FDA offers draft guidance on quality metrics used to assess drug manufacturing
The agency notes that an analysis of quality metrics can help FDA “better identify which facilities are at the highest risk for quality problems” so inspection resources can be used more efficiently, according to a blog post from Tuesday.
FDA expects that the initial use of the metrics will be “to consider a decreased surveillance inspection frequency for certain establishments.” For example, manufacturing facilities with “highly controlled manufacturing processes have the potential to be inspected less often” than similar establishments “that demonstrate uncontrolled processes.”
Companies that fail to report requested quality data also may elevate their facilities’ predicted risk in FDA’s prioritization of inspections, which may lead to earlier inspections, the agency says.
More specifically, FDA intends to calculate the following quality metrics for each product and establishment, where applicable:
• Lot Acceptance Rate = 1 – x (x = the number of specification-related rejected lots in a timeframe divided by the number of lots attempted by the same establishment in the same timeframe);
• Product Quality Complaint Rate = the number of product quality complaints received for the product divided by the total number of lots of the product released in the same timeframe;
• Invalidated Out-of-Specification (OOS) Rate = the number of OOS19 test results for the finished product invalidated by the establishment divided by the total number of OOS test results divided by the total number of tests performed by the establishment in the same timeframe;
• Annual Product Review (APR) or Product Quality Review (PQR) on Time Rate = the number of APRs or PQRs completed within 30 days of annual due date at the establishment divided by the number of products produced at the establishment.
The draft also offers some questions for stakeholders on how the agency intends to evaluate the interpretation and use of the metrics.
“For example, is it more meaningful to compare metrics for different products within the same establishment, or for the same product manufactured at different establishments, or as an establishment-specific trend over time? Is it more appropriate to use certain metrics to compare all types of establishments (or a subset making the same dosage form or same drug) against each other? What is the best way to compare metrics for products that vary in manufacturing complexity (e.g., biotechnology and biological products are often considered more complex to manufacture)?”
In addition to the metrics, the draft guidance includes an explanation of how the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) intend to collect data and use quality metrics to help “ensure that their policies and practices continue to support continuous improvement and innovation in the pharmaceutical manufacturing industry.”
On August 24, the FDA will host a public meeting on the draft guidance and in order to gain stakeholders’ perspective on various aspects of the development and planned implementation of a quality metrics program.
