GMP News No. 740
30 May 2006
Validation Requirements on the Packaging of Medical Devices
Through the standards DIN EN ISO 9001 and 13485, validation is present also in the field of medical devices. 21 CFR 820 requires validation for medical devices distributed in the US. However, all these regulations include few concrete statements.
On some specific topics, like e.g. sterilisation processes, there are a number of standards going deeper into technical matters. One current example is a final draft by ISO titled "Packaging for terminally sterilized medical devices -- Part 2: Validation requirements for forming, sealing and assembly processes (ISO 11607-2)".
This draft for a standard comprises 12 pages - with an informative annex on process development and a reference list. The draft also contains a matrix - also as an annex - showing the relationship between the EC Guideline 93/42/EEC and this standard.
The definitions listed in the draft reference ISO/TS 11139/2001. It is conspicuous that IQ OQ and PQ are defined in a similar way as in the pharmaceutical regulations. The same goes for the definition of process validation.
The focus of this standard is on chapter 5 "Validation of Packaging Processes". Apart from a general introduction, it contains the subchapters IQ, OQ and PQ as well as information on the release of process validation, process control, monitoring, on change control and on revalidation.
As a minimum requirement for process validation, IQ-PQ has to be conducted. After that, "old products" can be validated on the basis of data gained in earlier IQs and OQs. At least the critical parameters can be deduced from these data. In case of similar processes, a "worst-case" validation is allowed if based on a rationale.
The chapter IQ provides examples of the contents, reaching from specifications on design features to operating instructions that have to be observed within the framework of IQ. Safety aspects are also mentioned in the IQ chapter, as is software validation. An additional subtopic defines data concerning functional tests. What is especially mentioned with regard to IQ is the call for a definition of the critical process parameters as well as for their control and monitoring. The chapter also includes the requirement to have a maintenance programme and cleaning schedules.
In OQ, the upper and lower parameter limits are meant to be found. Quality aspects that have to be observed are mentioned with regard to forming/assembly, sealing and other container closure systems.
It is the aim of PQ to demonstrate that the process constantly generates a closure system within the limits tested during OQ. The requirements on the contents of the PQ again point out the importance of repeatability and processability. Challenge tests are set out in detail (e.g. power failure, shift change, upgrading the facility). As a minimum, 3 production runs of sufficient length are required. In addition, the text points to the predefined requirements that have to be fulfilled. Process validation is then to be revised and formally released. Afterwards, a summarizing documentation describes the validation status - taking into account monitoring of controls and the process and its documentation.
Besides, the standard requires a regulated process for change control and a revalidation - in case major changes have been made. It also includes a list of changes that could be relevant to revalidation. The necessity of a revalidation should be assessed. It is expressly mentioned that the scope of a revalidation does not have to be identical with that of a first validation. Periodic revalidations or reviews should be conducted, since minor changes could have a cumulative effect on the validation status.
Final analysis: The numerous parallels to qualification activities in the pharmaceutical industry are striking. However, Design Qualification is left out completely as there are differences in the terminology between the medical device area and the pharmaceutical sphere. A slight difference to the pharmaceutical environment is the global summary of IQ, OQ and PQ as process validation. It is surprising that 3 batches of product are still to be manufactured within the framework of PQ - a number from which the pharmaceutical industry is starting to depart.