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.
SFQRM
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SFQRM: Strategy roadmap for the implementation of a risk-based approach to pre-use post-sterilization integrity testing (Pupsit)
Nov 2020 | Annex 1, Deliverable, Fill Finish, POI - Fill Finish, Publication, Sterile Filtration QRM & PUPSIT, Sterile Filtration Quality Risk Management
Subject matter experts from the SFQRM Consortium has prepared this strategy roadmap with suggested actions and considerations to support the implementation of an effective risk-based approach:
SFQRM: The use of scientific data to assess and control risks associated with sterilizing filtration: a PDA and BioPhorum collaboration
Nov 2020 | Annex 1, Deliverable, Fill Finish, Publication, Sterile Filtration QRM & PUPSIT, Sterile Filtration Quality Risk Management
It is generally recognized that post-use filter integrity testing is sufficient to detect filter failure and ensure patient safety unless there is a possibility that a filter passing the post-use test could have allowed bacterial penetration during filtration. This possibility is the phenomenon referred to as filter “flaw masking”, hypothesized to occur when, for example, a filter is damaged during sterilization such that it allows bacterial penetration, but that the damage becomes plugged during the filtration process to such an extent that it allows the filter to exhibit a passing post-use integrity test result. Two workstreams within the SFQRM consortium were designed specifically to evaluate the risk of this filter flaw masking and to understand in what conditions it might occur: Masking Studies, and Bacterial Challenge Test (BCT) Data Mining.
