By: Cynthia L. Meyer
This week, the U.S. Food and Drug Administration (“FDA” or “Agency”) announced it is further delaying by one year the effective date of a final rule revising the definition of “intended use” in its drug and medical device regulations in order to invite public comment, adding to the flurry of activity we have seen in the past six months related to the Agency’s regulation of off-label communications. This update provides a brief overview of recent FDA activity in this area.
FDA and drug and medical device manufacturers have long grappled with the tension between the First Amendment and FDA’s restrictions on off-label communications and what evidence may be considered in determining a product’s intended use, which is critical in determining whether particular communications are considered off-label communications. FDA has asserted that it may consider a very broad range of evidence to establish a product’s intended use and that its restrictions on off-label communications are necessary to advance the public health. Drug and device manufacturers have argued that the appropriate scope of evidence that may be considered in establishing a product’s intended use is more limited and that FDA’s current restrictions on off-label communications violate their First Amendment right to free speech by preventing them from disseminating truthful and non-misleading information about off-label uses of approved products. Over the past several years, manufacturers have successfully challenged the scope of FDA’s authority to restrict off-label communications in several court cases, and industry has pressured FDA to revisit and clarify its policy on such communications, which the Agency has committed to do.
FDA Off-Label Communications Public Hearing and First Amendment Memorandum
In September 2016, FDA opened a docket to announce it would be holding a Part 15 public hearing (“Public Hearing”) to hear comments from stakeholders regarding the ability of drug and device manufacturers to engage in off-label communications as part of FDA’s comprehensive review of its regulations and policies governing such communications. The Public Hearing was held over two days on November 9-10, 2016, during which over 50 speakers presented their views on off-label communications. The initial comment period for the Public Hearing docket closed on January 9, 2017.
On January 19, 2017, FDA announced it was reopening the comment period for the Public Hearing docket for an additional 90 days (until April 19, 2017) and adding to the docket a document entitled Memorandum: Public Health Interests and First Amendment Considerations Related to Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products (“Memorandum”). FDA noted that some speakers at the Public Hearing expressed the view that FDA had not sufficiently discussed the First Amendment in the Public Hearing notice; thus, it was making available the 60-page Memorandum to provide additional background and seek input on the full range of issues to consider as part of its reexamination of its rules and policies relating to off-label communications.
The Memorandum summarizes the Agency’s statutory and regulatory authority and how the Federal Food, Drug, and Cosmetic Act (“FDCA”), the Public Health Service Act, and their implementing regulations (collectively, “FDA Authorities”) advance seven substantial public or individual health interests. In contrast, FDA acknowledged only two ways off-label communications advance public or individual health interests. Against this backdrop, FDA presented its perspective on various First Amendment issues and recent First Amendment cases regarding its restrictions on off-label communications, reiterating the ways the Agency strikes a balance between the competing interests and arguing that the FDA Authorities do not run afoul of the First Amendment. FDA closes its Memorandum by presenting and rejecting a dozen alternative approaches to its current off-label communications regulatory scheme.
While the Memorandum is represented only as a background document to serve as a springboard for comments and proposed alternatives from stakeholders, the lack of any indication of FDA’s changing its stance on First Amendment issues is notable. Given the recent string of industry victories in First Amendment cases and FDA’s commitment to comprehensively reexamine its regulations and policies on off-label communications in light of First Amendment concerns, many in the industry were cautiously optimistic that FDA may indeed revise its policies to be more permissive toward at least some forms of off-label communication. However, this Memorandum indicates that, at least as of the end of the last presidential administration, FDA’s views on off-label communications were not moving in the direction industry had hoped.
Manufacturer Communications Guidance Documents
On the same day, FDA reopened the comment period for the Public Hearing docket and announced the availability of the Memorandum, the Agency also announced it was releasing two draft guidance documents addressing manufacturer communications:
- Draft Guidance for Industry: Medical Product Communications That Are Consistent With the FDA-Required Labeling – Questions and Answers (“Consistent Communications Guidance”)
- Draft Guidance for Industry and Review Staff: Drug and Device Manufacturer Communications With Payors, Formulary Committees, and Similar Entities – Questions and Answers (“Payor Communications Guidance”)
The Consistent Communications Guidance provides FDA’s position that communications of information not included in a product’s approved labeling may be made if the information is consistent with the product’s labeling, truthful, and not misleading. It presents the three factors FDA considers when determining whether information is consistent with product labeling, examples of information and communications the Agency considers to be consistent with product labeling and those it considers to not be consistent with product labeling, and recommendations for firms regarding the appropriate evidentiary support and presentation of information that is consistent with product labeling.
The Payor Communications Guidance provides FDA’s current thinking regarding the communication of health care economic information (“HCEI”) to payors, formulary committees, or other similar entities about a firm’s approved or investigational medical products, particularly in light of changes to the law made by the 21st Century Cures Act allowing for broader sharing of HCEI. The Guidance provides recommendations on what types of HCEI information may be presented and to whom, what evidentiary support is appropriate, and what information should be included when disseminating HCEI about approved products or other information (e.g., anticipated timeline for possible FDA approval, product pricing information) about investigational products.
