On February 15, 2008, the Food and Drug Administration issued a Draft Guidance for Industry: Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical Devices. Its publication comes after several years of silence by the FDA on the dissemination of reprints discussing off-label uses following the U.S. Court of Appeals for the District of Columbia Circuit’s 2000 decision, Washington Legal Foundation v. Henney. It also closely tracks an internal working draft of the Guidance that was released by US Rep. Henry Waxman, D-Calif., in December 2007, along with a letter to FDA Commissioner Andrew von Eschenbach expressing concerns about the policy set forth in the working draft.

The Draft Guidance on Good Reprint Practices provides the FDA’s current thinking on the dissemination of reprints discussing off-label uses and is intended to address a policy gap that exists following the September 2006 expiration of Section 401 of FDAMA. Section 401 of FDAMA created a “safe harbor” for drug and device manufacturers to disseminate article reprints discussing unapproved uses of their approved products so long as several onerous conditions were met.1

In Washington Legal Foundation v. Henney, the Washington Legal Foundation challenged the FDAMA provisions permitting reprint dissemination on the grounds that they violated the First Amendment. In response to that legal challenge, FDA conceded that the FDAMA provisions operate as a “safe harbor” only and that, under the First Amendment, the agency cannot establish an outright prohibition or restriction that prevents drug manufacturers from distributing reprints outside of the FDAMA Safe Harbor. Ultimately, the decision in Washington Legal Foundation preserved Section 401 of FDAMA as a safe harbor, but did not provide additional guidance to industry on acceptable practices related to the dissemination of reprints. Since that time, FDA has done very little to develop a formal reprint policy: the FDAMA Safe Harbor was rarely invoked by industry and FDA has otherwise been conspicuously quiet on the issue.

The Draft Guidance sets forth a more permissible standard for the dissemination of reprints discussing off-label uses than did the FDAMA safe harbor. Nevertheless, like Section 401 of FDAMA, the Draft Guidance operates as a safe harbor - that is, if a company distributes reprints in accordance with the Draft Guidance and does not otherwise unlawfully promote its products, FDA says it will not use such dissemination as evidence of the manufacturer’s intent to promote an off-label use. While failure to comply with the Draft Guidance may not be used as an independent basis for enforcement action, the agency may use distribution of reprints outside its safe harbor as evidence of the company’s intent. In addition, as with Section 401 of FDAMA, the policy set forth in the Draft Guidance does not apply to scientific or medical information disseminated in response to unsolicited requests for information from healthcare professionals.

In order to fall within the safe harbor proposed by the Draft Guidance, manufacturers may only disseminate either (1) scientific or medical journal articles that are peer-reviewed and published by a journal that uses an editorial board and independent, recognized experts to review manuscripts or (2) scientific or medical reference publications that are generally available in bookstores or other independent distribution channels where medical textbooks are sold. Any reprints should not be part of a special publication funded in any part by a manufacturer of a product discussed in the article. The scientific or medical reference publications should not be written, edited, excerpted, or published specifically for, or at the request of, a drug or device manufacturer.

The Draft Guidance also presents criteria for the scientific or medical information itself. When contained in a publication disseminated by a pharmaceutical manufacturer, such information should be derived from adequate and well-controlled clinical trials that are considered scientifically sound, not false or misleading, and do “not put the public health at risk.” The Draft Guidance says that the distribution of the following would not fall within the scope of the Draft Guidance: letters to the editor, abstracts of a publication, reports of Phase 1 trials in healthy subjects, or reference publications that contain little or no substantive discussion of the relevant investigation or data.

Finally, the Draft Guidance includes standards for the physical act of disseminating a reprint or text to practitioners. Manufacturers would be in compliance as long as the reprint or text is complete and not altered by the company distributing them. In addition, the reprint or text should have a permanent and prominent label that discloses any conflicts of interest (e.g., whether an author has a financial interest in the product), the manufacturer’s interest in the product, any author known to the manufacturer as having a financial interest in the product (or the manufacturer itself) or receiving compensation from the manufacturer, and the fact that the use has not been approved or cleared by the FDA. The reprint or text should also be accompanied by the product’s approved labeling and a “comprehensive bibliography” of adequate and well-controlled clinical studies that have been previously published about the use. In cases where the conclusions of the article or text have been specifically called into question by another article or text, the reprint or text should be disseminated with a representative publication that reaches contrary or different conclusions regarding the unapproved use.

Further, if disseminated directly by sales representatives, the reprint or text should not accompanied by or linked to actual promotional materials. Indeed, the Draft Guidance stresses the importance of disseminating a reprint or text separately from promotional efforts. It suggests that any dissemination discussing off-label uses at medical or scientific conferences be done away from promotional exhibit halls and away from promotional speakers’ programs. Furthermore, if a sales representative delivers such reprints directly to a healthcare professional and receives questions from the recipient, such questions should be referred to a medical/scientific officer who is separate from the sales and marketing staff.

FDA will be accepting comments on the Draft Guidance until April 21, 2008.

The Federal Register notice announcing the availability of the Draft Guidance may be found at the following link:

http://www.fda.gov/OHRMS/DOCKETS/98fr/08-746.pdf

The Draft Guidance itself may be seen at the following link: http://www.fda.gov/OHRMS/DOCKETS/98fr/FDA-2008-D-0053-gdl.pdf

If you have any questions about this Draft Guidance or FDA’s policies related to the dissemination of off-label information, or are interested in submitting comments to FDA on the Draft Guidance, please do not hesitate to contact:

Wayne H. Matelski
matelski.wayne@arentfox.com
202.857.6340

Brian P. Waldman
waldman.brian@arentfox.com
202.857.8971

Julia C. Tierney
tierney.julia@arentfox.com
202.828.3427

Joanne S. Hawana
hawana.joanne@arentfox.com
202.715.8951

1 Among other conditions, in order to fall within the FDAMA Safe Harbor, a manufacturer was required to submit a reprint for pre-dissemination review by FDA and be seeking, or intend to seek, approval for the off-label uses discussed in the article.