Quality Assurance

GMP
Quality Control
Quality Management

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 WHAT IS QUALITY?
 The word ‘QUALITY’ is originated from a Latin word-
“QUALITAS” means “general excellence” or a
distinctive feature’.
 It is the best possible expected outcome of an effort
under given conditions and terms of skill, experience,
financial and available resources.
 Customer Satisfaction

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 QUALITY IN THE HEALTHCARE FIELD
Targets (customers) of the healthcare team:
•The Patient
•The Community
The aim of the healthcare team:
•To provide quality patient care
•To provide quality health service to the community

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 QUALITY IN PHARMACEUTICAL INDUSTRY

The degree to which a set of inherent properties of a

product, system or process fulfills requirements
specifically for quality of drug substance and drug
product (ICH Q9).

The suitability of either a drug substance or drug product

for its intended use. This term includes such attributes as
identity, strength and purity (ICH Q6A).

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 QUALITY ASSURANCE
•It is the sum total of the organized
arrangements with the objective of ensuring
that products will be of the quality required
for their intended use

ISO 9000 defines as "part of quality

management focused on providing
confidence that quality requirements will be
fulfilled"

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• According to WHO, quality assurance is a wide- ranging concept
covering all matters that individually or collectively influence the
quality of a product. With regard to pharmaceuticals, quality assurance
can be divided into major areas: development, quality control,
production, distribution, and inspections.

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Aim:
oTo prevent defects with a focus on the
process used to make the product. It is a
proactive quality process.
oTo improve development and test processes
so that defects do not arise when the product is
being developed.
How:
Establish a good quality management system
and the assessment of its adequacy.
Periodic conformance through audits of the
operations of the system.
Benefit:
Prevention of quality problems through
planned and systematic activities including
documentation.
Responsibility:
Everyone on the team involved in developing
the product is responsible for quality
assurance.
As Tool: Managerial Tool
Orientation: Process oriented
The objectives of Quality Assurance are achieved when processes
have been defined which, when followed, will yield a product that
complies with its specification, and when the finished product:
a. Contains the correct ingredients in the correct proportions,
b. Has been correctly processed, according to the defined
procedures,
c. Is of the purity required,
d. Is enclosed in its proper container, which bears the correct
label (or is otherwise suitably marked or identified), and
f. Is stored, distributed and subsequently handled so that its
quality is maintained throughout its designated or expected life.
 Responsibilities of QA in
Pharmaceutical Industry
To Ensure:
•Raw materials used in the manufacturing are approved and
procured from approved vendor.
•All data are recorded as per cGMP and is reviewed for accuracy
and traceability.
•Procedures are in place for performing the activities, operating
and calibrating the equipment
•Quality is built up in the plant, process, product. That a Robust
Quality system is in place
•Trainings like induction, On job, Scheduled and after any changes
are conducted to respective individuals on time.
• To prepare and approve Quality Policy, Quality Objectives, Quality
Manual and Validation Master Plan.
• Periodic Monitoring of the Quality Objectives.
• Monitors all validation & stability activities are completed as per the
schedule.
• Ensures that all changes impacting the product and the established
systems are documented and reviewed to analyze the impact.
• Ensures that all deviations, OOS/OOT & Market complaints are logged,
investigated to identify the root cause so as to take CAPA to prevent
recurrence.
• Preparation of Annual product quality reports, trending of data,
determining product and process performance.
• To arrange and conduct the self inspection, identify gaps and take
CAPA.
• Review of related batch manufacturing records and QC testing data Prior
to release of any batch.
 Job Description of QA
1. Technology transfer
2. Validation
3. Documentation
4. Assuring quality of products
5. Quality improvement plans
 1. Technology transfer
• Receipt of product design documents from research
centre
• Receipt of the trial and error data and its final
evaluation
• Distribution of documents received from research
centre
• Checking and approval of documents generated based
on research centre documents i.e. batch manufacturing
record
• Scale-up and validation of product
 2. Validation
• Preparation of Validation Master plans for
facility/equipment/process Utility, Cleaning and all
the sections of the validation
• Approval of protocol for validation of facility/
equipment/product/ process/Utility
• Team member for execution of validation of
facility/equipment / product/ process
• Final approval of the facility/ equipment/product/
process/Utility validation
 3. Documentation
• Written statement or proof. It is an essential part of Quality
Assurance and Quality Control system and is related to all
aspects of Good Manufacturing Practices (GMP). It is mainly
defines the specification for all materials, method
of manufacturing and control.

