WLF Redux? FDA Issues Final Guidance on Good Reprint PracticesJanuary 13, 2009
By Alan M. Kirschenbaum –
Today’s Federal Register announces FDA’s issuance of a final “Guidance for Industry 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.” We previously reported on FDA’s issuance of the draft guidance in February 2008.
The draft guidance elicited comments reflecting widely divergent views on this issue. Members of Congress and industry critics objected that draft guidance was more permissive than the forerunner FDAMA § 401 “safe harbor” regulations, and would encourage drug and device companies to promote off-label and forego rigorous studies needed for FDA approval. The industry, on the other hand, commented that certain provisions in the guidance were too restrictive and would violate First Amendment protection of commercial speech or pure scientific speech. Between these two poles, FDA has stuck to the middle ground, issuing a final document that contains surprisingly few substantive changes from the draft.
The few changes that have been made represent concessions to both sides. Where industry objected to a requirement that reprints be limited to reports on adequate and well controlled studies, the final guidance retained the requirement, but added that these can include historically controlled studies, pharmacokinetic studies, pharmacodynamic studies, meta-analyses in some cases, and, for devices, articles on significant non-clinical research. Where critics of the industry objected that the requirement for an article to be accompanied by reports of contrary studies should be strengthened, the final guidance expanded the requirement to all instances where such studies exist, not just those where the disseminated article has been specifically called into question. As advocated by industry, the final guidance retains a “safe harbor”-type statement that FDA will not consider reprints and texts distributed in accordance with the guidance as evidence of an intent that the product be used for an unapproved use, but adds a cautionary statement that compliance with the guidance will not save a manufacturer from enforcement if it engages in other unlawful off-label promotion. (Note also that, where a manufacturer engages in other unlawful off-label promotion, the guidance does not promise that FDA won’t consider reprints disseminated in accordance with the guidance as additional evidence of intent.)
The heart of the guidance sets forth FDA’s recommendations for the content, type, and manner of distribution of reprints and texts, which are largely unchanged from the draft. According to the guidance, the types of permissible journal articles are those that:
• Are published by an organization with an independent, expert editorial board and a publicly stated policy on conflicts of interest.
• Are peer reviewed.
• Are not false or misleading. Examples of false or misleading articles are those that have been withdrawn by the journal or disclaimed by the author, or that report on studies that are inconsistent with the weight of credible evidence.
• Do not pose a significant health risk, if relied upon.
• Are not special supplements funded by the manufacturer, letters to the editor, abstracts, or reports of phase 1 studies in healthy subjects.
FDA’s recommendations for distribution, which also remain largely unchanged from the draft, are that the journal article or text should:
• Be unabridged and not marked, highlighted, summarized, or characterized by the manufacturer in any way.
• Be accompanied by the approved labeling.
• Be accompanied by a comprehensive bibliography of publications discussing studies on the unapproved use, when such information exists.
• Be disseminated with a representative publication (if any) that reaches contrary conclusions on the unapproved use.
• Be distributed separately from promotional information.
• Not be distributed in a promotional exhibit.
• Not be the subject of discussion between a sales rep and a physician during a visit. A footnote explains that sales reps should refer questions to company medical staff, which should be separate from the sales or marketing departments.
Under the final guidance (as under the draft), the reprint or text should be accompanied by a prominently displayed statement disclosing that the uses discussed have not been approved or cleared, and disclosing the manufacturer’s interest in the product discussed, and any author known to have a financial interest in the product or manufacturer or known to be receiving compensation from the manufacturer. Going beyond the draft, the final guidance adds that the amount of the financial interest or the compensation and the affiliation of the author should also be disclosed, if known.
It remains to be seen whether this “middle-ground” guidance satisfies stakeholders on both sides of the issue. It is possible that the Washington Legal Foundation, which has long challenged FDA policies restricting dissemination of journal reprints, could target the guidance on Constitutional grounds. It is also possible that Representative Waxman or other Congressional opponents of the policy reflected in the guidance could intervene with legislation. It also remains to be seen what effect this guidance will have on enforcement against drug and device companies by the Department of Justice, which is not bound by the guidance, but presumably would take FDA’s views into account in making prosecutorial decisions.