With less than a week left in the Bush Administration, the US Food and Drug Administration has finalized its Guidance on 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. This Guidance – released on January 12, 2009 – finalizes and updates a draft version that was published in February 2008, which raised the ire of Rep. Henry Waxman, D-Calif., who is now the new Chairman of the House Energy and Commerce Committee. (Rep. Waxman had released an internal working draft of the document in December 2007 along with a letter to FDA Commissioner Andrew von Eschenbach expressing concerns about the FDA’s articulated policy.)

The final Guidance includes some changes requested by the regulated industry, but it also “encourages sponsors of medical products to seek [] approvals or clearances” for new indications and intended uses. Following the release of the final Guidance on January 12, Rep. Waxman called on the incoming Obama Administration to re-examine the policy, which he regards as a “parting gift” to industry from the Bush Administration.

The final Guidance sets forth a standard for the dissemination of reprints discussing off-label uses for approved products. In essence, the Guidance is intended to operate as a “safe harbor” – that is, if a company distributes reprints in accordance with the 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 Guidance may not be used as an independent basis for enforcement action, the agency may use distribution of reprints outside the parameters of the Guidance or other conduct promoting an unapproved new use as evidence of the company’s intent. In addition, the policy set forth in the Guidance does not apply to scientific or medical information disseminated in response to unsolicited requests for information from health care professionals.

In order to fall within the safe harbor proposed by the 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 (including the Internet) where medical textbooks or periodicals 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 Guidance also presents criteria for the scientific or medical information itself. The draft version of the document limited publications disseminated by a pharmaceutical manufacturer to information derived from adequate and well-controlled clinical trials that are considered scientifically sound, not false or misleading, and do not pose a risk to the public health. The final Guidance expands the types of permissible information to include “historically controlled studies, pharmacokinetic and pharmacodynamic studies, and meta-analyses if they are testing a specific clinical hypothesis.” These additional types of studies take into account industry comments on the draft document highlighting the fact that not all FDA-approved or cleared products are subject to randomized, controlled clinical trials; for example, medical devices that are marketed under the 510(k) notification clearance process generally do not go through such trials. Moreover, the final Guidance provides a more industry-friendly standard for determining when information would be considered “false or misleading.” The draft document described any information that was inconsistent with the weight of credible evidence to be false or misleading. The final Guidance notes that such inconsistent information “should not be characterized as definitive or representative of the weight of credible evidence” otherwise the information may be false or misleading. Distributing the following would not fall within the scope of the 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.

The final Guidance includes standards for the physical act of disseminating a reprint or text to practitioners and other health care entities (such as hospitals and drug formulary committees). Manufacturers would be in compliance as long as the reprint or text is complete and not altered by the company distributing it. 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 as well as the author’s affiliation; the nature and amount of any financial interest of an author (to the extent known by the manufacturer) or the nature and amount of compensation received from the manufacturer; and the fact that the use has not been approved or cleared by the FDA. The requirement to disclose the nature and amount of an author’s financial interest or any compensation the author received from the manufacturer was added to the final Guidance as a result of public comments on the draft document. The reprint or text also should 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 (if such information exists). 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 be accompanied by or linked to actual promotional materials. Indeed, the 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.

The Guidance is available here.

If you have any questions about this Guidance or FDA’s policies related to the dissemination of off-label information please do not hesitate to contact one of the following Arent Fox attorneys:

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

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

James R. Ravitz
ravitz.james@arentfox.com
202.857.8903

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