• Main objective
– To establish, monitor and record “Quality” for all aspects of Good
Manufacturing Practices (GMP) and other Quality System
pertaining

• Type of documents
– Standard operating procedures
– Protocols of tests
– Results
– Reports
 “IF you have not documented it
you have not done it”
• Laboratory records
– Description and identification of sample received
– Description of method of testing
– Record of all data secured in the course of the test
– Record of test results and how they compare with
standards of identity, strength and quality
– Record of all deviations and modification of test
– Record of standardization of reference standards
– Record of calibration of equipment
• SOP: Standard operating procedures describe
in a detailed form the activities performed in
the laboratory
• Provide uniformity, consistency and reliability
in each of the activities performed in the
laboratory
• Reduce systematic errors
• Provide training and guidance for new staff
 4. Assuring Quality of products
• CGMP training
• SOP compliance
• Audit of facility for compliance
• Line clearance
• In-process counter checks
• Critical sampling
• Record verification
• Release of batch for marketing
• Investigation of market complaints
 5. Quality improvement plan
• Feedback received from the compliance team
• Customer complaint history
• Proposals for corrective and preventive actions
• Annual Products review
• Trend analysis of various quality parameters for
products, environment and water
• Review of the Deviations, Change Controls, Out of
Specifications and Failures
 Good Manufacturing Practice
(GMP)
“Part of Quality Assurance which ensures that
products are consistently produced and
controlled to the quality standards appropriate to
their intended use and as required by their
Marketing Authorisation or Product
Specification”.

GMP is thus concerned with both production and

quality control
 Basic Needs of GMP
a) All manufacturing processes should be clearly defined, and known
to be capable of achieving the desired ends.
b) All necessary facilities are provided, including:
1. Appropriately trained personnel;
2. adequate premises and space;
3. suitable equipment and services;
4. correct materials, containers and labels;
5. approved procedures (including cleaning procedures);
and
6. suitable storage and transport.
c) Procedures are written in instructional form, in clear
and unambiguous language, and are specifically
applicable to the facilities provided.
d) Operators are trained to carry out the procedures correctly.
e) Records are made during manufacture (including
packaging) which demonstrate that all the steps required
by the defined procedures were, in fact , taken and that the
quantity and quality produced were those expected.
f) Records of manufacture and distribution, which enable the
complete history of a batch to be traced, are retained in a
legible and accessible form.
g) A system is available to recall from sale or supply any
batch or product, should that become necessary.
 Principles of GMP
• Design and construct the facilities and equipment properly.
• Follow written procedure and instruction.
• Documentation work
• Validation work.
• Check the facilities and equipment.
• Write step by step operating procedure and work on in
sanitation.
• Design , demonstrate, develop job competence.
• Protect against contamination
• Control component and product related to process.
• Conduct planned and periodic audit.
 Why GMP is important

•A poor quality medicine may contain toxic

substances that have been unintentionally added.

•A medicine that contains little or none of the

claimed ingredient will not have the intended
therapeutic effect.
 Importance of GMP

• Ensure that the product are safe for human use

and dose.
• Prevent the toxicity
• Side effect due to variation in drug content.
• Prevent or control contamination.
 Objective of GMP
• To understand where the regulation come from, who
has enforcement authority, and why you need to
comply.
• To understand the fundamental benefits, key part of
GMP.
• To minimize the risk involved in pharmaceutical
production that can’t be eliminated by testing the
final product.
• Poor chance for the patient to detect anything wrong.
 QUALITY CONTROL - QC
•Part of GMP concerned with sampling, specification &
testing, documentation & release procedures which
ensure that the necessary & relevant tests are performed
& the product is released for use only after ascertaining
it’s quality
•ISO 9000 defines quality control as "A part of quality
management focused on fulfilling quality requirements".
•QC is a set of activities (testing and analysis) for
ensuring quality in pharmaceuticals.

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 Scope of QC

Items concerned :
Starting materials
Packaging materials
Bulk products
Intermediate and finished products
Environmental conditions

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Aim:
To produce a defect free pharmaceutical, a
regulatory requirement to safeguard the health of
end user;

Objectives:
Use of latest techniques and technologies

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How:
Development of Standard Testing and Analytical
Procedures.
(mostly by the Pharmacopeias editing and
compiling teams with researcher who developed
the drugs molecules and brand leader companies)

Responsibility:
A specific team that tests the product for defects.

