ISO 11607 - 1 & 2 Packaging for Terminally Sterilized Medical Devices
Jan Gates: Adept Packaging LLC
10X Conference, May 2019
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Jan Gates
Principal Packaging Engineer, Adept Packaging
VP Client Solutions, West Coast
Over 35+ years in medical devices, foods, pharmaceutical and detergent industries
Packaging engineering experience in design, material and distribution testing, material and equipment validations,
PMA submissions, REACH/RoHS, EU Packaging Waste Directives, and sustainability
SoCal Institute of Packaging Professionals Chapter, Co-President
IoPP Medical Device Packaging Technical Committee, member
ASTM F02, Flexible Barrier Packaging member
ASTM D10, Rigid/Environmental Packaging and Testing committee member
D10.96 ISO TC122 SC3 TAG Liaison Chair
ISO TC122 WG5 Covenor – Vocabulary
ISO TC122 WG13 (Labels) & WG16 (Controlled Temperature Packaging) SME
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Some of My Old Work
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Some of My Current Work
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Package Engineering Summary
Minimize sizing to Minimize sizing to optimize
optimize shipping costs warehousing
Reduce product breakage Optimize packaging
materials for product shelf
Package life and costs
Engineering
Develop packaging
human factors for users saves money Assure label legibility
(end and production) with use and time
Good packaging is Enhanced
sustainable Functionality/Utility
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ISO 11607-1: Packaging for terminally sterilized medical
devices – part one
Standard Titles ✓ Design and development
ISO 11607-2: Packaging for terminally sterilized medical
devices – part two
✓ Equipment and process validations
Current revisions: 2019 February
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Background
2006 2007 2014 2019
EN ISO 11607-1 & -2 AAMI TIR 22 ISO/TS 16775 Revised ISO
✓ Replaced EN 868-1 Issued April 2007 Issued, May 2014, 11607-1/-2 published,
✓ FDA harmonized with ✓ US Guidance replaced TIR 22
standard in 2006 February 2019
Document to EN ISO ✓ ISO Guidance on ✓ Revisions with human
11607-1 & -2 the application of factors/use added and
✓ More DDD guidance ISO 11607-1 and critical process parameter
included for FDA ISO 11607-2 definition changes
✓ Minor revisions to
the ISO 11607-1/-
2 standard
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ISO 11607 -1/-2 Standards
Standardized packaging for terminally sterilized medical devices
(placed packaging on the same importance level as the product; a medical device does not remain sterile
without acceptable packaging; qualify/validate the packaging system)
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New Terminology was Introduced
Terminal Sterilization
Sterile Barrier System (SBS)
Preformed Sterile Barrier System
Protective Packaging
Packaging System
Seal Integrity
Aseptic Presentation
Stability Testing
Performance Testing
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Sterilization validation
Terminal Sterilization & ✓Follow sterilization standards with worst-case situations for packaging
Packaging ✓Understand Biological Indicators (BI) and placements
Short hand → Sterilization kills the microbes inside the packaging;
packaging must not have holes until opened for use
<keep holes out of the SBS during packaging, storage, shipment, and
handling>
Common Types of Sterilization
Gamma Ethylene oxide E-beam Hydrogen Peroxide
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Shall Statements : Statements required for compliance
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Sampling of Shall Statements
✓ Shall use sampling plans based on statistically valid rationale (-1, Clause 4.3)
✓ Shall establish and record a rationale for appropriate tests and acceptance criteria (-1/-
2, Clause 4.4)
✓ Shall allow aseptic product presentation from the sterile barrier system. Note:
Completing a usability evaluation can demonstration this. (-1, Clause 6.1.2)
✓ Shall have procedures for packaging system design and development (-1, Clause 6.2.1)
Over 115 “SHALL” ✓ Shall have test methods validated and documented by the laboratory performing the
statements in the ISO test (-1, Clause 4.4.3)
11607 documents, ✓ Shall have EQ: IQ/OQ equipment (-2, Clauses 5.2 and 5.3)
this includes: ✓ Shall have written preventative maintenance and cleaning schedules (-2, Clause 5.2.6)
✓ Shall have a minimum of three production runs for a PQ (-2, 5.4.4)
✓ Shall test product for acceptability after transit testing with or without the sterile
barrier integrity testing (-1, Clause 8.2.1 Note 2)
✓ Shall start real time stability testing within three months of accelerated testing before
commercialization (-1, Clause 8.3.4)
✓ Stability and performance testing are separate entities (-1, Clause 8.1 Note 2)
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Statistical Justification
A sampling strategy is needed for a statistical justification
Risk Based Statistically
Risk Confidence Based
Assessment and Sample Size
Reliability
ISO standards Individualized ISO/ASTM standards
available by company – and many books
include a defect available
catalogue
Statistical justification/rationale: -1, Clause 4.3
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Test Method Validation
Rationale Acceptance
for test criterion ASTM test methods must be validated in the
choice
laboratory conducting the test; publication of a
Must validate method by a standards body does not make it
tests methods, validated in any laboratory (-1, Clause 4.4.3 Note).
