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There’s an interesting new article in the current issue of the Food and Drug Law Journal, entitled “Criminalizing Knowledge: The Perverse Implications of the Intended Use Regulations for Off-Label Promotion Prosecutions.” The author is blog reader Greg Gentry at Morrison Mahoney. Here’s a link, to a reprint posted with the permission of the FDLI, which publishes the journal. The F.D.L.J. citation is 64 Food & Drug L.J. 441.
The article examines the FDA’s “intended use” regulation, 21 C.F.R. §201.128 (for drugs) and 21 C.F.R. § 801.4 (for devices) (both identically worded), and concludes that they can’t possibly actually mean what they say. That’s because a literal reading would criminalize mere awareness by a regulated manufacturer that doctors were likely to use its product off-label:

[I]f a manufacturer knows, or has knowledge of facts that would give him notice that a [drug/device] introduced into interstate commerce by him is to be used for conditions, purposes, or uses other than the ones for which he offers it, he is required to provide adequate labeling for such a [drug/device] which accords with such other uses to which the article is to be put.

Such “adequate” labeling, of course, can’t be added for a new use without going through the FDA’s entire drug/device approval process. Given how widespread off-label use is, many manufacturers would have to be wilfully blind not to know of such use. For one thing, they have to collect and submit adverse event reports, whether or not the use involved was a labeled one.
The thesis of the article is that this is a “Catch-22 regulation” that can’t possibly be (and hasn’t been) enforced as written without both violating the First Amendment rights of free speech and and the statutory rights of doctors to engage in off-label use. For one thing, “objective intent” is an oxymoron, describing something unknown to the law.
The article looks at the FDA’s enforcement history and concludes that until 1995 (during the regime of bureaucratic empire builder Commissioner Kessler), the FDA had confined itself pretty consistently to “actual statements made by a manufacturer in the marketplace about its product.” 65 F.D.L.J. at 445, see id. at 449-52. There’s also FDCA legislative history we haven’t seen compiled anywhere else. Id. at 446-48.
We were involved in off-label issues then, and we agree wholeheartedly. For this and lots of other reasons, we recommend this latest scholarship to anyone interested in scientific and corporate free speech issues – especially with respect to off-label use.