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Until recently it’s simply been accepted that the FDA administratively banned off-label promotion – no ifs, ands, or buts.  Bexis’ book used to read:  “It is illegal, however, for a manufacturer of a prescription medical product to promote an off-label use.”  §4.01[4] at p. 4.01-45.  We sort of took that much, at least, for granted – even though we vociferously dissented, on First Amendment grounds, from this “ban” applying to truthful promotion, as we’ve done in most of our posts under our “First Amendment” blog topic.

Not so fast.

As Einstein demonstrated, sometimes even the most seemingly established propositions are questionable.

In fact, as we learned in Caronia, the FDA’s path to prosecution of off-label promotion is anything but direct and certain.  United States v. Caronia, 703 F.3d 149, 160 (2d Cir. 2012).  In actuality, “[t]he FDCA and its accompanying regulations do not expressly prohibit the ‘promotion’ or ‘marketing’ of drugs for
off-label use.”  Id. (emphasis added).  Indeed, for all the frequency with which “promotion” gets bandied about, there isn’t even a definition of the term “promote” or “promotion” in either the FDCA or in FDA regulations.  Rather, the Agency seems to be hiding the ball with regulatory statements – notably in the investigational drug context – that “[t]his provision [barring but not defining “promotion”] is not intended to restrict the full exchange of scientific information concerning the drug, including dissemination of scientific findings in scientific or lay media.”  21 C.F.R. §312.7(a).

That’s a load of malarkey.  Barring “full exchange of scientific information” is precisely what the FDA’s been doing with its off-label promotion stance for decades.

But neither is that stance straight forward.  Rather, to understand FDA’s position that off-label promotion (whatever that is) is illegal, requires meandering
through several different statutory and regulatory provisions – none of which even specifically mentions off-label use.  We start with the FDCA’s general prohibition against the “misbranding” of drugs and devices.  21 U.S.C. §331(a).  FDA approved products are “misbranded” if (among other things) their labeling does not bear “adequate directions for use.”  321 U.S.C. §352(f).  However, “adequate directions for use” are limited by regulation to a product’s “intended use.”  21 C.F.R. §201.5 (drugs); 21 C.F.R. §801.5 (medical devices).  The FDA’s definition of “intended use” (which hasn’t been updated in 50 years) in turn provides that “intended use” “may change” if “the article is . . . offered and used for a purpose for which it is n[ot] labeled.”  Id.  If that happens, such as through off-label promotion, the product then lacks the required “adequate directions for use” because the agency deems the “intended use” to have changed.  21 C.F.R. §201.128 (drugs); 21 C.F.R. §801.4 (medical devices).  Thus, going back to the beginning of the process, with a different “intended use” the product no longer has the right “adequate directions for use” and is therefore “misbranded.”

Got that?

The federal government has made billions of dollars in recent years through fines for off-label promotion, all because of this kludgy administrative tour de farce.

That’s where the Second Circuit stepped in in Caronia.  Because neither the FDCA nor the FDA’s regulations explicitly bans off-label promotion, the court was able to salvage their constitutionality under the First Amendment by construing this thicket, as a whole, as not banning truthful speech:

[T]he FDCA and FDA regulations reference “promotion” only as evidence of a drug’s intended use.  Thus, under the principle of constitutional avoidance, explained infra, we construe the FDCA as not criminalizing the simple promotion of a drug’s off-label use because such a construction would raise First Amendment concerns.

703 F.3d at 160.  If the court had not been able to finesse the issue in this way, presumably, it would have declared the whole kit and caboodle unconstitutional, given the First Amendment analysis that followed – which we won’t repeat since we covered that thoroughly here and here.

In light of Caronia, it’s important for the defense bar to watch what it says, since the conventional wisdom has been overturned (to our clients’ great potential benefit) at least in the Second Circuit.  We should now be taking the position, consistent with Caronia, that there in fact is no current, express federal law or federal regulation that prohibits off-label promotion.  At most, there is a non-binding FDA Guidance Document, and there previously were safe-harbor-related regulations that have since sunsetted and thus are no longer in effect.  But no federal law or regulation that expressly prohibits off-label promotion is operative at the moment – only the FDA’s Steinfelt to Tinker to Evers to Chance regulatory interpretation.

Why do we care?

Two reasons:  (1) in preemption cases, this absence of an express federal prohibition means that no federal requirement is violated by off-label promotion, and thus there is no “parallel” claim that can survive express preemption; and (2) in the context of negligence per se, state law is universal that (a) “violation” of guidance documents, or other items not carrying the force of law, cannot serve as a basis for the imposition of civil liability, and (b) likewise, claimed violations of vague and imprecise regulations cannot support liability.

So let’s get this right.  The Caronia regulatory rationale – largely separate from the First Amendment questions that produced it − has the potential to be a powerful addition to the defense armamentarium in cases involving off-label use.  Thus, repeat after the Second Circuit:  “[t]he FDCA and its accompanying regulations do not expressly prohibit the ‘promotion’ or ‘marketing’ of drugs [and medical devices] for off-label use.”