SEEKING IMPROVEMENT

FDA officials say that drug approvals are returning to former on-time schedules after sagging in recent years as the agency struggled to implement a host of new requirements established by the FDA Amendments Act (FDAAA) of 2007. Last year, the Center for Drug Evaluation and Research (CDER) began to benefit from staffing increases and regulatory clarification, which helped employees achieve review timeframes more steadily. Now the agency is moving into a "period of consolidation," says CDER Director Janet Woodcock, as it completes multiple FDAAA initiatives, negotiates a new Prescription Drug User Fee (PDUFA) program, and establishes a quality-management system for more efficient 21^st century review process.

Woodcock reported in December 2010, at an FDA/CMS summit, that the agency once again was meeting user fee timeframes for processing applications, particularly submissions for NMEs, and that the "big wave in missing goals is coming down." There also are more first-cycle approvals, a key benchmark for both sponsors and regulators, and the rate of first launches in the US is holding steady.

The looming reauthorization of PDUFA in 2012 is prompting a re-evaluation of the agency's Risk Evaluation and Mitigation Strategies (REMS) program to meet industry concerns about too many diverse REMS formats; lead proposals are to have less burdensome controls for REMS that only require distribution of medication guides, and to devise common formats for such documents. FDA recognizes, says Woodcock, that REMS requirements should not delay product approvals.

FDA-industry user-fee negotiations also seek to make presubmission meetings more productive and to support new strategies for streamlining product testing and application review. Discussions regarding generic-drug user fees, moreover, are moving forward. A main objective for FDA is to gain additional support for more timely plant inspections in the face of a notable rise in foreign sourcing of active ingredients as well as generic-drug production.

Another area of focus is FDA's accelerated-approval process, which is designed to avoid delays in moving important new therapies to market. The system has been criticized because manufacturers often fail to complete agreed-on confirmatory trials in a timely manner, and some follow-up studies have shown limited efficacy and serious side effects, as with Roche's Avastin. FDA officials have proposed that sponsors launch confirmatory trials before the agency grants fast-track approval to ensure that additional studies are performed according to plan.

Great difficulties in developing new drugs for broad patient populations, such as diabetics and the obese, are prompting collaborative efforts to better understand approval requirements. Woodcock and her staff recently met with a group of obesity experts to discuss standards for bringing weight-loss drugs to market. The scientists proposed that regulators consider the broader health benefits of weight loss, such as reduction in sleep apnea, in assessing potential side effects from drug therapy.

FDA Commissioner Margaret Hamburg continues to stress the importance of advancing regulatory science in order for FDA to be able to support the translation of science into real-world therapies. New biomarkers for toxicology can identify drugs likely to fail much earlier in the process and also better target therapies to individuals most likely to respond, Hamburg noted. And innovative clinical-trial designs can yield answers using fewer patients and less money. The conventional thinking is that new discoveries from biomedical research will lead to new products. But, she explained at the ResearchAmerica forum, there is a regulatory science gap that can prevent new opportunities from coming to fruition.