible - suitable for Improves Compact benchtop Roller Rotational Speed: Fixed at 30 rpm • Qualification Kit available
both MDI and DPI reproducibility system Timer Control: Between 0 and 55 minutes • Extended Warranty available
Collection tubes and frees up
analyst time Dimensions (w x d) 570 mm x 610 mm

Complete drug recovery Partial loads Reduces risk

achieved via multi- DUSA Shaker
acceptable of RSI
directional mixing action
Cat. No. Description
8620 DUSA Shaker (without collection tubes) 8624 Re-calibration of DUSA Shaker Qualification Tools
8621 IQ/OQ Documentation for DUSA Shaker 8622 Pack of 10 Plugs (to plug P1 Port on DUSA for DPIs)
8623 DUSA Shaker Qualification Tools 1032 DUSA Shaker Extended Warranty - 1 year
1033 DUSA Shaker Extended Warranty - 2 years

282 283
 Inhaler Testing Aerodynamic
Semi-Automation
Particle
Size Distribution

Key Features:

Coating station provides the High precision Spring-loaded stainless

filling, levelling and drying multichannel dispenser steel dispense tubes ensure
functions which make up the with 8 channels, one for consistent contact with the
coating cycle each collection cup cup surface

Frame specifically
designed to
accept the NGI
Cup Collection Tray

NGI Cup Coater NCC 100i

Cup coating eliminates issues associated with particle bounce and re-entrainment during
the APSD measurement of OINDPs. The NGI Cup Coater reproducibly applies coatings
directly to the NGI Collection Cups whilst in situ in the NGI Cup Collection Tray. Using a
standardised method to ensure uniform application of the surface coating, the NGI Cup
Coater reduces sources of variability in testing associated with cup coating, while at the
same time boosting productivity. PTFE tipped tubes avoid Intuitive touchscreen
scratching and are control with icon-
connected to the dispenser based menu structure
by solvent-resistant tubing. simplifies operation

Easy to use touchscreen Cups coated in as

interface little as 2 minutes

Adjustable
drying time

284 285
 Inhaler Testing Aerodynamic
Semi-Automation
Particle
Size Distribution

NCC 100i: User Interface

Setting a parameter Set v Actual test parameters Set v Actual test parameters
(before test run) (during test run)

Settings menu Report output settings menu

NCC 100i: Technical Specifications

Dispense and Reverse Cycle Time: 0 - 10 minutes

Drying Time: 0 - 10 minutes

USB A
Connectivity:
USB B

Dimensions (w x d x h):
Cup Coater: 590 x 280 x 185 mm Gentle Rocker
Dispenser: 150 mm x 220 mm x 130 mm
Promoting easy and fully repeatable dissolution of the active drug present in the
NGI Collection Cups following testing, the Gentle Rocker gently agitates solvent
back and forth within the cups aiding assay sample preparation.
Compliance and Maintenance NGI Cup Coater NCC 100i
• Comprehensive IQ/OQ documentation
Cat. No. Description
packages available
5920 NGI Cup Coater Model NCC 100i (excl. NGI Cup Quick and easy NGI Adjustable run time for
• Extended Warranty available Tray & Cups) sample preparation flexible testing
1034 NGI Cup Coater Extended Warranty - 1 Year
1035 NGI Cup Coater Extended Warranty - 2 Years

Accessories
20 and 40 rpm
5901 500 mL Solvent Reservoir complete with 9-way Cap models available
5902 1000 mL Solvent Reservoir complete with 9-way Cap
5903 IQ/OQ Documentation for NGI Cup Coater
5904 NGI Cup Coater Qualification Tools
5905 Recalibration of NGI Cup Coater Qualifications Tools

286 287
 Inhaler Testing Aerodynamic
Semi-Automation
Particle
Size Distribution

Key Features:

Samples protected during

process by dust cover
Rocks back and
forth about a central
Small
benchtop
Gentle Rocker: Technical Specifications
longitudinal axis system
Speed: 20 or 40 rpm (dependent on model)

Run Time: Up to 99,999.9 minutes

Dimensions (w x d x h): 70 x 18 x 16 cm

Compliance and Maintenance

• Comprehensive IQ/OQ/PQ documentation
packages and toolkits available
• Qualification Kit available

Gentle Rocker

Cat. No. Description

5220 Gentle Rocker (complete with dust cover and 20 rpm motor)
5221 Gentle Rocker (complete with dust cover and 40 rpm motor)
1036 Gentle Rocker Extended Warranty - 1 year
Gentle Rocker Accessories 1037 Gentle Rocker Extended Warranty - 2 years

A number of accessories are available for the Gentle Rocker primarily designed to safeguard the integrity of
the samples concerned and maintain the condition of the collection cups which are performance critical and Accessories
particularly prone to damage.
5223 Evaporation Cover (with seals and clips to prevent solvent loss)
5255 Dust Cover (Spare)
5224 Storage Cabinet for 6 NGI cup trays (not included)
5225 IQ/OQ Documentation for Gentle Rocker
Storage Cabinet for 6 x NGI Cup Collection Trays 5235 Verification of Gentle Rocker
Accommodates up to six NGI Cup Collection Trays and 5256 Gentle Rocker Qualification Tools
their associated cups when not in use (NGI Collection 5257 Re-calibration of Gentle Rocker Qualification Tools
Cup Trays not included).

NGI Collection Cup Tray with Evaporation Cover

Fitted with seals and retaining clips to minimise
solvent loss during operation where evaporation
is a particular problem.

