FDA guidance on reprint practices: Dissemination of off-label information OK

In newly released guidance for industry regarding good reprint practices for the distribution of journal articles and reference publications on off-label uses of approved drugs, FDA states that distribution of such materials is acceptable if the publications meet certain criteria for objectivity.

Previously, section 401 of the FDA Modernization Act (FDAMA) addressed dissemination of information on off-label uses of approved drugs to healthcare professionals. This regulation stated that information on off-label use could be disseminated to healthcare professionals if the manufacturer had submitted or planned to submit a supplemental application for the indication under discussion. Manufacturers also were required to submit the materials to be disseminated to FDA for review. This regulation expired on September 20, 2006. FDA released a draft of good reprint practices guidance on February 15, 2008, asking for public comments on the draft. The final guidance was released earlier this month.

The new guidance sets forth several conditions for appropriate publications to be used for dissemination. Articles must be peer reviewed and published by an organization with an independent editorial board and with a publicly stated policy regarding full disclosure of conflicts of interest. Articles or reference publications must not be in the form of a special supplement funded partly or in whole by the manufacturer of the product under discussion. Publications should be generally available in bookstores or through other independent channels of distribution (eg, subscription, internet) and should not be written, edited, excerpted, or published specifically for the manufacturer. The publications must not be edited or significantly influenced by a drug manufacturer or by any individuals with a financial relationship with the manufacturer.

Articles can address randomized, controlled studies, as well as historically controlled studies, pharmacokinetic and pharmacodynamic studies, and meta-analyses that test a specific clinical hypothesis; letters to the editor, abstracts, reports of phase 1 trials in healthy volunteers, and reference publications with little or no substantive discussion of an investigation are not considered appropriate articles for dissemination.

According to this guidance, disseminated information should not be highlighted or summarized by the manufacturer; should be accompanied by the approved labeling for the drug and by a comprehensive bibliography of publications discussing studies about the drug under discussion; should be accompanied by a publication, when possible, that reaches contrary conclusions about the unapproved use; and should be distributed separately from information that is promotional. The reprint should also be accompanied by a prominent statement disclosing 1) that the drug is not approved for the indication under discussion; 2) the manufacturer’s interest in the drug; 3) financial interests of the authors; 4) identity of the study’s funders; and 5) any significant risks of the unapproved drug use that are known to the manufacturer.

Manufacturers are no longer required to submit the materials to be disseminated to FDA for review; nor are they required to submit or plan to submit a supplemental application to FDA for the indication under discussion. In the guidance, however, FDA states, “The Agency recognizes the value of having new indications and intended uses for products approved or cleared by FDA and encourages sponsors of medical products to seek such approvals or clearances.”

FDA states that “off-label uses or treatment regimens may be important and may even constitute a medically recognized standard of care. Accordingly, the public health may be advanced by healthcare professionals’ receipt of medical journal articles and medical or scientific reference publications on unapproved new uses of approved or cleared medical products that are truthful and not misleading.”

This guidance represents FDA’s current position on the issue of good reprint practices; it does not “establish legally enforceable rights or responsibilities.”

The complete guidance is available at http://www.fda.gov/oc/op/goodreprint.html.