Annex 1 of the EudraLex includes recommendations for filter integrity testing (FIT) of filters used for sterile filtration of sterile drug products. Manufacturers of low bioburden drug substances (DS) are seeking guidance on
the appropriate strategy for integrity testing of filters used in bioprocessing. The BioPhorum Closed Systems in CNC Spaces workstream developed a risk-based (and value-driven) approach for FIT testing of sterilizing grade filters used in the manufacture of low bioburden drug substances. This study yielded key criteria which served as the basis of a decision tree model for when and where FIT should be implemented to mitigate the risk of contamination. The findings of the study and the decision tree model were compared to current industry practice. Strong alignment was evident, suggesting the model could be used by DS manufacturers to develop a robust strategy for FIT which is congruent with regulatory guidance – specifically EudraLex Annexes 1 and 2. The risk-based approach is recommended to avoid dilution of effort on unnecessary FIT controls and target critical FIT use-cases that increase process reliability and patient safety outcomes.
microbial control
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Microbial Control: Detection of Cutibacterium acnes, a high-risk aerotolerant anaerobe recovered in the biopharmaceutical industry
Aug 2021 | Deliverable, Drug Substance, Microbial Control, POI - Drug Substance, Publication
This peer-reviewed paper outlines the risk of aerotolerant anaerobic bacterial contamination during the manufacture of biologic drug substance and the challenges of detection. It examines the issues that manufacturers may consider regarding anaerobic bioburden testing during mammalian cell culture biologics processing, focusing on the detection of aerotolerant anaerobes. It also contains case studies from multiple biopharmaceutical companies, which detected Cutibacterium acnes (C. acnes), the primary anaerobe of concern.
A survey of the BioPhorum Microbial Control Workstream found that more than half of the participants reported contamination events with C. acnes. This survey reported variability in the ability of the compendial microbial enumeration tests to detect C. acnes, thus presenting a challenge for bulk biologics manufacturers. This paper recommends testing conditions designed to increase the likelihood of detecting aerotolerant anaerobe contaminations.
