Applying an FDA lens to your business

Sparta Systems recently met with key leadership at FDA Center for Drug Evaluation and Research (CDER), Center for Device and Radiological Health (CDRH) and the Office of Regulatory Affairs (ORA) to discuss quality trends affecting pharmaceutical, biologics and medical device manufacturers. Based on those meetings, we’ve developed a series of reports on quality, technology and legislation. 

Medical product manufacturing companies are required to compile and use quality metrics to assess the quality, safety and efficacy of their sites and products. However, such metrics do not currently need to be routinely reported to the FDA.  

Such routine reporting was proposed in 2016 in the FDA’s Draft Guidance on Quality Metrics. Based on the effort required to implement the necessary reporting measures at that time, many in the life sciences industry challenged the proposal. To date, the reporting requirement has not been implemented—but that doesn’t mean it’s been shelved permanently. In fact, the idea of submitting quality metrics is still very top-of-mind to senior CDER leadership.

Changing Times

Certain quality metrics enable more effective risk-based decision-making. The FDA already requests and reviews such metrics during inspections. But without regular reporting, the agency is unable to create a database that normalizes the metrics and associates certain rates with “quality maturity.”

Such a framework would provide the FDA a way to inform its risk-based Site Selection Program. As a result, the agency could prioritize inspections of sites where metrics indicated higher risk and reduce the rate of inspection of low-risk sites, saving time and money for both the agency and compliant sites. Companies that document and submit good performance metrics may be audited less often (or perhaps only “virtually” in light of COVID-19), saving critical operating dollars and a significant amount of staff time.

This ability to prioritize is more important than ever. The volume of manufacturing, packaging, and distribution sites has expanded. And the emergence of COVID-19 makes in-person site inspections more onerous than ever. The FDA needs quality data to prioritize its “to do” list—as do the manufacturers that collect that data. And as many companies now electronically collect quality data, submitting reports is easier than it was four years ago.

While the metrics guidelines are still being finalized, preparation should be taken to assure that you aren’t left behind. We suggest that manufacturers prepare now, while the guidelines are being finalized.

Important Metrics

If the FDA implements annual reporting according to its original guidance, reports will be required by product application, which might cover multiple sites. The FDA will use the data to compile a Risk Profile Aggregate for all products made at a site, then prioritize audits according to those profiles.

The most-likely quality metrics for the FDA to require are:

  • Lot Acceptance Rates (LAR)
    • Calculated: The number of accepted lots divided by the number of lots started.
    • Why? To measure process performance.
    • What It Means: LAR provides insight into manufacturing efficiency and process quality. Batches or processes are started but not completed, either due to equipment failure or scheduling mix-ups and exceeded hold times, may indicate poor or inadequate manufacturing operations support infrastructure.
  • Product Quality Complaint Rates (PQCR)
    • Calculated: The number of quality complaints received for a product, divided by the total number of units or doses distributed.
    • Why? To assess patient and customer outcomes.
    • What It Means: PQCR is a general indicator of product quality with respect to label claims and patient perception. While there are many valid reasons for a manufacturer to be skeptical of some product quality complaints, a volume of related complaint may indicate an underlying issue that warrants response.
  • Invalidated Out-of-Specification Rates (IOOSR or OOS)
    • Calculated: The ratio of invalidated OOS test results for lot release compared to the total number of OOS test results (valid and invalidated).
    • Why? An indicator of lab operations.
    • What It Means: The process of invalidating any result is risky because it necessarily involves trusting one set of results over another. Even if the reasoning is scientifically defensible and valid, frequent instances of invalidated OOS results will raise questions either into the reliability or the suitability of lab operations.

You can see how these metrics could help the FDA prioritize audits. But there’s another reason to establish a reporting routine for these metrics: Regardless of FDA requirements, they can help you prioritize your own quality “to-do” list.

Prioritize Quality, Not Just Compliance

To report these metrics effectively and efficiently, you need to be able to capture, calculate, trend and electronically submit the related quality data. You also need to demonstrate how the metrics affect performance. Quality teams that are already collecting and configuring data digitally are a step ahead, but even they have some work to do.

To prepare:

  • Configure the specified measurements in your quality management system (QMS) and production processes. Remember to collect each metric by site/location.
  • Create metrics dashboards or reports that are easy to understand and drill down into.
  • Make sure reporting is adaptable based on timeframe, site and other variables that affect performance (e.g., processes, equipment, personnel). 
  • Determine how you will share quality metrics externally. For example, you could set up report to run on demand as well as on an automated schedule, or you could share dashboards with permitted users.

While it may take some upfront effort to collect these measurements and configure reporting, the insights they provide can lead to notable savings and other benefits. The potential to reduce the likelihood of inspections alone can produce significant savings in time and resources.

This time around, the FDA may not be asking for too much. It could be nudging life sciences companies toward a quality win-win. After all, manufacturers can—and should—continually improve performance. The benefits of doing so can quickly cascade across your organization.  Measuring, trending and regularly reviewing these quality metrics provide a clear path for doing so.