PDUFA IV expires Sept. 30, 2012, and several parties already are nervous about its renewal. 

PDUFA, the Prescription Drug User Fee Act (PDUFA)—enacted in 1992 and renewed in 1997 (PDUFA II), 2002 (PDUFA III) and 2007 (PDUFA IV)—authorizes the FDA to collect fees from companies that produce certain human drug and biological products. Since the passage of PDUFA, user fees have played an important role in expediting the drug approval process. 

This is “must-pass” legislation, according to Doug Peddicord, executive director of the Association of Clinical Research Organizations (ACRO), a CRO trade group. If Congress does not pass it this spring, 90 days in advance of its expiry, about 2,000 FDA employees will be laid off and the FDA will lose the huge amount of funding it receives from drug and device developers through PDUFA. 

“My concern would be a political one,” said Peddicord. “This Congress has obviously had difficulty passing what’s considered to be must-pass legislation. But there’s no reason not to pass it if the agency and the industry are in agreement. We’d just really like Congress to act in a responsible and timely manner on this one.” 

During the last PDUFA renewal cycle in 2007, the legislation was not signed into law until Sept. 21, explained Steve Grossman, a consultant and lobbyist who serves as Deputy Director of the Alliance for a Stronger FDA. Consequently, he said, the FDA had to delay hiring new staff and the agency was compromised in its ability to implement the new law during the first year of the cycle. With that still relatively recent history, hopefully this time Congress will act more swiftly, said Grossman. 

“However, this Congress has (thus far) a poor track record of reaching compromises on even simple matters and has demonstrated serious problems meeting deadlines,” Grossman wrote in his blog, FDAMatters. 

The basic structure of the human drug review program within PDUFA, including the FDA’s high review standards for safety and efficacy, remains unchanged. This past Sept. 1, the FDA published its PDUFA V goal letter on its web site. The key points among the regulatory science and patient safety goals were: enhancing FDA/sponsor communications during drug development; advancing development of drugs for rare diseases; advancing biomarker qualifications and pharmacogenomics; ensuring quality of patient-reported outcomes; ensuring quality in meta-analysis; implementing benefit/risk framework, including patient-focused drug development; REMS standardization and Sentinal; and electronic regulatory submissions (eCTD) and data standards. 

Another matter that might slow PDUFA V’s passage: the medical device industry and the FDA have not yet hammered out their agreement to be part of the legislation, said Grossman. 

Also of concern is what will be attached to the bill. Some early contenders, said Grossman, are amendments centering on drug re-importation, the exclusivity provisions of the new biosimilars law, approval of genetically engineered salmon, regulation of dietary supplements and the use of Bisphenol A (BPA) in consumer products. In addition, the current Congress has some members who might offer more fundamental amendments, such as revising the FDA’s authority to review the efficacy of drug products, he said. 

A very recent amendment, to be filed in January from North Carolina democratic Senator Kay Hagan, will aim to create two new FDA approval pathways to improve on the already existent accelerated approval for drugs under development for serious illnesses that have no other useful therapies. It puts forth the concept of “progressive approval,” which would require data “reasonably likely” to predict clinical benefit, the standard currently used for accelerated approval. Unlike accelerated approval, drugs could receive progressive approval without data from a surrogate endpoint. There’s also “exceptional approval,” which could be granted when the data necessary to satisfy the standard for approval “cannot ethically, feasibly or practicably be generated.” 

Hagan’s concepts will introduce some complicated issues to the bill, said Grossman. 

“FDA is open for the conversation, but they don’t think there are easy answers and they ask some very tough questions,” he said. 

In December, the FDA briefs HHS/OMB on any revisions to its recommendations for PDUFA V. On Jan. 15, the final FDA recommendations will be made to Congress, and that’s when legislation will begin to be introduced and bills attached to it, said Grossman. Hearings will begin in late February or early March. 

At this point, the bill could sail right through, get bogged down and delayed or be stopped all together. 

“There are lots of shifting sides on a broad range of issues, and the danger of being late is very high,” said Grossman. “Also, it’s not written in stone that Congress has to accept what’s been negotiated between industry and the FDA. On the other hand, the countervailing trend is that those on the Hill know they need to get this done before July 1. I don’t think people are going into PDUFA saying ‘The PDUFA agreement can’t possibly work,’ but the question will be: will something upset the balance? It still could.” 

Suz Redfearn