The U.S. Food and Drug Administration (FDA or the Agency) issued the June 6, 2014, draft guidance (Draft Guidance) in response to stakeholder inquiries into the Agency’s views on disseminating new scientific or medical publications regarding safety information for approved drugs.  In contrast to a draft guidance the Agency released in February 2014—which pertains to the distribution of publications that include information on unapproved new uses of approved drugs—the June 2014 Draft Guidance addresses how manufacturers may disseminate new risk information relating to approved uses of a prescription drug (human or animal).  Specifically, the guidance is intended to address issues specific to the distribution of new information about risks that further characterizes risks discussed in the approved labeling.  In this regard, the FDA acknowledges that it may be helpful for health care professionals to be apprised of “significant new risk information about an approved product in a timely manner,” as drug safety assessments may “evolve throughout [the drug’s] lifecycle as the extent of exposure to the product increases ....”  In light of the variability in evidence and the potential for new risk information to generate confusion among providers, however, the FDA found that guidance was necessary to help ensure the appropriate distribution of such information.   

Scope of the Draft Guidance

Notably, the Draft Guidance does not apply to risk information that indicates that a risk described in approved labeling is more serious than previously understood or that relates to newly identified risks.  Likewise, it does not apply to medical devices.  Rather, the Draft Guidance applies to “new risk information” relating to a prescription drug, defined as “information that becomes available after a drug is marketed and that rebuts or mitigatesinformation about a risk already identified in the approved labeling or otherwise refines risk information in the approved labeling in a way that does not indicate greater seriousness of risk” (emphasis added).  It should also be noted that, for purposes of the Draft Guidance, “new risk information” does not refer to “new safety information” as defined in Section 505-1(b)(3) of the Federal Food, Drug, and Cosmetic Act (the Act), and as to which the Agency has the authority to require a change in labeling as it determines appropriate. 

Finally, because the Agency anticipates that new risk information largely takes the form of recently published studies rather than as textbooks or clinical practice guidelines, the recommendations in the Draft Guidance focus on the distribution of new risk information in the form of reprints and digital copies of a published study.

Parameters for Appropriate Distribution of New Risk Information

The FDA recommends that manufacturers “carefully consider the reliability and persuasiveness of” new risk information before distributing such information to health care professionals and health care entities.  Accordingly, the FDA states that manufacturers should review the strength of the existing evidence that underlies the drug’s approved labeling when assessing whether it would be appropriate to disseminate the new risk information. 

With regard to enforcement policy, the Agency indicates that it “does not intend to object to the distribution of new risk information that rebuts, mitigates, or refines the risk information in the approved labeling” and that is in the form of a reprint or digital copy of a published study, provided that the study and manner of distribution comply with the standards set forth in the Draft Guidance.  In contrast, the FDA asserts that distribution of risk information “that is not consistent with this guidance may render the labeling of a drug false and misleading” under the Act (emphasis added).  As described below, the Draft Guidance articulates several criteria relating to the data sources for new risk information as well as how such information should be distributed. 

New Risk Information Data Sources

  • A study or analysis should meet design and other methodologic standards accepted for a study or analysis of its type and should be adequately well-designed and informative
  • If used to rebut a prior determination that a drug may have a causal relationship with the occurrence of an adverse event, or if used to mitigate a described risk, the study or analysis should be at least as persuasive as the evidence underlying the risk assessment of causality, severity and/or incidence of the adverse reaction as reflected in the approved labeling
  • The study or analysis conclusions should constitute a fair characterization of and give appropriate weight and consideration to all relevant information (including contrary or otherwise inconsistent findings)
  • The study or analysis should be published in an independent peer-reviewed journal

Method of Distributing New Risk Information

  • When distributing any reprint or digital copy of a published study, manufacturers should include a cover sheet that contains certain information, including:
    • a description of the study, its critical findings and any significant methodologic or other limitations relevant to the persuasiveness or scope of the findings;
    • a statement that the information is inconsistent with certain risk information in the drug’s approved labeling (and should specifically identify the inconsistent information);
    • a statement that the FDA has not reviewed the new risk information; and
    • any conflicts of interest (financial interests or affiliations) between the manufacturer and study author(s)
  • Manufacturers should include a copy of the approved labeling with the disseminated reprint or digital copy of the published study
  • Any promotional materials should be separated from the reprints or digital copies
  • If a representative of the manufacturer makes any statements regarding the reprint to the health care professional or health care entity recipient, such statements should be consistent with the reprint and the above-referenced cover sheet


The Draft Guidance provides some welcome clarity on a prescription drug or biological product manufacturer’s ability to distribute post-market, risk-related information outside of the approved product labeling.  However, the Draft Guidance includes limits on the type and content of the information to be provided, such as limiting it to information that does not rise to the level of safety information that would require a labeling change, and proscriptions on the type of data sources that may be relied upon and how they must be presented.  Likewise, the Draft Guidance does not discuss how a manufacturer should assess or determine if the type or degree of post-market, risk-related information might constitute safety information that would require a labeling change. 

The Draft Guidance, in addition to the February 2014 draft guidance regarding the distribution of scientific and medical publications on unapproved new uses of approved drugs or approved or cleared devices, is one of several guidance documents relating to manufacturer communications that FDA intends to issue by the end of the year.  Other guidance that the FDA has stated is forthcoming includes how manufacturers should respond to unsolicited requests for information, manufacturer discussions regarding scientific information more generally and health care economic information.  The Agency’s effort to provide additional clarity on these topics and on its position regarding how manufacturers may permissibly discuss off-label use is part of a broader-stated commitment by the Agency to review its regulatory framework for manufacturer communications regarding medical products.  It remains to be seen, however, whether such efforts and additional guidance will produce policies that more closely align with developing judicial case law on the interplay between First Amendment principles and a regulated product manufacturer’s discussion of labeled and of off-label use. 

Manufacturers should consider submitting comments regarding the Draft Guidance to the FDA.  Any comments should be submitted by August 25, 2014, to ensure consideration by the Agency in connection its preparation of the final version of the guidance.