As tool: QC is a corrective tool

Orientation: It is product oriented

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HOW: BASIC REQUIREMENTS OF QUALITY
CONTROL
1. Adequate facilities and staff should be available for
sampling, inspecting and testing starting materials,
packaging materials, intermediate, bulk and finished
products.
2. Samples of starting materials, packaging materials,
and of intermediate products, bulk products, finished
products should only be taken by, and methods
approved by the person responsible for Quality
Control.
3. Results of the inspection and testing of materials, and
of intermediate, bulk or finished products should be
formally assessed against specification by the person
responsible for Quality Control (Qualified Person - or
a person designated by (him/her) before products are
released for sale or supply.
4. Product assessment should include a
review and evaluation of relevant
manufacturing (including packaging)
documentation.
5. Sufficient reference samples of starting
materials and products should be retained (the
latter, where possible, in the final pack) to
permit future examination if necessary.
• Sampling of raw materials
•Initially quarantined
•Sample are taken and tested to ensure that the materials meets
strict purity guidelines
•Microbiological and chemical testing as written in
Pharmacopeia
• In process check
•At intervals QC staff takes samples to check for contamination
and ensure that the composition is as expected
•E.g. 5 tablets (every 15 minutes)
• Final Product checking
• All results are compiled and recorded with name and
batch number on it
 Responsibilities of QC in
Pharmaceutical Industry
• QC is responsible for the day-to-day control of quality
within the company.
• This department is responsible for analytical testing of
incoming raw materials and inspection of packaging
components, including labeling.
• They conduct in-process testing when required, perform
environmental monitoring, and inspect operations for
compliance.
• They also conduct the required tests on finished dosage
form.
• Improve the quality of production and reduction in the
production cost.
• Uniform the production and supply of standard quality goods
to consumers.
• Offers full return of the price paid by the consumers and
giving convenience and satisfaction to consumers.
• Reduces spoiled production and rejection from consumers
and dealers.
• Promote exports due to superior and standard quality
production.
• Reduces inspection cost.
• Make products popular in market.
 Job Description of Quality Control

The 4 Main responsibilities of quality control in pharmaceutical industry

include :
a)Efficacy
b)Safety
c)Quality
d)Compliance
 Job Description of Quality Control
• Quality Control in the pharmaceutical industry is required for :

• Raw Materials and API: The techniques used include Raman

and IR spectroscopy, Assay( HPLC and Titration ), Physical
tests.

• Packaging Components : The various packaging components

which are in contact with the drug are tested. The techniques
include appearance, color, text and monograph etc.

• Finished Products : The techniques include HPLC, Assay,

Dissolution, Content uniformity.
Steps in quality control

a)Devising the control over raw materials:

– The quality of the finished products is determined mostly by the
quality of raw materials.

b)Fixing standards and specifications:

– In order to make any scheme of quality control successful, it is
necessary to predetermine standards and specifications.

c)Exercising control over production operations:

– In order to execute efficient practices, the technical expert of the
quality control department must investigate the operating methods.
d) Locating inspection points:
– When the points at which defects occur are wrongly located
or located with delay, it hinders quality control. Hence there
should first be inspection of raw material at vendors place,
then at company’s plant then at various stages during process.

e) Maintaining quality of equipment:

– The final quality of the products is conditioned by the quality
of the equipment and other devices used.

f) Maintaining records:
– The QC department is responsible for setting records related
to quality inspection and control and the number rejected
 Relationships between GMP, QA
& QC

QA GMP QC

QA serves as a management tool while GMP and quality control are

interrelated aspect of quality management.

 QA QC
•Quality of process •Quality of product

•All those planned actions •Operational laboratory

necessary to provide techniques and activities
adequate confidence that a used to fulfill the
product will satisfy the requirements for that a
requirements for quality, product will satisfy the
includes implementation of requirements quality
cGMP, personnel control.

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 QA QC

•QA is company Base •QC is Lab based

•Improving the process and •Finding defects and then

prevents defects fixing them

•Receive Complaints from •Test and correct the

Market complaints

•QA is a managerial tool •QC is a corrective tool

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 What are its goals and on what does it focus?

 QA aims to prevent  QC aims to identify (and

defects with a focus on correct) defects in the
the process used to finished product. Quality
make the product. It is a control, therefore, is a
proactive quality reactive process.
process.  The goal of QC is to
 The goal of QA is to identify defects after a
improve development product is developed and
and test processes so before it's released.
that defects do not arise
when the product is
being developed.
 What and how does it work?

