Page 81 - Assurance of Sterility for Sensitive Combination Products and Materials

Aseptic processing 67

process. The intent of the study is to confirm that the process or process
change achieves its intended outcome and that there are no unintended
consequences or residual risks introduced by the process or process change
that pose a risk or can adversely affect product quality.
Aseptic process simulations should also be performed periodically to
determine that unintended or missed changes or variables have not been in-
corporated into the process that poses a risk to product quality. Aseptic pro-
cesses are complex, and it would not be realistic to expect that all changes
can be captured all the time. To this point, many health authorities have
expressed expectations that these periodic studies be performed on a semi-
annual basis.

4.24 What process steps should be included in the aseptic
process simulation?

As presented in Fig. 4.7, any process steps that may pose a risk or adversely
affect the sterility of the product should be included in the aseptic process
simulation, unless those steps are adequately validated by some other means
or study.
Aseptic process simulations should include such process steps as:
• aseptic additions during compounding,
• product transfer,
• material transfer,
• component transfer,
• fill line setup,
• aseptic connections—including those to sterilizing filter outlets,
• special assemblies—such as PUPSIT (pre-use, post-sterilization integrity
test) assemblies,
• inherent (routine) and representative corrective (nonroutine)
interventions,
• filling and sealing operations,
• environmental monitoring,
• fill checks conducted in the aseptic processing area,
• shift changes,
• component loading,
• intervention response sanitization,
• lyophilized product transfer and cycle mechanical operations.