FDAnews Inspections Summit
I recently had the opportunity to moderate a panel discussion on pharmaceutical quality metrics at the 10th Annual FDAnews Inspections Summit in Bethesda, Maryland. The panel included leading experts involved with the FDA and industry initiatives currently underway with pharmaceutical quality metrics.
The panel members included:
- Karthik Iyer, Acting Branch Chief, Quality Intelligence Branch, OC, OPQ, CDER, FDA;
- Nuala Calnan, PhD, Regulatory Science Research Fellow, Pharmaceutical Regulatory Science Team, School of Chemical & Pharmaceutical Sciences, Dublin Institute of Technology;
- Denyse Baker, Senior Advisor, Scientific and Regulatory Affairs, PDA, former Quality Assurance Specialist, Office of New Drug Quality, Assessment, CDER, FDA;
- Dina Maines, Managing Consultant, Compliance Architects LLC;
- Louis W. Yu, Ph.D., Executive Vice President, Global Quality & Compliance, Perrigo Company plc; and
- Dan O’Leary, President, Ombu Enterprises.
The objectives of the panel discussion were to provide the audience with a summary of the status of the current industry and FDA initiatives; what those initiatives mean to 
regulated industry; and what regulated industry should be doing to address these new requirements. Please click here for a copy of the presentation framing the panel discussion.
One of the more remarkable aspects of the program was the acknowledgement that, despite extraordinary amounts of time and effort dedicated to educating industry on the industry programs and FDA’s program, the level of angst and concern with respect to program specifics is still very significant. Of particular concern is how FDA will use collected data. Karthik Iyer, of FDA’s Office of Surveillance, did an exemplary job of trying to help both the panel members and regulated industry understand the Agency’s intent with respect to pharmaceutical metrics. Karthik was very clear, and very open, that the initiative is an evolving program, and the Agency is seeking to learn from the data, and how best to use it, and not to necessarily use this information as another enforcement tool, which could place companies at risk.
FDA’s Initiative vs. Industry Initiatives
Also remarkable is the difference between the various industry initiatives and what FDA is attempting to accomplish. It is clear that the industry metrics initiatives are focused around business management and quality operations best practices, which is laudable; however, FDA has a singular mission: ensuring drug product supply security, and product quality and safety. Although these differing objectives are not incompatible, they are also not necessarily congruent. This is somewhat akin to how industry often uses different frameworks – like process excellence / six sigma for example – as a framework for CAPA. Given that, my first area of concern and recommendation to regulated industry is as follows: ensure you understand what the Agency wants, and is looking for, and not what any particular industry group thinks is important. If you have the time and resources to accomplish both – and you see value in the industry proposals – then great. But be clear, the FDA’s data requirements are significant in their own right, and need plenty of attention to address properly.
In addition to the foregoing, there are other learnings and recommended actions that flow from this panel discussion that are particularly important for companies that are currently working on readiness initiatives for the metrics reporting requirements:
- Definitions, definitions, definitions: The definitions of metrics matter. A lot. They matter almost as much as the number itself. If you as a company cannot explain in a very cogent manner exactly what the number is defined as, and what the constituent inputs to that number are defined as, and how you established the number, then the number itself is essentially meaningless. The point here is that this number will be another thing for FDA to question. You need to have the answers to potential questions BEFORE you submit any number.
- Derivations: It is essential for companies to establish how they have derived the figures that will be reported to the FDA. This is closely related to number 1 above, but, it is not the same. Establishing the derivation for how you determined the number submitted is a complicated process akin to figuring out whether you are one nationality or another. There’s a story that needs to be told relative to the genealogy of a number, and you better be able to tell that story. Further, FDA will be checking that story, and assessing the derivation, when they come to visit.
Processes and Procedures: Who is responsible? What is the reporting timeframe? What is the review process? Where do the data come from? What happens if source data sets change? How is the number calculated? Who will approve? Who will submit?These are all questions that need to be answered, and need to be established in policies, standards, and/or procedures. If you are submitting data to the FDA – at their request – in advance of, or potentially in lieu of, current inspection activities, then you need to be very clear regarding the processes and responsibilities that culminate with that submission. With metrics, process definition and procedural documentation are not just nice to haves – they are the backbone of reliability. All of regulated industry should understand the importance of data integrity – an area that is currently one of the Agency’s biggest enforcement focuses. The production of metrics data needs an analogous focus and framework to that of data integrity. If the submitted numbers are not reliable, and are subject to question, you may open your entire operation up to Inspection review and enforcement risk.- Systems: Companies will struggle to address these requirements without computer-based systems. To my knowledge, most quality management systems do not have the intrinsic capability for producing quality metrics. Now they may offer reporting, and I’m sure there will be some more advanced features coming soon, but metrics reporting is not currently an out-of-the-box solution because the data sources are just too disparate for existing QMS data alone to be effective. And while the idea of pushbutton reporting is doable (we’ve done it), you need to have a clear picture of your enterprise data model, sources, and integration capabilities. There are not many people out there who understand the quality requirements, diversity of data models, definitional disconnects, and possibilities for enterprise integration that are needed to address the FDA’s requirements efficiently and effectively.
- Infrastructure: Finally, all companies are going to need a new infrastructure within which to aggregate, review, and report metrics regularly. This infrastructure is NOT just the systems piece mentioned above. The infrastructure needs to be multilayered, and well thought out, and includes people (to manage, review, report, and approve) process (for consistency and documentation) and technology (for efficiency, flexibility and effectiveness).
Companies need to be moving on this initiative today – the reporting timelines will come sooner than most people think – as early as next year for some companies. Further, failure to report will not serve you well with the FDA. If at this point in 2015 you can’t produce reliable, easily explainable, well-structured metrics, then I think it’s a valid question to ask how you are reliably producing your product.
With the FDA’s pharmaceutical quality metrics proposal there are opportunities for the bold and risks for the timid. Stasis, however, is not an option.
For questions on or help with getting ready for FDA’s pharmaceutical quality metrics program, please contact Jack Garvey at john.garvey@compliancearchitects.com or call Jack at 888-734-9778, ext. 1.
