What If We Win? Off-Label Promotion & Product Liability

by Reed Smith

Since the nomination of Dr. Scott Gottlieb to head the FDA, we’ve seen quite a few references to his opposition to the current FDA prohibition against off-label promotion – regardless of the truth of the promotion itself.  We don’t think we can add a lot to those descriptions of Dr. Gottlieb’s views, so we won’t try.  We will, of course, be very pleased if the FDA ends its unconstitutional ban on truthful off-label promotion before ultimately being forced to by the courts.

We’ve also read a recent (3/15) Bloomberg piece (here, for those with a subscription) entitled “Off-Label Promotion Could Mean More Drug Company Liability.”  Although apparently written before the Gottlieb nomination, this article consists largely of the interviews with two avatars of the other side of the “v.”:  fellow blogger Max Kennerly (who regularly writes intelligent critiques of our posts) and Lou Bogrod, with whom we’ve tangled before over off-label issues.  Needless to say, we disagree with the “more liability” spin they put on any would-be FDA retreat on off-label promotion.

Here’s why – and we apologize to all of you who can’t read the article we’re responding to, but it’s behind a paywall, and Michael Bloomberg didn’t get to be a billionaire by giving things away that he could charge for (that’s what we do).

The first contention is that, once truthful off-label promotion is legal, “drug companies would lose the protection afforded by preemption.”  We don’t think that’s grounds for “more liability.”  First of all, “drug companies” – at least those making innovative branded drugs, don’t have much of a preemption defense.  The Supreme Court unfortunately took care of that in Wyeth v. Levine, 555 U.S. 555 (2009), limiting preemption to cases of “clear evidence” that the FDA would have rejected the label change in question.  There are other possible preemption grounds concerning design defect claims (which we’ve advocated here), but off-label promotion doesn’t involve design.  So, while there may be liability issues raised concerning specific instances of off-label promotion, we don’t see any basis for calling it “more” liability than already exists for on-label promotion.  Most branded drug warnings don’t have a preemption defense now.

Indeed, the result could very well be less liability. Even if truthful off-label promotion were to become broadly legal, the off-label use itself remains off-label.  The FDA, however, can order a drug’s label to contain statements (usually warnings) about an off-label use.  21 C.F.R. §§201.57(c)(6)(i), 201.80(e) (both phrased in terms of “required by” the FDA).  That’s important because, as we discussed in more detail here, only the FDA can do this.  Drug companies are not allowed to discuss off-label uses in their labels whenever they want.  Without the FDA telling them to, that is a form of misbranding.

Should truthful off-label promotion become legal, it may be expected that the FDA would react by ordering more warnings about those uses to appear on drug/device labeling. That’s actually good for preemption, in a number of ways.

First, with the FDA picking the language it wants, an order to put “X” in the label about a particular off-label risk is (to our defense-oriented way of thinking) “clear evidence” under Levine that the FDA doesn’t want some plaintiff-advocated statement “Y” on that same label.  Once the FDA itself is in the business of imposing precise wording, the agency’s actions pretty much preclude other statements about the same risk.

Second, there’s also preemption by way of PLIVA, Inc. v. Mensing, 564 U.S. 604 (2011), and Mutual Pharmaceutical Co. v. Bartlett, 133 S.Ct. 2466 (2013), to deal with.  We’ve already discussed the “independence principle” that these cases articulate for the application of impossibility preemption.  The cases on our preemption cheat sheet demonstrate that this principle is in no way limited to generic drugs (heck, it’s been applied to airplanes).  Thus, in a truthful off-label promotion case, plaintiffs shouldn’t even be able to argue that an additional warning about the use at issue should appear on the label, because (as just discussed) any such change would have to come from the FDA.

Third, physicians put medical devices as well as drugs to off-label use. In addition to items (1) and (2), an FDA order that a Class II device manufacturer should put specific language about a specific off-label use of a specific device should constitute a “device specific” requirement justifying preemption under Medtronic, Inc. v. Lohr, 518 U.S. 470 (1996).  Since Lohr currently precludes most arguments concerning express preemption (invoking a since-abolished presumption against preemption), this would be yet another way that preemption would be greater, not less, in some cases involving legal off-label promotion.

