Until recently it’s simply been accepted that theFDA administratively banned off-label promotion – no ifs, ands, or buts. Bexis’ book used to read: “It is illegal, however, for a manufacturerof 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, forgranted – even though we vociferously dissented, on First Amendment grounds,from this “ban” applying to truthful promotion, as we’ve done in most of ourposts 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’spath 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]heFDCA and its accompanying regulations donot expressly prohibit the ‘promotion’ or ‘marketing’ of drugs foroff-label use.” Id. (emphasisadded). Indeed, for all the frequencywith which “promotion” gets bandied about, there isn’t even a definition of theterm “promote” or “promotion” in either the FDCA or in FDA regulations. Rather, the Agency seems to be hiding theball with regulatory statements – notably in the investigational drug context –that “[t]his provision [barring but not defining “promotion”] is not intendedto 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 scientificinformation” is precisely what the FDA’s been doing with its off-labelpromotion stance for decades.
But neither is that stance straightforward. Rather, to understand FDA’s positionthat off-label promotion (whatever that is) is illegal, requires meanderingthrough several different statutory and regulatory provisions – none of whicheven 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 (amongother things) their labeling does not bear “adequate directions for use.” 321 U.S.C. §352(f). However, “adequate directions for use” arelimited 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 definitionof “intended use” (which hasn’t been updated in 50 years) in turn provides that“intended use” “may change” if “the article is . . . offered and usedfor a purpose for which it is n[ot] labeled.” Id. If that happens, suchas through off-label promotion, the product then lacks the required “adequatedirections 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 tothe beginning of the process, with a different “intended use” the product nolonger has the right “adequate directions for use” and is therefore“misbranded.”
Got that? The federal government has made billions of dollars in recent yearsthrough fines for off-label promotion, all because of this kludgyadministrative tour de farce.
That’s where the Second Circuit stepped in in Caronia. Because neither the FDCA nor the FDA’sregulations explicitly bans off-label promotion, the court was able to salvagetheir 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 constitutionalavoidance, explained infra, we construe the FDCA as not criminalizing thesimple promotion of a drug’s off-label use because such a construction wouldraise 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 kaboodle unconstitutional,given the First Amendment analysis that followed – which we won’t repeat sincewe covered that thoroughly here and here.
In light of Caronia, it’s important for thedefense bar to watch what it says, since the conventional wisdom has beenoverturned (to our clients’ great potential benefit) at least in the SecondCircuit. We should now be taking theposition, consistent with Caronia, that there in fact is no current, expressfederal law or federal regulation that prohibits off-label promotion. At most, there is a non-binding FDA GuidanceDocument, and there previously were safe-harbor-related regulations that havesince sunsetted and thus are no longer in effect. But no federal law or regulation thatexpressly 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 preemptioncases, this absence of an express federal prohibition means that no federalrequirement is violated by off-label promotion, and thus there is no “parallel”claim that can survive express preemption; and (2) in the context of negligenceper se, state law is universal that (a) “violation” of guidance documents, orother items not carrying the force of law, cannot serve as a basis for theimposition of civil liability, and (b) likewise, claimed violations of vague and impreciseregulations cannot support liability.
So let’s get this right. The Caronia regulatory rationale –largely separate from the First Amendment questions that produced it − has thepotential to be a powerful addition to the defense armamentarium in casesinvolving off-label use. Thus, repeatafter the Second Circuit: “[t]he FDCAand its accompanying regulations donot expressly prohibit the ‘promotion’ or ‘marketing’ of drugs [andmedical devices] for off-label use.”
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