Our post last week on the three-ringed FCA circus in U.S. v. King Vassel, got us thinking about another way that misguided plaintiffs try to criminalize off-label use.  Deviating from the FDA’s (recently) consistent exercise of its prosecutorial discretion, we’ve seen some plaintiffs argue for a literal interpretation of the two archaic FDA “intended use” regulations (21 C.F.R. §210.218 (drugs) and 21 C.F.R. §801.4 (medical devices)) – employing language originating in the 1950s – to argue that a manufacturer’s mere knowledge of a product’s being put to off-label uses changes the product’s “intended use.”  That regulatory language provides:  

if a manufacturer knows, or has knowledge of facts that would give him notice that a [drug or medical device] 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 device which accords with such other uses.

We quoted the entire provision (the two regs in this respect are verbatim identical) here .

Having taken the leap from knowledge of off-label use to a changed intended use, these plaintiffs (but not the FDA itself) then seize upon the convoluted and questionable regulatory interpretation that the FDA uses to prohibit truthful off-label promotion.  See United States v. Caronia, 703 F.3d 149, 154 (2d Cir. 2012) (describing multi-regulation FDA interpretation). Plaintiffs finish by arguing that if a manufacturer simply knows that its product is used off-label, then that product is “misbranded,” which in turn (they claim) means that all federal reimbursement for that use of the product is somehow a “false claim.”

[Barnyard expletive].

Just as courts have limited another federal statute – the Lanham Act – to prevent private plaintiffs from interfering with the FDA’s prosecutorial discretion by interpreting the FDCA (which prohibits private rights of action) in ways that the FDA does not, so should courts restrict use of the False Claims Act. The Lanham Act precedent doing so is widespread and we’ve discussed it here .  Here’s one relatively recent appellate statement of the principle before we move on to what we really want to discuss:

Section 337(a) of the FDCA bars private enforcement of the statute, stating that “all such proceedings for the enforcement, or to restrain violations, of this[Act] shall be by and in the name of the United States.”  [This section] “leaves no doubt that it is the Federal Government rather than private litigants who are authorized to file suit for noncompliance. . . .  [T]this section also limits the ability of a private plaintiff to pursue claims under state law theories where such claims collide with the exclusive enforcement power of the federal government.

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The statute assigns to the FDA the responsibility for taking enforcement action against Defendants. . . .  [Plaintiff] is not permitted to circumvent the FDA’s exclusive enforcement authority by seeking to prove that Defendants violated the FDCA, when the FDA did not reach that conclusion.

PhotoMedex, Inc. v. Irwin, 601 F.3d 919, 924, 928 (9th Cir. 2010) (various citations omitted).

Now, the FCA is a little different because private plaintiffs are ostensibly acting “in the name of the United States,” but the FDCA also provides the FDA with exclusive prosecutorial discretion whether to pursue claimed violations.  21 U.S.C. §336.  We delved into the precedent (including under the Lanham Act) precluding private plaintiffs from distorting the FDA’s prosecutorial discretion through interpretations at odds with those of the FDA here .  Again, we’ll quote one appellate decision (of many) to illustrate the point:

[A]n agency [the FDA] decision not to enforce often involves a complicated balancing of a number of factors which are peculiarly within its expertise.  Thus, the agency must not only assess whether a violation has occurred, but whether agency resources are best spent on this violation or another, whether the agency is likely to succeed if it acts, whether the particular enforcement action requested best fits the agency’s overall policies, and, indeed, whether the agency has enough resources to undertake the action at all.  An agency generally cannot act against each technical violation of the statute it is charged with enforcing.  The agency is far better equipped than the courts to deal with the many variables involved in the proper ordering of its priorities.

Heckler v. Chaney, 470 U.S. 821, 831-32 (1985).

So under this precedent, we believe that §§336-337 of the FDCA preclude private plaintiffs, including those purporting to hijack the FDA’s prosecutorial powers under the False Claims Act, from taking a position, at odds with the FDA, that bare manufacturer knowledge of off-label use renders a product “misbranded” by changing the product’s “intended use.“  Make no mistake about it, attempts to equate mere knowledge of off-label use with “misbranding” are in effect attempts to ban all off-label uses.  After all, manufacturers are required by the FDCA to gather and report – and therefore obtain “knowledge” about − both adverse events and information about product risks appearing in scientific/medical literature, including off-label uses.  Plaintiffs would create a Catch-22 – with manufacturers being required by the FDCA to obtain the same “knowledge” of off-label uses that then supposedly “misbrands” their products by changing their “intended uses.”

