Washington Editor

WASHINGTON - Language to establish a pathway for approving follow-on biologics will be incorporated into a comprehensive FDA bill advancing through the Senate, the "Food and Drug Administration Revitalization Act," Sen. Edward Kennedy (D-Mass.) said late Wednesday.

"It will be a part" of it, he confirmed at the end of an executive session of the Senate Health, Education, Labor and Pensions panel, which reported the wide-ranging legislative package out of committee. "I think what we have done today is strengthen the institution and hopefully given it an opportunity to deal with future scientific challenges."

However, a provision for follow-ons was not included among amendments to the broad FDA bill considered by panel members. They voted against six amendments and in favor of two others.

But the comments by Kennedy, the committee's chairman, are the most definitive signal yet of what's to come on the follow-on issue, confirming many months of rumors. (See BioWorld Today, Oct. 23, 2006.)

A final version of the broad FDA legislation, designated S. 1082, should reach the Senate floor in the next couple of weeks, according to a staffer for Ranking Member Mike Enzi (R-Wyo.). She spoke with less certainty on follow-ons, noting that while an agreement on the issue could get worked out before the bill hits the Senate floor, no "artificial deadline" has been applied by either side.

It's not clear how strictly a follow-on attachment would adhere to language in the bill that's been introduced by Sens. Charles Schumer (D-N.Y.) and Hillary Rodham Clinton (D-N.Y.), along with Rep. Henry Waxman (D-Calif.). Called the "Access to Life Saving Medicine Act of 2007," or H.R. 1038, it would give the FDA case-by-case flexibility to determine whether such products require clinical testing and allow the agency to determine whether there are clinically meaningful differences between follow-ons and original biologicals. Draft language on alternate follow-on legislation has begun circulating, though it's yet to be officially introduced.

Existing language in S. 1082 primarily relates to renewing the Prescription Drug User Fee Act (PDUFA) and authorizing new safety powers for the FDA. Additional provisions focus on requiring public disclosure of clinical trial results and registries, limiting FDA advisory committee members' conflicts of interest, changing pediatric exclusivity laws, promoting FDA transparency on safety actions, setting up a nonprofit foundation to advance product development and enhance safety and renewing medical device user fees. (See BioWorld Today, April 16, 2007.)

The six amendments defeated during the committee's markup missed by narrow margins, signaling a high probability for some compromises to come before S. 1082 gets finalized. Enzi, conceding that "we have some unintended consequences" written into the bill's existing language, said some middle ground would be found ahead of full Senate consideration.

Defeated amendments included a proposal from Sen. Judd Gregg (R-N.H.) to dial back the bill's chief safety component, the creation of risk evaluation mitigation strategies (REMS). Such an approach is designed to place safety reviews on new drugs and biologicals upon approval, but Gregg called it a "finger-in-the-wind" tactic, implying that there are no data available at that point to determine whether a REMS should be applied. Instead, he suggested that a REMS should come into play after a safety problem has been detected through active post-approval surveillance of databases on drug usage. But the amendment failed by a vote of 12-9, as did another Gregg amendment to exempt from prescribing limits drugs developed for bioterrorism.

Another defeated amendment would have struck S. 1082's limits on direct-to-consumer advertising. It was offered by Sen. Pat Roberts (R-Kan.), who said that such a provision violates the first amendment and cautioned that it would turn the FDA into "an editorial review board," but his amendment failed 11-10.

An amendment from Sen. Wayne Allard (R-Colo.) would have preserved six months of patent exclusivity on drugs that companies test in children, but it too failed 11-10. Instead, S. 1082 caps exclusivity at three months for drugs that generate $1 billion or more in sales.

Another defeated amendment was offered by Sen. Tom Coburn (R-Okla.) to ensure that the legislation doesn't interfere with physicians' prescribing practices, such as off-label usage, but it failed 12-9. In addition, another Coburn amendment to suspend sales of drugs cleared under accelerated approval, but instead are allegedly harmful, failed 12-8. That language essentially was aimed at removing the so-called abortion drug RU-486 from the market.

The only amendments accepted by committee members would give the FDA clearer authority on making drug label changes and require the agency to review state-approved medical marijuana as it would any other therapeutic, subjecting it to a REMS as well.

Coburn said he planned to offer an amendment on the Senate floor to protect rural patients from access problems that REMS could pose to them. Additionally, Clinton withdrew an amendment to remove the pediatric exclusivity laws' five-year expiration, and Sen. Sherrod Brown (D-Ohio) withdrew his amendment to curtail the abuse of citizens' petitions.

The Senate activity on PDUFA and other FDA-related proposals comes on the heels of a House subcommittee hearing on renewing the user fee law. Similarly, many of those members have indicated their desire to merge the reauthorization process with efforts to improve the agency's safety regulations, and some - namely Waxman - also have expressed their wish to incorporate follow-on biologics language into a final package. (See BioWorld Today, April 18, 2007.)

In addition, all the action coincides with a concentrated industry lobbying effort dedicated to a range of issues that's been going on this week. Sponsored by the Biotechnology Industry Organization, the annual legislative event included more than 200 industry representatives who scheduled more than 275 meetings with key congressional members.