Guest Column | February 27, 2017

Pharma Off-Label, On-Label, And Free Speech

Pharma Off-Label, On-Label, And Free Speech

By Peter Claude & Joseph Rogel

The FDA gives manufacturers additional guidance for scientific communications, but is it much ado about a little?

The line between off-label communications and “truthful, nonmisleading” free speech has been questioned for many years. Particularly in light of First Amendment court cases protecting “speech promoting the lawful, off-label use of an FDA-approved drug” (e.g. United States v. Caronia, and Amarin Pharma, Inc. v. United States Food and Drug Administration), industry has been anxious for further guidance to loosen off-label communication restrictions. However, the FDA has continued to prohibit off-label communications, and followed through on its intent through the issuance of several draft guidance documents/communications that attempt to clarify their position on the topic of legitimate scientific information dissemination:

The memorandum, in particular, is designed to both clarify the type and nature of communications the FDA considers in-line with an approved label, while also defending the agency’s stance on the prohibition of off-label communications to protect public health interests.

New FDA Guidance: What Does It Mean?

The recent guidance documents are meant to help manufacturers understand FDA thinking regarding on-label communications. This includes what may be considered “truthful and not misleading,” “scientifically appropriate and statistically sound,” and also what may be interpreted as contradictory to, or an inappropriate expansion of, the approved label. While conclusive definitions outlining off-label vs. on-label are absent, clarifying examples of on-label topics have been provided. Some examples include:

  • comparisons between competitor products for safety and efficacy data,
  • analyses of subgroup data within approved patient populations,
  • use of real-world patient-reported product outcomes,
  • information about dosing related to long-term safety and efficacy of the product for chronic use.

The clarifying examples provided by the FDA, as well as changes in the criteria for valid communications (current communications must use evidence that is “scientifically appropriate and statistically sound” as opposed to requiring “substantial evidence”), appear to indicate a softening in tone from the FDA, but not an upending of traditional thinking.

Furthermore, despite speaking primarily to off-label communications rather than actual off-label promotion, the new guidance also clarifies that healthcare economic information (HCEI) distributed under 502(a) of the FD&C Act (21 U.S.C. 352(a)) is still considered promotional material and subject to the FDA’s requirements for submission of promotional materials. As such, delivery of new scientific information to payors, formulary committees, or other similar entities (which have been identified as the target audience of HCEI communications) should originate from a "competent and reliable scientific source," and as has historically been the case, may not branch off into uses not under their label. A notable exception for communications outside an approved label is the safe harbor for investigational drug communications involving a drug having no other cleared use (this rule’s application to drugs having an existing label have not been specified).

Bottom Line For The FDA And Industry

In its memo, the FDA has pushed back on the court rulings mentioned earlier, arguing that broad allowances for off-label communications may undermine their ability to fulfill their responsibility of “Preventing harm to members of the public, protecting against fraud, misrepresentation, and bias, and preventing the diversion of healthcare resources toward ineffective treatments”. As a result, they may find themselves in continued legal battles with manufacturers emboldened by the court’s historical precedent and looking for more flexibility than what the guidance documents offer. Faced with this dilemma, the FDA may have to decide whether or not an appeal to the Supreme Court should be made — a risky move that may undercut the FDA’s ability to conduct further off-label action if an unfavorable ruling is made. In the interim, it is clear that the FDA intends to continue and take action against manufacturers who, in its opinion, cross the boundaries of off-label communication.

For manufacturers, the new draft guidance documents represent an opportunity for compliance officers to discuss with their medical, regulatory, and other relevant personnel, the policies and processes associated with creating medical product communications (including health economic data) and to evaluate whether the new guidance requires expansion or change to current business approaches. In particular, compliance officers will want to make sure their organizations understand that, despite all the press around the recent guidance, little has changed on a day-to-day basis. Some actions for compliance teams and their stakeholders to consider include:

  • Conduct a review of the company’s HCEI and payor communications strategy to identify gaps and improvement areas. Focus on:
    1. Procedural updates related to management of HCEI content creation, including treatment of such content under the context of “promotional material” and subject to FDA review
    2. Update of policies, procedures, and materials used for payor discussions, including appropriate on-label topics, pipeline discussions, and competitor-product comparisons
    3. Disclosure practices to ensure on-label claims relying on study data are presented in the appropriate context and with relevant background information such as study design, methodology, limitations, and unfavorable or inconsistent findings
  • Develop and deploy compliance training to relevant stakeholders specific to FDA viewpoints regarding on-label communications and product labeling.
  • Implement updates to internal monitoring requirements using the revised FDA guidance.

The new FDA guidance, while neither the definitive interpretation of off-label vs. on-label, nor the expansion of off-label free speech that manufacturers may have been seeking, will offer some consolation to industry players craving more structure in the FDA’s position regarding on-label exchanges. But there is no cure for existing uncertainty in the new guidance; greater latitude, yes, but controversy remains around the conflicting rights of free speech and the bounds of FDA power as regulator and guardian of public safety.


Peter Claude is a health industries, risk and regulatory consulting leader at PWC.

Joseph Rogel is a Health industries risk and regulatory manager at PWC.