The only time in recent years that the FDA itself has approached that position was in a “draft” 2011 guidance document that we excoriated here.  Fortunately, that draft has gone nowhere.  Two years have passed, and it remains “distributed for comment purposes only” according to the FDA’s website .  It was a limited foray concerning a very limited number of devices, and it hasn’t gone anywhere.

On the other side of the ledger, we have the FDA’s statement of its prosecutorial position in a brief it filed in 2010 rejecting a similarly broad reading of its “intended use” regulations:

[Plaintiff] also suggests that §201.128 treats an unapproved use by physicians as an intended use whenever a manufacturer knows of the use, even if the manufacturer does not promote the use and there is no other evidence that it intends such use. . . .  Nothing in the regulation obligates FDA to treat known uses as intended uses. Rather, the regulation leaves FDA with discretion not to equate the two.  In practice, FDA usually does not treat an unapproved use as an intended use solely because the manufacturer knows that the unapproved use is taking place. . . .  Thus, plaintiff] is wrong when it suggests that it commits a crime.

Defendants’ [the United States and FDA] Memorandum Of Points And Authorities In Support Of Motion To Dismiss Or For Summary Judgment, Allergan, Inc. v. United States, No. 1:09-cv-01879-JDB, at 21-22 (D.D.C. filed Jan. 11, 2010) (emphasis added) (we’ve pulled this off PACER, and it’s here).  So the FDA has stated, specifically invoking its “discretion,” that it does not consider mere knowledge, without affirmative conduct promoting the product, as sufficient to change a product’s “intended use.”  Then the Allergan case settled.

Courts have said the same thing.  The FDA’s brief cited Sigma-Tau Pharmaceuticals, Inc. v. Schwetz, 288 F.3d 141 (4th Cir. 2002), where the plaintiff sought to infer knowledge, and therefore a changed intended use, from the claimed fact that 80% of a particular drug’s consumption was for a particular off-label use.  Id. at 145.  The court agreed with the FDA that nothing in these regulations’ definition of “intended use” required the Agency to treat common and foreseeable off-label uses of drug as intended uses.  First of all, the position was unprecedented:

[N]o court has ever found that a product is “intended for use” or “intended to affect” within the meaning of the FDCA absent manufacturer claims as to that product’s use.

Id. at 417 (quoting Brown & Williamson Tobacco Corp. v. FDA, 153 F.3d 155, 163 (4th Cir. 1998), aff’d, 529 U.S. 120 (2000)) (emphasis added).  Second, the regulation invests the FDA with discretion with respect to what post-approval evidence to consider with respect to intended uses:

[Plaintiff] maintains [that]the reality of the situation . . . lies in treating patients [off-label]. But this point is unavailing.  [The intended use regulation] provides that “intent is determined by such persons’ expressions or may be shown by the circumstances surrounding the distribution of the article”.  The regulation is phrased in the disjunctive, not the conjunctive.  And it states that intent “may be shown” by the surrounding circumstances, not that it must be so shown.  The district court correctly found that [the regulation] grants the agency discretion to decide what evidence of intent it will examine.  The regulation does so for good reason. . . .  This is because many of the sources of evidence and market data . . . cannot be effectively analyzed in the pre-approval context.

288 F.3d at 147 (emphasis original).  Third, equating knowledge without conduct with a changed intended use would interfere with − you guessed it − off-label use:

[T]his course of events . . . also might frustrate the longstanding practice of Congress, the FDA, and the courts not to interfere with physicians’ judgments and their prescription of drugs for off-label uses.  In light of the ensuing effects on the delivery of health care and drug prices in this country, such interference with off-label use is not something we would be wise to welcome, let alone help to bring about.

Id. (citations omitted).

Nor is Sigma-Tau the only relevant precedent.  In a smoking case, Action on Smoking & Health v. Harris, 655 F.2d 236 (D.C. Cir. 1980), the court quoted a Senate Report from 1934 stating that the “manufacturer of the article, through his representations in connection with its sale . . . determine[s] the use to which the article is to be put.”  Id. at 238-39.  Thus it was Congress’ “understanding even in 1934 that the crux of FDA jurisdiction over drugs lay in manufacturers’ representations as revelatory of their intent.”  Id. at 239.  Mere knowledge, without a representation, doesn’t cut it.  Likewise, in a laetrile-related case (involving sale of apricot pits) the court noted:

While the seller’s knowledge of the consumers’ uses for his product is a factor to be considered,we do not agree with the apparent theory of the government that if any consumers use a product as a drug, such use, if known by the seller, is determinative on this issue.  Carried to its logical extreme, this would mean that every merchant who sells carrots to the public with knowledge that some of his consumers believe that the ingestion of carrots prevents eye diseases holds the carrots out for use as a drug, as that term is defined in the Act.

