Page 127 - Assurance of Sterility for Sensitive Combination Products and Materials

Package/container closures 111

the benefits outweigh the risks.” The document should be useful to provide
guidance and clarity on how partial revalidations can be tailored avoiding
unnecessary testing while maintaining a high degree of protection of the
patient.
Managing changes and revalidations is an essential part of each prod-
ucts life cycle. As the regulatory scrutiny increases, the impact of design
upgrades or unexpected changes can be minimized by careful design of
the initial validation paying close attention to some of the issues previously
discussed.

5.3.8 Examples of validation approaches

Validation is the process to generate data to provide objective (typically
scientific data) evidence that the requirements for a specific intended use
or application have been fulfilled. The intended use requirements for the
validation of sterile packaging can be summarized with the following key
questions:
– Can the worst-case SBS withstand the hazards of distribution, handling,
and storage without losing integrity?
– Does the SBS maintain integrity over the entire shelf life?
– Is aseptic presentation possible as planned under all intended
circumstances?
– Is the peeling and opening behavior within specifications over the entire
shelf life?
– Is the packaging process in statistical control, repeatable and does the
packaging meet specifications even under worst-case conditions taking
into account all sources of variability?
– And in case of a change, is the new material functionally equivalent to
the previously validated material?
Developing the questions to be answered is the key input for developing
a good validation protocol. The protocol should clearly identify the objec-
tives of the validation including all information necessary for its execution,
data analysis, and final reporting. See Fig. 5.7 for an example of a sterile
packaging validation protocol outline.
Fig. 5.8 shows an example of a validation work flow based on the one
presented by N. Kaller, Packaging Engineer at DuPont in a webinar in
2014 [89]. Please note that this example is based on the definitions of IQ,
OQ, and PQ of ISO 11607-2 [2]. The approach will be slightly different
if the US FDA guidance for process validation [86] is used or the Global
Harmonization Task Force (GHTF) validation guidance [85].