In the last week of the Obama administration, the Food and Drug Administration (FDA or Agency) released a document titled "Memorandum: Public Health Interests and First Amendment Considerations Related to Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products" (Memo) as a follow-up to a public meeting that the Agency held on off-label promotion issues in November 2016. The Memo sheds light on current FDA thinking on manufacturers’ communication of unapproved or off-label information about their medical products, accounting for the First Amendment and the Agency's regulatory mandate to protect the public health.

Reopening a comment period for stakeholders until 19 April 2017, FDA invites feedback and input on the Agency’s views expressed in the Memo and potential alternative approaches to regulating dissemination of off-label use information. After reviewing additional comments, the Agency may issue a more comprehensive off-label guidance for industry.

Consistency of FDA's off-label policy with the First Amendment

In the past few years, court decisions in Caronia, Amarin and other cases have repeatedly supported that the Agency must not penalize manufacturers for communicating or disseminating truthful and non-misleading off-label use information about their medical products to stakeholders, such as health care providers. FDA has long struggled to balance its off-label policy with the First Amendment, with the struggle becoming more pointed in the face of recent case law. This struggle is evident in the Memo where FDA states that “Integrating the many substantial interests, some of which are in tension with each other, in a way that best promotes public health and comports with recent First Amendment jurisprudence is a complex task.”

In the Memo, FDA articulates the public policy considerations guiding its decision to continue to restrict off-label communications. It believes the intent of its off-label policy is to protect public health interests. As the Agency states, dissemination of information regarding the safety and effectiveness of a medical product for a particular use without proper scientific evidential support likely will lead to harmful prescribing or use decisions by physicians and patients. The Agency points out historic events of patient harm caused by medical products in this regard, many of which were related to activities of major pharmaceutical manufacturers operating in the U.S. FDA also presents findings from recent studies that the risk of adverse events is higher for unapproved uses than approved uses if such unapproved uses are not supported by reliable scientific data.

While acknowledging recent court decisions, FDA argues that allowing manufacturers to promote use of unapproved or unevaluated indications more freely may also enhance the probability of public health tragedies, increase society’s costs, and produce more fraud on the public. From the policy perspective, FDA also argues that such off-label practice may also diminish the incentives for product sponsors to conduct research or clinical development into new innovative indications for use. FDA believes that its current off-label policy produces the appropriate degree of regulation, requiring manufacturers to conduct studies for subsequent new uses of medical products and to demonstrate the safety and effectiveness of medical products for each marketed indication for use.

Review of alternative approaches to regulate dissemination or promotion of off-label use information

In the Memo, FDA examines alternative approaches to regulate dissemination or promotion of off-label use information. These alternatives tend to show FDA’s historical tendency of wanting to assure the safety and effectiveness of medical products by motivating or asking manufacturers to engage in continuous product development activities for each indication for use.

FDA also highlights the importance of a practical approach in administering an off-label policy. For instance, one proposal example in the Memo is to require manufacturers to list all potential product uses in the initial premarket application to enable tracking of the development of all of the medical product's uses. However, this approach is perceived as impossible by the Agency because all of potential uses cannot be identified upfront in a complex and evolving medical area.

In addition, FDA notes that some proposals have suggested initiatives to change health care providers’ prescription behavior by educating them on how to differentiate false and misleading promotion from truthful and non-misleading information or by alerting practitioners as to the potential malpractice issues that can arise from off-label use prescription. The Agency, however, seems reluctant to adopt these approaches because they will not change any potential objectionable behavior in the manufacturers’ practices of disseminating off-label use information.

FDA also stresses the importance that off-label regulation should not place unnecessary burden on medical practice which may be detrimental to public health in the end. While some advocates would push to eliminate off-label use or communication, create ceilings or caps on such off-label use, or limit Medicare and Medicaid reimbursement to approved uses, FDA disagrees with these proposals because health care providers and patients’ freedom to determine the best treatment option in specific circumstances serves the public health interest.

Beyond the Memo

In addition to the Memo, FDA published a new draft guidance document dealing with the communication of health care economic information (HCEI) about approved drugs under Section 502(a) of the Federal Food, Drug, and Cosmetic Act, which was recently amended by the 21st Century Cures Act. The draft guidance addresses HCEI communications to payers, formulary committees and other similar entities. For the first time, FDA explicitly approves the practice to disseminate certain HCEI to payors in advance of drug approval. The Agency also proposes several recommendations as to how manufacturers communicate to payors about investigational drugs and devices that are not approved or cleared for any use.

Moreover, FDA issued another new draft guidance offering eleven questions and answers to explain FDA’s current thinking about manufacturers’ medical product communications that include data and information that are not contained in their products’ FDA-required labeling. The guidance provides three factors to help stakeholders determine whether the information not contained in the FDA-required labeling is consistent or inconsistent with the labeling. Unless the nature of data and information meets all of three factors, FDA would not consider the communication of such data and information consistent with FDA-required labeling.

Regardless of whether the Memo or the two additional guidance documents present any politically-motivated actions of an out-going Administration, the Memo and draft guidances indeed offer stakeholders useful insight into Agency views on communication of off-label use and related information. If you would like more information, or may be interested in filing comments, on any of the above topics, please let us know.