Millet, Pit & Seed Co., Inc. v. U. S., 436 F. Supp. 84, 89 n. 4 (E.D. Tenn. 1977) (emphasis added), vacated and remanded for merits hearing, 627 F.2d 1093 (6th Cir. 1980).  See United States v. Prigmore, 243 F.3d 1, 20 (1st Cir. 2001) (“we are not persuaded that a criminal fraud prosecution can be premised upon a failure to file a PMA supplement in connection with a modification to an approved device that affects the device’s safety or effectiveness only with respect to a sincerely unintended and warned-against, albeit known, condition of use”).

In 2002, the FDA asserted the “mere knowledge” approach to intended use – and lost.  It attempted to force manufacturers to seek approval of pediatric uses for drugs known to be used off-label in pediatric populations.  While a labeling disclaimer concerning that use might indicate knowledge that it exists, such disclaimers did not “suggest” such uses so as to modify the product’s intended use.  “This court concludes that use of a drug nowhere indicated by the label and, in fact, specifically disclaimed by the label is, quite simply, not “suggested” by that label.  For that reason, the court finds that the FDA’s expansive interpretation of the FDCA lacks firm support in law.”  Ass’n of American Physicians & Surgeons, Inc. v. FDA., 226 F. Supp. 2d 204, 217 (D.D.C. 2002).  That interpretation “also lacks support in [regulatory] tradition.  Id.

[T]he FDA has repeatedly stated that it may only regulate claimed uses of drugs, not all foreseeable or actual uses. . . .  [T]he FDA’s argument proves too much.  If [the FDCA] truly gave the FDA the authority that it claims, the door would be open to FDA’s regulation of all off-label uses, based solely on the manufacturer’s knowledge that those uses are common-place.  This authority would surely conflict with Congress’ will and would eviscerate the long-established foundation of federal food and drug law, which allows, not the FDA, but the manufacturer of the article, through his representations in connection with its sale, to determine the use to which the article is to be put. . . .   There would be almost no limit to the FDA's authority were its view adopted.

Id. at 217-18 (citations and quotation marks omitted) (emphasis added).

We’ve also seen the same argument advanced (rarely) in product liability litigation − unsuccessfully.  In Riley v. Cordis Corp., 625 F. Supp.2d 769, 782 (D. Minn. 2009), the court pointed out that the literal interpretation of “intended use” as depending on mere knowledge conflicted with “other statutes and regulations governing both a manufacturer’s right to disseminate information about off-label uses and a manufacturer’s ability to alter a label that has been approved by the FDA.”  Id. at 781.  Federal law allowed some dissemination of information about off-label uses, which assumed the knowledge of those doing the dissemination:

It seems highly unlikely that, at the same time, [the intended use regulation] was forcing manufacturers who knew of off-label uses of their devices but did not promote those off-label uses to provide instructions or warnings.  It would make no sense to impose on manufacturers who were not promoting off-label uses of their devices a duty to instruct or warn, but to impose no such duty on manufacturers who were promoting off-label uses.  The existence of this statutory scheme . . . strongly suggests that [this regulation] did not impose additional labeling requirements on manufacturers . . . when those manufacturers become aware of off-label uses of their products.

Id. at 782 (footnote omitted) (emphasis added).  Nor was the intended use regulation “intended to establish an open-ended requirement that the manufacturer . . . seek permission to alter its label every time the manufacturer becomes aware of a new off-label use.”  Id.

As demonstrated, both the courts and the FDA (at least after it tried and failed 15 years ago) refuse to read FDA regulations as changing the “intended uses” of drugs and devices merely on the basis of manufacturer knowledge of off-label uses, in the absence of any conduct promoting such uses.  Therefore, under both 21 U.S.C. §337(a), forbidding private enforcement of the FDCA, and 21 U.S.C. §336, recognizing the FDA’s prosecutorial discretion, private plaintiffs, including False Claims Act relators, should not be permitted to interpret the same FDA regulations in a manner rejected by the FDA itself – so as to turn all off-label use into some sort of criminal act.