A Revised “Intended Use” Definition?
Separately, on January 9, 2017, FDA issued a final rule (“Final Rule”) purportedly intended to clarify when products made or derived from tobacco would be regulated as drugs, devices, or combination products. Although the preamble to the Final Rule primarily focuses on products made or derived from tobacco, the rule itself includes revisions to the definitions of “intended use” under the drug and medical device regulations at 21 C.F.R. §§ 201.128 and 801.4, respectively, which apply to drugs and devices generally. The revision to the intended use definition includes a “totality of the evidence” standard that was not included in the proposed rule (“Proposed Rule”).
On February 8, 2017, a Petition to Stay and For Reconsideration (“Petition”) was filed on behalf of the Medical Information Working Group (“MIWG”), the Pharmaceutical Research and Manufacturers of America (“PhRMA”), and the Biotechnology Innovation Organization (“BIO”) challenging the Final Rule. The Petition recounts the history of FDA’s “intended use” definition and its application by the Agency and courts, stating that the Proposed Rule would have acknowledged key limits on the scope of “intended use,” namely that a firm’s knowledge of a use could not be the sole basis for finding a new intended use. Instead, the Petition asserts, FDA introduces in the Final Rule a new “totality of the evidence” standard that departs from established understanding and case law, creating a substantive rule that was not subject to notice-and-comment rulemaking, thus violating the fair notice requirements of the Administrative Procedure Act.
On March 20, 2017, in response to the Petition, FDA announced that it was further delaying the effective date of the Final Rule until March 19, 2018. The Agency noted that its purpose in amending the intended use definition both in the Proposed and Final Rules was to clarify that FDA would not regard a firm as intending an unapproved new use for an approved medical product based solely on that firm’s knowledge that its product was being prescribed or used for such use while also embodying FDA’s position that intended use can be based on “any relevant source of evidence,” including a variety of direct and circumstantial evidence. However, FDA noted that the Petition suggested that FDA limit the evidence that may be considered to establish a product’s intended use to the manufacturer’s promotional statements and raised other substantive issues. FDA announced the delay to seek public comment on and fully evaluate these substantive issues.
So where are we now? While much remains unknown, particularly in light of the potential revised definition of “intended use,” the uncertainty of a new presidential administration, and the likelihood of further industry challenges of FDA’s restrictions on off-label communications in the courts, all of this recent activity by FDA indicates that the Agency is actively considering its regulations and policies related to off-label communications. FDA is currently accepting comments to all of the above dockets, and stakeholders should consider submitting comments to help shape the Agency’s thinking. Specifically:
- Comments to the Public Hearing docket and on the Memorandum are due by April 19, 2017.
- Comments on the Consistent Communications Guidance and Payor Communication Guidance may be submitted anytime, but FDA requests comments by April 19, 2017, in order to ensure that the comments are considered before the Agency begins work on the final versions.
- Comments on the Final Rule and Petition regarding the definition of “intended use” are due by May 19, 2017.
 See, e.g., United States v. Caronia, 703 F.3d 149 (2d Cir. 2012); Pacira Pharmaceuticals, Inc. v. FDA, No. 15-cv-7055 (S.D.N.Y. 2015); Amarin Pharma, Inc. v. FDA, 119 F. Supp. 3d 196 (S.D.N.Y. 2015); United States v. Vascular Solutions, Inc., No. 14-0926 (W.D. Tex. Feb. 26, 2016).
 81 Fed. Reg. 60299 (September 1, 2016).
 More information about the hearing, including archived webcasts and transcripts, can be found at https://www.fda.gov/NewsEvents/MeetingsConferencesWorkshops/ucm489499.htm
 82 Fed. Reg. 6367 (January 19, 2017).
 82 Fed. Reg. 6575 (January 19, 2017).
 82 Fed. Reg. 6568 (January 19, 2017).
 Final Rule – Clarification of When Products Made or Derived From Tobacco Are Regulated As Drugs, Devices, or Combination Products; Amendments to Regulations Regarding “Intended Uses.” 82 Fed. Reg. 2193 (January 9, 2017).
 Proposed Rule – Clarification of When Products Made or Derived From Tobacco Are Regulated As Drugs, Devices, or Combination Products; Amendments to Regulations Regarding “Intended Uses.” 80 Fed. Reg. 57756 (September 25, 2015).
 Petition to Stay and For Reconsideration submitted on behalf of the MIWG, PhRMA, and BIO. Docket Nos. FDA-2016-N-1149-0048; FDA-2015-N-2002; FDA-2013-P-1079; FDA-2011-P-0512 (February 8, 2017).
 Id. at pp. 7-9; Proposed Rule at 57764-65.
 Petition at pp. 9-13; Final Rule at 2217.
 82 Fed. Reg. 14319, 14320 (March 20, 2017).
 Id. at 14321 (citing Petition).