Eudralex volume 4, Annex 1, the EU GMP for sterile products, requires that ″The integrity of the sterilised filter should be verified before use · · ·″ (1). Implicit in this requirement for a pre-use, post-sterilization integrity test (PUPSIT) is the rationale that the sterilizing filter could sustain damage during sterilization or use (i.e. subsequent to any pre-use test conducted prior to sterilization), causing a defect which would not be detected by the post-use integrity test. That is, that such a defect could be ″masked″ during filtration.
To assess whether a filter defect could be masked by partial filter plugging the Consortium evaluated the impact of bacterial retention testing on the bubble point (BP) of the test filters.
The paper concludes that filtration processes producing bubble point changes sufficient to present a risk of masking defects are not common, and detectable during the routine BCT. Thus the BP ratios observed during routine bacterial retention testing is one means to assess the potential of a given filtration process for masking of defects and can be considered when determining whether a PUPSIT should be implemented.
This article presents an update on the efforts of the joint PDA and BioPhorum collaboration workstreams—masking studies, historical data mining, filter manufacturing and use risk assessments and PUPSIT risk assessment and the development of a best practice guide.
This paper is one in a series of publications that are the result of the collaboration, and these should be considered together and viewed holistically in order to determine the best course of action with regard to PUPSIT. This paper examines the test process and looks at the results of potential masking of sterilizing grade filters.
This article draws conclusions from the scientific studies, workstreams, and publications delivered by the Sterile Filtration Quality Risk Management (SFQRM) consortium formed between BioPhorum and PDA. It uses those conclusions to provide guidance to industry (sterile drug manufacturers, filter suppliers, and regulators) on the use of quality risk management principles and scientific data to prevent undetected non-integral sterilizing filters.
- 10th November 2020
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.