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Preparing the industry to tackle risk assessment around PUPSIT

As the BioPhorum and Parenteral Drug Association (PDA) SFQRM Consortium prepared to move to a BioPhorum Community of Practice at the end of 2020, its members took a moment to reflect on the many accomplishments the coalition had achieved since its inception in 2017. The team set out to tackle industry and regulatory concerns surrounding pre-use, post-sterilization integrity testing, or PUPSIT, of sterilizing grade filters used in aseptically processed biopharmaceutical products. BioPhorum took the helm for coordinating the effort and promoting participation by its member companies and industry thought leaders, while PDA consented to provide scientific guidance, laboratory support, technical experts, filter manufacturers participation, and a venue for public communication and publication. The collaboration’s overarching goal was to provide “objective, unbiased, scientific data both industry and regulators can use to make informed decisions on the need for and use of further control measures such as PUPSIT.

Passion for process improvement,” is how Brian Thome, Principal Engineer, Global Manufacturing Sciences, BiogenM, summed up his motivation for first joining the collaboration. The team was composed of “a really wide group of people who were all passionately involved in getting to a good state where we had a path forward that made sense,” he said. “It was a truly cross-functional, unique group.” The team ranged from engineers to chemists, thereby enabling a rich cross pollination of ideas and experience.

Mandar Dixit, Principal Process Expert, Sartorius Stedim Biotech, agreed. “It was really exciting to have participation not only from different user groups—so many of our major customers—but also representation from other prime filter manufacturers,” he said. “It was a unique opportunity to work together not only with our customers, but also with our colleagues in the filtration world who were all SMEs in the same field.

While the collaboration initially began as the Pre-Use Post-Sterilization Integrity Testing (PUPSIT) consortium, it was renamed Sterile Filtration Quality Risk Management (SFQRM) in 2018, just a few months after its launch. The name change recognized a significant change in emphasis not just for the team but for the biopharmaceutical industry. “We soon recognized that we were actually trying to manage the risk of sterile filtration as a unit operation when it comes to sterile claimed products,” noted Dixit. “The name change definitely represented a highlight in collectively coming together.

Other benefits of the collaboration included “having regular conversations with our customers and especially sterile filtration SMEs at our customers and having debates to answer questions related to filters with our customers,” said Dixit.

 

PUPSIT surveys identify impact on time, cost, and effort

One of the team’s key objectives has been to better understand the use of PUPSIT.  To help to achieve this, the SFQRM consortium issued the PUPSIT survey to generate a clear and well evidenced argument with data that reflects the reality of implementing PUPSIT and the impact it has on time, cost, and effort.

The PUPSIT survey was completed by the consortium members three times in 2017, 2019, and again in 2021. The survey captured feedback from integrated and interdependent workstreams to provide industry and regulators alike with information that could be used to make informed decisions on how best to control and prevent sterilizing grade filter failures or improve detection of failures.

Questions highlighted media fill, sterility and other failures linked to PUPSIT.  With the most recent 2021 survey, the goal was to refresh the 2017 and 2019 PUPSIT surveys and to focus on the use of the SFQRM consortium deliverables, implementation of risk assessments, and regulatory interactions on the topic of PUPSIT.   

The initial conclusions from the data comparison will be presented at the 2021 PDA Pharmaceutical Manufacturing and Quality Symposium on September 14-16 by BioPhorum SFQRM community of practice member Marjo Peters, Director Drug Product Technical Steward Europe, AstraZeneca, with the goal to publish the full publication shortly thereafter.

 

Sustaining momentum through a Community of Practice

In the years since its formation, the collaboration has reviewed available industry data, performed risk assessments from the filter production to installation, and performed fouling studies on flawed filters to expand the available scientific data, all while keeping regulatory authorities informed and collaborating closely with them. Four work streams were developed, leading to the following essential conclusions:

  • Filter masking will only happen at extreme conditions and blocking rates (>80%)
  • The quality control measurements within filter production are excellent and filter flaws are rare
  • The implementation of PUPSIT is a major undertaking requiring careful assessment
  • A robust risk assessment of the terminal sterilizing filtration step is much more valuable than the generic implementation of PUPSIT

In December 2020, the collaboration transitioned to a BioPhorum Community of Practice where key topics include case study sharing of both completed risk assessments that have led to effective risk mitigations, and interactions with inspectors; as well as a publication comparing the PUPSIT benchmark survey results.

The Community of Practice is a way to “…keep this really good group of people that we have together,” said Thome. He added, “We are really going the last mile to turn this into something that will pay dividends for years. And as we go through this process of implementation, it will provide a support group, partly to see how regulatory interactions go with others.

“Now that we have generated scientific evidence which shows that potentially a filter with a minor defect or flaw could be masked, it will be interesting to see how the filter users take this information, and how their discussions with regulators go as they look at risk assessment around PUPSIT,” added Dixit. “I’m especially looking forward to getting feedback from our customers, and understanding if and how the regulatory landscape, especially in the European Union, will change, as a result of this data generation.”

Reference

Morris T, Jornitz M, Gori G, Baseman H. PUPSIT and the Annex 1 revision. Accessed March 27, 2021. https://www.pda.org/pda-letter-portal/home/full-article/pupsit-and-the-annex-1-revision

Celebrating collaborative efforts

Prior to launching its Community of Practice, the SFQRM Consortium held an informal team awards ceremony to acknowledge the outstanding efforts of its members. Thome was among those recognized for his contributions, earning awards for Leading the Way, Exceptional Innovative Thinking, and Collaborative Behavior. “I’m quite humbled by this,” he said. “But it wasn’t just because of me. It’s the work of a whole group of people who reached this result.”

Dixit was also among those recognized for Exceptional Innovative Thinking and Collaborative Behavior. “I was deeply honored and touched with that recognition,” he said. “To have been recognized by peers, by SMEs in the same field, was quite humbling and an honor for me.”

 

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