Meeting Halfway?

The cut results in large part from meetings between industry and the FDA, a central facet of PDUFA meant to navigate companies through the approval process. The meetings have helped to improve predictability and transparency of the review process, says Radcliffe. In the past two years, the number of industry-requested meetings has almost doubled, to 2,132 meetings in 2004.

In bringing a single drug to market, a company might request dozens of meetings, in which company representatives come to FDA officials ?with a series of questions, [such as:] ?We realize there could be an issue with this, that, and the other. Do you agree??? explains Robert Roth, medical director at the Weinberg Group, an international scientific and regulatory consulting firm based in Washington, DC. ?The drug companies that are smart will try to nail down the FDA as much as they can,? says Roth, for example, in what percentage of patients must respond to the drug for it to pass approval. ?The FDA can clearly influence what happens when a drug gets in or not by expressing what data set they want to have, what endpoints they want to have.?

These meetings, however, come at a cost for industry. The yearly and one-time drug fees associated with PDUFA have nearly doubled in the third version, from approximately $133 million in the 2001 fiscal year to a projected $259 million for fiscal year 2006, according to BIO. The purpose of user fees is to put the FDA on sound financial footing and bolster its ability to respond to industry?s needs, say industry and government observers. Rather than charge per meeting, the FDA lumps user fees into the agency?s total revenue, creating a ?firewall? between payment and individual results that John Jenkins, director of the FDA?s Office of New Drugs in Rockville, Md., says is necessary to counter claims that the FDA is cozying up to industry.

But despite these increased funds, the FDA is finding itself a victim of its own success. As the number of industry-requested meetings increases and protocol assessment requests pile up, the FDA says its resources are strained and its staff overworked. ?With several hundred hours of staff time per meeting, and over 2,000 meetings each year, you do the math,? says Jenkins. Though the staff has increased by 100% since 1992, Jenkins says that individual employees are expected to take on more and more work.

?There?s been some complaints about a sweatshop-type environment,? says Chris Milne, assistant director of the Tufts CSDD.

Jenkins says the agency is agnostic about where additional money comes from, ?but we need to have adequate funding.? According to him, this issue will be at the forefront of negotiations for the terms of the next PDUFA approval. ?They?re either going to have to require more user fees or somehow get more money out of Congress, which isn?t likely,? says Milne. ?If industry continues to [want] more meetings, then the FDA [will] probably have them foot the bill.?

According to Roth at the Weinberg Group, if an approved drug makes a million dollars a day, shortened timelines may be worth even an augmented user fee. ?Industry is willing to pay as long as it can be documented that there?s a need for increased resources,? says Alan Goldhammer, associate vice president for regulatory affairs at the Pharmaceutical Research and Manufacturers of America (PhRMA), based in Washington, DC. Moreover, a 2004 Massachusetts Institute of Technology survey reports that company heads are prepared to shell out even more cash in exchange for increased interaction with the FDA.

What industry actually expects, however, is a ?minimal increase in fees with minimal changes to the act,? says Alison Lawton, senior vice president of regulatory affairs and corporate quality systems at Cambridge-based Genzyme. Other companies like Thousand Oaks, Calif.-based Amgen have begun to strategize over their negotiations with the FDA for PDUFA IV but are not willing to reveal their hand yet, according to an Amgen spokesperson. BIO?s Radcliffe adds that the recent, relatively slight reduction in approval times and several unfinished initiatives from PDUFA III do not justify a large fee hike in the next iteration. Both Lawton and Radcliffe say that they and their colleagues are concerned by the extent to which the FDA relies on user fees to run its operation, and perhaps not surprisingly, would like to see Congress allocate additional funds to take up more of the burden. Stagnant Senate appropriations for the FDA, which account for less than 50% of its drug review budget, are the reason PDUFA fees were necessary in the first place, says Goldhammer. ?Nobody wants to be in the situation where industry is paying the full cost,? adds Radcliffe.

Wherever the funding comes from, some say that celebrating shortened approval times might miss the ultimate point of PDUFA: getting drugs to market faster. Approval times, after all, represent only the final phase of a long, complex, and costly process. Industry players say the real issue is the time it takes to conduct clinical trials, which reached a low between 1999 and 2001 but now ?seem(s) to be going back up, almost to what [it was] before PDUFA,? says Milne.

Additionally, drug approvals have declined by 47% between 2002 and 2004, according to the Tufts study. Both Lawton and the FDA?s Jenkins attribute these statistics in part to a greater focus on more complicated drugs, such as those for chronic diseases that require larger and costlier clinical trials. To counter this effect, the FDA is working on approaches such as the Critical Path Initiative, which aims to use scientific advancements such as biomarkers and critical imaging to make better assessments of a drug during its development. In the next iteration of PDUFA, efforts must be made not just on the approval end of the process, says Kaitin, but also on getting ?a handle on the rising time for clinical development.? n