288 289
 Inhaler Testing Aerodynamic
Semi-Automation
Particle
Size Distribution

Key Features:

Designed to simultaneously
accept any two fixtures

Sample Preparation Unit SPU 200i Easy rinsing with

automatic positioning
of the fixtures to the
Ensuring full, reproducible drug recovery from the NGI, ACI and FP/Salmeterol Induction Ports loading position upon
and the NGI Preseparator, the Sample Preparation Unit SPU 200i automates repetitive drug system initialisation

recovery procedures, alleviating testing bottlenecks and reducing the unwanted effects of
repetitive strain injury (RSI).

Intuitive touchscreen Small unit footprint Brackets and silicone rubber

control with icon-based caps secure and seal the
Easy to use touchscreen Reproducible sample menu structure simplifies equipment during operation
operation
interface preparation

Variable speed control Ideal for use with Preseparator and Induction
for different dissolution Induction Ports and/or Port with Rinsing Caps
applications Preseparators

290 291
 Inhaler Testing Aerodynamic
Semi-Automation
Particle
Size Distribution

SPU 200i: User Interface

SPU 200i fitted with 2 x NGI Setting a test parameter Set v Actual test parameters Set v Actual test parameters
Preseparators (before test run) (during test run)

Settings menu Report output settings menu

SPU 200i fitted with 2 x ACI

Induction Ports
SPU 200i: Technical Specifications
Speed: Variable (20 and 60 rpm (+/- 1 rpm))

Rinsing Cycle Duration: 0 - 120,000 revolutions or 99h 59min 59sec

Rotational Direction Fixtures reverse rotation direction half way through run

RS-232
Connectivity: USB A
USB B

285 x 335 x 295 (with a single Induction Port Fixture)

Dimensions (w x d x h):
420 x 335 x 310 (with a single Preseparator Fixture)

Compliance and Maintenance Accessories

Fixture wth ACI/Albuterol Fixture with NGI Induction Port Fixture with FP Induction Port
Induction Port • Comprehensive IQ/OQ/PQ documentation
Cat. No. Description
packages and toolkits available
9226 Fixture for ACI/NGI/Albuterol & FP Induction Port (each)
• Qualification Kit available
8503 Set of 2 Silicone Rubber Rinsing Caps for FP Induction Port
• Extended Warranty available 8504 Set of 2 Silicone Rubber Rinsing Caps for ACI/Albuterol
Achieve sample preparation time savings of up to 40%* and improvements in drug recovery reproducibility by combining the
SPU 200i with the NGI Assistant (page 294) - an optimal NGI sample preparation system. Induction Port
9227 Fixture for NGI Preseparator (each)
Data from a back-to-back study reported in ONDrugDelivery, November 2020 Sample Preparation Unit 200i 5265 Set of 2 Silicone Rubber Rinsing Caps for NGI Induction Port
5266 Set of 2 Silicone Rubber Rinsing Caps for NGI Preseparator
Cat. No. Description
9223 IQ/OQ Documentation for SPU 200i
9222 Sample Preparation Unit Model SPU 200i (without Fixtures)
9213 SPU 200i Qualification Tools
1038 SPU 2000 Extended Warranty - 1 year
9214 Re-calibration of SPU 200i Qualification Tools
1039 SPU 2000 Extended Warranty - 2 years
8766 Printer

292 293
 Inhaler Testing Aerodynamic
Semi-Automation
Particle
Size Distribution

Key Features:

Automated aspiration Precise volume of solvent

of aliquot of dissolved added to each cup via an
sample into HPLC vials, x-y-z robotic pipette
ready for analysis
Up to 3 NGI cup collection
trays with dust covers
accommodated

Active drug dissolved

via gentle rocking
motion of tray

NGI Assistant
Automating the complete APSD measurement drug recovery process, the NGI
Assistant makes the conversion of NGI samples to solutions for HPLC analysis
simple and completely reproducible. Providing an accurate and efficient means
of recovering samples from the NGI following testing, the NGI Assistant is Accommodates dual HPLC vial
racks for collection of both primary
designed to increase throughput and protect data integrity by reducing analyst- and back-up samples for each NGI
test undertaken
related variability introduced in drug recovery procedures.

Significantly improves ~ 30 minutes to Easy method

productivity process 3 collection transfer – follows
cup trays* NGI Gentle
Rocker principle

‘Load and go’ Customisable Security and

walkaway operation recovery methods electronic records Also suitable for rinsing
of NGI Presepartor and
management NGI Induction Port
safeguard data
integrity

*depending on method

294 295
 Inhaler Testing Aerodynamic
Semi-Automation
Particle
Size Distribution

NGI Assistant: Automated Drug Recovery Process

1 2 3 4

Dispenses solvent Samples are dissolved Aspirates samples Dispenses the samples
and/or standards via gentle rocking from the NGI cups to the vials

Manual Recovery Automated Recovery

PC-Controlled
The NGI Assistant is controlled by a separate PC, via
easy-to-use Windows-based software that provides
four default routines including:

Manual shaking Gentle agitation (of NGI cups) Automated shaking Automated drug recovery 1. Pump conditioning
(of NGI cups) 2. System priming
3. Calibration
1 run ~ 75 minutes 1 run ~ 50 minutes
4. System validation
3 runs ~ 225 minutes 3 runs ~ 140 minutes
Customer-specific routines can be configured using
additional or modified methods.
Reduce drug recovery time by up to 40%
For Health & Safety
A safety enclosure together and an emergency stop
button and provision for extraction facilities is supplied
NGI Assistant with Safety Enclosure
The most efficient way to increase throughput is by using the NGI Assistant together with the Sample as standard.
Preparation Unit SPU 200i to achieve time-savings of up to 40%.
Data from a back-to-back study reported in ONDrugDelivery, November 2020
NGI Assistant: Technical Specifications
Dispense and Reverse Cycle Time: Method dependent (8 – 12 min per NGI cup tray is typical)

