M-19: Disparities Between FDA and EMA Regulatory Review Processes
Doctor of Pharmacy Candidate, 2020
USC School of Pharmacy United States
Increasing effort has been dedicated to harmonizing regulatory requirements for drug approvals between the United States and Europe, but differences continue to remain. This study explores the differences between the regulatory review processes and the resulting labeling approved by the FDA and EMA.
ORAL PRESENTATION: 2:45PM
Utilizing the regulatory agency websites, FDA Summary Reviews and prescribing information (PI) as well as European Summary of Product Characteristics (SmPC) and Public Assessment Reports (EPAR) for all new drugs (NMEs) approved between 2014-2016 were extracted and analyzed.
From 2014-2016, 40 new drugs were found to have shared approvals by both the FDA and EMA. The average approval times for FDA and EMA were 283 days and 438 days, respectively in 2015 and 334 days and 403 days, respectively in 2016. Over the 2-year period, FDA’s average approval time was 309 days, which was 111 days shorter than EMA’s average approval time of 420 days. The two agencies differ greatly in the number of available regulatory designations and expedited pathways, but orphan drug designation is one that is provided by both agencies. In 2015, 47% of the approved drugs were designated as orphan drugs by the FDA as compared to 33% by the EMA. This disparity between the two agencies was even greater in 2016 with 41% designated as orphan drugs by the FDA and 18% by the EMA. The FDA provides a variety of different expedited pathways, including Fast Track and Breakthrough Therapy designations, Priority Review, and Accelerated Approval. In addition to these formal processes, FDA may also consider “first in class” for novel drugs with new and unique mechanisms for treating medical conditions. Many of the U.S. drug approvals utilized expedited pathways—with the majority using multiple approaches. For example, 60% of the 31 NDAs in 2015 and 73% of the 9 NDAs in 2016 used expedited pathway(s). The most commonly used regulatory mechanisms besides orphan designation were priority review—53% in 2015 and 68% in 2016—and first in class—36% for both years. In contrast, during this period, the EMA only provided two expedited pathways – Accelerated Assessment, which is temporary and applies only under exceptional circumstances, and Conditional Approval. These pathways were rarely used: 0% in 2015 and 23% for 2016. The observed disparities in the regulatory review processes extend to disparities in product labeling between the two regions, including indication and clinical trial data to side effects and special warnings.
The two regulatory agencies have their distinct history, legal frameworks and organizational structures, which have likely contributed to the observed disparities in approval times and regulatory pathways. The FDA, a U.S. federal agency, empowered by congress, charged with the regulation and supervision of pharmaceutical products and other consumer goods for one country. It has internal resources to conduct the review process. In contrast, the EMA is responsible for coordinating the scientific evaluation of applications to market medical products across 28 member states, utilizing resources within the EU across various member states. The review process in the U.S. follows timelines established as part of the Prescription Drug User Fee Act (PDUFA), which is law. In the EU, the regulatory review process is administered by “Consolidated Directive” which provides the timing for the regulatory reviews but also allows for “clock stops”. Delays may result from these clock stops, but also, additional time may be needed to receive a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) and European Commission approval. However, disparity between U.S. and EU timelines may be in large part due to the greater availability and use of expedited regulatory and development pathways in the U.S. During the period studied, the EMA only offered accelerated assessment and conditional approval, which were both underutilized. It should be noted, however, that the EMA has since developed the PRIME pathway aimed at increasing support and early dialogue for the development of medicines for unmet medical needs. It remains to be seen if this new PRIME pathway will affect EMA’s approval times. Despite recent efforts by global regulatory bodies, it is evident that great dissonance still pervades everything from product labeling and clinical trial data to regulatory approval time. It is our hope that calling attention to this disparity will lead to future harmonization.