FDA NDA/BLA Early Input Letters: How Much Should Be Publicly Disclosed?

FDA is concerned about how companies will communicate information included in the agency's early feedback letters on pending applications, Office of New Drugs Director John Jenkins, MD, said Oct. 8.

If FDA issues a letter saying that it has not identified any deficiencies during the initial filing review, "it would be very misleading and a false sense of security for the company and others to go out and tout that [as a] 'no deficiency identified letter' or something more significant than it really is," Jenkins told attendees of the Regulatory Affairs Professionals Society annual meeting in Washington, D.C.

"Any time we give you preliminary comments on a review, particularly after we've only seen it for 60 days, those are very preliminary comments," Jenkins said. "You may run risks that you're responding to something that won't be a problem later."

FDA is "somewhat concerned that industry not misuse a statement...that we haven't identified any substantial issues in the filing. We'd be very disappointed if companies are going out and touting them as being 'oh, FDA's reviewed our application and everything looks great.'"

Under the Prescription Drug User Fee Act III, FDA must report to sponsors within 14 days any deficiencies in an application that are identified during the agency's initial 60-day filing review. The commitment was included as part of FDA's effort to improve its first-cycle review record (¹ (Also see "PDUFA III Implementation Begins: FDA Working Groups Under Way" - Pink Sheet, 17 Jun, 2002.), p. 3).

FDA has termed the first-cycle review performance letters "74-day filing letters," Jenkins said, because they are to be issued 14 days after FDA's 60-day deadline for issuing preliminary comments.

Jenkins said that FDA is developing language to clarify the purpose of 74-day letters. "We are planning to include caveat language in all those communications," he noted. "We've been working hard to draft that language to make very clear what these communications are. Obviously we hope that people will use them wisely and not abuse them, but this was one of our major concerns during the discussions."

AstraZeneca VP-Regulatory Affairs Anthony Rogers agreed that preliminary comments from FDA about a pending application could be problematic.

"The early feedback is a double-edged sword," Rogers said. "The last thing we want to see are press releases coming out saying, you know, 'for 74 days, you know, everything is looking okay."

"You have to treat [the '74-day filing letter'] for what it is. It's an early look....We have to measure our response around that."

Pharmaceutical Research & Manufacturers of America Associate VP-Regulatory Affairs Alan Goldhammer, PhD, noted that if a company considers the information provided in a 74-day filing letter to be material, it would be obligated by law to disclose it.

"It boils down to what the Securities & Exchange Commission wants. If something's material, you know, you really have to disclose it to the investment community," Goldhammer said.

"It's a very difficult issue and I think it probably is more so for small companies," he added. "It will be interesting to see how that goes."

It sounds as if the agency is suggesting "a code of FDA regulatory behavior practices," Goldhammer said. "We just did a code of marketing practices, we just did a principle of clinical trials....We have not considered a code of principles for how we would react."

PhRMA announced its voluntary guidelines for interactions with healthcare professionals in April and adopted a code on clinical trial results publication and data ownership in June ("² (Also see "PhRMA Clinical Trial Principles Restate Proprietary Rights To Protocols" - Pink Sheet, 24 Jun, 2002.), p. 3). PhRMA is now considering a code on direct-to-consumer advertising (³ , p. 13).

Jenkins said that an FDA working group convened over the summer to develop internal procedures for implementing the 74-day filing letters.

"We're hoping to have an internal procedure...a [Manual of Policy & Procedures]...done very shortly," Jenkins said. "Applications as of last week would need these filing deficiency letters. We've got 74 days from Oct. 1 to make sure we have the procedures in place."