Liquid Handler: 95 x 68 x 97 cm
Dimensions (w x d x h):
Safety Cabinet: 117 x 72 x 97 cm

Compliance and Maintenance NGI Assistant

• Comprehensive IQ/OQ/PQ documentation
Cat. No. Description
packages and toolkits available 5415 NGI Assistant (3-Tray) complete with Safety Enclosure
• Qualification Kit available 5223 Evaporation Cover (with seals and clips to prevent solvent loss)*
5255 Dust Cover (Spare)*
* Note: 3 required for NGI Assistant

296 297
 Inhaler Testing Aerodynamic
Semi-Automation
Particle
Size Distribution

Clean your impactor in 4 easy steps:

1. Cleaning 2. Rinsing 3. Aspiration 4. Drying

Impactor Ultrasonic Impactor Rinse Bath Impactor Suction Aspiration Impactor Drying Oven
Cleaning Bath

Impactor Cleaning System

3
Ensuring the thorough, reproducible and controlled cleaning and drying of
cascade impactors, the Impactor Cleaning System has been designed to clean
component parts of both the NGI and ACI. Regular cleaning and drying are an
essential element of good impactor practice. They ensure that the instrument Step 1. Ultrasonic Step 2. Impactor Step 3. Impactor Step 4. Impactor
is free of debris prior to testing and that it remains in optimum condition Cleaning Bath Rinse Bath Suction Aspirator Drying Oven
throughout its life. Using ultrasound (usually Following cleaning, the Used to remove the small Following sonication, rinsing
from 15-400 kHz) to promote impactor parts are normally amounts of excess water and aspiration, the impactor
the effective cleaning of rinsed in clean cold water and that collect in the bottom parts should be dried using a
nozzles and other difficult-to- left to drain. of the impactor stages and heated cabinet. The Impactor
access places, the Impactor preseparator parts following Drying Oven has a temperature
Available as a complete Consistent, Ultrasonic Cleaning Bath is rinsing and prior to drying, the range of 25 – 70 +/- 1 degrees C,
system, or as individual able to efficiently remove Impactor Suction Aspirator ideal for impactor part drying.
reproducible cleaning
sticky, adhering and embedded comprises a hand-held probe Designed to accept 3 individual
components
particles from solid surfaces. linked via a water collection carrying racks, the unit is fitted
jar to a vacuum pump, which with an inner glass inspection
provides the necessary suction. door together with a wipe-clean,
all stainless-steel interior for
Suitable for both NGI
Benchtop system ease-of use and cleaning.
and ACI cleaning
The 4-speed forced air
circulation means that the oven
reacts rapidly to change and is
ideally suited to impactor drying,
where maximum accuracy
and warm-up are required and
the door is to be opened on a
frequent basis

298 299
 Inhaler Testing Aerodynamic
Semi-Automation
Particle
Size Distribution

Impactor Cleaning System Accessories

Impactor Cleaning System

Carrying/Wash Racks
Cat. No. Description
The impactor parts are normally placed in a rack prior to immersion (a) to segregate them during 5400 Impactor Cleaning System (excluding Carrying/Wash Rack)
the cleaning process and (b) to maximise the surface area exposed to the cleaning process. The 5205 NGI Carrying/Wash Rack
Impactor Carrying/Wash Racks are constructed from heavy duty polypropylene and fitted with 5401 ACI Carrying/Wash Rack
neoprene cushions to prevent scratching to the outer surfaces of the parts. 5401A FP/Salmeterol ACI Carrying/Wash Rack

Modules Only

5402 Impactor Ultrasonic Cleaning Bath (including basket and lid)

5403 Impactor Rinse Bath
NGI Rack 5404 Impactor Suction Aspirator
The NGI rack has 12 apertures corresponding to the 8 5405 Impactor Drying Oven
Collection Cups, NGI Induction Port and the three parts 5406 Stainless Steel Drip Tray
of the NGI Preseparator.

ACI Rack
The ACI Rack has 21 apertures corresponding to the 8 stages,
the 8 Collection Plates, the Inlet Cone, Induction Port and the
2 parts of the Preseparator of the ACI.

FP/Salmeterol ACI Rack

Available to accommodate the special Induction Port and Preseparator used.

Each rack measures 420 mm (w) x 230 mm (d) and is designed to fit inside the basket used in the Impactor
Ultrasonic Cleaning Bath. The basket prevents the carrying rack from touching the bottom or sides of the bath.

300 301
 Inhaler Testing Qualification/
Aerodynamic Particle
Servicing & Training
Size Distribution

Qualification/ The USP Chapter <1058> Analytical Instrument Qualification describes in detail
the four phase approach to qualification based on design (DQ), installation (IQ),

Servicing & Training

operational (OQ) and performance (PQ) qualification.
It is important to note that the purpose of AIQ and its counterpart, AMV, is to ensure
the quality of analysis before conducting the test, whereas system suitability tests
and quality control checks ensure the quality of analytical results immediately before
Good Manufacturing Practices (GMP) regulations require that: or during sample analysis.
The performance of inhaler testing equipment and the methods associated with
A. The test methods used to monitor pharmaceuticals must meet proper them can be influenced by factors other than the equipment itself:
standards of accuracy and reliability • Analytical (human error)
B. Companies should establish procedures to ensure the fitness for use of • Instrument (errors in instrument and/or ancillary equipment)
instruments that generate data supporting product testing
If these sources of error can be eliminated then it is fair to assume that any
anomalies in results are a product of the device/formulation combination itself.

