by Julian Ginos

Often thought of as a bastion of countercultural resistance—think the Pentagon Papers, flag burning, the Nazi march in Skokie, IL—the First Amendment is enjoying a renaissance as a powerful antiregulatory tool for business interests. Citizens United, Hobby Lobby, and Zubik are some of the better-known examples of this phenomenon, but drug and device manufacturers have also made strides challenging the regulations governing them on First Amendment grounds. That’s because the Food and Drug Administration (FDA) often acts by exercising its power over a product’s “label,” which means not only the actual label on the drug or device itself but also educational and marketing material about the product, where the First Amendment has some sway. The FDA can, for example, punish a manufacturer for falsely claiming that its drug, approved for use A, is also approved for use B. But can it punish the same manufacturer for saying merely that its drug is effective for use B? What if that manufacturer is telling the truth?

First, some background: “Misbranding” a product overseen by the FDA is a crime, and a product is misbranded if introduced into interstate commerce lacking “adequate directions for use,” which FDA regulations say means “directions under which the lay[person] can use a drug safely and for the purposes for which it is intended.” One determines the “intended use” by looking at “the objective intent of the persons legally responsible for the labeling of drugs,” including, among other things, “oral or written statements by such persons or their representatives” which show “that the article is, with the knowledge of such persons or their representatives, offered and used for a purpose for which it is neither labeled nor advertised.” So if a manufacturer intends an unapproved use, but fails to label the product for that use—which it can’t, legally, because it doesn’t have permission to—the product is misbranded upon distribution.

This may sound simple, but the government has discovered a number of pitfalls in bringing these cases, in no small part because of the FDA’s deeply-held belief that it has (or at least ought to have) the power to directly regulate off-label promotion. Take United States v. Caronia, the leading case on misbranding and the First Amendment. The government had charged Caronia, a pharmaceutical representative, with conspiring to criminally misbrand the drug Xyrem. Xyrem had FDA approval to treat cataplexy and excessive daytime sleepiness, but Caronia had promoted the drug for unapproved uses as well. The government, however, made the mistake of asserting at trial, and perhaps most importantly, suggesting in the jury instructions, that merely promoting the drug was itself a crime.

The relevant portion of the jury charge described the law as follows:

A misbranded drug may be shown by a promotion of the drug by a distributor for an intended use different from the use for which the drug was approved by the [FDA].

. . .

The manufacturer, its agents, representatives and employees, are not permitted to promote uses for a drug that have not been cleared by the United States Food and Drug Administration. These non-cleared uses are commonly referred to as ‘off-label uses’ because they are not included in the drug’s labeling.

The Second Circuit disagreed. Applying Central Hudson’s test of First Amendment sufficiency, the court overturned the conviction because it found that Caronia had been effectively tried for merely talking about the drug’s off-label use, even though (1) Caronia’s speech was neither inherently false or misleading nor about unlawful activity, (2) criminally punishing it did not directly advance the government’s stated interest (as off-label use would continue to be legal even if promotion itself were punished), and (3) punishing speech was not the only effective regulatory tool available, and should have been a last resort.

An unhappy result for the FDA, but one with a silver lining: All the government need do from now on is make clear at trial—and in the jury charge—that while truthful, nonmisleading off-label promotion is not itself a crime, it can be evidence of a crime. An acceptable post-Caronia jury charge might look like this:

A person criminally misbrands a drug when he or she introduces that drug into interstate commerce without a label that explains all the uses that person intends for the drug. For example, if a person introduces a drug approved to treat heartburn—and heartburn only—into interstate commerce, the label on the drug must say it is intended to treat heartburn. And if that person instead introduced that same drug into interstate commerce intending for it to be used to treat the flu (instead of, or in addition to, treating heartburn) without a label explaining that she intends for the drug to be used to treat the flu, she has criminally misbranded that drug.

