On March 3, 2014, FDA issued a new draft guidance allowing manufacturers to distribute journal articles, textbooks, and clinical practice guidelines containing information about off-label uses of approved/cleared drugs and medical devices.  The draft updates FDA’s 2009 reprints guidance and represents the first time FDA has ever acknowledged in a guidance or regulation that it is permissible for a manufacturer to distribute such guidelines, and represents FDA’s continued effort to respond to the issues raised by the Medical Information Working Group (MIWG) and its member companies in two citizen petitions filed with FDA in 2011 and 2013.  Comments on the draft are due on May 2, 2014.  Sidley Austin is counsel to the MIWG.

FDA also issued an interim response to the citizen petitions, stating the Agency continues to follow up on MIWG’s request to examine the entire FDCA regulatory regime that governs manufacturer communications.

Significant aspects of the draft guidance are:

  • The document (pp. 2-7) removes language regarding the public health value of information about off-label uses and includes a largely new and lengthy background discussion addressing the public health value of FDA review and approval of new intended uses of approved or cleared products and the related regulatory scheme. Of note, the draft guidance includes the familiar refrain that past experience with drugs such as encainide and flecainide demonstrates the need for restrictive FDA rules. It also provides, relative to the 2009 document, more legal analysis, including commentary on the authority of the Agency to regulate medical products according to their “intended uses.” Here, the document cites case law supporting an expansive interpretation of FDA’s authority—for example, cases purporting to authorize FDA to refer to not only labeling and advertising but also “any other relevant source” in determining intended use.
  • The new draft omits the language from the 2009 guidance (p. 4) indicating that information contained in a scientific or medical journal article “can include historically controlled studies, pharmacokinetic (PK) and pharmacodynamic (PD) studies, and meta-analyses if they are testing a clinical hypothesis.” The new document (pp. 7-8) states that meta-analyses and non-clinical research “may be consistent with this guidance,” but only “[i]n the case of devices” and in certain scenarios specified in the document.
  • The distinguishing feature of the draft’s recommendations for clinical practice guidelines is that they should “incorporate the Institute of Medicine’s (IOM’s) standards for . . . ‘trustworthiness.’” The draft includes a list of indicia of “trustworthiness” that largely track those for reference texts. As with other materials covered under the new draft, FDA states that clinical practice guidelines should be disseminated separately from information that is promotional in nature. The document thus raises questions regarding manufacturer use, in promotion, of information from clinical practice guidelines (e.g., references to ACIP guidelines in vaccine promotion).
  • The draft guidance also includes a footnote providing additional commentary on the recommendation that medical journal articles not “[b]e edited or significantly influenced by a drug or device manufacturer or any individuals having a financial relationship with the manufacturer.” Footnote 27 states: “FDA considers many factors when assessing whether a manufacturer is exercising significant influence over something or someone. For example, FDA examines the extent of control exercised by a manufacturer in a given scenario. See the FDA guidance for industry, Industry-Supported Scientific and Educational Activities (62 FR 64094, December 3, 1997) . . . for more examples of when something or someone may be considered to be independent from the significant influence of a firm.” This may signal FDA’s effort, also reflected in the recently published draft guidance on social media, to broaden the circumstances in which the Agency can assert that a publication or activity has been influenced or controlled by industry.

According to the NOA, FDA is continuing to review, analyze, and develop approaches to respond to the issues raised by MIWG members, and soliciting public comment on the draft guidance is “part of this process.” FDA continues to solicit public input and consider approaches with respect to several related issues, including (1) scientific exchange, on which FDA continues to review comments in response to the December 2011 Federal Register notice, (2) responses to unsolicited requests, as to which FDA is considering comments on the draft guidance, and (3) industry interactions with formulary committees, payors, and similar entities, including clarifying FDA’s interpretation of FDAMA 114 and providing recommendations “for evidentiary support for” HCEI, where FDA is considering draft guidance. All of these issues have been the subject of MIWG engagement.