However, these GMP regulations do not provide definitive guidance as to how these aims
are to be achieved.
Analytical Errors (Human Errors)
The USP has sought to address this problem by the introduction of a series of chapters
as follows:
Training Use of semi-automation
(see page 266)
<1058> Analytical Instrument Qualification

<1225> Validation of Compendia Procedures

Instrumentation-Related Errors
<1226> Verification of Compendia Procedures

<1603> Cascade Impactor Practices (Draft) Qualified Validated analytical

instrumentation procedures

It is interesting to note that the scientific community has used the terms “validation” and Ways to Reduce Errors in Orally Inhaled and Nasal Drug Product (OINDP) Testing
“qualification” on an interchangeable basis thus creating a degree of ambiguity as to their
use. For this reason, USP have suggested that:
Copley recognises the scientific and regulatory importance of these initiatives.
A. The term “qualification” be applied to instrumentation Therefore, we have designed a selection of products, services and documentation
to assist you through the OINDP testing journey:
B. The term “validation” be applied to processes and software

The term “Analytical Instrument Qualification” (AIQ) is used for ensuring that an instrument
is suitable for its intended application and the term “Analytical Method Validation (AMV)”
is used for ensuring that the analytical and software procedures employed are suitable for
their intended application.
Qualification Warranty Support Training
Services See page 311 See page 312 See page 313
See page 304

302 303
 Inhaler Testing Qualification/
Aerodynamic Particle
Servicing & Training
Size Distribution

Mensuration certificates are supplied as standard

with all new impactors, preseparators and induction
ports, detailing how each component conforms to the
pharmacopoeial requirements.
As impactors and ancillaries are put into use, regular
re-mensurations (at least annually) should be
performed to monitor and confirm their
“in-use” compliance.

Data Interpretation
Copley adopts Effective Diameter and In-Use Margin
as recognised by the European Pharmaceutical Aerosol
Group (EPAG) as a means of determining the suitability

Qualification Services Mensuration Certificate of cascade impactors for use.

Derived from the area-mean and area-median
diameters of multi-nozzle impactor stages, ED is a
Impactor Qualification useful parameter that can be used to monitor “drift” in
the D50 of impactor stages (median nozzle diameter).
Stage and Components Mensuration The In-Use Margin is calculated as the % of USP/Ph.Eur.
Both the Ph. Eur. and USP lay down certain criteria which the cascade impaction system and tolerance that remains, relative to the ED. If the ED is
equal to the stage nominal diameter then the In-Use
method selected for the inhaler must fulfil prior to and during use.
Margin would be 100%. If, however, the ED is equal
The performance and reproducibility of a cascade impactor are dependent on a number of to the diameter defined by the upper or lower USP/
factors, the most critical being the nozzle dimensions (and their spatial arrangement) on each Ph.Eur. tolerance then the In-Use Margin would be 0%.
It follows that if the ED falls outside the compendia
stage together with the air flow rate passing through it.
tolerance then the In-Use Margin would be a
Providing these critical parameters are within the Stage mensuration, is used to ensure that cascade negative value.
quoted specification, then the impactors concerned impactors conform to the critical dimensions stated Successive mensuration reports allow the tracking and
can be expected to give comparable results. in USP Chapters <601> and <1603> and Ph.Eur. Chapter monitoring of any deterioration of In-Use Margin, a
Mensuration of ACI Stages using the Mitutoyo QV404 Vision
2.9.18 and are therefore fit for use. Inspection System useful way of investigating how an impactor is wearing
The process of measuring the nozzle diameters and
other critical dimensions of cascade impactors is called Stage mensuration replaces the need for repetitive with time. This approach allows the likelihood of an
impactor mensuration. calibration using standardised aerosols. out-of-specification (OOS) stage occurring within the
next calibration cycle to be predicted, indicating when
Both the Ph.Eur. and USP recommend the stage remedial work will be required.
mensuration of impactors prior to use and
TOP
periodically thereafter. TIP All our mensuration
certificates are supplied
In practice, cascade impactors often corrode and electronically
wear with use owing to their repeated exposure to
formulations and recovery solvents. This is particularly
true of aluminium impactors.
Copley provides a one-stop, quick turn-around
This can lead to full or partial nozzle occlusions causing mensuration service for all types of Ph.Eur. and USP
changes in the impactor aerodynamics and hence specified impactors, including induction ports
particle collection characteristics. and preseparators

Stage Mensuration Certificate with Histogram Option

304 305
 Inhaler Testing Qualification/
Aerodynamic Particle
Servicing & Training
Size Distribution

TOP
TIP

Effects of improvements in the NGI

manufacturing processes relating to Stage
5 of the NGI with serial number. Every nozzle
on the NGI has always met pharmacopoeial
specifications (heavy black lines). Now though,
every NGI has an ED within just half the range
of the pharmacopoeial specification (heavy
blue lines). These data therefore provide
evidence of our commitment to continuous
quality improvement.

