FDA is proposing that the application of the right quality metrics could help create a more flexible and rationalized review and inspection system and is asking for industry input on what metrics would provide the most effective leverage.
On the review side, use of the metrics could serve to loosen the constraints of application/supplement filings to making quality improvements. In turn, more objective and transparent metrics could allow the agency to move from an inspection to a more proactive surveillance mode that would significantly extend its oversight reach.
The use of metrics that span across the industry would enable FDA to better target which sites, and which products, processes and systems at those sites, require agency attention, and decrease the inspection burden on sites that have robust quality systems.
The agency’s outreach to industry for help with identifying appropriate metrics has included a Federal Register notice in February that sought input on how to better predict and prevent drug shortages.
The mid-February FR notice was issued with a 30-day comment period. It included a series of five questions to industry intended to help guide the agency’s selection of quantitative, objective, and meaningful metrics (see box at right).
Comments were submitted to the docket by 127 organizations and individuals, the vast majority from individual patients and physicians impacted by drug shortages. Three industry associations – PDA, PhRMA, and BIO – submitted substantive feedback on the metrics questions (links provided below).
All three cited error rates (non-conformances, deviations, and batch failures), customer complaint rates, and internal/external inspection outcomes in their list of metrics commonly used by manufacturers to monitor production quality. Also prominent in two of the three sets of comments were: monitoring the timeliness and effectiveness of corrective and preventive actions (CAPAs); and the use of a “right first time” metric.
Based on its review of all the responses submitted on the metrics issue, FDA has chosen three that it is considering using and is seeking additional feedback on: ● batch failure rate ● right first time, and ● out-of-specification (OOS)/laboratory failure investigation rates.
CDER Reports on Metrics Initiative at GPhA/FDA CMC Workshop
At a “CMC Workshop” cosponsored by the Generic Pharmaceutical Association (GPhA) and FDA in early June in Bethesda, Maryland, Center for Drug Evaluation and Research (CDER) Office of Pharmaceutical Science (OPS) Scientific Coordinator Russ Wesdyk fleshed out the agency’s “preliminary” thinking regarding the use and content of industry-wide quality metrics.
Wesdyk’s presentation at the GPhA workshop encompassed: ● the current state of quality and the increase in field alerts and recalls since the 21st Century vision was put forth a decade ago ● the need for a “common language” within and between industry and regulators on what metrics mean and which are important ● the agency’s desire to establish metrics that allow them to differentiate between low-risk and high-risk manufacturers and to include surveillance metrics along with inspection metrics ● the need for metrics to be quantitative, objective, applicable across all sectors, nonintrusive, and relevant ● the importance of common definitions and statistical confidence in data ● FDA’s future plans, and ● key takeaways (Wesdyk’s complete remarks are provided below).
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