Three Regulatory Agencies: A Comparison

FDA resources dedicated to reviewing applications for drugs for humans and enduring efficacy and safety were augmented in 1992 with the passage of the Prescription Drug User Fee Act (PDUFA). To support the infrastructure required for review of new drugs, in exchange for meeting specific performance standards, PDUFA enables the FDA to collect user fees for each new drug application. This act has aided in shortening the time needed for application review; however, according to researchers, meeting the new standards of performance has been associated with increased rates of drug withdrawals and black box warnings.

PDUFA is subject to mandatory reauthorization every 5 years, and renewals have emphasized specific areas. The 1997 renewal focused on drug safety and postmarketing surveillance (PDUFA IV). The act is scheduled for reauthorization in 2012 (PDUFA V), and the FDA, in cooperation with the pharmaceutical industry, has developed a structure of performance goals.

One of those goals is implementation of a program to “improve the efficiency and effectiveness” of the review process for new-drug applications for new molecular entities (novel biologic drugs), also known as novel therapeutics. The emphasis on enhancing transparency and communication between the agency and applicants is designed to increase the number of novel therapeutics approved after a single regulatory review cycle.

Researchers recently completed a comparison of review times for novel therapeutics among the FDA, the European Medicines Agency (EMA), and Health Canada. The analysis also evaluated review times across PDUFA periods to “explore the potential effect of PDUFA IV on review times at the FDA.” Results of the comparison were reported in the New England Journal of Medicine [2012;366(24):2284-2293].

The researchers identified a sample of applications involving novel therapeutics that received regulatory approval from each agency between January 1, 2001, and December 31, 2010. After applying inclusion and exclusion criteria, the analysis included 225 novel therapeutics approved by the FDA,186 approved by the EMA, and 99 approved by Health Canada. Among these applications, there were 289 unique agents; 72 of those were approved by all 3 agencies.

There were no significant differences among the 3 agencies in terms of type of drug being reviewed, therapeutic class of the drug reviewed, or use of priority review. The EMA approved a larger proportion of orphan-designated therapeutics compared with the FDA (28.0% vs 16.9%; P=.007).

The analysis of review cycles found that 61.8% (n=139) of applications for novel therapeutics were approved by the FDA in a single review cycle and 38.2% (n=86) required ≥2 cycles. For the EMA, 96.2% (n=179) were approved in 1 cycle and 3.8% (n=7) approved in ≥2 cycles; for Health Canada, the values were 68.7% (n=68) approved in 1 cycle and 31.3% (n=31) approved in ≥2 cycles (P<.001 for the comparison across the 3 agencies).

The median length of time for completion of the first review was 303 days for applications approved by the FDA, 366 days for those approved by the EMA, and 352 days for those approved by Health Canada (P<.001 for the comparison across the 3 agencies). The median total review time was also shorter at the FDA than at the other 2 agencies (322 days vs 366 at the EMA and 393 at Health Canada) (P=.002). Of the 72 products approved by all 3 agencies, the median total review time was shorter at the FDA than at the EMA and Health Canada (268 days vs 356 days vs 366 days, respectively).

There were 190 unique novel therapeutic agents approved in both the United States and Europe; of those, 121 were first approved in the United States. There were 154 unique novel therapeutic agents approved in both the United States and Canada; 132 of those were first approved in the United States.