Pinning various stages of the ACI Pinning Kit with close-up of Pin

Impactor Performance Restoration

Impactor Mensuration Services
Following impactor mensuration there are three possible results; ED within specification, ED in excess of an upper
limit and ED below the lower limit for the stage:
Cat. No. Description Cat. No. Description
8590 Induction Port Mensuration 5290 NGI Stage Mensuration
8390 ACI Stage Mensuration 5291 NGI Preseparator Mensuration
ED within specification
8990 60 L/min Conversion Kit Mensuration 8591 Alberta Idealised Throat Mensuration
No restoration is required when mensuration shows ED within specification.
5236 90 L/min Conversion Kit Mensuration 8340 FSA Stage Mensuration
8490 ACI Preseparator Mensuration 5270 FSI Insert Mensuration
8311 ACI Stage Mensuration Histogram (per stage) 8917 GTI Mensuration
ED in excess of an upper limit 8890 MSLI Stage Mensuration and Leak Test

This is a sign that the nozzles have worn, either as a result of corrosion from the solvents
used to dissolve the active drug or erosion from the constant passage of particles through
Mensuration ‘Returns’ Boxes Leak Testing
the nozzles concerned. In this case tno restoration is feasible as it is not practical to
reapply metal to impactor nozzles. Replacement of the stage will be required. 8391 ACI Mensuration ‘Returns’ Box 5233 ACI or NGI Leak Test Certificate
5292 NGI Seal Body Mensuration ‘Returns’ Box 5234 ACI or NGI Delta-P Certificate
5251 NGI Leak Tester Re-calibration
5251A Re-calibration of LTK2 Leak Test Kit tools
ED below the lower limit
Pinning Kits and Services 5442 ACI Cut-Point Particle Calibration Certificate
The vast majority of impactors tend to drift out of specification because ED decreases below the
lower limit for the stage. This can be caused by a build-up of hardened particulates or, more likely, 5430 ACI Pinning Service (per stage)

because corrosion produces metal salts that occlude the nozzle. The formation of oxidised impurities 5431 ACI Pinning Kit

at the nozzle exit is a commonly encountered cause of occlusion, particularly for aluminium 5432 NGI Pinning Service (per stage)

impactors, which is why materials such as stainless steel and titanium are often also used. 5433 NGI Pinning Kit

In this case of ED below the lower limit, performance can sometimes be improved or restored.

Rigorous cleaning and ultrasonics (see page 298 for the Impactor Cleaning System) can be used to
remove deposits and restore performance.

Stage Pinning can also be attempted as a secondary option. Pushing stainless steel “go” pins with
a diameter between the nominal diameter and the lower tolerance limit for the stage through each
nozzle can serve to clear accumulated debris.

Stage Replacement is recommended in cases that the restoration of the impactor stage is not
achievable via stage pinning.

306 307
 Inhaler Testing Qualification/
Aerodynamic Particle
Servicing & Training
Size Distribution

In-House and On-Site Equipment Servicing Qualification Tools and Documents

and Calibration IQ/OQ Documentation
Copley offers a comprehensive range of servicing, maintenance and qualification options,
tailored to individual customer needs, providing quality maintenance and calibration procedures
at competitive prices:

• In-house equipment servicing • On-site equipment servicing

• In-house equipment calibration • On-site equipment calibration
• On-site equipment IQ/OQ

What is included?

Qualified engineers and

Tailored services
technicians trained to a high
for your needs
standard

Choose between: Documentation supplied and

completed to GxP standards as According to USP Chapter <1058>, Analytical Instrument It includes:
• Service contract
Qualification is “the collection of documented • Master Plan
• One-off offering per regulatory requirements
evidence that an instrument performs suitably for • Defines the aim and scope of the qualification
its intended purpose”
• Installation Qualification
It is important to note that the stage mensuration • Outlines the test plan, the standard operating
Single account manager contact We will be pleased to discuss your individual process described on previous pages is intended to procedures and test protocols necessary to
to ensure excellent service requirements and quote accordingly. replace the need for repetitive impactor calibration perform the IQ for the system concerned
based on standard aerosols. It ensures that only
• Operation Qualification
impactors that conform to specification are used
• Outlines the test plan and the standard operation
in testing. Whilst mensuration or calibration is an
procedures and test protocols to perform the OQ
important part of the qualification process, it does not
of the system concerned
in itself qualify the whole inhaler testing for use.
This is a separate process. The Installation Qualification/
Operation Qualification Documentation (IQ/OQ)
Documentation provided by Copley guides the user Qualification Documents
through this important process and confirms that the
Cat. No. Description
system is fully qualified for use.
8000 IQ/OQ Documentation for Inhaler Testing Systems
9500 Respiratory Drug Delivery Essential Theory &
Practice Book

Individual ancillaries and semi-automation IQ/OQ

documentation can be found in the relevant sections

308 309
 Inhaler Testing Qualification/
Aerodynamic Particle
Servicing & Training
Size Distribution

Qualification Tools

Inhaler Testing Qualification Kit

Includes all the tools required to perform IQ/OQ Qualification procedures
and can also be used for calibration of the Flow Controllers TPK 100i/R
and BAC 100i/R.

