Recently, the Food and Drug Administration (FDA) issued a draft guidance document to make “recommendations” and clarify its position regarding the dissemination of scientific information discussing off-label information1. In 2009, the agency issued a guidance, entitled “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.”2 FDA issued the most recent guidance, in part, in response to some industry concerns that the 2009 guidance was too limiting on companies’ ability to distribute off-label information that might benefit the public. The focus of FDA’s guidance is on scientific education, not product promotion. Many of the 2014 recommendations are consistent with the 2009 guidance, but there are differences. A notable change is the addition of recommendations specifically addressing scientific and medical reference texts and clinical practice guidelines (CPGs). 

In this article, we summarize the highlights of the 2014 draft guidance and offer our own observations.

  Highlights of the 2014 Draft Guidance

  • Scientific and medical publications should come from a peer-reviewed journal.   
  • The material should be distributed in an unabridged form, such as a reprint.   
  • The information should be “scientifically sound” and from an “adequate and well-controlled clinical investigation.”   
  • The company should distribute the product’s approved or cleared labeling with the literature, and provide a comprehensive bibliography of information from other publications, including contradictory literature with the scientific information.   
  • The publication should be delivered separately from any promotional materials. The 2014 draft guidance adds the instruction that, if a sales representative delivers the material, the representative should refer any questions to a medical/scientific officer or department that is independent of sales and/or marketing.   
  • Not surprisingly, FDA uses strong language to caution against false or misleading information or information that “makes the product dangerous to health when used in the manner suggested.” This language seems to broaden the previous standard from the 2009 guidance, which prohibited information that “pose[d] a significant risk to the public health, if relied upon.”   
  • The agency recommends that the information disseminated be independent of any company ownership or control. For example, the company should not fund, influence, edit, highlight, or summarize the information distributed. Additionally, the information should not be distributed primarily by the company or individuals having a financial relationship with the company.   
  • Scientific or medical journal reprints should provide a disclosure, “prominently displayed and permanently affixed,” which includes:  
    • any company interest in the product(s) discussed in the material;   
    • a statement that some or all of the claims have not been FDA-approved or cleared;   
    • any financial interests of the authors;   
    • the sources of funding of the study, if known to the manufacturer; and  
    • all significant risks or safety concerns known about the unapproved use(s).   
  • The guidance for information from medical reference texts and CPGs is similar to that for scientific and medical journal articles, but FDA reminds the industry to ensure the information is current and is the latest version. Additionally, the required disclosure statement for these types of publications requires slightly less information (e.g., any additional significant risks or safety concerns are not required to be disclosed).   
  • FDA allows the distribution of chapters from medical reference texts and sections of CPGs, but they should be unabridged and not changed.   
  • The agency discusses the use of CPGs, which must be “trustworthy” and should meet the following conditions, at a minimum:   
    • be based on a systematic review of the existing evidence;   
    • be developed by experts and representatives from affected groups;   
    • consider important subgroups and patient preferences;   
    • be part of a transparent process;   
    • provide a logical explanation of care options; and   
    • be part of an ongoing revision process based on evidence.   
  • Any distributed CPG should be current, separated from promotional materials, identify the manufacturer and its interests, and be unabridged.

AGG Observations

  • FDA’s focus is clearly on scientific education and exchange of information to benefit public health. It does not want proactive off-label promotion.  
  • The agency is trying to find a balance where it does not infringe on companies’ commercial free speech rights to educate about a product’s potential new uses, where it has lost legal challenges, and reaffirming its role as having jurisdiction over product promotion and ensuring the importance and integrity of the marketing approval or clearance process.   
  • FDA wants the company to tell a truthful and complete story. Disclosures may be needed to tell this complete story, but we will caution that disclosures alone might not eliminate regulatory risk.   
  • The recommendations are very similar to those regulatory requirements first described in 21 C.F.R. Part 99, which were prepared in response to the Food and Drug Administration Modernization Act of 1997. FDA was challenged on its regulations as being overly burdensome, so these recommendations may indicate FDA’s recognition of its limits while also making its views and expectations heard.   
  • While not legally binding, the draft guidance represents FDA’s current thinking and should be considered, as it will likely become best industry practice.

We will continue to monitor and update on any new developments.