also need:
Test method
Test method repeatability/
sensitivity for reproducibility
whole package (part of
integrity tests validation)
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Shall have procedures for packaging system design and
development (-1, Clause 6.2.1)
Design and Development
Documentation (DDD) ✓ Most companies have gate checks for devices included
in the DDD
✓ Need to include the packaging work or have a separate
DDD for packaging
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Equipment EQ: IQ and OQ (-2; Clause 5.2) or EIOQ
DQ
PQ
OQ
EIOQ
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Must be a minimum of three lots (-2; Clause 5.4.4)
Best practices include:
Production ✓ Analyze the test lots separately to assure they are statistically
Qualification (PQ) equivalent*
✓ Consecutive lots used
✓ Production stoppages, material lot changes, and similar that may
occur should occur during the qualification to simulate ‘normal’
production
* Remember there can be ‘no practical difference’ when something is ‘not statistically equivalent’, this must be explained
in the protocol before testing or a deviation or a protocol failure is required.
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Packaging Stability Testing
Aging the packaging system is independent of the physical configuration or contents, as long as:
✓ The processing is the same, and
✓ The contents do not affect the materials
✓ -1, Clause 8.1 Note 2
ASTM F1980 Standard Guide for Accelerated Aging of Sterile Barrier Systems for Medical Devices
✓ Uses a modified Arrhenius equation:
• Assumes the chemical reaction rate in a material is a logarithmic change for each 10 degree increase
− Q10 = 2 is the usual assumption
− Q10 ≠ 2 for most PETG (many thermal formed trays)
• Humidity is not part of the Arrhenius aging considerations
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Relative Humidity Note
Relative Humidity is the number of water
molecules in the air
The number of molecules in the air is effected by
Temperature
Temperature and humidity are inversely
proportional (with a given quantity of moisture)
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Aging verses Performance Testing
Two separate entities per the FDA, ISO, and chemistry books
Aging tests a material’s stability over time
Performance testing evaluates the interaction between the packaging system and the products
in response to the stresses imposed by the manufacturing (and sterilization) processes and the
handling, storage, and shipping environment
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Performance Testing – ASTM D4169
Test Plan Description
Handling 6 impacts, 24 inch
Vehicle Stacking Apply & release calculated
(Compression) top load
Loose Load Repetitive shock
Vibration 1 hour
14,000 ft
High Altitude 1 hour
Random Three levels for trucks
Vibration 3 hours
Concentrated 1 impact
Impact 36 inches
5 impacts, 24 inch
Handling 6th at 48"
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Performance Test Standards
ASTM D4169: Standard Practice for Performance Testing of Shipping
Containers and Systems
ASTM D7386: Standard Practice Performance Testing of Packages for Single
Parcel Delivery Systems
ISTA 3A or Higher
ASTM and ISTA Test
Standards ISTA 2A Package Conditioning for Testing
ASTM D4332: Standard Practice for Conditioning Containers, Packages, or
Packaging Components for Testing
ASTM F2825: Standard Practice for Climatic Stressing of Packaging Systems
for Single Parcel Delivery
Develop performance standards based on company distribution system →
the best option but hard for many companies
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Performance Defect Example
✓ Performance defect (package
design issue), not an aging
defect
✓ Do not confuse the two types
of defects
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Product Acceptability after Performance/ Distribution/Transit/Ship Testing
“Shall” statement to test product (-1, Clause 8.2.1 Note 2)
Package Engineering or Product Development must test the product after transit tests
Logistically, usually easiest to keep product testing and package testing separate
✓However, must assure both departments use the same transit tests
✓Many companies test packaging and product separately
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Understand the Distribution System Using
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Distribution Mapping -- General
Transfer/sorting hub
Load truck Ship to hub Unload truck Ship to airport
Pack for sterilization Note:Over 150 g drops measured Load truck Unload truck
Note: 1 to 200 Hz vibration
Fly
Ship to customer Load truck Unload plane Load plane
Stack in tarmac Note: -15oC measured, Stack in tarmac
Note: Some 82oC measured Note: 82oC have been measured
10 to 300 Hz
Summary: Many drops, temperature
extremes and vibration points seen
with distribution mapping.
