1. Medical Packaging Standards Requirements
A high-level overview
Dec 2012
Thierry Wagner
Regulatory Affairs Director
Europe, Middle East and Africa
DuPont Medical & Pharmaceutical Protection
2. Medical Packaging
Learning Objectives
• What are the key medical packaging
standards and what is their global impact?
• What are the basic functions of medical
packaging?
• Why it is so difficult to test for sterility?
• What is the process to overcome these
difficulties and to achieve a high level of
patient protection?
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3. Global Medical Packaging Standards
EN ISO 11607-1:2006 Packaging for terminally sterilized medical devices -
Part 1: Requirements for materials, sterile barrier systems and packaging
systems.
PART 1 FOCUS IS ON MATERIALS AND DESIGN
EN ISO 11607-2:2006 Packaging for terminally sterilized medical devices –
Part 2: Validation requirements for forming, sealing and assembly
processes.
PART 2 FOCUS IS ON PACKAGING PROCESS VALIDATION
4. Medical Packaging
EN ISO 11607 Global Status
US
Adopted as American National Standard without revision
“Recognized” by the FDA Centers for Devices and Radiological
Health (CDRH)
Europe
Both documents approved as European Norms (EN)
Harmonized Standard (published in the Official Journal)
4
5. EN ISO 11607 Global Status
Japan
Japanese versions available from Japan Association for Medical
Instrumentation (JAMI)
Adopted as Japanese National Standard
China
Previous version adopted as National Standard
Current versions undergoing adoption as Chinese National Standard
Other Known Adoption Activities
Taiwan, Singapore, Australia, Korea, Canada,
Russia (previous version) …
5
7. Sterilisation of packaged devices
Sterilisation Processes
Radiation
Gamma
Electron beam
Gaseous
Ethylene oxide
Low temperature oxidative
VHP
High temperature steam
…
Key Questions:
• Does the packaging material allow for sterilisation?
• Is the material compatible with the sterilisation process?
• After sterilisation, does the material and the package
preserve sterility?
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8. Sterility is defined as being
Sterility free from living germs or micro-organisms
Historically: sterility viewed as absolute condition
Today: using sterility assurance level (SAL) to express
probability of survivors (typically 10-6)
Before 1970: sterility test to assess sterilization efficiency
The problem: with sterility testing, there is no meaningful
statement possible regarding the entire population
8
9. The Limitations of Sterility Testing
Let’s assume the SAL of a batch is 10-2 which is relatively high.
• With one sample, the probability to accept that batch is 1-10-2 = 99%
• With 2 samples (1-10-2) x (1-10-2) = 98%
• With n samples (1-10-2)n
• With 20 samples the batch is still accepted in 82% of the cases
• With 300 samples (with no false positives or negatives) the batch is
accepted in 5% of the cases, which is still not really acceptable.
• With a SAL of 10-6 → 3 million samples to achieve a similar confidence.
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10. Conclusion
• Sterility cannot be verified
• What cannot be verified, needs to be validated
• For this reason sterilisation and medical packaging
standards introduce
a number of requirements that have to be met and
validation steps that have to be followed successfully
• The overall objective is to achieve a high level of
patient safety and protection
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11. Sterile Barrier Systems
Top web
Seal
Bottom web
Sterile Barrier Systems
Must prevent the ingress of microorganisms
in order to maintain sterility
Films and non-porous materials
Must be free of holes and cracks
Porous barrier materials
Allow the sterilisation gazes to enter and exit the package
Allow the package to adapt to changing pressures and temperatures
as well as volume changes
Adequate Microbial Barrier Properties are required!
Integrity of seals must be guaranteed
12. Protection through Transportation & Storage
Will your design
survive and
protect as
required?
Performance & Stability Testing is required to qualify the design
14. Basic Functions of Medical Packaging
Allow for sterilization
Product protection
Physical protection from damage and environment
Maintain sterility and integrity until point of use
Microbial barrier
Easy opening and aseptic presentation
Identify the product, clearly state information
and cautions
Hello, I am Thierry Wagner, Regulatory Affairs Director at DuPont Medical and Pharmaceutical Protection. I would like to give you a high-level overview of the requirements of medical packaging standards.
As learning objectives, I would like to tell you what those key medical packaging standards are and what their global impact is.I would like to cover the basic functions of medical packagingI would like to provide you with an inside on why it is so difficult to test for sterilityAnd finally, we will see what process the standards introduced to overcome these difficulties and to achieve a high level of patient protection.
