FDA will begin a pilot program for end-of-Phase IIa meetings in advance of a draft guidance expected to be issued in early 2004.

The meeting would be a voluntary additional component of the product development process.

In deciding whether to accept a sponsor's request for the meeting, FDA will consider: (1) the drug compound and mechanism of action, (2) the data and methods of analysis presented by the sponsor, and (3) questions raised by the sponsor.

FDA is particularly interested in first-in-class new molecular entities, fast-track products or drugs with continuous marketing applications. FDA is also interested in drugs with well-understood mechanisms of action.

The goal of the meetings is "to decrease any avoidable product development costs and increase the quality of drug applications through early meetings with sponsors," an FDA ¹ concept paper states.

The concept paper was included in briefing documents for the Nov. 17 Pharmaceutical Science/Clinical Pharmacology Advisory Subcommittee meeting.

FDA believes that the end of Phase IIa is a good time to meet with sponsors because it balances the benefit of meeting early on with having adequate data to properly assess the clinical trials.

"The rationale for the meeting time, end of Phase IIa, we think it's at this point that there's basically complete information on preclinical pharmacology and exposure-response," FDA Office of Clinical Pharmacology & Biopharmaceutics Director Lawrence Lesko, PhD, said. "We have some initial efficacy, or 'proof-of-concept,' data. So, taken together, this information forms a fairly rich database."

FDA said that it expects to issue an end-of-Phase IIa "process guidance" by January.

The goal of the meetings would be "to discuss exposure-response issues" and "use of dose-response and pharmacokinetics-pharmacodynamics studies and data" which would be used in part "to support drug dosing."

FDA previously indicated that establishing "a true dose-response relationship early in clinical development" is beneficial to sponsors (² Also see "“Optimal” Dose Finding Could Result In More Late-Stage Drug Success" - Pink Sheet, 28 April, 2003., p. 9).

During the meeting, several case studies were presented by FDA to illustrate that early dose selection reduces approval time (see ³ Also see "Bayer Repinotan Development Slowed By Dosing Issue, FDA Documents Show" - Pink Sheet, 24 November, 2003. ).

Subcommittee member Howard McCleod, Washington University in St. Louis, said that the case studies discussed did not sufficiently illustrate the benefit of end-of-Phase IIa meetings. "We really don't have enough data to say that this is a good thing," he said.

Asked why industry might make poor dose selections, Lesko said, "I don't think it's an issue of people are too dumb to know what do to. I think it's an issue of a fair amount of uncertainty in the drug development process for a number of reasons and the agency can offer some experience that it has from its NDA review."

Subcommittee member Wolfgang Sadee, PhD, Ohio State University, expressed concern that an early meeting could actually be problematic. "The strategy could be reviewed and agreed upon, but that might be dangerous, too, because it could lock the agency into something and we're going to move forward and it could turn out to be wrong, " he said.

Another possible drawback of an early meeting could be bureaucratic inefficiency, subcommittee member David Flockhart, MD/PhD, Indiana University, said.

"To me, it's a trade-off between whether this would really make drug development better versus it would just be another piece of red tape, another hurdle that people would have to jump through," Flockhart said.

FDA expects to run its pilot program on the meetings for several years.

"We think it'll be at least two or three years out before we have enough examples of this to determine whether it's even helpful or not," Lesko said. "I think we can look at this somewhat systematically and see what impact it might have."

FDA Will Begin End-Of-Phase IIa Meetings Prior To January Guidance

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