Delta-P
Nozzle dimensional performance can be indirectly monitored
by measuring the pressure drop (Delta-P) across each stage of
the impactor at a particular flow rate. Theoretically, for example,
a 2% shift in ECD corresponds to an approximate 5% shift in
Delta-P. Delta-P can be measured by the addition of a pressure
port at each impactor stage. In the case of the NGI, this is
achieved by means of a specially designed lid in conjunction
with the TPK 100i/R (see page 180). It is then a simple matter to
determine the pressure drop across each stage using a sensitive
Warranty
pressure meter.
Standard 12 Months Warranty
Copley offers a 12 months supplier’s warranty as standard with our entire product range.
A B
Extended Warranty
Anti-Electrostatic Equipment
For selected items, Copley offers the option to obtain extended warranty for a further period
A - Antistatic Grounding Kit
of 12 or 24 months after the standard warranty expires. We have confidence in our excellent
B - Electrostatic Eliminator
product quality but an extended warranty provides the peace of mind that comes with an
C
C - Digital Static Meter added layer of assurance.
Products that extended warranty is available for:

Qualification Tools
Ancillaries and Semi Automation
Cat. No. Description
Equipment Qualification Kits
5440 Inhaler Testing Qualification Kit Model ITQK2
Flow Controllers Vacuum Pumps Breathing Simulators Semi-Automation Tools
Separate tools are required for the 5445 Re-calibration of ITQK2 Kit tools
see page 172 see page 188 see page 156 see page 266
qualification of various ancillaries and semi 5216 ‘Delta-P’ Apparatus for NGI
automation equipment. Please refer to the 5217 NGI Leak Tester
relevant chapters for more information
Electrostatic Effects Minimisation
9300 Antistatic Grounding Kit
9301 Electrostatic Eliminator
9302 Digital Static Meter

310 311
 Inhaler Testing Qualification/
Aerodynamic Particle
Servicing & Training
Size Distribution

Support Training Services

Buy with confidence from Copley. When you purchase equipment from us, you not only get
outstanding instrumentation but also a complete customer care package which extends from
the start of the sales process through to installation, training, after-sales support and beyond.
With a global network of experienced and knowledgeable distributors you can rest assured that,
wherever you may be, there is support every step of the way.

Design Support
Our design team has many years’ experience
working closely with the inhaler testing
community in helping to develop ideas for solving
particular problems.
Whether you have a longstanding problem, or one As a world leader in the provision of equipment for testing OINDPs, Copley offers a range of
that has been created by the introduction of a tailored training packages for both analysts and lab managers of pharmaceutical companies.
new process, an idea for a new product, or even a
Training is planned and executed according to your exact requirements and can focus on both application and
bespoke design that you need manufacturing, we
installation/qualification topic areas.
would be delighted to hear from you.

Application Training Installation/Qualification Training

In-house purpose built facility In-house purpose built facility
On-line training On-line training
On-site training On-site training

Example training topics:

· In-vitro testing methods for OINDPs (MDIs, DPIs,

nebulisers, ADIs, nasal products)

· Improving the clinical relevance of in-vitro test methods

· IQ/OQ and maintenance of inhaler testing systems

Book your training course.

Highly experienced trainers
Bespoke training programs
On-site training available
Certification provided

Please contact us to find out more about our range of training packages.
Contact us at: sales@copleyscientific.co.uk
or call: +44 (0)115 961 6229

