Though development of Risk Evaluation and Mitigation Strategies delayed FDA review decisions in 2008, the agency said that going forward sponsors can expect to begin REMS discussions with FDA as early as Phase II.

Speaking at a CDER "town hall meeting" at the Drug Information Association annual meeting June 25, FDA Office of New Drugs Deputy Director Sandra Kweder and Office of Surveillance and Epidemiology Director Gerald Dal Pan acknowledged the delays that that occurred as FDA tried to apply the new provisions of the FDA Amendments Act to product development programs that had been under way for years.

"There is no question that [FDAAA] and its provisions surrounding REMS have negatively affected our ability to meet PDUFA goals," Kweder said, adding that in FY 2008 the agency was very honest about saying "'we're gonna miss some goals because we've gotta get this right and we're just putting it together.' We didn't have a lot of lead time on how to do this, either internally or externally for folks in the industry" (¹ Also see "FDA New Drug Review Performance May Miss Lowered Expectations – Jenkins" - Pink Sheet, 29 September, 2008., p. 21).

But as both FDA and industry gain comfort and familiarity with the FDAAA changes, those will become "business as usual" and start being considered and discussed earlier in the process, Kweder added, "and we'll have more models to have learned from." She pointed out that the agency was very honest about saying that, for FY 2008, "'we're gonna miss some goals because we've gotta get this right and we're just putting it together.' We didn't have a lot of lead time on how to do this, either internally or externally for folks in the industry."

Though many applications wound up with missed user fee goals, in most cases FDA has taken action within weeks (See "Running Late: What It Means When FDA Misses A Deadline," ² The RPM Report, August 2008).

The bigger impact has come from implementation of the biggest change under FDAAA: the REMS authority. An early analysis found that developing a REMS proposal and the subsequent FDA review has added from two to nine months to approval times (³ [A#00710020003], p. 14).

As REMS decisions and requirements become more a part of the daily business at FDA and industry, she said the agency is hoping and expecting "we will be doing this better and it will not affect PDUFA deadlines, as it has this year."

Kweder said that understanding what has gone smoothly and what has presented unforseen difficulty will inform future REMS discussions and allow those discussions to begin earlier in the development process. "We have told our staff, 'look, there are some situations where you can probably anticipate some of this stuff as early as Phase II.'"

Also speaking at the CDER town hall session, Dal Pan explained that earlier risk management discussion have been and will continue to be an agency goal.

"Since the initiation of PDUFA III we have tried to send someone in my shop, in risk management, to the pre-NDA meeting, and we're still doing that. I think ideally we would be sending people to the end of Phase II meeting as well, and if we can staff-up to do that, we will be doing that."

"REMS are as new for [the risk management staff] as they are for all of you. It's not that we hold some secret and we're just not telling anybody about it. We're all navigating through this and trying to figure it out," he said. Dal Pan echoed Kweder's assertion that as REMS become more routine, the discussions will move earlier in the process.

Still, he said, there are some situations in which the need for a REMS may not be uncovered early enough to guarantee on-time review decisions.

"That having been said, it's hard to manage a risk if you don't know what that risk is. So sometimes very early in development, we're not going to know what that risk is unless it's a class issue. Sometimes we're still learning in the fourth, fifth, sixth and seventh months of the review cycle how the medical review division is really thinking about the particular risk that may need a REMS, and until that risk is really clarified, we really don't know what that REMS will be."

-Jamie Hammon (j.hammon@elsevier.com)

Sponsors Can Expect REMS Discussions As Early As Phase II, FDA Says

More from Archive

More from Pink Sheet