Page 227 - Biomedical Engineering and Design Handbook Volume 2, Applications

206 MEDICAL DEVICE DESIGN

documented validation program demonstrating the efficacy and reproducibility of all sterilization
and packaging processes (i.e., forming, sealing, capping, cutting, and handling). At this point, the
engineering staff has realized that the package design and development process should have been an
integral part of the product development program and should not have been left to the very end of
the development process. Serious delays in distribution of the product have resulted since the pack-
age validation process requires significant time and effort to complete. The engineering team now
turns to the Regulatory Affairs (RA) department for help in identifying the regulatory requirements
for packaging.
Investigation by the RA department for the requirements imposed on packaging reveals an array
of documents on the subject. Foremost is the quality systems regulation (QSR) found in Title 21
CFR, Part 820. The requirements for components, device master records, and environmental controls
that affect the selection and use of packaging appear throughout the QSR. However, the specific
requirements for packaging are in Sec. 820.130.
Further investigation discloses two international documents regulating the design and develop-
ment of packaging: the International Standards Organization (ISO) 11607 “Packaging for Terminally
Sterilized Medical Devices” and European Norm (EN) 868-1, “Packaging Materials Systems for
Medical Devices which Are to Be Ssterilized-Part 1: General Requirements and Test Methods.” Both
of these documents provide an outline of general requirements and test methods for validating the
complete package system. RA has reviewed the two international documents and has found that they
are very similar, but with a few significant differences. “What standard do we follow?” becomes the
next basic question to answer. Since ISO 11607:2000 was published, the new two-part standard has
been harmonized the EN 868-1. So, for general requirements of developing a package system, there
is only one standard to comply with—ISO 11607.
FDA has helped further answer this question by acknowledging the importance of international
consensus standards. The FDA stated in the FDA Modernization Act of 1997: Guidance for the
Recognition and Use of Consensus Standards that

. . . conformance with applicable consensus standards can provide a reasonable assurance of safety
and/or effectiveness. Therefore, information submitted on conformance with such standards will have a
direct bearing on determination of safety and effectiveness made during the review of IDEs and PMAs.
Furthermore, if a premarket submission contains a declaration of conformity to recognized consensus
standards, this will in most cases, eliminate the need to review actual test data for those aspects of the
device addressed by the standard.

Consequently, FDA has recognized the ISO 11607 standard as the consensus standard for manufac-
turing and quality control of packaging processes, materials, product package and design, and ster-
ilization processes. Confusion about the existence of two packaging standards in which to conform
is a concern for medical device companies. However, conformance to the EN 868-1 standard has
become a moot issue as the ISO 11607 standard has been harmonized by the ISO TC 198 Working
Group 7. So now we know what needs to be accomplished in regards to packaging, right? We just
need to perform a package process validation. That’s simply a matter of following the ISO 11607
standard. Yes, but unfortunately it’s not a cookbook recipe to success.

7.7.2 What Is Process Validation (PV)?
The FDA defines validation as “establishing by objective evidence that the process, under anticipated
conditions, including worst-case conditions, consistently produces a product which meets all prede-
termined requirements (and specifications).” Likewise, the ISO 11607 standard, Packaging for
Terminally Sterilized Medical Devices, defines validation as a “documented procedure for obtaining
and interpreting the results required to establish that a process will consistently yield product com-
plying with predetermined specifications.” What these definitions are really saying in a practical
sense are that a process validation must address the requirements or application of the package, the
interaction of people and equipment used in the manufacture of the package, the consistency with
which a package can be made, the effects of processing (e.g., sterilization) on the performance of the