In recent years, a desire to minimize the risks associated with sterilizing filtration has prompted much discussion on the need for preuse/post-sterilization integrity testing (PUPSIT) to detect nonintegral filters before they are used if there is any risk of not detecting them after the filtration process. The purpose of this article is to present guidance to industry (sterile drug manufacturers, filter suppliers, and regulators) on how to develop and evaluate scientific data to prevent undetected non-integral sterilizing filters.
Potential shortcomings of some previous discussions and publications on this topic are:
Lack of published scientific data and evidence presenting relative risks and controls, thus leading to subjective evaluation of risk based on anecdotal information.
Emphasis on detection of failures rather than prevention of failures.
Use of biased risk assessments with predetermined outcomes.
Efforts to eliminate all filter failure risk, ignoring additional risks posed by the addition of new control measures.
Recommendation of a single means to control filter integrity risks for all products and conditions, without regard to process-specific differences in risk.
The underlying principle of the work described in this article is the use of objective scientific data to address these shortcomings, characterize risk, prevent sterile filter failure, and ensure product sterility and patient safety.
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.