 Prevention of quality  The activities or techniques

problems through planned used to achieve and maintain
and systematic activities the product quality, process
including documentation. and service.
 Establish a good quality  Finding & eliminating
management system and the sources of quality problems
assessment of its adequacy. through tools & equipment so
Periodic conformance audits that customer's requirements
of the operations of the are continually met.
system.
Whose responsibility is it and what is the example of it?

 Everyone on the team  Quality control is usually

involved in developing the responsibility of a
the product is responsible specific team that tests
for quality assurance. the product for defects.
 Verification is an  Validation is an example
example of QA. of QC.
TOTAL QUALITY MANAGEMENT IN
PHARMACEUTICALS
“The aspect of management function which
determines and implements the “quality
policy”, i.e. the overall intention and direction
of an organization regarding quality, as
formally expressed and authorized by top
management”.
 The pharmaceutical industry is a vital segment of health care
system which is regulated heavily because; any mistake in
product design or production can be severe, even fatal.
 The poor qualities of drug are not only a health hazard but
also a waste of money for both the government and the
individual customers.
 So, the maintenance of the quality with continuous
improvement is very important for pharmaceutical
industries.
 From this concept, Total Quality Management (TQM) was
established.

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 The aim of TQM is “prevention of defects rather than
detection of defects”.
 So TQM is very important for pharmaceutical industries to
produce the better product and ensure the maximum safety
of health care system and also protect waste of money for
both government and individual customers.
 The basis of this approach is that the organizational units
should be working harmoniously to satisfy the customer.

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 Therefore, total quality management (TQM) means:
1. Satisfying customers first time, every time;
2. Enabling the employees to solve problems and eliminate
wastage;
3. A style of working, a culture more than a management
technique;
4. Philosophy of continuous improvement, never ending,
only achievable by/or through people.

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 Definition:
 TQM has been defined as an integrated organizational effort
designed to improve quality at every level.
 The process to produce a perfect product by a series of
measures requiring an organized effort by the entire company
to prevent or eliminate errors at every stage in production is
called Total Quality Management.

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 According to International Organization for Standards (ISO)
TQM is defined as, a management approach for an
organization, centred on quality, based on the participation of all
its members and aiming at long-term success through customer
satisfaction and benefits to all members of the organization and
to the society.
 It uses strategy, data and effective communications to integrate
the quality discipline into the culture and activities of the
organization.

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TQM Model:
Customer
Focus

Total Planning
TQM
Participation MODEL Process

Process Process
Improvement Management
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 Basic elements of quality management
The basic elements of quality management are:
oan appropriate infrastructure or “quality
system”, encompassing the organizational
structure, procedures, processes and resources;
osystematic actions necessary to ensure
adequate confidence that a product (or service)
will satisfy given requirements for quality. The
totality of these actions is termed “quality
assurance”.

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Requirements of Quality Management
Sanitation & hygiene
The scope of sanitation and hygiene covers personnel, premises,
equipment and apparatus, production materials and containers, products for
cleaning and disinfection, and anything that could become a source of
contamination to the product.
Potential sources of contamination should be eliminated through an
integrated comprehensive program of sanitation and hygiene.

Qualification & validation

Identify what qualification and validation work is required to prove that
the critical aspects of their particular operation are controlled.
The key elements of a qualification and validation program of a company
should be clearly defined and documented in a validation master plan.
It is of critical importance that particular attention is paid to the validation
of analytical test methods, automated systems and cleaning procedures.
Complaints
All complaints and other information concerning potentially
defective products should be carefully reviewed according to
written procedures and the corrective action should be taken.

