In summary, what is expected is documented evidence of process, equipment and environmental in-depth understanding about microbial controls and the rationale for the current design and use. First example, an open system aseptic operation such as inoculum preparation is required by the EU GMPs[i] is to be performed in Grade A environment, where as a closed aseptic operation with no environmental exposure such as fermentation can be performed in CNC environment. Second example, also required by the EU GMPs[ii], pre-viral reduction protein A affinity chromatography must be performed in a separate room from post-viral reduction ultrafiltration/diafiltration, if they are open systems. If closed systems, pre-viral reduction protein A affinity chromatography can be performed in the same room as the post-viral reduction ultrafiltration/diafiltration.
A well-documented closure analysis that proves your system is closed and/or being performed in a room of the appropriate classification, will bolster your in-process and hold time data, and provide additional evidence that your process is not at risk for microbial or endotoxin contamination. In addition to supporting audit inquiries, closure analysis is a powerful tool for evaluating process or facility changes Do not be surprised during your next audit, have a well-documented closure analysis ready!