Regulatory review of novel therapeutics--comparison of three regulatory agencies

Abstract

Background: The upcoming reauthorization of the Prescription Drug User Fee Act focuses on improving the review process for new drug applications at the Food and Drug Administration (FDA).

Methods: Using publicly available information from the FDA, the European Medicines Agency (EMA), and Health Canada, we compared the time for completion of the first review and the total review time for all applications involving novel therapeutic agents approved by the three regulatory agencies from 2001 through 2010 and determined the geographic area in which each novel therapeutic agent was first approved for use.

Results: There were 510 applications for novel therapeutic agents approved from 2001 through 2010--225 by the FDA, 186 by the EMA, and 99 by Health Canada; among the applications, there were 289 unique agents. The median length of time for completion of the first review was 303 days (interquartile range, 185 to 372) for applications approved by the FDA, 366 days (interquartile range, 310 to 445) for those approved by the EMA, and 352 days (interquartile range, 255 to 420) for those approved by Health Canada (P<0.001 for the comparison across the three agencies). The median total review time was also shorter at the FDA than at the EMA or Health Canada (P=0.002). Among the 289 unique novel therapeutic agents, 190 were approved in both the United States and Europe (either by the EMA or through the mutual recognition process), of which 121 (63.7%) were first approved in the United States; similarly, 154 were approved in both the United States and Canada, of which 132 (85.7%) were first approved in the United States.

Conclusions: For novel therapeutic agents approved between 2001 and 2010, the FDA reviewed applications involving novel therapeutics more quickly, on average, than did the EMA or Health Canada, and the vast majority of these new therapeutic agents were first approved for use in the United States. (Funded by the Pew Charitable Trusts.).

Figure 1. Identification of the Sample of Novel Therapeutic Applications for the Current Analysis

The analysis includes applications approved by the Food and Drug Administration (FDA), the European Medicines Agency (EMA), and Health Canada from 2001 through 2010. Health Canada has posted Summary Basis of Decision documents, which list the dates needed to calculate review time, only for therapeutics approved since 2005. As a result, 623 applications were excluded from the analysis because regulatory dates were not available from Summary Basis of Decision documents.

Figure 2. Median First-Review Times and Total Review Times for Applications for Novel Therapeutics Approved by the FDA, the EMA, and Health Canada

Information on application approvals by Health Canada is available only from 2005 on. Status with respect to priority or standard review was not analyzed for the EMA because the EMA Accelerated Assessment procedure, which is similar to priority review at the FDA, was not established until 2007. The overall P value is for the comparison across the three agencies. P<0.02 for all of the following comparisons: overall first-review time between the FDA and the EMA and between the FDA and Health Canada and overall total review time between the FDA and Health Canada; total review time during PDUFA I–II between the FDA and Health Canada and between the EMA and Health Canada; first-review and total review times during PDUFA III between the FDA and the EMA and between the FDA and Health Canada; first-review time during PDUFA IV between the FDA and the EMA and between the FDA and Health Canada and total review time during PDUFA IV between the FDA and Health Canada; and first-review time for small-molecule drugs between the FDA and the EMA and between the FDA and Health Canada, total review time for small-molecule drugs between the FDA and Health Canada, and first-review time for biologic agents between the FDA and the EMA.

Figure 3. Geographic Areas in Which Novel Therapeutics Approved in Multiple Markets Were First Approved for Use

The data for Europe include both drugs approved by the EMA and those approved through the mutual recognition process.