Application Backup Clogs the Pipes of Progress

Despite approving record numbers of generic drugs, the FDA is failing to keep pace with the surge in applications. As a result, the backlog of generic drugs awaiting approval has grown rapidly.

The FDA issued a total of 467 full and tentative generic drug approvals last year, far fewer than the 766 applications the agency received from generic drug makers. The backlog of pending applications has continued to grow, swelling to about 800 by early this year. "The backlog is growing, and clearly it's growing every day," Gary Buehler, director of the FDA's Office of Generic Drugs, said at the Generic Pharmaceutical Association's (GPhA's) annual conference in February.

The number of applications rose sharply in 2005, when the FDA received about 200 more applications than in the previous year. The primary reason is that more manufacturers are making competing generic versions of the same branded products, according to Tommy Erdei, director of health care at ABN AMRO.

For example, Indian companies are rapidly becoming major players, with more than 150 applications pending approval, Erdei said. Analysts also expect the market to be fueled by expiring patent exclusivity for several blockbuster drugs.

Faced with the increase in applications, the FDA has been approving generics more quickly. Median approval times have shrunk by 40% since 1996 to about 16 months, and the agency approved about 50 more applications in 2005 than in the previous year. According to Scott Gottlieb, the FDA's deputy commissioner for Medical and Scientific Affairs, the Generic Drug Office's budget has doubled since 2001, and the office is increasing its staff.

Gottlieb suggested that approvals of generics might be further accelerated if the industry were prepared to fund the process with user fees, like those paid by makers of branded drugs and medical devices.

Generics proponents, however, criticized the FDA's proposals. Rep Henry Waxman (D, Calif) told the GPhA conference that the Bush administration has failed to devote adequate resources to the FDA's generic-review program. He compared the user-fee proposal with what happened with medical-device fees, saying that other funding was cut once user fees were in place.

GPhA President Kathleen Jaeger also is pushing for more federal funding, saying that even a modest investment of $15 million could have a big effect in speeding the review process. She said that it is not clear whether user fees would accelerate review of generics in the same way that they did with brand name drugs.

Approval of generics is subject to an intellectual property-based approval system, in which generic applications can be delayed by the efforts of brand name pharmaceutical companies. This system "is fraught with unintended legal and regulatory loopholes," Jaeger said. She added that the generic pharmaceutical industry would consider paying user fees if the FDA and the Bush administration would guarantee legislative and other changes to speed the approval of generics.

One bone of contention is the citizen-petition process, a mechanism that pharmaceutical companies have increasingly used to file objections to generic drugs under review with the FDA. Even though most petitions are not successful, the FDA still must spend precious time considering them?which often delays approval of a generic. Sometimes, FDA officials said, companies file petitions just before approval of a generic, describing issues that could have been brought up months earlier.

Yet, the process needs to be fixed, not eliminated, the officials said, because it also provides a way for the public to put valid scientific arguments to the FDA.

A bill recently introduced by Sens Debbie Stabenow (D, Mich) and Trent Lott (R, Miss), the Lower Priced Drugs Act of 2006, aims to curb abuses of the citizen-petition process and other mechanisms used by branded pharmaceutical companies against generics. One solution proposed in the act and discussed by the FDA is that petitions could be reviewed separately from the drug-approval process.

FDA officials also say that the industry is partly to blame for slow approvals, because the majority of applications lack information or have other problems that keep them from being approved in the first pass. Many of those problems occur with applications from non-US manufacturers, Gottlieb said.

The agency also is making some changes in its processes in an attempt to speed generic approvals. It is reviewing some data sooner and providing more information on-line to help generics companies prepare applications. The agency is lifting long-standing restrictions on telephone conversations between reviewers and generic drug makers to allow reviewers to resolve minor issues faster.

For example, when a blockbuster's marketing exclusivity is due to expire, the FDA often receives simultaneous applications from several generics manufacturers. The FDA has started to assign the entire cluster of applications to a team of reviewers.

Buehler said that, although the FDA is increasing its staff this year, the budget for 2007 remains very uncertain.

Mr. Faden is a freelance medical writer based in Portland, Ore.