To what degree are review outcomes aligned for new active substances (NASs) between the European Medicines Agency and the US Food and Drug Administration? A comparison based on publicly available information for NASs initially approved in the time period 2014 to 2016

Abstract

ObjectiveTo compare review outcome alignment between European Medicines Agency (EMA) and US Food and Drug Administration (FDA) for medicines approved by both agencies in the time period 2014–2016.DesignUsing publicly available information from FDA and EMA websites, new active substances (NASs) approved by each agency from 2014 to 2016 were identified and their characteristics assessed. Divergences in regulatory outcomes for simultaneous (within 91 days) submissions to both agencies were identified and then examined for use of facilitated regulatory pathways and orphan designations; submitted versus approved indications; and approval times.ResultsIn 2014–2016, 115 NASs were approved by EMA or FDA or both; 74/115 were new chemical entities and 41 new biological/biotechnology entities; 82/115 were approved by both agencies, 24 only by FDA and nine only by EMA. Simultaneous submission occurred for 52/115; 13/52 received expedited review by both agencies and 18 only by FDA; 8/52 received conditional approval from both agencies, 2/52 only from FDA and 1/52 only from EMA; 17/52 were designated as orphans by both agencies and 10/52 by FDA only; 31/52 indications were approved as submitted and 21 changed by EMA and 29/46 were approved as submitted (six not assessed) and 17/46 changed by FDA. Median FDA review timelines were 319 days compared with 409 days for EMA.ConclusionsThere was general agreement in EMA / FDA conditional approvals. FDA used expedited pathways and orphan designation more often than EMA, suggesting stricter EMA criteria or definitions for these designations or less flexible processes. Despite consistency in submitted indications, there was lack of concordance in approved indications, which should be further investigated. FDA review times are faster because of a wider range of expedited pathways and the two-step EMA process; this may change with recent revisions to EMA accelerated assessment guidelines and the launch of Priority Medicines.

Transparency in European Medicines Agency and US Food and Drug Administration Decision Making: Is It Possible to Identify the Rationale for Divergences in Approved Indication From Public Assessment Reports?

“…The 9 NASs identified in a previous study 4 were the focus of this analysis. The characteristics of the 9 NASs are as follows: simultaneously submitted to EMA and FDA, defined as a submission occurring within 3 months of each other; initially approved by the EMA or FDA between 2014 and 2016, with outcome at second agency tracked until end of 2017; had the same indication submitted to EMA and FDA; and had a different indication approved by the EMA and FDA (this was defined as treating a different population or conditions of use, such as type of therapy or use with other products).…”

“…Divergent outcomes may result from the submission of a data package that may be more updated than for the first-in-world application. [4][5][6] Instances in which the same indication is proposed, yet approved indications differ from those proposed or differ across agencies may be the result of complexities and uncertainties in assessing pharmacology, tolerability, and efficacy parameters associated with new medicinal products or therapeutic principles or regional differences in medical practice. In addition, such differences in risk tolerance could be attributable to subjective influences on the process as well as varying agency decision-making practices.…”

“…In a recent study, 4 we examined in detail the characteristics of submissions between 2014 and 2016. Of 115 new active substances (NASs; as defined below) that were approved by the EMA or the FDA, 82 were approved by both agencies, and for 33 of those, the same indication was submitted to the EMA and the FDA through a simultaneous submission (defined as a submission occurring within 3 months of each other).…”

“…This work was performed for the 9 products with a different indication approved that we identified in our original study on NASs with a simultaneous submission and same indication. 4 We sought to determine to what extent it may be possible to identify the decision rationale based on data in the PARs, in which section of the PAR this was described, and whether we could determine the product characteristics that pointed toward a divergent decision.…”

Are Regulators Talking to Each Other Across Borders?

“…Through a survey, they identified 30 clusters for scientific collaboration and information exchange in certain disease areas or specific topics such as biosimilars, pediatric medicines, pharmacogenomics, and real‐world evidence/big data . Two recent, independent comparisons between outcomes of reviews by the FDA and EMA showed a high degree of concordance, which could indicate that such international collaboration has a positive impact on the consistency of regulatory decision making.…”