2022 - Aseptic Processing in the Manufacture of Biotech and Pharmaceutical Products

Aseptic Processing involves risk assessment on an on-going basis because of the inherent risks due to consequences of management and process failure and challenges within the detection, isolation, control, and management of product contamination. Within aseptic processing, the severity of the consequences of a failure can be severe to the end user while detection through sterility testing remains rather limited because of the small number of final products tested.
The FDA and EMA require that any product that may be terminally sterilized be managed in that fashion. However, almost all large molecules and some small molecules can only be sterilized by aseptic processes, i.e., membrane filtration.
With membrane filtration, it is essential to establish acceptable levels of microbiological contamination to ensure both product safety and compliance. Meeting sterility claims for Phase 1, 2, 3 and commercial products in a timely and effective manner is important in avoiding costly delays. In addition, since aseptic processes are associated with endotoxin control, it too, must be managed to acceptable levels.
A variety of variables can impact sterility assurance and the accompanying endotoxin level. These include the personnel, process, equipment, components, sterilization, depyrogenation as well as facilitates and utilities that impact the management and processing of the ultimate products. Issues that need to be considered include the monitoring of environmental areas and personnel, water sources, media, and media fills, gowning and sanitization.
Products that have historically been aseptically filled have relied upon the use of USP <71> Sterility Tests to demonstrate sterility. However, since no more than 20 containers are tested per media (TSB and FTM) regardless of the production lot size, the use of sterility tests does not provide a high degree of sterility assurance (SAL). Thus, media fills are now utilized to simulate the actual fills and to demonstrate at least a 10-3 sterility assurance level of no contamination. If the facility uses RABS or isolators to meet their filling requirements, a SAL of 10-5 to 10-6 is possible since the interactions with personnel and the environment decrease markedly.
Media fills are required during the commissioning of an aseptic operation within a new facility, when a new container configuration (volume or neck size) or other unique activities associated with aseptic filling occur. Following the on-going performance of a new aseptic filling line, a requalification is required at six-month intervals.
The objective of this live, interactive training seminar is to explore the role of aseptic filling to assure that manufactured product will retain the sterility assurance level prescribed by GMPs. It will review the issues regarding preparing media and setting up the “filtration train”, environmental monitoring, interruptions that may occur during the operation of the Clean Room (planned and unplanned) and the cleaning of the room and its equipment. Equipment used to monitor the equipment and personnel will also be reviewed along with gowning issues that periodically arise. The seminar will also discuss media failures and how to “work through” them. Because of the sensitivity and importance of media fills, this live, interactive training seminar is a MUST for anyone in your organization that is involved in aseptic filling in general and media fills in particular. Please plan to attend this as part of an interactive group project.