If FDA is going to establish standards for assessing the quality of manufacturing sites and products, it should seek data on a few well-defined measures that reflect longer-term results and trends, rather than “snapshots of current numbers.” And such metrics should include more leading—vs. lagging—indicators to reflect a firm’s commitment to continuous improvement in production processes. Those recommendations come from a PDA “points to consider” paper, written to help FDA set standards to measure product quality and manufacturing capabilities.
The recommendations were compiled by a committee of experts representing all aspects of the biopharmaceutical industry who participated in a December 2013 PDA conference on the issue. The panel specifically proposes that FDA seek data on quality complaint rates, batch reject rates and confirmed out-of-specification (OOS) rates in assessing product quality, and on OOS and batch reject rates for sites. There should be room, moreover, for companies to provide explanations or interpretations of actual numbers and trends when submitting such information.
FDA should be very careful, though, in using metrics to rate products, sites, and companies, the report says, noting that differences in dosage forms and production volume could undermine straight comparisons. No single set of standardized metrics can serve as a surrogate for quality, the committee says, in advising FDA to take steps to understand the context of metrics and to avoid using data reports as evidence of GMP violations that could trigger regulatory action. Instead, those manufacturers that demonstrate quality performance based on metrics should benefit from “preferred handling” of post-approval changes supplements, plus less frequent plant inspections.
To help FDA implement this quality measurement program, PDA proposes to conduct a pilot project to collect metric data. This pilot project could help identify issues and challenges that FDA should address upfront and to assess the ease of collecting data and the value gained from metrics reports. PDA also will continue to develop a process capability metric, which manufacturers regard as a key indicator of long-term continuous improvement.
Manufacturers hope this initiative will be beneficial by helping to control drift, to steer inspections to high-risk situations, and to prevent problems that could lead to drug shortages. Yet industry fears unintended consequences: Using metrics to directly compare production sites and products could prompt manufacturers to focus more on achieving certain rates, as opposed to achieving high quality products and systems.