Page 76 - Assurance of Sterility for Sensitive Combination Products and Materials

62 Assurance of sterility for sensitive combination products and materials

4.20 Aseptic process simulation design
Aseptic process simulations are part of the overall aseptic process validation.
Aseptic process simulations provide confidence that the aseptic process was
designed and performed properly. Aseptic process simulations are but one
tool used to validate the aseptic process. Other qualification and validation
studies might include:
⚬ microbial retentive capability of the sterilizing filter,
⚬ clean room classification, certification, and qualification,
⚬ clean room disinfectant efficacy studies,
⚬ airflow profile and visualization studies,
⚬ filling and sealing equipment qualification,
⚬ sterilization of product contact parts, utensils, containers, and closures,
⚬ depyrogenaton of containers and closures
⚬ visual inspection of filled units
⚬ container closure integrity studies
Aseptic process simulations, sometimes referred to as media fills, are
a
studies conducted on the aseptic filling process. The aseptic process is sim-
ulated or run as close to the actual production procedure as possible except
the product is replaced with growth media. The growth media is selected
to act as closely to the product properties as practical and still support and
indicate relatively low levels of microbial contamination. If there are flaws
or weakness in the process resulting in product contamination, then the
contamination will likely be discovered in a growth supporting media.
As noted earlier in the chapter, one of the reasons aseptic processes are
difficult to validate is trying to prove something has not happened. Filling
media in place of product is an attempt to challenge the process and find
process weakness. Passing the aseptic process simulation is essentially a fail-
ure to find weakness in the process, which proves, in part, the validity of
the aseptic process. Conducting multiple aseptic process simulations will
increase the likelihood of uncovering process flaws, weakness, or variables.
Part of the overall process validation approach is challenging the capabil-
ity of the aseptic process to produce sterile products. Aseptic process simula-
tions are a useful tool to confirm the aseptic process design. The simulations

a Aseptic Process simulations and media fills are not the same. All media fills, for the most
part, are aseptic process simulations. But not all aseptic process simulations are media fills.
Media fills involve the filling of media into product containers. Aseptic process simulations
often involve such fills, but can also involve bulk compounding simulations, where no fill
is performed.