Page 80 - Assurance of Sterility for Sensitive Combination Products and Materials

66 Assurance of sterility for sensitive combination products and materials

The validation study should then have focused on ensuring that those con-
trol measures were effective and reliable. Using the aseptic process simulation
could have been a part of that approach, but to identify unaddressed process
variables, rather than as the primary means of process qualification.

4.22 Aseptic process simulation study design

An important question to consider when designing the aseptic process sim-
ulation study is whether the objective of the study is to provide confidence
of aseptic filling operator performance or confirm the capability of the aseptic
manufacturing process. Decisions made during the design, such as duration of
the aseptic process simulation, inclusion of interventions, and qualification of op-
erators may change depending on what you are trying to do. Human behavior
is complex, subject to variability, and unreliable and is difficult if not impossible
to validate. The closer one’s intent is to qualifying the process, the more effective
the aseptic process simulation as a validation tool will be. The closer the intent is
to qualifying the person, the more problematic and ineffective it will be.
Whatever the design intent is, a written plan subject to quality review
should be in place. This plan should present:
1. intent and objective of the study,
2. clear instructions, written to avoid the potential for individual interpre-
tation, for preference of the study,
3. risk-based rationale for study design, configuration, conditions, and
parameters,
4. objective, quantifiable, and measurable acceptance criteria, and
5. provisions for aborting, invalidating, investigating, and addressing devia-
tions related to the study.
A risk assessment should be performed to uncover information needed
to make informed decisions on aspects of study design, such as number of
runs, number of units to be filled, including worst-case configuration, fill
duration, and intervention inclusion.

4.23 When should aseptic process simulations
be performed?

There should be written procedures and risk-based criteria or rationales for
the frequency of aseptic process simulation studies. Typically, aseptic process
simulation studies should be performed for any new or changed aseptic