Red Flags in Process Validation: Expert Insights from the FDA

Strategic Insights -

The FDA has identified several key areas of concern when inspecting process validation in the biotechnology industry. According to Gregory Bobrowicz, a former FDA investigator and compliance officer, four primary red flags include partial lack of validation, inadequate failure investigation, uncontrolled variation within specs, and problems with documentation. To address these concerns, it is essential to clearly delineate the responsibilities of all parties involved in the validation process. Additionally, developing a comprehensive protocol that includes a sampling plan, specified sampling points, frequencies, quantities, and collection procedures is crucial.

Key Takeaways:

  • Partial lack of validation is a significant red flag for FDA inspectors, indicating a lack of attention to detail and a potential lack of understanding of the process.
  • Inadequate failure investigation can lead to a lack of understanding of the root cause of failures, which can compromise product quality and safety.
  • Uncontrolled variation within specs can indicate a lack of process control and a potential risk to product quality and safety.
  • Problems with documentation, such as sloppy or disorganized records, can lead to a lack of transparency and accountability.
  • Having too much flexibility in the validation process can compromise its effectiveness and lead to a lack of accountability.
  • Clear delineation of responsibilities is essential to ensure that all parties understand their roles and expectations.
  • Developing a comprehensive protocol with a sampling plan, specified sampling points, frequencies, quantities, and collection procedures is critical to ensuring the accuracy and reliability of process validation.
  • Raw materials validation is a critical area that requires attention, particularly in the biologics industry where companies often use human albumin and other complex ingredients.
  • Device firms tend to have a better understanding of purchasing controls compared to biologics firms, which highlights the need for biologics companies to improve their raw materials testing and controls.

Statistics:

  • 10% is the typical failure rate standard for non-stereility processes (note: the article does not provide the specific dataset or source for this statistic)
  • 8% is the general lower failure rate standard for sterilization processes (note: the article does not provide the specific dataset or source for this statistic)
  • FDA is increasingly taking a broader definition of sterility, which includes processes that involve filtering through 0.2 micron filters and autoclaving
  • Biologics firms tend to have a lower understanding of purchasing controls compared to device firms (no specific numerical data provided)

Sources:

Gregory Bobrowicz, director of biotechnology for Quintiles, South San Francisco, CA

Institute for International Research (IIR) conference, San Francisco, Sept. 23