Same Drug Different Outcomes in Breakthrough Designation at FDA and EMA
(Thursday, November 10, 2022)
A joint report of the review of internal processes at the FDA for the Breakthrough Therapy Designation (BTD), and at the European Medicines Agency (EMA) for its breakthrough drug program called the Priority Medicines (PRIME), shows that the two agencies when presented with the same data for a product, interpreted in an opposite manner about a third of the times. Both FDA and EMA are often compared to each other due to the similarities in their processes and mission. Both agencies share several Guidance documents and frequently adopt each other’s processes and policies. Over the last 40 years, there have concerted efforts to harmonize the two agencies to facilitate global drug development and concurrent approval of new drugs and biologics. And these efforts have been reasonably successful with sponsor developing products via commonly accepted processes, creating market approval applications on a common format, submitting, and getting concurrent approval from both the agencies frequently. But FDA and EMA are inherently quite different as well, particularly in their resources and priorities. EMA has a total of less than 1000 employees while FDA’s drug and biologics divisions have a total of almost 7000 employees. Due to its smaller size, EMA has a much smaller mandate than the FDA, and much different approach to review data. It is well documented that FDA and EMA frequently disagree on similar products, particularly those intended to treat serious life-threatening diseases. The BTD and PRIME programs are quite similar in their goal, namely, to expedite the regulatory process for exceptional drugs and biologics. So, one would expect that there would be close to 100% concurrence between the two agencies regarding such products. But that’s not the case. Hence, for such products, companies approach the two agencies differently. The report showed that a smaller fraction of applicants applied for both BTD and PRIME. Although in about two-thirds of the cases, the agencies agreed on their decision to grant or reject the request for a given product, it is the one-third cases where they disagreed that shows discordance between the review processes of the two agencies. Since the BTD and PRIME applications rely on preliminary clinical data, it would be expected that different reviewers would come to divergent conclusions regarding the impact of the data on the potential treatment outcomes based on smaller datasets. But it would also be expected that when both reviewers were presented with the exact same data and sponsor’s analysis, they would consult each other and try to reach a consensus. Since, there is no process for the FDA and EMA to jointly review such applications, and it would be safe to assume that the sponsors presented one agency’s opinion to the other, particularly the positive ones, there are no clear indicators for why the two agencies came to divergent conclusions. This report confirms the conventional wisdom to never take either of the agencies for granted. Just because FDA agreed with a sponsor does not guarantee agreement by the EMA, and vice versa. The different decisions by EMA and FDA have a huge impact in global development of therapeutic products, particularly for serious, life-threatening diseases, since most other countries in the world look towards these two agencies for guidance and leadership. When these two don’t agree on issues, it creates greater chaos in other regions where regulators have far fewer resources and expertise in such products. For the sponsors, the best practice is to still package information about their product differently for FDA and EMA and try to use the opinions provided by one to polish their responses to the other. It’s a longer process but it works.
Dr. Mukesh Kumar
Founder & CEO, FDAMap
Linkedin: Mukesh Kumar, PhD, RAC