FDA/EMA Study Examines Drug Approval ‘Concordance’

A new study in Clinical Pharmacology & Therapeutics shows that FDA and European Medicines Agency (EMA) reviewers have a “high concordance” (91–98%) in approving/rejecting new drug applications, and that this suggests that “engagement and collaboration on regulatory science has a positive impact.” Conducted by officials from both agencies, the study compared EMA and FDA decisions on new drug marketing applications over three calendar years (2014–2016).

“FDA and EMA decisions on whether to approve a product for marketing upon first submission and review were concordant (both agencies had the same regulatory outcome) for 92% (98/107) of the applications and discordant for 8% (9/107),” the study says. “Both agencies approved 84% (90/107) of the applications and both had initial negative outcomes (nonapproval or withdrawal) for 4% (4/107).”

According to the study, 15 submissions were initially not approved by one or both agencies — one not approved by the EMA only, 12 by FDA only, and two by both agencies. After the first cycle, eight applications were resubmitted to FDA and three went under an EMA reexamination. “The FDA approved seven of the eight resubmitted applications, and the EMA approved two of the three reexamined applications,” it says. “Overall, most applications that had a second submission were ultimately approved in both jurisdictions.”

Additionally, the study found that FDA’s initial nonapproval decisions (13% FDA vs. 3% EMA) “reflected a variety of factors, led by differing agency conclusions about efficacy, which is not surprising as some difference in judgment is expected from independent assessments... Differences in clinical data submitted in support of an application was the second most common root of divergent FDA and EMA outcomes. Although our study did not focus on comparisons of time to submission of or agency approval of an application, we noted that some instances of dissimilarities in clinical data related to differential timing of submissions and availability of data. For example, for applications submitted to FDA first, it was not uncommon for data in the EMA submissions to be more mature, including trials that were ongoing at the time of submission to FDA, often because they were now completed.”