Food and Drug Administration vs European Medicines Agency: Review times and clinical evidence on novel drugs at the time of approval

Abstract

The Food and Drug Administration (FDA) and European Medicines Agency (EMA) now have expedited review procedures for new drugs. We compared the review times of medicines licensed by the 2 agencies and explored differences in the evidence submitted. In 2015-2017 the FDA licensed 113 drugs, 66 of which reached Europe. The median review time was longer at the EMA than FDA and was shorter for drugs undergoing FDA-expedited programmes compared to the same drugs approved by the EMA through the standard procedure. We identified differences regarding the evidence submitted to the 2 regulators for 7 drugs. The greater use of expedited programmes by the FDA and administrative time at the European Commission mainly explain the later access of new drugs to the European market. The additional evidence submitted to the EMA is generally scant and limited to a few drugs. K E Y W O R D S drug regulation, health policy, therapeutics 1 | BACKGROUND Regulatory agencies face constant pressure to speed up the development, review and approval of drugs for serious diseases. Both the Food and Drug Administration (FDA) and European Medicines Agency (EMA) support clinical drug development and accelerated review and authorisation procedures (Box 1). 1 These programmes are intended to meet the expectations of drug manufacturers and patients, the former eager to launch new drugs promptly to maximise the return on investment and the latter to have access to potentially innovative therapies as soon as possible. Expedited programmes implemented by the FDA provide shorter overall review times than standard ones, 2 and account for the reportedly faster process than at the EMA. 3-6The earlier application and shorter review times at the FDA compared to the EMA may offer the European agency the possibility to assess the same drugs on the basis of more comprehensive information. To test this, we first assessed the delays in the application dates of the novel drugs-namely, new molecular entities and original biologic agents-licensed by both FDA and EMA, and compared their review times. Then we explored the differences in the evidence available at the time of EMA approval of medicines already licensed by the FDA through expedited programmes. | METHODSWe identified the drugs approved by the FDA from January 2015 through December 2017 using 3 reports published by the agency. [7][8][9] We extracted the date of approval, information on the type of authorisation procedure, and information on the evidence submitted in the marketing authorisation (MA) application from the Drugs@Fda database. 1,10 Review times in USA were calculated as the number of days elapsed from the Investigational New Drug application to the first FDA approval. Investigational New Drug application dates were obtained from FDA documents and administrative correspondence.We classified applications as either expedited or non-expedited procedures (Box 1).

Evolving Landscape of New Drug Approval in Japan and Lags from International Birth Dates: Retrospective Regulatory Analysis

“…Second, we focused on the IBD and analyzed the drug lag between Japan and overseas among the new drugs approved in Japan. Many drug lag studies have focused on its magnitude among two or three major regulatory authorities, including Japan, the United States, and Europe by comparing the approval date with each other 1,2,12,16,28‐30 . This method seems suitable to detect the whole lag between specific regions but disregards the fact that there are many products first approved by the regulatory authorities other than those three.…”

“…Many drug lag studies have focused on its magnitude among two or three major regulatory authorities, including Japan, the United States, and Europe by comparing the approval date with each other. 1,2,12,16,[28][29][30] This method seems suitable to detect the whole lag between specific regions but disregards the fact that there are many products first approved by the regulatory authorities other than those three. Finally, the methodology in this study to address the issues of drug lag in each therapeutic area may be generalizable in other regions and shall provide important findings for improving public health disparities and concerted collaboration with patients, academia, industries, and governments.…”

Approval of Cancer Drugs With Uncertain Therapeutic Value: A Comparison of Regulatory Decisions in Europe and the United States

“… 18 , 20 , 24 , 25 , 26 Although some studies documented regulatory decision making under uncertainty, they were limited to the perspective of a single regulatory agency. 9 , 21 Comparative studies of the FDA and the EMA mainly examined differences in time to market approval 9 , 27 , 28 , 29 , 30 or focused on the use of individual regulatory tools such as approval decisions or wording of approved indications. 29 , 31 , 32 Previous studies have not systematically compared the use of a comprehensive set of regulatory tools by the FDA and the EMA in situations with limited clinical evidence about the benefit‐risk profile of new drugs.…”

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?

“…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.…”