In December of 2020, the PDA/BioPhorum Sterile Filtration Quality Risk Management (SFQRM) consortium focused on Sterile Filter Quality Risk Management (QRM) and Pre-Use/ Post-Sterilization integrity testing  (PUPSIT) concluded its work activities started in December of 2017.

The consortium was formed to address inspector derived concerns that PUPSIT was needed to detect non-integral filters before they are used to eliminate any risk of not detecting them after the filtration process as been completed and post use integrity testing is performed.  The implementation of PUPSIT requires manipulation of the filter on the downstream side or sterile side to the filter and  runs counter to the long-standing principle that there should be minimal interventions performed on the downstream or sterile side of the filter that could potentially impact sterility

The consortium was comprised of more than 50 subject matter experts from 25 biopharmaceutical manufacturing companies and filter suppliers.  The consortium considered the different aspects of sterile filtration risk management as it related to PUPSIT. The experts were experienced in sterile filtration and authors drew upon their collective experiences, current company practices, consultations with stakeholders and colleagues, and a review of current regulatory guidelines.

The consortium worked to address potential shortcomings of previous discussions and publications on this topic including:

  • 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.

Based on the work performed, the SFQRM consortium recommended the use of risk-based assessments (as noted in the consortium publications) to determine what controls are needed to mitigate and prevent filter related risks.  These assessments should take into account available scientific evidence, such as that suggested by the consortium studies (including product fouling and masking potential), risks of and effectiveness of controls to prevent filter defects, other failure detection methods, benefits and risk of PUPSIT related complexities, filter stress, and associated manipulations. Where PUPSIT is determined to be a sound (or appropriate) method for risk mitigation and process control, then the points raised by the consortium to better design and control the PUPSIT process should be considered.