Rx Safety Bill Would Require Renegotiation Of User Fees, FDA Tells Senate

An expansion of FDA's drug safety authorities as envisioned by legislation from Sens. Ted Kennedy, D-Mass., and Michael Enzi, R-Wyo., would require a renegotiation of user fees with industry, Commissioner Andrew von Eschenbach said.

Testifying at a Senate Health Committee hearing March 14, von Eschenbach said that "the current negotiation, the package that has been finalized, does not include provisions that may be contained in the outcome of Sen. Kennedy and Sen. Enzi's bill."

The agency would have to go back and renegotiate for the additional resources, he said. Von Echenbach was asked about the user fee issue by Sen. Richard Burr, R-N.C.

While the Kennedy/Enzi legislation (¹ S. 484) contains provisions for user fees, the discussion at the hearing of the potential resource burden on FDA and industry may complicate the senators' plans to include the legislation as part of the reauthorization of the Prescription Drug User Fee Act.

Burr suggested to von Eschenbach that "I think you've got all the tools that are currently in this bill. They may not be statutory, but you've got regulations."

In the drug safety area, FDA has been arguing that it can make effective use of the new resources it negotiated with industry as part of the PDUFA IV proposal, but it does not need additional authority (² , p. 3).

Post-Market Funding Triples Under PDUFA IV

During the hearing, von Eschenbach described how PDUFA IV user fees will be used for safety oversight.

In terms of post-marketing surveillance, he said, "PDUFA IV triples the PDUFA investment in post-marketing safety that will provide and enable us with the tools to help protect and mitigate unforeseen and unexpected risks after the drug has been approved."

Kennedy said that in terms of post-marketing surveillance, "We've been reluctant, industry's been reluctant, now they're for it and we're trying to do it in such a way that its going to be responsive to the particular kind of item, giving that kind of flexibility and authority to the FDA."

One safety initiative that will be a key component of the FDA's post-marketing efforts will be the expansion of its database and database mining resources, von Eschenbach said.

"There are opportunities for us now to access databases that have been developed, for example, in large health care plans," he said. Von Eschenbach said the agency has entered into an agreement with United Healthcare, the Department of Veterans Affairs, and CMS.

"By accessing those databases, we are bringing to them, modern tools of information technology, including sophisticated data mining...we will begin to have a system in place that will actively - not just something passive but actively - early on be able to give us insights into unexpected adverse outcomes occurring in a real world population," he said.

Von Eschenbach was also pressed by Sen. Barbara Mikulski, D-Md., about post-marketing surveillance of Merck's Gardasil vaccine for human papillomavirus (see ³ (Also see "Gardasil Use Suggests Need For PDUFA Post-Market Provisions, Senator Says" - Pink Sheet, 19 Mar, 2007.)).

The Clock Is Ticking On PDUFA

During his testimony, von Eschenbach stressed the importance of passing PDUFA by its Sept. 30 deadline.

"In order to maintain this trajectory of continuous improvement and this process of maintaining the infrastructure that's been established, and it's critical that the reauthorization occurs seamlessly without any gap between expiration of the old law and the enactment of PDUFA IV," he said.

However, FDA has not completed the full proposal.

Enzi agreed that "now we're facing disastrous consequences if this program is allowed to expire...but so far we haven't received all of the PDUFA IV proposal. We got part of it yesterday, and we're still missing the second half, which outlines the agency performance goals."

The senator said that the committee would have liked to have seen the entire proposal prior to the hearing and pressed von Eschenbach for a timeframe as to when they could expect to get the final proposal.

"We continue to move this process through the administrative structure to get all of the details and all of the final parts and pieces of this proposal before you," von Eschenbach said.

"Clearly, there is a real complexity associated with this particular process and we're trying to expedite this as quickly as possible. I would expect this to occur in the matter of the next few weeks to have the entire package to you," he said.

"Sept. 30 is coming up and we can't do our work if you haven't done your work," Enzi said. "So I hope you'll put a lot of emphasis on getting that done."

House Energy and Commerce/Health Subcommittee chairman Frank Pallone, D-N.J., told reporters at a breakfast held the day before the Senate hearing that his panel's hearings would likely not start until FDA delivered its final proposal.

Separation Would Be A Trial, von Eschenbach Says

Kennedy asked von Eschenbach for his thoughts on separating drug review and drug safety programs at FDA. Sens. Chuck Grassley, R-Iowa, and Christopher Dodd, D-Conn., have introduced legislation that would create a separate drug safety center within FDA (⁴ (Also see "FDA Safety Act Calls For “Expedited Procedures” For Drug Withdrawals" - Pink Sheet, 2 May, 2005.), p. 8).

The commissioner said he believed in "the need for a very distinct and very clear focus on both sides of the equation" to address efficacy and adverse events.

"However, I do not believe that those two processes should be separated," he said. "I believe that with new tools that are emerging in the large field of medicine, we actually will benefit in the future from having much greater integration of those two aspects of understanding a drug."

In fact, von Eschenbach said that separating the two would do "more harm than good."

FDA is piloting a program that would integrate surveillance staff much more closely in the initial review and approval of drugs.

Senators Push For Restricting DTC

Sherrod Brown, D-Ohio, who introduced a bill in 2005 mandating that FDA establish rules on direct-to-consumer advertising, asked the commissioner why a one- or two-year moratorium on DTC advertising should not be required.

In response, von Eschenbach cited cultural changes occurring in society which have resulted in better educated patients.

"Patients have become much more active participants in their care and much better informed; for example, the internet and access to information. So I think the earlier you get information out to patients in a proper and appropriate way, I think it's a great opportunity to be had for them," he said.

The commissioner also said FDA is asking for more funds through PDUFA IV to effectively preview advertisements "to help make certain advertising is in fact appropriate." Under the new, separate user fee review program for DTC TV ads, FDA promises a 45-day review for submissions (⁵ (Also see "User Fee Deal For Ad Review Funds Stems From PhRMA DTC Principles" - Pink Sheet, 4 Dec, 2006.), p. 4).

Brown asked if FDA did not get those additional resources, would it not be better to err on the side of caution and put a one year moratorium on DTC ads.

Von Eschenbach said that that would have to be balanced against the potential downsides that may arise from withholding such information from the patient.

The Kennedy/Enzi bill would allow FDA to impose a two-year moratorium on DTC advertising. Pallone also emphasized increased monitoring of DTC advertising during his March 14 briefing.

Burr, a former physician, said during the hearing that while he was not in favor of DTC ads, he did not feel Congress has the right to regulate it.

"I'm not a big fan of direct-to-consumer advertising but I'm a big fan of the Constitution," he said. "And there is no authority in this Congress to say what a company can advertise and what a company cannot advertise."

"It will never pass muster with the courts. It sounds great, it's a great political play, but drug companies have a right to advertise their products, just like everybody else."

In response to another question from Brown about dissemination of trial data prior to a product's approval, von Eschenbach took a more conservative tack then he had when discussing DTC ads.

"There are clearly important safeguards that we have to have in place to make certain the public accurately interprets the information by virtue of the fact we appropriately communicate it," he said.

At the same time, the Commissioner acknowledged that "It's very important that we continue to pursue a strategy of open sharing of data and information regarding the utilization of drugs," von Eschenbach said.

- Kathryn Phelps ([email protected])