312 313
 Inhaler Testing Index

Index
A B D F I N

Abbreviated Impactor Book, Reference 309 Delta-P Testing 310 Fine Particle Dose (FPD) Installation Qualification 308, 309-310 Nasal Aerosols 10, 64-68, 141-146
Measurement (AIM) 252, 253-259 Breath Actuation Design 312 76, 80, 98, 141, 147, 200, 210, 215 Internal Filter Holder, NGI 85, 87 Nasal Delivery Systems 10
ACI 77, 88-93 Controller BAC 100i 176-179 Device Resistance 42, 90, 116, 172-173 Fine Particle Fraction (FPF) 80 International Pharmaceutical Nasal, Idealised 222
ACI Carrying/Wash Rack 92, 300 Breath-Actuated MDIs 7, 20, 21, 102, 172 DFM 2000 Flow Meter 185, 187 Fine Particle Mass (FPM) 76, 254, 258 Consortium on Regulation and Nasal Powders 10, 70-74, 147-152
ACI, Cleaning 298-301 Breathing Flow Controllers: Science (IPAC-RS) 16, 17
DFM 4 Flow Meter 185, 186 Nasal Spray Modification,
ACI Cleaning System 298-301 Simulators 25, 154, 156-171 - TPK-100i 180-183 International Standards Twin Impinger 99, 100
Dissolution Cup 232, 233
Bounce, Particle 94, 102, 116, 284 Organisation (ISO) 2, 14, 16, 17
ACI Collection Plate Rack 91, 93 Dissolution Inhaled 230-235 - TPK 100i-R 180-183 Nebulisers 9, 48-52, 122-127
BP Content Uniformity Apparatus 25 Inter-Stage Losses 83, 94, 98
ACI Drying Oven 299, 301 Dissolution Testing - BAC 100i 176-179 Nebulisers, Delivered Dose 48-52
In vitro - in vivo
ACI Pinning Kit 307 – Dose Collection 231-233 - BAC 100i-R 176-179 Nebulisers, Particle Size 122-127
correlation 14, 79, 156, 157, 214-217
ACI Pinning Service 307 C Dosage Unit Sampling Apparatus Flow Meters 184-187 In-Use Margin 305 Next Generation Impactor (NGI) 82-87
ACI Rinse Bath 299, 301 (DUSA) for DPIs 22-23 Flow Rate 173, 184, 185 IPAC-RS 16, 17 NGI 82-87
Caps, Rinsing 291, 293
ACI Sample Preparation Unit 290-293 Dosage Unit Sampling Apparatus Flow Rate Stability 174 IQ/OQ Documentation 309 NGI + 83, 87
Carrying/Wash Rack ACI 92, 300 (DUSA) for MDIs 21
ACI Suction Aspirator 299, 301 Flow Resistance 22, 42, 44, 173, 216, 257 ISO 20072 16, 17 NGI Assistant 294-297
Carrying/Wash Drug Delivery Devices 6-11
ACI Ultrasonic Cleaning Bath 299, 300, 301 Fluticasone Propionate Aerosols ISO 27427:2013 17, 158, 162, 167 NGI Carrying/Wash Rack 86, 300
Rack, NGI 86, 87, 300, 301
Active Pharmaceutical Ingredient (API) 18, 78 Drug Losses, Inter-Stage 83, 94, 96 - Testing 261, 263 NGI Cooler 194-195
Cascade Impactors 78-81, 82-101 ISO 9001:2015 Quality
Active Substance Delivery Drying Oven, ACI 299, 301 Fluticasone Propionate Powders Management System 2 NGI Cup Coater 284-286
CDER 12, 16, 17
Rate (Nebulisers) 48, 49 Dry Powder Inhalers (DPIs) 8 - Testing 261, 262, 263 ITW 196-199 NGI Cup Tray Storage Cabinet 288, 289
CDRH 12
Actuation Sensor for MDIs 179 DUSA Shaker 267, 282-283 Food and Drug IVIVC 14, 79, 156, 157, 214-217 NGI Gentle Rocker 287-289
Chinese Pharmacopoeia (ChP) 16, 17
Adapters, Mouthpiece 203-205 Administration (FDA) 12, 13, 14, 16, 17 NGI Gravimetric Cup 85, 87
Cleaning Systems, ACI/NGI 298-301
Adapters, Nosepiece 203, 205 NGI Leak Tester 310
Coarse Particle Mass (CPM) 254, 256, 258 E J
Add-on Devices 7, 28, 36-40, 109-114 NGI Pinning Kit 307
Coating, Cups 102, 116, 120, 268, 284-286 G
Aerodynamic Particle Size (APSD) 13, 76-153 Effective Cut-off Diameter (ECD) 90, 310 Japanese Pharmacopoeia (JP) 16, 17 NGI Pinning Service 307
Cold Freon® Effect 247-251
AIM - HRT Model 255-258 Efficient Data Analysis (EDA) 253 Generic Drug Development 260-265 Jet Nebulisers 9 NGI Plus 83, 87
Collection Tubes for DPIs 22-23
AIM - QC Model 253-256 Electrostatic Effects 310 Glass Expansion Chambers 200-202 NGI, Reduced (rNGI) 257
Collection Tubes for MDIs 21
AINI 222 Electrostatic Eliminator 310 Glass Impinger 98-100 NGI Sample Preparation Unit 268, 290-293
Connectors, Quick-Release 199 L
Alberta Idealised Nasal Inlet (AINI) 222 Emitted Dose 18, 230 Glass Twin Impinger 98-100 Nosepiece Adapters 203, 205
Conversion Kits, 60 & 90 L/min 93
Alberta Idealised Throat (AIT) 220-221 Entire Contents (DDU) 19, 20, 29, 37, 43 Gentle Rocker 287-289 Large Particle Mass (LPM) 253, 254
Cooler, NGI 194-195
Albuterol Aerosols, Testing 26, 264-265 European Medicines Geometric Standard Deviation (GSD) 80, 82 Leak Testing 81, 176, 180, 272, 307
Critical Quality Attributes (CQAs) 15, 18, 76, 216 Agency (EMA) 12, 14, 17 O
Analytical Instrument Global Harmonisation Task Force (GHTF) 14 Leak Test Kit 307
Qualification (AIQ) 302, 303 Critical (Sonic) Flow 174, 180, 191 European Pharmaceutical Gravimetric Cup, NGI 85, 87 Losses, Inter-Stage 83, 94, 98
Cup Coater 284-286 Aerosol Group (EPAG) 16, 17, 195, 305 OINDPs 6-11
Analytical Method Validation (AMV) 302, 303 Losses, Wall 82
Cut-Off Diameter European Pharmacopoeia Operation Qualification 309
Ancillaries 154-205
84, 90, 96, 99, 208, 255, 257, 258 (Ph.Eur.) 15 I Organisations 12-17
Andersen Cascade/Impactor (ACI) 88-93, 233
Cup Tray Storage Cabinet, NGI 288, 289 External Filter Holder, NGI 85, 87, 209, 258 M
Andersen Fast Screening ICH Guidelines 14
Impactor (FSA) 255-256 Extra-fine Particle Mass (EPM) 254, 257
Idealised Nasal 222 Mass Balance 82 P
Antistatic Grounding Kit 310 D Idealised Throat 220-221 MDI Actuation Sensor 158, 179, 183
APSD 13, 76-153 F P1 Measurement Adapter 118
Impactor Choice 101 MDI Angle of Rotation 276, 280
Aqueous Droplet Inhalers 6, 10, 54-58, 128-133 Data Analysis Software (Inhalytix) 206-212 Particle Bounce 94, 102, 116, 284
Impactor Cleaning System 298-301 MDI Semi-Automation 270-281
Assistant, NGI 269, 294-297 DecaVertus II 278-281 Facemask-based products 217, 236-245 Particle Size 76-81
Impactor Performance Testing 304-307 MDI Shake and Fire 267, 270-281
Automated Fire 267, 270-277 Delivered Dose Sampling Apparatus for: Facemask Stand for Nebulisers Pharmacopeial Forum 15
(FMS) 242-245 Impactor Qualification 304-307 Mensuration (impactor) 81, 304-307
Automated Flow Control 172-183 - Nebulisers with a Mouthpiece 48-51 Pharmeuropa 15
Facemask Test Apparatus for Impactor Sized Mass (ISM) 218, 220, 253 Mesh Nebulisers 9
Automated Nasal - Nebulisers with a Facemask 242-243 Ph.Eur. 15
Spacers and VHCs (FMA) 238-241 Impinger, Glass, Twin 98-100 Meter, Flow 184-187
Testing System 26, 61, 138, 275 - Spacers & VHCs 36-39 Pinning Kits 307
Fast Screening Andersen (FSA) 255-256 Inhaled Dissolution 230-235 Meter, Static 310
Automated Shake 267, 270-277 Delivered Dose Uniformity (DDU) 18-74 Pinning Service 307
Fast Screening Impactor (FSI) 258-259 Inhaled Drug Products 6-11 Metered-Dose Inhalers (MDIs) 7, 28-40, 102-114
Automated Shake and Fire 267, 270-281 Plume Temperature Testing 250-251
Fast Screening Impactors 255-259 Inhaler Testing Software (Inhalytix) 206-213 Metered Nasal Spray Pump 10
Automation 266-301 Powder-Based
Fast Screening NGI (rNGI) 257 Inhaler Testing Workstation (ITW) 196-199 MHLW (Japan) 12, 14
Nasal Devices 10, 70-74, 147-152
Inhalytix Software 206-213 Mitutoyo QV404 Vision
Inspection System 305 Pressure Drop
Inlet, Mixing 219, 226 22, 42, 44, 70, 90, 116, 118, 173, 310
Inspiration Volumes 173, 174 Mixing Inlet 219, 226
Process Analytical
Mouthpiece Adapters 203-205
Technologies (PAT) 14
Multi-Stage Liquid
Product Quality Research
Impinger (MSLI) 94-96
Institute (PQRI) 16