The standards that I would like to talk about obviously are EN ISO 11607 part 1 and 2 with the title “Packaging for terminally sterilized medical devices ”Part 1 focuses on packaging materials and designPart 2 focuses on packaging process validationEN ISO 11607 is a so called horizontal standard applying to different medical packaging types used in the industry and in healthcare facilities
EN ISO 11607 can be called a global standard since it is adopted as an American National standard without revision, it is recognized by the US FDA andit has been adopted as a European and harmonized standard in Europe. But there is more…
It has been adopted as National Standard in Japan. China has adopted the previous version and is working on adopting the current version.And there are known adoption activities in other countries like Taiwan, Singapore, Australia, Korea, Canada… while Russia has adopted the previous version.With all of these countries, it is my opinion, that ISO 11607 has truly achieved the critical mass to be called a global standard.
To achieve sterility, packaged devices have to exposed to a sterilisation process, with the most common processes being either radiation sterilisation like gamma or e-beam, or gaseous sterilisation with the most common using ethylene oxide, low temperature oxidative processes like vaporized hydrogen peroxide, high temperature steam sterilisation and many others.This raises a number of key questions likeDoes the packaging material allow for sterilisation? Since the sterilisation process is applied on the packaged deviceIs the material compatible with the sterilisation process? Since most of these sterilisation processes tend to be aggressiveAfter sterilisation, does the material and the package preserve sterility? Until the point of use over the indicated shelf life of the product
But then it raises the question, what is sterility?Sterility is defined as being free from living germs or micro-organismsHistorically: sterility viewed as absolute conditionToday we are using sterility assurance level (SAL) to express the probability of surviving micro-organisms(typically 10-6 )Before 1970 it was common to use a sterility test to assess sterilization efficiencyThere is a problem with that approach: with sterility testing, there is no meaningful statement possible regarding the entire populationTo illustrate that, I would like to provide you with an example:
Let’s assume the SAL of a batch is 10-2 which is relatively high…So, it is obvious, that we cannot really prove sterility of a population with sterility testing
Sterility cannot be verifiedWhat cannot be verified, needs to be validatedFor this reason sterilisation and medical packaging standards introducerequirements that have to be met and validation steps that have to be followed successfullyThe overall objective is to achieve a high level of patient safety and protection
Protection is a key word here. The standard introduces specific terminology, the sterile barrier system, which is the minimum package that prevents the ingress of microorganisms. They can take different shapes. Most are made of 2 sheet materials, a bottom web and a top web that are sealed together to form pouches, bags or rigid tray packaging like on this picture, while hospitals typically also use reusable containers or sterilisation wrap, which is folded into a sterile barrier system.To prevent the ingress of microorganisms, films and non-porous materials must be free of holes and cracks obviously andPorous barrier materials, which allow the sterilisation gazes to enter and exit the packageWhich also allow the package to adapt to changing pressures and temperatures as well as volume changesMust of cause have adequate Microbial Barrier Properties.Finally the Integrity of seals must be guaranteed Seal integrity and microbial barrier properties are the key tests to be performed and are considered state of the art. If you are interested why, I covering that in another presentation.
Now, when a sterile barrier system is made of adequate materials and is properly sealed, then the question is if it will survive the hazards of transport and storage and if it protects the device appropriately.It is obvious that any loss of integrity due to tears and perforations or loss of microbial barrier properties could have a direct impact on sterility. And there should be no deterioration over time, the characteristics and properties should be stable over the shelf life of the product.So the standard requires us to do performance & stability testing to qualify the design and its materials.
In summary, what do EN ISO 11607 part 1 and 2 say?Well the standard simples states, thatYou must:- Design to minimize the safety hazard while meeting the requirements that are stated- Test your package, to validate the design, to demonstrate that the package capable to withstand the hazards of distribution, handling and storage- Validate your packaging process, to show that you are capable to produce consistently a level of quality meeting the specificationsAnd you need to maintain your packaging process under control, with process control measures to detect any deviations due to raw materials variations or packaging process issuesThat is in a nutshell all you have to do.
If you have questions, comments suggestions, do not hesitate to get in touch with me. If you want to hear more, watch out for upcoming presentations.Many thanks for your attentionBye, bye.
