APR Sept/Oct 2023 - 34

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BIOPHARMACEUTICAL
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Aseptic Process Simulation
Cell and Gene Therapy Manufacture
Robert Dream
Managing Director
HDR Company
Aseptic process simulation (APS, AKA Media Fill) is a critical
microbiological test carried out to assess the performance of an
aseptic manufacturing procedure by replacing the pharmaceutical
product with a sterile culture media. Aseptic manufacturing is
a complex process used in the pharmaceutical industry. Good
manufacturing practices (GMP) requires pharmaceutical companies
to regularly perform Aseptic process simulation tests to verify the
microbiological state of their aseptic production process. The nutrient
medium is selected based on the product quantity and the selectivity,
clarity, concentration, and suitability of the medium for sterilization.
The process simulation test should imitate, as closely as possible,
the routine aseptic manufacturing process and include all critical
subsequent manufacturing steps.
* Aseptic process simulation test procedure/protocol
* Culture media for aseptic process simulation tests
*
Incubation conditions for aseptic process simulation tests
* Frequency of aseptic process simulation tests
* Define aseptic boundary for cell and or tissue processing
* Open versus closed processing system steps
* Cryopreserved product versus fresh product
* Process scale-up and scale-out
* Aseptic process simulation study design considerations
* A cell therapy aseptic process simulation protocol for validation
of aseptic processing
Aseptic Process Simulation
Aseptic process simulation challenges the overall process with worst
case microbial contamination risks/conditions to evaluate aseptic
process robustness and to comply with cGMP requirements.
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| September/October 2023
It is a tool to evaluate the capability of aseptic processing activities,
using microbiological growth promoting media in place of product.
APS simulates the aseptic process from the product and component
sterilization to final sealing of the container. The media is made
to contact all product contact surfaces of the equipment chain,
container closure, critical environment and process manipulations
which the product itself will undergo. Media is then incubated and
inspected for microbial growth. This information is used to assess
the potential for product units to become contaminated during the
aseptic processing operations
Purpose of Aseptic Process Simulation
To assess the capability of the aseptic process to produce sterile
products repeatedly. Assess the contamination risk factors of the
process and hence the state of control:
* Assess vulnerability to microbial contamination.
* Demonstrate that the aseptic operating practices and
procedures are appropriate.
* Evaluate the aseptic processing personnel practices
* Qualify/requalify/disqualify personnel
* Compliance with Good Manufacturing Practices and regulatory
expectations
Environmental Control
and Monitoring
The extent of environmental control depends on the manufacturing
process and the working conditions: Less stringent when adopting
automated closed manufacturing systems or environment (e.g.,
APR Sept/Oct 2023

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