Page 78 - Assurance of Sterility for Sensitive Combination Products and Materials

64 Assurance of sterility for sensitive combination products and materials

• Qualify support processes and systems: There are more effective ways to
validate support processes, such as wrapping or sterilization of sterilized
filler parts, holding conditions for sterile materials, or sterilizing capabil-
ity of in-line filters, than inclusion in aseptic process simulations.
• Qualify poor aseptic technique or practices: Aseptic process simulations should
not be used to attempt to qualify a poorly designed or poorly performed
aseptic process. If the aseptic process simulation passes, that should not
mean that such a process step is acceptable.
• Train personnel: Untrained personnel should not participate in aseptic
process simulations designed to “qualify” the aseptic process. Trained
personnel are a means to eliminate (or reduce) the variability of per-
sonnel. In other words, if the aseptic process simulation fails, and the
operators were not trained, then those investigating the failure would
not know if the failure was due to a process flaw or an operator error.
• Shakedown an unqualified filling operation: Using unqualified systems or
equipment in an aseptic process simulation should be avoided for two
reasons. (1) If the aseptic process simulation fails, and the line was not
qualified, then those investigating the failure would not know if the
failure was due to a process flaw or an equipment issue, and (2) if the
aseptic process simulation passes, and the line qualification is performed
later, then any changes which may occur on the line because of the
equipment qualification would not be captured in the simulation and
therefore that simulation study may not be valid [5].

4.21 Microbial contamination case study

To illustrate the importance of understanding the limitation of the aseptic
process simulation test capabilities, consider the case of the qualification
of the new aseptic filling operation. The filling process involved the use
of an autoclaved, sterilized holding vessel stored for a period in a Grade C
environment. To validate the holding of the sterilized vessel, the vessel was
held and used in a series of aseptic process simulations. The initial aseptic
process simulations passed but failed 6 months later during a periodic re-
qualification (Fig. 4.6).
The source of the contamination was found to be from the contact of
environmental microorganisms in the Grade C environment with mate-
rial used to wrap the open ends of the sterile vessel. The material became
wet, and an ineffective barrier because of condensation forming during the
storage of the vessel. While this appeared to be a logical explanation for