On January 13, 2008, the U.S. Food and Drug Administration (FDA) issued its final “Good Reprint Practices” guidance regarding the distribution of medical or scientific journal articles and reference publications that involve unapproved (off-label) uses of FDA-approved drugs and medical devices.1 The final guidance largely follows the draft guidance, but does include several notable new or revised provisions. Congressman Henry Waxman, now the Chairman of the House Energy and Commerce Committee (with jurisdiction over the FDA in the House) who disagreed with the content of the draft guidance, has already objected to the final guidance. We expect that there will be pressure on the new administration to re-examine2 the guidance. Nonetheless the final guidance contains important principles for all companies that disseminate (not promote from) off-label reprints.
On February 15, 2008, the FDA issued a draft guidance on “Good Reprint Practices” to guide industry practice in light of the expiration of Section 401 of the Food and Drug Administration Modernization Act (21 U.S.C. § 360aaa). Section 401 set out parameters for dissemination of information on unapproved uses of FDA-approved products and provided that if the guidelines were met, the dissemination of such materials would not be considered evidence of an intent that the product be used for an unapproved new (off-label) use.
The draft guidance provided recommended principles regarding the types of articles, reprints, or reference publications suitable for dissemination, as well as principles governing the manner in which to disseminate such information. The agency accepted comments on the draft guidance and, on January 13, 2009, issued its final guidance.
The Final Guidance
The final “Good Reprints Practices” guidance largely follows the draft guidance and we have noted all changes from the draft on the annotated copy sent along with this Update. There are, however, three notable (non-editorial) changes that are important as companies evaluate any current policies:
- Additional detail on what may qualify as “adequate and well-controlled clinical investigations,” with the addition of “historically controlled studies, pharmacokinetic (PK) and pharmacodynamic (PD) studies, and meta-analyses if they are testing a specific clinical hypothesis.”3
- Revised language on the manner of dissemination providing that the off-label information “be disseminated with a representative publication, when such information exists, that reaches contrary or different conclusions regarding the unapproved use; especially those in cases where the conclusions of articles or texts to be disseminated have been specifically called into question by another published article(s) or text(s)[.]”4
- New language on disclosure of financial interests of authors: “any author known to the manufacturer as having a financial interest in the product or manufacturer or who is receiving compensation from the manufacturer, along with the affiliation of the author, to the extent known by the manufacturer, and the nature and amount of any such financial interest of the author or compensation received by the author from the manufacturer[.]”5 (Emphasis added.)
- While final, this document remains a guidance and is not a legally binding safe harbor. A company’s ability to disseminate appropriate reprints remains grounded in the responsible application of First Amendment principles of commercial free speech.
- No appellate court has addressed the strength or limits of this First Amendment protection.
- FDA’s guidance is not unique in recognizing the importance of off-label uses or treatment regimens to the practice of medicine and the role of companies in helping medical professionals receive timely and accurate publications regarding off-label uses. Since publication of the draft guidance, one settlement of a state consumer protection case involving off-label drug promotion joined the FDA in acknowledging the importance of distributing off-label information and setting parameters of appropriate reprint dissemination for the company involved.6
- With a finalized guidance document, and where the guidance is followed and there is no other conduct which violates the law, prosecutors are likely to be constrained in attempting to rely solely on the dissemination of off-label information as evidence of intent to promote a product for off-label uses.
- Companies that choose to distribute off-label reprints in ways that go beyond the guidance do so at some increased risk and do so based solely upon First Amendment protection.
- Companies should evaluate current policies against the final guidance.
Representative Waxman has come out strongly against the final guidance calling it “a long-coveted parting gift” issued “in the final hours of this administration” by “political appointees at FDA.”7 Waxman also commented that the guidance “fundamentally undermines the requirement that companies prove to FDA that each new use is safe and effective” and expressed his hope that it “will be carefully re-examined by the new administration.”8 Waxman will likely continue to exercise oversight in this area. It is premature to speculate as to what companies should do in the event that the new administration withdraws this guidance.