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FDA to Reassess Policies on Unsolicited Requests for Off-Label Information

Differentiating ‘Scientific Exchange’ From ‘Promotion’ Is Complicated
Stephen Barlas

Not just drug manufacturers, but patient advocacy groups too, are pushing the FDA to ease its prohibitions on the dissemination of off-label medication (and medical device) information. The situation with regard to Genentech’s Avastin and Lucentis (bevacizumab) is just one reason why.

Lucentis is indicated for the treatment of the wet form of age-related macular degeneration (AMD), and Avastin is indicated for cancer. Physicians have been using Avastin instead of Lucentis off-label for treating wet AMD for one main reason: Avastin costs $50 per dose, whereas Lucentis costs $2,000 per dose. However, Genentech is limited in what it can tell physicians, P&T committees, and others about how Avastin works when it is used in an off-label fashion for wet AMD.

Michelle H. Rohrer, PhD, Vice President of Regulatory Affairs at Genentech, says:

We believe there is an urgent need for FDA to reassess how it regulates manufacturer speech relating to drugs and biologics in a way that preserves the drug-approval process while permitting the free exchange of truthful, non-misleading scientific information that advances science and benefits patients.

The FDA is in the midst of that reassessment, stimulated by receipt of a Citizen Petition from seven pharmaceutical companies last July: Allergan, Eli Lilly, Johnson & Johnson, Novartis, Novo Nordisk, Pfizer, and Sanofi.1,2 The petition argued that there was a “significant lack of clarity” in the FDA’s policy on off-label communication; this policy must be pieced together from various documents that are not only difficult to find but also “non-binding.” The petition requested that the FDA clarify its policies in the following areas:

  • drug manufacturers’ responses to unsolicited requests
  • scientific exchange
  • interactions with formulary committees, payers, and similar entities
  • dissemination of clinical practice guidelines to third parties

The FDA responded to the petition by issuing two different, but closely aligned, documents within 2 days of each other in December. One was a draft guidance,3 and the other was a request for comments to assist the FDA in evaluating policies for off-label uses of both approved and investigational drugs and devices, particularly the kind of “scientific information” manufacturers may supply without being cited for “promoting” off-label uses, which is illegal. The comment periods closed March 27, and the FDA has been pondering its next move.

It is noteworthy that a number of AIDS foundations responded to both FDA notices. Robert Reinhard, a board member of the AIDS Vaccine Advocacy Coalition (AVAC), said that “much ambiguity remains or is created by the Draft Guidance. That ambiguity may frustrate medical, non-promotional delivery of data to improve patient care.”4

Communication by pharmaceutical companies about off-label uses for drugs and medical devices has been a controversial issue for decades, with the industry chafing at the FDA’s restrictions against promoting these uses. Drug manufacturers claim that these restrictions are a restraint against the First Amendment, free speech rights of companies. A case brought by the Washington Legal Foundation in 1998 resulted in a ruling by the federal court that forbade the FDA from blocking manufacturers from disseminating certain journal articles or medical texts that discussed off-label uses of their FDA-approved products.5

The key aspect of the draft guidance is that it would establish a “safe harbor” for companies whose dissemination of off-label information, in response to an unsolicited request for such data, meets guideline requirements. The FDA says that scientific or medical information should be “truthful, non-misleading, accurate, balanced, and non-promotional” and “tailored to answer only the specific question(s) asked.”3 To meet this standard, the guidance recommends that firms disclose certain information to others beyond the questioner when responding to their unsolicited requests. These requirements differ when the company is responding to an unsolicited request in a public forum.

The FDA says that a company would be inside the safe harbor if it uses the Academy of Managed Care Pharmacy’s Format for Formulary Submissions as the basis for tailoring its response to an unsolicited request.6 This format is widely used by managed care organizations and their P&T committees.

As for the FDA’s attempt to distinguish “scientific information” from “promotion,” that is likely to be a more controversial effort. Any policy that the FDA establishes for scientific exchange would be new, and drug companies in particular are nervous about this. If the policy is too restrictive, it could limit researchers’ speech at conferences or their writing in medical journals, especially if the topic concerns drugs in development—even if the information is truthful, non-misleading, and significant.

Jeffrey K. Francer, Assistant General Counsel for Pharmaceutical Research and Manufacturers of America (PhRMA), says:

Particularly in the area of scientific speech, FDA policies that limit the ability of biopharmaceutical companies to participate in scientific discourse are subject to challenge. Payers and formulary committees require up-to-date scientific information about marketed products, including information about uses that have not been approved by FDA, as well as data and information about health care outcomes and the economic consequences of various therapies. Access to such scientific information allows payers to make informed choices about the clinical use of drugs and help ensure that patients receive the best possible care.

The counterargument is that the more leeway drug companies are given, the less incentive they have for applying for approval of a new use of an existing drug. The FDA will weigh both sides of the issue and will need a sensitive scale to balance opposing positions.


  1. Levy DK. FDA Law Blog. Joint Citizen Petition Asks FDA for Clarity on Off-Label Use Manufacturer-CommunicationsJuly 112012;Available at: Accessed May 4, 2012.
  2. Ropes & Gray. Citizen Petition, July 5, 2012 Available at: Accessed May 4, 2012.
  3. Guidance for Industry: Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices December 2011;Available at: Accessed May 4, 2012.
  4. Reinhard R. Re: Docket No. FDA-2011-D-0868. March 262012;Available at: Accessed May 4, 2012.
  5. Washington Legal Found. v. Friedman, 13 F. Supp.2d 51 (D.D.C. 1998).
  6. Fry RN, Avey SG, Sullivan SD. Format for Formulary Submissions: An Evolving Standard—A Foundation for Managed Care Pharmacy Task Force Report Alexandria, Va.: The Academy of Managed Care Pharmacy. 2003;6:5Available at: Accessed May 4, 2012.