314 315
 Inhaler Testing Index
Aerodynamic Particle
Size Distribution

P S U Notes
Propellant-Based Nasal Aerosols 6, 10 Salmeterol Aerosols, Testing 260, 261-263 Ultrasonic Cleaning Bath, ACI 299, 301
PTT 1000 Plume Temperature Tester 250-251 Salmeterol Powders, Testing 260, 261-263 Ultrasonic Nebulisers 6, 9
Pumps, Vacuum 155, 188-192 Sample Preparation Unit 268, 290-293 United States Pharmacopeia (USP) 15, 17
PVC Tubing 199 Semi-Automation 266-301
Semi-Automation (NGI) 284-301
V
Semi-Automation (MDI) 270-281
Q
Servicing (Qualification) 302-308 Vacuum Pumps 155, 188-192
Qualification 302 Shake and Fire 267, 270-281 Validation 302
Qualification, Servicing & Training 302-313 Shaker, DUSA 267, 282-283 Valved Holding
Qualification Documentation IQ/OQ 309 Simulators, Breathing 25, 154, 156-171 Chambers (VHCs) 7, 36-40, 109-114

Qualification Tool Kit 310 Small Particle Mass (SPM) 253, 254 Verification 302

Quality by Design (QbD) Soft Mist Inhalers 10 Vertus II 271, 272-277

2, 13, 14, 156, 216, 252, 253 Software (Inhalytix) 206-213 Vertus Plus 271, 272-277
Quality Control Checks 303 Sonic Flow 23, 174, 180, 189, 191 Vision Inspection System,
Quick Clamp 91, 93, 202 Mitutoyo QV 404 305
Spacers 7, 36-40, 109-114
Quick-Release Connectors 199 Volume, Inspiration 173, 174
Spray Force Tester SFT 1000 248-249
Spray Pattern 247

R SPU Sample Preparation Unit 268, 290-293 W

Stage Cleaning 81, 298-301
Reduced NGI (rNGI) 257 Wall losses 82
Stage Mensuration 81, 304-307
Re-entrainment 94, 102, 116, 284 Waste Shot Collector 24, 250, 267
Static Meter 310
Reference Book 309 Wash Rack, ACI 92-300
Storage Cabinet, NGI Cup Tray 288, 289
Regulatory Bodies 12-17 Wash Rack, NGI 86, 300
Suction Aspirator 299, 301
Repetitive Strain Injury 266, 290 Watchglass/PTFE Assembly 231, 233
System Suitability Tests 303-313
Resistance to Flow 22, 42, 44, 173, 216, 257 System Qualification 304-310
Reverse Valved Holding Chambers 36
-
Rinsing Caps 86, 87, 92, 93, 263, 291, 293
21 CFR Part 11 157, 207, 212, 272, 278
T
60 L/min Conversion Kit 90, 93
Target Delivered Dose (TDD) 29, 43 90 L/min Conversion Kit 90, 93
Throats, Idealised 220-221
Total Active Substance
Delivered (Nebulisers) 48, 49
TPK 100i Flow Controller 180-183
Training 313
Tubing 199
Twin Impinger, Glass 98-100

316 317
 Inhaler Testing Notes
Aerodynamic Particle
Size Distribution

318 319
 Inhaler Testing Notes
Aerodynamic Particle
Size Distribution

320 321
 Inhaler Testing Notes
Aerodynamic Particle
Size Distribution

322 323
Austria, France, Germany and Switzerland
Copley Scientific AG
Erlenstrasse 27
Postfach 152
CH-4106 Therwil
Switzerland

+41 (0)61 725 25 35

+41 (0)61 721 31 87
sales@copleyscientific.ch
copleyscientific.com

UK, Ireland and International Sales

Copley Scientific Limited
Colwick Quays Business Park, Road No.2
Nottingham, NG4 2JY
United Kingdom

+44 (0)115 961 6229

+44 (0)115 961 7637
sales@copleyscientific.co.uk
copleyscientific.com