A newly released FDA draft guidance detailing a roadmap for acceptable dissemination of information on off-label drug use implies that companies need to garner enough data for a new drug application before distributing content.

How that recommendation is received may go a long way toward deciding the utility of the document once it is finalized, as the agency tries to balance the guidance to address the concerns of congressional critics who think the guidance is too permissive, and outside watchdogs who find it too restrictive. Comments are due by April 21.

FDA must perch its recommendations between these two chasms: the agency is working from an expired congressional mandate and is still under injunction from a suit brought the last time it tried to formally advise firms on how to disseminate reprints.

While the basic tenor of the ¹ draft guidance is the same as the 1998 rule that it essentially replaces, FDA has made several changes (see chart: "² Not Merely A Reprint: FDA's Off-Label Draft Departs From FDAMA"). For example, whereas the rule said that sponsors must intend to file for a supplemental indication if they are going to distribute reprints, the draft guidance says only that that the studies should describe "adequate and well controlled investigations."

Judging from the reaction to the draft, FDA has not quite satisfied all parties. "By saying that the minimum requirement is the study has to be adequate and well-controlled - they don't define what they mean by that, but those terms are used in the drug approval business to refer to the kind of studies that are adequate to support an NDA," Richard Samp, chief counsel for the Washington Legal Foundation, told "The Pink Sheet."

"If they're serious about that, of course no one's ever going to be able to send out a reprint."

The draft is not a replacement for section 401 of the 1997 FDA Modernization Act, which expired Sept. 30, 2006, Samp argued. "This doesn't really replace § 401 - it's far more draconian."

WLF challenged FDA's dissemination policy in FDAMA on the grounds of violating the First Amendment in 2000 (³ Also see "WLF Appeals Court Decision Leaves Free Speech Question Open" - Pink Sheet, 14 February, 2000., p. 3). But an appellate court declared the case moot on FDA's assurances that the provisions provided a safe harbor (⁴ Also see "Off-Label Promotion Cases Need Better Oversight In Justice Dept., WLF Says" - Pink Sheet, 23 May, 2005., p. 22).

"If you wanted to say, 'Okay, the safe harbor has been eliminated so we're going to create a new safe harbor,' that would be fine. But they're not calling this a safe harbor, they're calling this a guidance document."

The guidance does contain a statement similar to a safe-harbor. If distributors follow the guidance recommendations, "FDA does not intend to use the distribution of medical and scientific information as evidence of an intent by the manufacturer that the product be used for an unapproved use."

"Guidance documents, unlike safe harbors, are not things that can be just freely tossed aside," Samp continued. "What is it about the current guidance that is somehow more lenient than the one that was already struck down? I've yet to find something - it seems to be, if anything, stronger."

FDA Not Yielding To Congressional Pressure

FDA notes in the Feb. 15 draft that off-label promotion is prohibited but released the draft guidance "in recognition of the public health value to health care professionals of receiving truthful and non-misleading scientific medical information."

The draft was issued unchanged from a confidential internal copy Rep. Henry Waxman, D-Calif., released Nov. 30, the same day he sent a strongly worded letter to Commissioner Andrew von Eschenbach (⁵ Also see "FDA’s Off-Label Dissemination Guidance Opens “Loophole” – Rep. Waxman" - Pink Sheet, 3 December, 2007., p. 7).

Calling the draft "ill-advised" both in his letter and in a statement released Feb. 15, Waxman said the document "is great news for the drug industry but terrible for the public health. It caters to the industry's desire to market their products without adequate testing or review. FDA should suspend their proposal to weaken the law until Congress can ensure that the new policies will protect the American people."

A key provision in FDAMA was the requirement for companies to pre-submit dissemination materials and intend to submit a supplement for the off-label use. This requirement was dropped in the draft guidance, Waxman noted.

"The draft guidelines would permit far more dissemination of articles on unapproved uses than was sanctioned under FDAMA," Waxman wrote in his Nov. 30 letter.

Since Congress let the statute expire, Waxman wrote, "The draft guidelines appear to be an effort by FDA to displace Congress and establish by administrative fiat a new system for use of journal articles that lacks the safeguards set by Congress."

FDA Has Questions To Answer

The draft makes the statement that anything not on the label is off-label, said Scott Bass, a partner at law firm Sidley Austin. "The problem is, that's not the law," he told "The Pink Sheet." "You can have information given out that's not in the approved indication language that's not illegal off-label promotion. It's not illegal if you go beyond the label but not into new indications."

WLF plans to file comments on the draft guidance, asking FDA to explain how the agency is not in contempt of court for the draft, "which appears to be at least as restrictive, if not more so," than the policy under injunction.

"One of the things I want to clear up during the course of the comment period is, are they serious about saying that this has to be a study that meets the requirements for getting a new drug approved? If they are, clearly they're in violation of the current court injunction," Samp said.

He also indicated that the various disclaimers FDA imposed in the draft are so severe "that probably they're going to discourage most reprints."

Companies are less willing now to disseminate off-label materials, Samp believes, because there have been more criminal investigations into promotional practices.

Samp is "unaware of a single investigation" based on safe-harbor violations alone, but the government can use the reprints as evidence in investigations for associated activities like obstruction of justice (⁶ Also see "Schering-Plough Faces Criminal Case; Off-Label Promotion May Be One Count" - Pink Sheet, 2 June, 2003., p. 12).

While the guidance clarifies some issues, it is still "neither a safe harbor from FDA nor a protection against [the Department of Justice]," Larry Freedman, a partner in the Health Care Practice at law firm Patton Boggs, told "The Pink Sheet." "DoJ has no buy-in to the guidance, but it is driving the investigations," Freedman added.

- Becky Jungbauer (r.jungbauer@elsevier.com)

Good Reprint Practices: FDA’s Draft Guidance Aims For Middle Ground

More from Archive

More from Pink Sheet