The Supreme Court’s recent landmark decision in Loper Bright Enterprises v. Raimondo, 144 S. Ct. 2244 (2024), has generated more commentary than anyone could possibly read.  Reed Smith alone has issued four Loper Bright alerts and established a resource center.  Overall, we think that Loper Bright’s assertion that judges know better than administrative agencies how to interpret and apply those agencies’ organic statutes smacks of judicial triumphalism.  However, it is what it is, and we’ll be living with it for some time.

Loper Bright essentially tells courts to ignore administrative interpretations and to give statutes “the reading the court would have reached if no agency were involved,” 144 S. Ct. at 2266 (citation and quotation marks omitted).  One thing that we (and Mark Herrmann, who first suggested this topic) haven’t seen in any commentary on Loper Bright are the implications of that mandate on the FDA’s questionable basis for its ban on all “off-label promotion” – particularly truthful off-label speech – by the firms it regulates.

Most of the Blog’s extensive commentary on off-label speech has been in the context of the ban violating the First Amendment, but we have commented on the jerry-rigged “Tinker to Evers to Chance” agency reading of the FDCA that underlies its off-label speech ban.  Here’s how we described it in 2013:

[T]o 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” . . . 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?

In his most recent law review article on off-label use issues, Bexis repeated that analysis more formally, concluding that “the regulatory basis for a complete FDA ban on off-label promotion is problematic, since ‘[t]he FDCA and its accompanying regulations do not expressly prohibit the ‘promotion’ or ‘marketing’ of drugs for off-label use.”  James Beck, “Off-Label Use in the Twenty-First Century:  Most Myths & Misconceptions Mitigated,” 54 UIC J. Marshall L. Rev. 1, 44 (2021) (quoting United States v. Caronia, 703 F.3d 149, 154 (2d Cir. 2012)).  The FDA’s ban on all off-label speech, whether or not truthful, arises from “a convoluted series of statutory provisions and regulations.”  In re Actimmune Marketing Litigation, 2010 WL 3463491, at *6 (N.D. Cal. Sept. 1, 2010), aff’d, 464 F. Appx. 651 (9th Cir. 2011).

Specifically, the FDA’s regulatory rationale for its ban on off-label speech requires a four-step excursion through a regulatory thicket, meaning that to be completely accurate, our previous baseball-based description would have to include the trivia question answer, Harry Steinfeldt.  First, the FDCA generally prohibits the “misbranding” of drugs and devices.  21 U.S.C. §331(a) (prohibiting “The introduction or delivery for introduction into interstate commerce of any [regulated] product that is adulterated or misbranded.”); §331(b) (same for “The adulteration or misbranding of any [regulated] product, or cosmetic in interstate commerce”).  What’s missing from this section?  Any reference to “intent.”

Second, even an FDA-approved product is “misbranded” if its labeling does not include “adequate directions for use.”  21 U.S.C. §352(f).  The second stage is also questionable.  Congress directed the “adequate directions” requirement at an entirely different type of drug – over-the-counter products.  “To satisfy §352(f)’s requirement of providing ‘adequate directions for use,’ a drug’s label must provide ‘directions under which the layman can use a drug safely and for the purposes for which it is intended.’”  United States v. Regenerative Sciences, LLC, 741 F.3d 1314, 1323-24 (D.C. Cir. 2014) (emphasis original).  Such “adequate directions” cannot be adequate for a prescription product, which is why a physician’s prescription is required.  Id. at 1324 (“A prescription drug, however, is by definition ‘not safe for use except under the supervision of a practitioner licensed by law to administer such drug.”) (quoting 21 U.S.C. §353(b)(1)(A)) (emphasis original).  Any prescription drug that relies solely on “adequate directions for use” would be “presumptively misbranded.”  Id.  Searching for “intend” or “intent” in this section yields only a little more than the first step.  The statute contains references to products “intended for human use” and “intended for use in health care facilities” or “intended for use by health care professionals.”  21 U.S.C. §§353(e)(1)(A)(ii-iii), 353(f).  Nothing in these sections uses “intended use” in any way resembling how the FDA does to get to step three.

