Cell and gene therapy aseptic process simulation reflections

Aseptic process simulation (APS) plays a critical role in demonstrating that the processes, equipment, and materials involved in sterile manufacturing (e.g., facility/air handling units, gowning procedures, and personnel) work in synergy to maintain sterility. However, guidelines on APS design for advanced therapy medicinal products (ATMPs) are not well established; in particular, ATMPs do not necessarily start from a sterile starting material. For this reason, a new concept of extrinsic vs. intrinsic contamination needs to be introduced.

Applying existing APS guidelines to ATMPs can also be challenging as ATMP processes often differ significantly from those for traditional drugs, such as therapeutic antibodies and small molecules.

This paper explores the regulatory landscape, reviews and identifies gaps in existing guidelines on APS for ATMPs, and outlines technical limitations and challenges. It also proposes recommendations to guide industry in establishing viable and comprehensive APS programs with patient safety and regulatory compliance of paramount importance.

An important element of the paper is that it contains a different approach toward how operators are qualified, with the concept of operator-specific APS and different qualification types for the different grades (Grade A, B, etc.). This is exactly the discussion you need to have when setting up a new facility and implementing the updated Annex 1 following a risk-based approach.

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• Create Date 31st May 2023
• DOI https://doi.org/10.46220/2023CGT007
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