FDA Reform Bill Will Keep Firms Scrambling To Stay Ahead On Safety Issues
Pharmaceutical companies need to immediately begin assessing whether their drugs are subject to the risk evaluation and mitigation strategies provisions of the FDA Amendments Act, participants were warned during a Food and Drug Law Institute audioconference on the new law, Oct. 4.
If an approved drug already is governed by restrictions to ensure safe use, the REMS provisions become effective 180 days after the Sept. 27 enactment date of FDAAA and companies have another 180 days to submit their REMS for approval.
"It's going to be very important for companies right now to start assessing" whether their product is subject to the "existing" REMS provision and get a proposal "together and ready to be submitted," Scott Lassman of WilmerHale said.
A drug will be "deemed" to have an existing REMS if it already is subject to safety requirements, such as distribution and use restrictions, he explained.
If a firm has "a grandfathered REMS product, you better get cracking," Bruce Burlington, an independent consultant and former Wyeth VP, agreed. Companies have a year to actually submit the REMS, and "part of that initial submission is undoubtedly going to be expected to be an assessment of how well it's working."
Companies also must get aggressive in looking at safety issues associated with their other drugs, Burlington said. (see chart: "1Waking the REMSing Giant")
The new law directs FDA to review adverse events databases every two weeks to look for new safety information or safety signals of serious adverse events, he pointed out. Such a finding can trigger a REMS request for already approved drugs (see chart: "2Stages of REMS").
"What the potential signal of a serious adverse event is, as opposed to the risk of a serious adverse event, as opposed to the de facto demonstration of an adverse event, I don't know," Burlington said. "But if it turns out that you get a notice from the [HHS] Secretary saying you've got one, you better get prepared to start talking about one of these risk mitigation elements."
Despite the urgency expressed at the FDLI conference, FDA experience with Risk Minimization Action Plans could be an indication that implementation of REMS will be slow going.
The agency has been setting safety-based restrictions on drugs through risk management plans since 2002. But at a public workshop last summer, Office of New Drugs Deputy Director Sandra Kweder indicated that the agency has yet to develop criteria for when a RiskMAP should be imposed (3"The Pink Sheet" July 2, 2007, p. 13).
The agency also lacks standards for when to remove RiskMAP restrictions from a product and methods to evaluate the impact of RiskMAP elements. Understaffing has also undercut FDA's efforts to implement an effective program.
For its part, industry has been lax in its approach to developing plans. The agency says that only about 25 percent of 130 plan submissions received by December 2006 follow FDA guidance for organization of the materials (4"The Pink Sheet" March 5, 2007, p. 9).
As of February 2007, 30 products had RiskMAPs, nine of which were developed post-approval.
The extent to which FDA utilizes the REMS authority remains to be seen. "It may be that FDA, now that it has more explicit authority, will be more likely to use it than they have in the past when the authority's been more questionable," Lassman said.
John Kamp, of Wiley Rein, predicted that the REMS authority will be used and noted that past plans have included restrictions on advertising. Although formal prohibitions on ads were not included in the final bill, "the possibility of the FDA using the REMS program for limiting marketing is something that is very real."
Burlington stressed that the new active surveillance system put in place by FDAAA necessitates that companies keep on top of their drugs' safety issues.
Because the new system will be a public/private partnership and examine a wide variety of databases, including electronic health records, safety information will become public "much more rapidly" than is the case now, he said.
To keep up with the information curve, he noted that firms must access the same or similar databases and have the analytical tools to conduct prospective studies. Drug manufacturers must "take broader responsibility and new approaches to understanding the safety profile of your drug and what is likely to turn up when other people start digging into the databases."
Another option, he suggested, is for pharmaceutical companies to consider "ways that you can improve [a drug's safety] profile through the way you position and market and detail your drug. If you can get patients who are likely to have good outcomes and avoid patients who are likely to have bad outcomes using your drug, then the databases will have better results in them and you'll be in better shape when people start poking around in the database."
The new safety authorities will not only affect how industry conducts its business but also impact FDA activities, Bret Koplow of Patton Boggs predicted. FDAAA's new safety authorities will make it easier for Congress and watchdog groups to assess FDA's performance, he said.
"By setting forth all of these different types of tools and by explicitly giving FDA these authorities, to the extent that they're not used, it will be that much more apparent," he concluded.
The result is the safety authorities could "become a club that will be used to attack FDA." In the past few years, FDA already has taken "a lot more cautious actions, knowing that they're under scrutiny and ... these additional authorities will lead probably to some sustained additional imposition of risk management by FDA."
But no matter what the law dictates, complete drug safety cannot be achieved, conference moderator Wayne Pines, APCO Worldwide, pointed out.
Congress has enacted a law that "it regards as a solution to all drug safety issues," he said. So "the next time - and it's inevitable it will happen; there will be a drug safety issue - people on the Hill will be scratching their heads, ... and say, 'Well, what else do we need to do in order to make sure that there aren't any drug safety problems?' And all of us who have been in this world for a long time know that there's not a whole lot that you can do to avoid the likelihood that there will be drug safety problems at some point in time."
- Cathy Dombrowski
This article is reprinted from "The Pink Sheet" – October 8, 2007
Click here to start your 30-day, risk-free trial of "The Pink Sheet" – Top down, comprehensive weekly industry insight and analysis.
© FDC Reports 2007 - All Rights Reserved
