The Food and Drug Administration (FDA) issued a revised draft guidance document in February 2014 entitled, “Guidance for Industry: Distributing Scientific and Medical Publications on Unapproved New Uses – Recommended Practices.” The guidance updates the draft guidance issued in January 2009 entitled, “Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or Scientific Reference Publications on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.” The Food and Drug Modernization Act (FDAMA) (21 U.S.C. § 360aaa) amended the Food, Drug, and Cosmetic Act (FD&C Act) to include the regulatory conditions under which a reprinted published medical or scientific article may be distributed by a manufacturer to healthcare professionals and related healthcare businesses.The regulatory issue continues even though the FDAMA amendment is no longer in effect.
The purpose of establishing Good Reprint Practices was to describe the conditions under which medical or scientific literature concerning off-label use of a drug, biologic or medical device could be distributed without prompting FDA to say the information misbranded a product that has an approved use. The Good Reprint Practices created a “safe harbor” for off-label use information that would otherwise be prohibited based on a misbranding charge. Manufacturers must heed the guideposts of “should” and “should not” when navigating within the safe harbor.
FDA uses several factors to determine whether or not a medical or scientific journal article stays within the safe harbor. By following FDA’s guidance on what a manufacturer should and should not do, FDA will not use the dissemination of the reprinted medical or scientific article as evidence of a manufacturer’s intent to promote and market an off-label use.
A manufacturer should consider the following before it disseminates a reprint of a medical or scientific article about an unapproved use:
1. The article should be published by an entity with an independent editorial board with relevant expertise and objectivity.
2. The editors, authors and contributors associated with the article are subject to full disclosure of a conflict of interest based on a publicly stated policy.
3. The article should be peer-reviewed under the publishing organization’s established procedures.
4. The article should appear in its unabridged form.
5. The article should describe the information in the context of being derived from adequate and well-controlled clinical investigations.
6. The article should be disseminated with the product’s approved labeling.
7. A comprehensive bibliography should be disseminated with information from other publications that is contrary to the results.
8. The article should not be used in conjunction with or associated with any other promotional literature or activity.
The following are steps that a manufacturer should not take when disseminating a medical or scientific article about an unapproved use:
1. It should not be funded to any degree by one or more of the manufacturers’ products that are related to the article’s subject.
2. It should not be altered to highlight, emphasize or promote an unapproved use.
3. It should be disseminated primarily by the manufacturer as opposed to through an independent distribution channel.
4. It should not be written, edited, excerpted, significantly influenced or published for, or at the request of, the manufacturer.
5. The article should not be attached to other specific product information.
In addition to the above steps that a manufacturer should and should not take, FDA also looks at the context in which the information is provided. For example, the article should not be placed in proximity of the manufacturer’s products and promotional literature at a trade show for products it markets legally. The reprint should be marked with a disclosure about the manufacturer’s interest in the product and state that the off-label use has not been approved by the FDA. Financial conflicts of interest on the part of the manufacturer, author and any entity affiliated with the author are a major concern. Conflicts of interest should be fully disclosed. Likewise, the source of funding for the medical or scientific study should be identified.
Apart from providing a safe harbor for medical and scientific information about off-label use, there are practical professional considerations that involve the off-label use of the product for treating patients. The manufacturer should provide what information it has regarding the risks associated with the unapproved use and include precautionary information and warnings that are already associated with the product.
The boundaries for FDA’s safe harbor are not new. FDA started to develop the concepts for Good Reprint Practices in 1997 in response to FDAMA. The updated draft guidance serves to illustrate how manufacturers should avoid creating false or misleading or otherwise violative information, even under the guise of professional education. The safe harbor raises questions about the information itself, how and where it is disseminated and any conflicts of interest that may be associated with the reprinted article.