FDA Regulator Panel Discussions: Part III

FDA regulator panels at industry association meetings in Fall 2021 brought to the forefront issues that agency compliance personnel are seeing during inspections and interactions with industry.

Warning Letters FY2020 and FY2021

This final part of a three-part article series provides a synopsis of comments made at the 2021 ISPE Annual Meeting held in late October by FDA Commander (CDR) Tara Gooen Bizjak in response to a question asking what she sees as significant new or emerging global compliance issues. Gooen Bizjak is Center for Drug Evaluation and Research (CDER) Office of Manufacturing Quality (OMQ) Office of Compliance (OC) Manufacturing Guidance and Policy Staff Director.

The other articles in this series consist of the following:

  • Part I examines discussions at the 2021 PDA/FDA Joint Regulatory Conference around data integrity with special attention to analytical instrument audit trails and the use of consultants
  • Part II focuses on discussions at the PDA/FDA conference around quality culture and concerns voiced by FDA officials regarding responses to record requests and the scope of remediation efforts for issues identified during inspections

Sustainable Compliance and Contract Operations

When asked about what she sees as significant new or emerging global compliance issues, Gooen Bizjak pointed to sustainable compliance, cross-contamination in manufacturing, issues with contracted operations, and continued data integrity concerns.

“One thing that has been emerging the last few years in the light of quality metrics and quality management maturity is the concept of sustainable compliance,” she said.

From the agency perspective, “sustainable compliance” involves “continuing to encourage companies to think about not only meeting the minimal expectations within the CGMP requirements but really thinking about how to achieve a level of sustainable compliance. Rather than periodically dipping below the acceptable level of compliance then coming back into compliance, companies should have mature systems and continually operate above that bar.”

Another “continuing and emerging trend that extends globally” is the continued trend of contracting operations—specifically, owner responsibilities and senior management responsibilities and not establishing clear quality agreements on who is responsible for which activities.

From the agency perspective, ‘sustainable compliance’ involves ‘continuing to encourage companies to think about not only meeting the minimal expectations…’

[Editor’s Note: Looking for information drafting quality agreements? Check out the articles, “Quality Agreements: Why They are Critical” and “Quality Agreements: How to Write Good Ones.”

“This includes the importance of having very clear and robust senior management responsibility for setting a strong quality culture, which is something that we have been talking about the last few years— establishing a quality policy per ICH Q10: Pharmaceutical Quality System,” Gooen Bizjak pointed out.

“We have seen a big, important evolution in this area in the last two years that is continuing to emerge and we will continue to see it as the global supply chains continue to evolve and change based on some of the pandemic lessons learned. This compliance issue is reflected in warning letters that discuss unclear responsibilities and a lack of senior management responsibility for operations.”

Cross-Contamination and Data Integrity

Other trends the agency has seen include not updating equipment and prevention of cross-contamination between products. “We have seen this as a continuing issue over the years. We have seen a re-emerging trend of cross-contamination in ductwork.”

“When I started as a U.S. FDA investigator almost 20 years ago,” the CDER official recounted, “one of the things that we were told was, ‘It is not just unit operations but what is happening between the unit operations as well.’ We have seen a trend with ductwork that supports the unit operation but is in areas that maybe are not considered when thinking about cleaning.”

[Editor’s Note: For more on cross-contamination, read Jerry’s earlier article, “Cleaning and Cross-contamination Issues with an Encapsulator.”]

The agency, she said, continues to see data integrity issues. “This is something that we have seen historically certainly, and we have a policy in place. But we continue to see it. In fact, a large percentage of our cases, I think around a third of our cases, include some aspect of data integrity. When I say cases, I mean Warning Letters that have published in the last few years. We are continuing to see different flavors of data integrity issues. It is a continuing trend that is important to mention.” 

During the pandemic with periods of high absenteeism, there has been “a potential for a lack of documentation or following existing procedures,” she commented. “I think we will potentially continue to see that after the pandemic as well—different flavors of data integrity issues.”

Warning Letters FY2020 and FY2021

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