Third, according to FDA regulations, “adequate directions for use” may only be included with respect to “the purposes for which it [the product] is intended.”  These regulations are chiefly 21 C.F.R. §201.5 (for drugs) and 21 C.F.R. §801.5 (for medical devices).  Again, these regulations are directed primarily at OTC products, since they both define “adequate directions for use” as “directions under which the layman can use a device safely and for the purposes for which it is intended.”  Rather than precluding references to off-label use, these regulations appear to embrace it, at least if it is “common,” since said directions include:

Statements of all conditions, purposes, or uses for which such [product] is intended, including . . . conditions, purposes, or uses for which the [product] is commonly used. . . .

21 C.F.R. §§201.5(a); 801.5(a).  Since this definition treats OTC “advertising” separately, “common use” necessarily must refer to unadvertised uses.

Fourth, by virtue of an “intended use” cross-reference from the previous sections, the FDA has asserted that, “intended use,” as used in various other regulations, “refer[s] to the objective intent” of the regulated entities responsible for the product in question – even though the addition of the adjective “objective” is found nowhere in the FDCA.  21 C.F.R. §§201.128; 801.4.  These regulations define “objective” to include just about any communicative aspect:

The intent may be shown by such persons’ expressions, the design or composition of the article, or by the circumstances surrounding the distribution of the article. This objective intent may, for example, be shown by labeling claims, advertising matter, or oral or written statements by such persons or their representatives.  Objective intent may be shown, for example, by circumstances in which the article is, with the knowledge of such persons or their representatives, offered or used for a purpose for which it is neither labeled nor advertised. . . .  The intended uses of an article may change after it has been introduced into interstate commerce.

Id.

Courts have long been skeptical of this FDA sleight of hand.  “On the basis of this web of statutes and regulations, the FDA takes the position that off-label promotion can constitute misbranding in violation of the FDCA” even though “[f]ederal law does not expressly define, or ban, off-label promotion.”  McCormick v. Medtronic, Inc., 101 A.3d 467, 485 (Md. App. 2014).  “[N]othing in the FDCA actually prohibits manufacturers from promoting off-label uses.”  Underwood v. Rhone-Poulenc Rorer Pharmaceuticals, Inc., 890 So.2d 429, 431 (Fla. App. 2004).  The Second Circuit gave the FDA’s rationale a resounding thumbs down.  In Caronia, it recognized that “the government has treated promotional speech as more than merely evidence of a [product’s] intended use − it has construed the FDCA to prohibit promotional speech as misbranding itself.”  703 F.3d at 155.

While the FDCA makes it a crime to misbrand or conspire to misbrand a drug, the statute and its accompanying regulations do not expressly prohibit or criminalize off-label promotion.  Rather, the FDCA and FDA regulations reference “promotion” only as evidence of a drug’s intended use.  See 21 C.F.R. § 201.128 (discussing how drug’s intended use can be demonstrated).  Thus, under the principle of constitutional avoidance . . ., 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.  Because we conclude from the record in this case that the government prosecuted [defendant] for mere off-label promotion and the district court instructed the jury that it could convict on that theory, we vacate the judgment of conviction.

Id. at 160.

Numerous district courts have similarly pointed out the problems with the FDA’s criminalization of off-label speech without specific statutory authorization.

[T]he law governing such a claim [off-label promotion] is far from settled.  In fact, federal law does not expressly define, or ban, off-label promotion; rather the FDCA prohibits the adulteration or misbranding of any [regulated product] in interstate commerce.  Accordingly, there has been some dispute over the extent to which federal law actually prohibits a manufacturer’s promotion that is not false and misleading but that nonetheless fails to comply with federal regulatory requirements.