Unload truck Customer unloads shipper Prep product for use
User
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Distribution Mapping: Detailed Multiple Shipping Count Example
Domestic System and Domestic Repetition
Round trip Handling Truck Transit Plane Transit Compression
1 23 6 1 3
2 47 13 3 7
3 71 20 5 11
4 95 27 7 15
5 119 34 9 19
6 143 41 11 23
International with Subassembly and International Repetition
Round trip Handling Truck Transit Plane Transit Compression
1 37 10 3 7
2 77 21 7 15
3 124 32 11 23
4 171 43 15 31
5 218 54 19 39
6 265 65 23 47
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2019 ISO 11607-1/-2 Standards:
New Changes in the revised documents
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Opinions on the ISO 11607-1/-2 Revisions
Most revisions for clarifications
My opinion:
The revisions have some good changes by removing a few
unnecessary complications. The wording more clearly defines
some previously implied intents and adds human factors (called
“usability requirements”).
Removing “critical” process parameters in -2 gives more focus
on the whole production process.
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Major Changes Summary from ISO 11607-1 (2014)
Eliminates the sample testing requirements of 23°C ± 1°C and 50% RH ± 2%
The sterile barrier system shall allow the product to be presented in an aseptic manner (with notation
to see the “usability” clause).
New clause on Usability Evaluation added (human factors)
Clause added for Reusable Sterile Barrier Systems and potential degradation limiting shelf life labeling
requirements
More explanation on “hazards” and “performance testing” with worst-case packaging system/SBS, and
validated packaging system changes
Real-time testing and accelerated testing shall start within three months of each other
Sustainability Annex D added
Labeling requirements for sterile barrier system to be inspected for integrity before use (Annex E)
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Major Changes Summary from ISO 11607-2 (2014)
New definitions for process - variables, parameter, and specification
Added Risk Management section
Harmonize definitions with ISO 11139
“Critical” process parameters is discontinued - to include all elements required to manufacture a
product that consistently meets specifications
Note added to “revalidation” allowing targeted process validations based on design validation work
Periodic review removed with minor process changes to be documented for potential to require the
process validation status to be reviewed
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Information to Understand
Human factors
✓ FDA and AAMI have guidance documents
• Both are very device oriented so hard to
determine what is best
• Pharmaceuticals are conducting human
factor testing on child resistant closures
and blister tablets
• Michigan State University, Dr. Bix and her
graduate students, are doing studies
• Document the company studies
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Human Factors and Design
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ISO 11607-1: 2019
Proposed New Symbol Examples
Complying with the new ISO 11607-1
requires:
✓Sterile barrier inspection before use
required and a symbol to show what
is the sterile barrier layer
✓Proposed symbols are not finalized
and require validation
Note: UDI for Europe and the USA to
comply with trace-ability requirements
but is not discussed in ISO 11607-1/-2
standards or in this presentation
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New Challenges: New Concerns in Discussion
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Third Party Distributors
✓ Product often packed into plastic
boxes, placed on wire racks, and
shipped by truck to a hospital
✓ Some are repacking, relabeling,
and bundling products without
performing validations
✓ Handling unclear
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Hospital Handling
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Questions?
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Engineering Packaging Excellence
Jan Gates
Adept Packaging
VP, Client Solutions - West Coast
E-mail: jan.gates@adeptpackaging.com
Based in Temecula, CA
Adept Group LLC
One East Broad Street, Bethlehem PA 18018
+1.484.373.2504 | info@adeptpkg.com
www.adeptpkg.com
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