Sterile filtration QRM & Pupsit​


What is PUPSIT ?

Do you need to implement 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 PUPSIT 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.

Pupsit integrity testing

More specifically, you will need to be able to answer the following questions:

  • How could a sterile filter and its system fail through its lifecycle from manufacture to post-use testing?
  • What are the levels of these risks and how are they controlled by your suppliers?
  • How should you control potential failure modes in-use?
  • Is it possible for your biological solution to blind/mask a fault in a damaged/faulty sterilizing filter and cause the filter integrity test to pass in error?
  • What tests or data could you use to understand if your process solutions could cause mask/blind filters in normal operating conditions?
  • What risks must be considered if you add a PUPSIT control strategy, and how can these be mitigated in the design of equipment and operational protocols?

The lack of availability of science-based, documented answers to these questions has become an uncomfortable problem for industry. To gain clarity, BioPhorum and the Parenteral Drug Association (PDA) formed the Sterile Filtration Quality Risk Management (SFQRM) consortium in 2017.  The consortium aims to fill existing gaps in scientific data with studies and industry guidance that provide professionals and license holders with the ability to make informed decisions about appropriate risk management strategies.

In total 25 manufacturers and filter suppliers have contributed to the work of the Consortium, deploying their filtration experts, pooling their collective knowledge and applied science experience to address these questions.  This effort has also been supported by  independent experts  that have contributed to and driven the PDA Filtration Interest Group.

We hope that collectively the publications aid decision making, create greater certainty and confidence and above all alignment between suppliers, manufacturers and regulators alike on these important questions