Pre-use post-sterilization integrity testing (PUPSIT) continues to generate considerable debate in the industry. Committing to a PUPSIT strategy is no mean feat because, while it is recommended by regulatory bodies, it may compromise downstream sterility and it is expensive to mitigate these risks. To help clarify industry thinking, the Sterile Filtration Quality Risk Management (SFQRM) Consortium is sharing its knowledge and expertise on...
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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.
SFQRM: The use of scientific data to assess and control risks associated with sterilizing filtration
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.
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.
How to learn about PUPSIT in terminal sterilizing filtration – the science, implications and implementation
How to learn about PUPSIT in terminal sterilizing filtration – the science, implications and implementation Pre-use post-sterilization integrity testing (PUPSIT) continues to generate considerable debate in the industry. Committing to a PUPSIT strategy is no mean feat because, while some regulatory bodies are asserting its need, it may compromise downstream sterility and it is expensive to mitigate these risks. To help clarify industry...
Do you need to commit to a pre-use post-sterilization integrity test (PUPSIT) strategy? Is it a control needed for your product? If so, what is the best way to implement it?
These are questions that have been challenging operations and their filtration experts since the inclusion of PUSPIT in Annex 1. Finding the correct answers has become increasingly significant with the ongoing debate about the wording and interpretation in the current Annex 1 redraft.
At October’s PDA/BioPhorum meeting in Berlin, it was agreed that the Pre-Use Post-Sterilization Integrity Testing (PUPSIT) consortium would be renamed Sterile Filtration Quality Risk Management (SFQRM).
May 2017 | Technology Roadmapping
This chapter of the First edition Biomanufacturing technology roadmap published in 2017, describes the vision, scope and benefits that could be gained in the biopharmaceutical manufacturing industry from the development and adoption of effective in-line monitoring and real-time release capabilities. To help the industry achieve this future state it describes the scenarios considered, the future needs, challenges and potential solutions as well as the linkages and dependencies on other parts of the roadmap. It considers the contribution that disruptive and emerging technologies can play and regulatory considerations before finalizing with conclusions and recommendations.