Raab v. Smith & Nephew, Inc., 150 F. Supp.3d 671, 697 (S.D.W. Va. 2015) (citations and quotation marks omitted).  See United States v. Facteau, 2020 WL 5517573, at *1 (D. Mass. Sept. 14, 2020) (“there is no statute that specifically prohibits off-label marketing”); Nagel v. Smith & Nephew, Inc., 2016 WL 4098715, at *7 (D. Conn. July 28, 2016) (“[f]ederal law does not explicitly ban off-label promotion unless it is false or misleading”) (citations omitted); Otis-Wisher v. Fletcher Allen Health Care, Inc., 951 F. Supp.2d 592, 600 & n.3 (D. Vt. 2013) (tort-related off-label promotion allegations “d[id] not aver any of these alleged misrepresentations or omissions were in violation of any specific federal law” and the FDA”s definition  is not “sufficiently specific” to plead a crime), aff’d, 616 F. Appx. 433 (2d Cir. 2015).  Several courts have found that the FDA’s interpretation of these various statutory and regulatory provisions is “muddy” or “murky.”  Thorn v. Medtronic, Sofamor Danek, Inc., 81 F. Supp.3d 619, 626 (W.D. Mich. 2015) (“muddy”); Wright v. Medtronic, Inc., 81 F. Supp.3d 600, 610 (W.D. Mich. 2015) (“muddy”; identical opinion); Schouest v. Medtronic, Inc., 13 F. Supp.3d 692, 702 (S.D. Tex. 2014) (“muddy”); Mendez v. Shah, 28 F. Supp.3d 282, 292 (D.N.J. 2014) (“murky”); see also Rodney Adams & Leslie Crudele, “The Eroding Off-Label Drug Use Promotion Prohibition, 12 J. Health & Life Sci. L. 1, 5 (2019). (“an explicit, flat ban on off-label use promotion is nowhere to be found in the FDA’s implementing regulations or the . . . FDCA”) (footnote omitted); Rodney Smolla, “Off-Label Drug Advertising & the First Amendment,” 50 Wake Forest L. Rev. 81, 82 (2015) (“No federal statute or regulation imposes, in so many words, a direct ban on off-label promotion of drugs.”).

We could probably delve further into the intricacies of the FDA’s off-label speech ban, but we think that we’ve made the point.  Maybe, under the former Chevron regime, where courts were required to defer to any agency statutory construction that that was “based on a permissible construction of the statute,” Chevron, U.S.A., Inc. v. National Resources Defense Council, Inc., 467 U.S. 837, 843 (1984), the FDA could get away with such an extravagant expansion of “intent” beyond its sparse use in the FDCA.  But under Loper Bright, where courts are expected to “exercise their independent judgment in deciding whether an agency has acted within its statutory authority,” 144 S. Ct. at 2273, and are expected to do so as “if no agency were involved,” id. at 2266, we believe that it is unlikely that the best reading of the FDCA is the FDA’s nearly complete ban on off-label speech, without regard to truth or scientific merit, where the statute itself does not define or even mention “promotion.”

Further, the Supreme Court nearly simultaneously held that the Administrative Procedure Act’s (“APA”) statute of limitations runs from whenever a plaintiff is actually injured.

A right of action accrues when the plaintiff has a complete and present cause of action” − i.e., when she has the right to file suit and obtain relief.  An APA plaintiff does not have a complete and present cause of action until she suffers an injury from final agency action, so the statute of limitations does not begin to run until she is injured.

Corner Post, Inc. v. Board of Governors of Federal Reserve System, 144 S. Ct. 2440, 2450 (2024) (citations and quotation marks omitted).  That means that the FDA’s Steinfeldt-to-Tinker-to-Evers-to-Chance basis for its off-label speech ban may be challenged under Loper Bright whenever a plaintiff is injured by a new FDA application of that ban.  Among other things, the FDA has pending off-label-speech-related guidances on both Internet “Misinformation” and communications with health care providers.  Any enforcement of either of these could cause a Loper Bright APA challenge to the FDA’s off-label speech ban to accrue.  And we know from another recent Supreme Court case that calling something a “guidance” does not prevent that “guidance” from creating cognizable injury.  See National Rifle Assn. v. Vullo, 602 U.S. 175, 194 (2024) (administrative “guidance” was actionable when it “targeted” a plaintiff with a “threat[] to wield [administrative] power”).

Since the beginning of the Blog, we have considered the FDA’s off-label speech ban to be an unconstitutional infringement on the rights of our FDA-regulated clients to engage in truthful scientific speech.  We still do.  However, it is also a very suspect assemblage of statutory and regulatory provisions that don’t really fit together to create such a sweeping ban.  After Loper Bright, the APA may be a quicker and easier way to consign the off-label speech ban to the dustbin of history where it belongs – as to truthful scientific speech.