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.
Medical Packaging Standards RequirementsA high-level overview Dec 2012 Thierry Wagner Regulatory Affairs Director Europe, Middle East and Africa DuPont Medical & Pharmaceutical Protection
Medical PackagingLearning 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?4/9/2013 2
Global Medical Packaging StandardsEN 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 DESIGNEN 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
Medical PackagingEN ISO 11607 Global StatusUS 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
EN ISO 11607 Global StatusJapan Japanese versions available from Japan Association for Medical Instrumentation (JAMI) Adopted as Japanese National StandardChina Previous version adopted as National Standard Current versions undergoing adoption as Chinese National StandardOther Known Adoption Activities Taiwan, Singapore, Australia, Korea, Canada, Russia (previous version) … 5
Sterilisation of packaged devicesSterilisation ProcessesRadiation Gamma Electron beamGaseous Ethylene oxideLow temperature oxidative VHPHigh 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?4/9/2013 7
Sterility is defined as being Sterility free from living germs or micro-organismsHistorically: sterility viewed as absolute conditionToday: using sterility assurance level (SAL) to expressprobability of survivors (typically 10-6)Before 1970: sterility test to assess sterilization efficiencyThe problem: with sterility testing, there is no meaningfulstatement possible regarding the entire population 8
The Limitations of Sterility TestingLet’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. 4/9/2013 9
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 protection4/9/2013 10
Sterile Barrier Systems Top web Seal Bottom webSterile Barrier Systems Must prevent the ingress of microorganisms in order to maintain sterilityFilms and non-porous materials Must be free of holes and cracksPorous 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
Protection through Transportation & Storage Will your design survive and protect as required? Performance & Stability Testing is required to qualify the design
Basic Functions of Medical PackagingAllow for sterilizationProduct protection Physical protection from damage and environment Maintain sterility and integrity until point of use Microbial barrierEasy opening and aseptic presentationIdentify the product, clearly state informationand cautions