In a 3 March 2014 Federal Register notice, the U.S. Food and Drug Administration (FDA or the agency) distributed a revised draft guidance document titled Distributing Scientific and Medical Publications on Unapproved New Uses — Recommended Practices (Draft Guidance) for comment. The Draft Guidance, when finalized, is intended to replace FDA’s January 2009 final guidance titled Good Reprint Practices for the Distribution of Medical Journal Articles and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 (2009 Guidance). While the Draft Guidance is largely consistent with the 2009 Guidance, restating and providing additional details that build on the existing criteria for distribution of journal articles describing unapproved uses of drugs and medical devices, it does include new requirements for the dissemination of medical or scientific reference texts and clinical practice guidelines (CPGs), neither of which are explicitly discussed in the 2009 Guidance.
The most notable difference between the Draft Guidance and the 2009 Guidance is the introduction of a new category of publications, i.e., CPGs, that can fall within the “safe harbor” for distribution of publications that discuss unapproved uses of drugs and devices. To fall within the scope of the Draft Guidance, CPGs must meet the Institute of Medicine’s standards for CPG “trustworthiness,” which require that the CPG:
- be based on a systemic review of existing evidence;
- be developed by a knowledgeable, multidisciplinary panel of experts and representatives from key affected groups; consider important patient subgroups and preferences;
- be based on an explicit and transparent (i.e., publicly accessible) process by which the CPG is developed and funded that minimizes distortions, biases, and conflicts of interest;
- provide a clear explanation of the logical relationships between alternative care options and health outcomes, clearly articulated recommendations in standardized form, and ratings of both quality of evidence and strength of recommendations; and
- be reconsidered and reviewed when important new evidence warrants modifications of recommendations.
In its Draft Guidance, the FDA has also introduced new concepts for distribution of reference texts disseminated in their entirety (as opposed to select chapters). While new, these requirements are not wholly different from those previously articulated, and the new concepts are consistent with the agency’s 2009 Guidance. For example, as articulated in the 2009 Guidance, reference texts should be peer reviewed and published in accordance with peer-review procedures for the publisher, which should be easily accessible to the public. Among the newly articulated guidance for these publications are requirements that the reference text should:
- be based on a systematic review of the existing evidence;
- be published by an independent publisher, not substantially dependent on financial support from the manufacturer, who publishes scientific or medical educational content for healthcare professionals and students;
- be authored, edited, and/or contributed to by experts who have demonstrated expertise in the subject area; and
- be sold through usual and customary distribution channels.
In addition, reference texts and CPGs distributed in their entirety under this guidance should meet the following requirements:
- be the most current version of the publication;
- be distributed separately from delivery of information that is promotional in nature;
- be provided with the approved or cleared labeling of the manufacturer’s product or products that are the subject of a primary substantive discussion within the publication; and
- contain a prominently displayed and permanently affixed statement identifying the distributing manufacturer and disclosing that some of the uses of drugs and/or devices described in the publication might not be approved or cleared by FDA. The statement should also disclose that the author(s) of some sections might have a financial interest in the manufacturer or its products, unless the manufacturer has verified that none of the authors for the publication has a financial interest in the manufacturer or a product being written about. This statement should be placed by sticker, stamp, or other similar means on the front cover or front page of the reference text or CPG, respectively.
The criteria for distribution of reference texts and CPGs when disseminated in their entirety serve as the foundation for distribution of selected chapters or sections from these publications, although additional requirements have been set forth for distribution of such materials when only a selected chapter or section is disseminated. Should the manufacturer wish to distribute a specific chapter or section of a reference text or CPG, respectively, the excerpted chapter or section should:
- be unaltered/unabridged and extracted directly from the publication in which it appears;
- when necessary, to provide context, be disseminated with other unaltered/unabridged chapters or sections extracted directly from the same publication, such as chapters or sections that provide related or supportive information; and
- contain a prominently displayed and permanently affixed statement consistent with that required under the 2009 Guidance.
Regardless of the type of publication distributed, the restrictions for what the publication must not and should not be are identical and consistent with the restrictions articulated in the 2009 Guidance, including that the publication cannot be false or misleading or contain information recommending or suggesting a use of the manufacturer’s product that the manufacturer knows to be dangerous to health.
In sum, the FDA’s new Draft Guidance articulates criteria for dissemination of scientific and medical publications that are largely consistent with those in its 2009 Guidance. The major differences between the Draft Guidance and the 2009 Guidance are: (1) the broadening of the scope of the guidance to include CPGs as an additional type of publication that can disseminated under the guidance’s “safe harbor” and (2) the articulation of specific criteria for dissemination according to the type of material disseminated.
Consistent with prior agency policy and practice, if manufacturers follow the recommendations in the Draft Guidance to disseminate scientific or medical publications describing unapproved uses of their products, the FDA does not intend to use such distributions as evidence of the manufacturer’s intent that the product be used for an unapproved new use.
The Draft Guidance has been published in the Federal Register to give the public the opportunity to provide comments and suggestions on the agency’s recommendations. Any such comments and suggestions should be identified with Docket Number FDA-2008-D-0053 and submitted on or before May 2, 2014, to http://www.regulations.gov or to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.