FDA Revises Quality Metrics Guidance for Comment

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FDA has revised its draft guidance to provide greater clarity and focus. This version would establish an initial voluntary phase to allow regulators and industry to focus, first, on a limited set of metrics.

FDA has released a revised draft guidance on quality metrics, and has asked pharmaceutical manufacturers for their opinions and comments on the draft.  The original draft guidance was released in 2015, with the aim of helping improve risk-based plant inspections and the agency’s response to threats of product shortages, but also to help manufacturers focus on the most important metrics required for product quality. Its goal is to establish better ways of detecting the signals that identify products and plants that pose higher risks of producing lower quality products, as well as situations where there might be a higher risk of shortages developing.

The pharmaceutical industry was critical of the original guidance, complaining, among other things, that it did not allow sufficient time for implementation and that its scope was too broad. This version of the draft guidance includes detailed definitions within each metrics category and defines specific reporting tiers for different types of organizations.  It also establishes an initial voluntary reporting period that will allow the agency to focus on, and learn more deeply about, a limited set of metrics and the analytics that are required.

The quality metrics are:

  • Lot acceptance rate, or the number of accepted lots within a timeframe divided by the total number of lots started, for primary and secondary distribution and packaging, during a given timeframe.  Included will be number of lots started, released and rejected.

  • Product quality complaint rate, or the number of complaints received divided by the total number of dosage units of that product distributed during that time frame.

  • Invalidated OOS rate, or the number of out-of-specification batch-release test results and long-term stability test results that were invalidated due to measurement process issues at the facility, divided by the total number of such tests performed at the facility during the time frame.  Every OOS result will trigger an investigation, and the guidance specifies best practices.

FDA says that information from product and process development should serve as a foundation for a control strategy that will allow products with the desired quality attributes to be consistently manufactured.  Under current good manufacturing practices (cGMP), the agency writes, manufacturers need to maintain and evaluate product and process data related to this control strategy.

FDA recommends that the metrics in this draft guidance be included in process validation lifecycle and pharmaceutical quality systems assessments, and in such periodic reports as the Annual Product Review.  The metrics apply to both APIs and finished drug products.

FDA has asked that comments and suggestions on this version of the draft be submitted within 60 days of its publication in the Federal Register.  Comments may be submitted electronically via www.regulations.gov, or in writing to the Division of Dockets Management, HFA, FDA, 5630 Fishers Lane, Room 1061, Rockville, MD 20852.  For questions regarding the document, the agency asks that companies contact Tara Gooen Bizjak at 301-796-3257, or the Center for Biologics Evaluation and Research’s office of communication, outreach and development, at 800-835-4709.