We’ve long known that quality metrics, when accurate and well defined, can help pharma/biotech companies monitor quality processes and systems while also helping to drive continuous improvement. The FDA has realized that if pharma/biotech companies were to provide them with some of these same metrics, it would help the Agency to 1) predict drug shortages, 2) manage resources within the Agency, and 3) encourage the development and implementation of innovative and consistent quality management systems across the industry.

This particular initiative started in 2012 with the passage of the Food and Drug Administration Safety and Innovation Act (FDASIA). This Act authorized the FDA to collect quality data from the manufacturing organizations of pharmaceutical companies and to obtain specific records from a pharmaceutical manufacturer in advance of an inspection, or in lieu of an inspection. This, in effect, transformed the 2-year inspection frequency to a risk-based schedule.

The FDA’s initial Draft Guidance for Industry: Request for Quality Metrics was published in July 2015 and requested industry input. And the industry had a lot of input. Trade groups as well as pharma/biotech companies contributed to the response to the Agency. From the mountain of input obtained from the industry and trade groups, there came a second draft guidance: Submission of Quality Metrics Data: Guidance for Industry November 2016 (the “2016 Draft Guidance”). This guidance, like the first, has evoked a lot of thought-provoking discussion in the industry around the metrics, the manpower/cost needed to collect and manage the data, the consistency of companies in collecting the correct data, the confidentiality of data, the legal use of data, and the list goes on. The remaining metrics in the 2016 Draft Guidance are the following:

1. Low Acceptance Rate (LAR). This is an indication to companies and the Agency of how well the manufacturing process is performing. Please keep in mind that this is a rate, not an actual number of accepted lots. Therefore, the number of accepted lots divided by the number of lots started will give you this rate (for the same time period).
2. Product Quality Complaint Rate (PQCR). Companies are already tracking customer complaints as part of their Quality Management Systems. Again, this is a rate of complaints divided by the number of dosage units (for the same time period).
3. Invalidated Out of Spec Rate (IOOSR). This metric would give an indication to a company and Agency of how well the labs perform. This would cover not just the lots released, but also the stability testing performed in the labs and would be reflected by the number of OOS results obtained for both activities that were invalidated divided by the number of total OOS results (for the same time period).

While the FDA continues to work with the industry through presentations at conferences and open panel discussion, it is clear there is some work to be done in order to achieve the FDA’s intended objective as outlined in the first paragraph of this article. Having just attended an industry conference in the last two days for which the FDA sent a team to discuss these metrics and the 2016 Draft Guidance, I can say that the Agency is listening and the industry continues to provide a lot of input. Many of the quality leaders at the conference were concerned about the clarity and consistency of the metrics being provided to the Agency. Were all companies interpreting the guidance and selecting and submitting the same data points and metrics? What about CMOs that have many clients? Would the burden be borne by CMOs already strapped with low margins? These were just a few of the questions being asked by quality leaders who are struggling to gain complete clarity and consistency of the 2016 Draft Guidance.

While it may seem that many good questions came from those in the room, there was a question that was levied by the FDA panel that made me think that this is a collaborative effort. The FDA panel asked the audience how they thought the FDA could best convert this from a “voluntary phase” to a mandatory program. Although a good discussion ensued, there didn’t seem to be any alignment around how best to accomplish this task. Clearly there is more discussion to be had.

So, where are we today?  With continued dialogue and collaboration from both the Agency and industry, I’m confident that we will be able to align and eventually move us gracefully into the 21st Century.

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David Lonza
Lachman Consultant Services, Inc.

David Lonza is Deputy Advisor to the President/CEO – Strategic Initiatives at Lachman Consultant Services, Inc. in Westbury, NY. He can be reached by phone, 516-222-6222; or email him at d.lonza@lachmanconsultants.com.