On September 25, 2015, the Food and Drug Administration (FDA) published in the Federal Register a proposal to amend its existing “intended use” regulations for drugs and medical devices. The proposal would remove language defining intended use to include a manufacturer’s knowledge that its product is to be used off-label—a revision that the Medical Information Working Group (MIWG), a coalition of drug and medical device manufacturers, has been requesting since September 2013. The regulatory change will assist manufacturers in defending allegations of misbranding liability based on evidence of knowledge of off-label use. Nonetheless, FDA continues to assert an impermissibly broad interpretation of intended use that conflicts with the relevant case law and creates constitutional issues.
The intended use definitions, found in 21 C.F.R. §§ 201.128 and 801.4, define the scope of a manufacturer’s liability for misbranding under Section 502(f)(1) of the Federal Food, Drug, and Cosmetic Act. The existing regulations define intended use to refer to the “objective intent” of the manufacturer, which includes “labeling claims, advertising matter, or oral or written statements.” In addition, under the final sentence of the regulations, “if a manufacturer knows, or has knowledge of facts that would give him notice,” that its product “is to be used for conditions, purposes, or uses other than the ones for which he offers it,” then the manufacturer is responsible for providing adequate directions in labeling for those uses. This language thus purports to hold manufacturers responsible for submitting off-label uses for FDA approval even if those uses are not among those the manufacturer promotes.
Not surprisingly, objections to this “knowledge” standard of the intended use definition are as old as the definition itself, as demonstrated by comments1 filed by drug manufacturers to the proposed definition in 1952. Prosecutors have invoked the final sentence of the regulation in alleging that manufacturers committed misbranding violations based solely on evidence that the manufacturers knew that their products were being put to off-label uses. In the Allergan litigation, the Department of Justice (on FDA’s behalf) disavowed2 this interpretation of intended use, but prosecutors have continued to invoke it, including recently in Facteau.3 In the September 25 proposed rule, FDA cites its position in Allergan, asserting that “the Agency does not regard a firm as intending an unapproved new use for an approved or cleared medical product based solely on that firm’s knowledge that such product was being prescribed or used by doctors for such use.”
The accompanying preamble, however, includes language indicating that FDA still holds an impermissibly broad view of intended use. The preamble states that “intended use may be determined from any relevant source and is not based solely on claims made in a product’s labeling or advertising materials,” notes that “objective evidence” “may include a variety of direct and circumstantial evidence,” and states that “FDA may also take into account . . . the context in which [a product] is sold.” In addition to raising serious issues in view of the case law interpreting the intended use doctrine,4 this interpretation in the preamble raises constitutional questions. This series of statements describes a broad and impermissibly vague standard, ostensibly enabling FDA and prosecutors to pursue theories that exceed the objective intent standard that relies on a manufacturer’s promotional claims to determine intended use.
The proposed rule does not disclose the impetus for the change, but it is clearly in response to the citizen petitions filed in 2011 and 2013 by MIWG, a coalition of drug and device manufacturers focused on improving the regulatory and enforcement environment affecting manufacturer communications about their products. Sidley lawyers are co-counsel to the group and will continue to monitor FDA actions in this area and engage with agency officials, as appropriate. In the meantime, manufacturers confronting off-label investigations will benefit from examining FDA’s proposed rule and assuring that prosecutors are aware of the agency’s disavowal of the knowledge theory of intended use.
1 See Letter from John L. Hammer, Jr., Vice President, Smith, Kline & French Laboratories to Hearing Clerk, Federal Security Agency (Mar. 4, 1952) (if manufacturer’s “market research department learns that 20% of the purchasers use the preparation as a sedative . . . [and] he inserts in his label directions for use as a sedative . . . he is forced into the position of recommending his product for a use of which he heartily disapproves and for which his drug may be largely ineffective”).
2 Defendants’ Memorandum of Points and Authorities in Support of Motion to Dismiss or for Summary Judgment at 23, Allergan v. United States, No. 09-CV-01879 (D.D.C. Jan. 7, 2010).
3 Government’s Opposition to Defendants’ Motion for Production of Legal Instructions to Grand Jury at 13-14, United States v. Facteau, Fabian, No. 15-CR-10076 (D. Mass. Aug. 6, 2015).
4 “[C]ourts ‘have always read . . . ‘intended’ to refer to specific marketing representations.’” Amer. Health Prods. Co. v. Hayes, 574 F. Supp. 1498, 1505 (S.D.N.Y. 1983) (citations omitted).
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