The manufacturer of a drug, as well as its agents, representatives, and employees, are allowed to truthfully promote uses for a drug that have not been cleared by the FDA. These uncleared uses are commonly referred to as “off-label uses” because they are not included in the drug’s labeling.

If you find that the manufacturer of a drug, or its agents, representatives, or employees, promoted the manufacturer’s drug for off-label use, you may infer from such promotion that the manufacturer intended for the drug to be used for off-label uses.  If you find that the manufacturer of a drug, or its agents, representatives, or employees, introduced a drug into interstate commerce with the intent that it be used for off-label use, you must find them guilty of criminal misbranding.

Did the government learn its lesson? Well, in the recent prosecution of Vascular Solutions, Inc. (Vascular) and its CEO Howard Root, on criminal misbranding charges, among others, the government took great pains to make clear that it would use the defendants’ speech only if the speech was deceptive or misleading, or as evidence of intent (which the First Amendment allows). To summarize, the device at issue in the case against Vascular and Root was designed to close varicose veins with a laser. The three relevant veinous systems are the superficial veins, close to the skin’s surface; the deep veins, further from it; and the perforator veins, connecting the two. The government argued that Vascular’s device was approved for superficial veins only, while Vascular argued it was approved for perforator veins as well. Because the government also offered evidence that Vascular had marketed the device for what it alleged was an unapproved use, it seemed like an easy case. Instead, the government lost by jury verdict; a defeat to the untrained eye, but a mighty leap forward in the sense that no court ruled the prosecution inherently illegal.

Why did they lose? We can’t be sure, but the case might have fallen apart when the FDA’s own expert testified that the FDA’s approval for the device could be read to cover perforator vein use. While plenty of evidence suggested that Vascular contemporaneously disagreed with his conclusion, it may still have convinced the jury (and could theoretically be right, contemporaneous interpretation notwithstanding).

From the FDA’s perspective, though, this is good news! After repeated setbacks on legal grounds, the only remaining obstacle to their enforcement goal is correct execution. Sure, prosecuting manufacturers for mere off-label marketing is forbidden. But it’s hard to see why that would ever be necessary. Putting products into the stream of commerce is what drug and device manufacturers do; they will, without fail, satisfy the act requirement of any criminal misbranding case. All that remains is showing the manufacturer “objectively intended” their product for an unapproved use, which will be a cinch in any case where the manufacturer has helpfully prepared marketing materials saying things like “this product has been shown to be effective for [insert unapproved use].” It’s conceivable that a manufacturer could engage in off-label marketing without also engaging in the culpable conduct—introduction into interstate commerce—that would consummate the crime. For example, a manufacturer might get FDA approval for an unprofitable use, then delay actual distribution until it had promoted the profitable off-label use to the point that distribution would pay off. But the scheme would unravel the moment its first product touched ground and completed the elements of a misbranding charge.

An interesting open question is how far the “speech is usable as evidence of a crime” principle extends. As it stands, manufacturers are free to sell drugs and devices for uses the FDA deems safe and effective. But the instant the manufacturer speaks aloud—even if truthfully—about an unapproved use, it is, in practical terms, guilty of criminal misbranding, given that nearly all manufacturers are constantly introducing their products into the stream of commerce. It is not hard to see how this sort of regulation arguably amounts to making a crime out of unapproved speech. The speech alone is not enough, of course; it must be paired with an act. But how banal can an act be before we object to making it culpable? Is any act sufficient? The First Amendment obviously won’t tolerate the crime of “breathing while criticizing the President,” or “selling ink to newspapers”; the acts there are transparently pretexts for criminalizing speech. So what kind of precedent are we setting when we tell manufacturers: “We don’t care if it’s true—you’re the wrong person to say it?”

Julian Ginos is an attorney at Kellogg, Huber, Hansen, Todd, Evans, & Figel PLLC and former law clerk to Judge Royce C. Lamberth, where he worked on the case of United States v. Vascular Solutions, Inc.

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