Product recalls
There should be a system to recall from the market, promptly
and effectively, products known or suspected to be defective.
The progress of the recall process should be monitored and
recorded. Records should include the disposition of the
product. A final report should be issued, including a
reconciliation between the delivered and recovered quantities
of the products.
Self-inspection and quality audits
To evaluate the manufacturer’s compliance with GMP in all
aspects of production and quality control.
Should be designed to detect any shortcomings in the
implementation of gmp and to recommend the necessary corrective
actions.
Should be performed routinely, and may be, in addition, performed
on special occasions, e.G. In the case of product recalls or repeated
rejections, or when an inspection by the health authorities is
announced.
The team responsible for self-inspection should consist of
personnel who can evaluate the implementation of gmp objectively.
All recommendations for corrective action should be implemented.
The procedure for self-inspection should be documented, and there
should be an effective follow-up program.
Personnel
The establishment and maintenance of a satisfactory system of
quality assurance rely upon people.
Sufficient legally qualified and professionally competent personnel
must be employed to carry out all the tasks for which the
manufacturer is responsible;
 Pharmacists
 Microbiologist
 Chemist / biochemist
 Biotechnologist
Individual responsibilities should be clearly defined and understood
by the persons concerned and recorded as written descriptions.
Personnel should be aware of the principles of gmp that affect them
and receive initial and continuing training, including hygiene
instructions, relevant to their needs.
All personnel should be motivated to support the establishment and
maintenance of high-quality standards.
Premises
Premises must be located, designed, constructed, adapted, and maintained
to suit the operations to be carried out.
 The layout and design of premises must aim to minimize the risk of errors and
permit effective cleaning and maintenance in order to avoid cross-
contamination, build-up of dust or dirt, and, in general, any adverse effect on
the quality of products.
 Premises should be designed to ensure the logical flow of materials and
personnel.
 Premises should be situated in an environment that, when considered together
with measures to protect the manufacturing process, presents minimum risk of
causing any contamination of materials or products.
 Premises used for the manufacture of finished products should be suitably
designed and constructed to facilitate good sanitation, carefully maintained,
electrical supply, lighting, temperature, humidity and ventilation should be
appropriate and such that they do not adversely affect, directly or indirectly,
either the pharmaceutical products during their manufacture and storage, or the
accurate functioning of equipment.
 Rest and refreshment rooms should be separate from manufacturing and control
areas.
 Facilities for changing and storing clothes and for washing and toilet purposes
should be easily accessible and appropriate for the number of users. Toilets
should not communicate directly with production or storage areas.
Equipment
Equipment must be located, designed, constructed, adapted, and
maintained to suit the operations to be carried out.
The layout and design of equipment must aim to minimize the risk
of errors and permit effective cleaning and maintenance in order to
avoid cross-contamination, build-up of dust or dirt, and, in general,
any adverse effect on the quality of products.
Equipment should be installed in such a way as to minimize any
risk of error or of contamination.
 Production equipment should be thoroughly cleaned on a
scheduled basis.
Laboratory equipment and instruments should be suited to the
testing procedures undertaken.
Washing, cleaning and drying equipment should be chosen and
used so as not to be a source of contamination.
Material
Both apis, excipients, regents etc. Should be quarantined
before use and when testified by the QC as are according to
the specs should then be used.
All materials and products should be stored under the
appropriate conditions established by the manufacturer and in
an orderly fashion to permit batch segregation and stock
rotation by a first-expire, first-out rule.
Water used in the manufacture of pharmaceutical products
should be suitable for its intended use.
Documentation
Good documentation is an essential part of the quality assurance
system and, as such, should exist for all aspects of GMP.
To define the specifications and procedures for all materials and
methods of manufacture and control;
To ensure that all personnel concerned with manufacture know
what to do and when to do it;
To ensure that authorized persons have all the information
necessary to decide whether or not to release a batch of a drug for
sale,
To ensure the existence of documented evidence, traceability, and
to provide records and an audit trail that will permit investigation.
To ensures the availability of the data needed for validation,
review and statistical analysis.

The design and use of documents depend upon the manufacturer.

 Categories of TQM
 Total quality management ensures that every single
employee is working towards the improvement of work
culture, processes, services, systems and so on to ensure
long term success.
 Total Quality management can be divided into four
categories:
 Plan
 Do
 Check
 Act
 Also referred to as PDCA cycle.

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 Planning Phase
 Planning is the most crucial phase of total quality
management.
 In this phase employees have to come up with their problems
and queries which need to be addressed.
 They need to come up with the various challenges they face in
their day to day operations and also analyze the problem’s
root cause.
 Employees are required to do necessary research and collect
relevant data which would help them find solutions to all the
problems.

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 Doing Phase
 In the doing phase, employees develop a solution for the
problems defined in planning phase.
 Strategies are devised and implemented to overcome the
challenges faced by employees.
 The effectiveness of solutions and strategies is also
measured in this stage.

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 Checking Phase
 Checking phase is the stage where people actually do a
comparison analysis of before and after data to confirm the
effectiveness of the processes and measure the results.

Acting Phase
 In this phase employees document their results and prepare
themselves to address other problems.

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Thanks

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