The Bloomberg article then discusses the big First Amendment win for our side in Amarin Pharma, Inc. v. FDA, 119 F. Supp. 3d 196 (S.D.N.Y. 2015), with the Amarin subsequent settlement somehow “bring[ing] more liability exposure.”  Exactly how Amarin would increase liability isn’t explained, in the article, and we frankly don’t see it.  Here’s a copy of the Amarin settlement agreement.  The most significant aspect of the settlement in the liability context is found in paragraph 5 – providing for an FDA pre-clearance mechanism for off-label promotion:

Amarin may submit to FDA under the preclearance procedure described in this paragraph up to two proposed communications per calendar year about the off-label use of [the drug] before communicating them in promotion to doctors to determine if FDA has concerns with Amarin’s proposed communications. If FDA has concerns with a proposed communication that Amarin submits to FDA under this paragraph, FDA will contact Amarin with its specific concerns or objections within 60 calendar days.

To the extent that that the Amarin settlement were to become a model for a future legal off-label promotion regime, this kind of arrangement isn’t likely to increase liability either.

First, there’s both Mensing/Bartlett and “clear evidence” preemption in play.  FDA pre-clearance of off-label promotional statements implicates the aforesaid “independence principle” and thus impossibility preemption.  It would also provide “clear evidence” that the statement is OK with the FDA.  Second, as a practical matter, if off-label promotion follows the Amarin model with FDA pre-clearance (or a litigated court approval if the FDA refuses to allow the particular statements), juries aren’t likely to think much of off-label liability claims.  If off-label promotion comes with FDA clearance/court approval attached to it, such statements would have a significantly greater “cachet” than many on-label warning defect claims where there isn’t the same kind of evidence that the statements at issue received the kind of particularized and detailed scrutiny by either the FDA or a court that is provided by the Amarin model.

The article then, under the heading “no preemption defense,” asserts that companies being “less handcuffed” by the FDA “exposes [them] to liability for off-label promotion because they won’t be able to use FDA approval as a shield.”  We’re not 100% clear what this means, but the notion that off-label use ipso facto makes preemption evaporate has been raised repeatedly in PMA medical device litigation and, aside from one outlier case, has failed miserably.

“[T]he FDA’s “approval process generally contemplates that approved devices will be used in off-label ways.”  Aaron v. Medtronic, Inc., ___ F. Supp.3d ___ (S.D. Ohio Sept. 22, 2016).  The FDCA “preempt[s] any claim that seeks to impose a state law duty that differs from or adds to federal duties, whether those duties concern on- or off-label uses.”  Caplinger v. Medtronic, Inc., 784 F.3d 1335, 1346 (10th Cir. 2015) (Gorsuch, J.).

[Plaintiffs] are incorrect to argue that the absence of affirmative approval mandates the finding that no federal requirements exist.  Federal requirements for off-label use manifestly exist. . . .  Furthermore, plaintiffs’ argument presumes off-label use to be inherently suspect or substandard, which Congress rejected by enacting 21 U.S.C.A. §396.

Cornett v. Johnson & Johnson, 998 A.2d 543, 561 (N.J. Super. A.D. 2010), aff’d, 48 A.3d 1041 (N.J. 2012).  Preemption analysis thus does not depend on how the device is to be used, or promoted to be used.  E.g., Clements v. Sanofi-Aventis, U.S., Inc., 111 F. Supp.3d 586, 600 (D.N.J. 2015); Byrnes v. Small, 60 F. Supp.3d 1289, 1299 (M.D. Fla. 2015); Arvizu v Medtronic, Inc., 41 F. Supp.3d 783, 790 (D. Ariz. 2014); Martin v. Medtronic, Inc., 32 F. Supp.3d 1026, 1035 (D. Ariz. 2014); Caplinger v. Medtronic, Inc., 921 F. Supp.2d 1206, 1218 (W.D. Okla. 2013), aff’d, 784 F.3d 1335 (10th Cir. 2015); Riley v. Cordis Corp., 625 F. Supp.2d 769, 779 (D. Minn. 2009); Cales v. Baptist Healthcare System, Inc., ___ S.W.3d ___, 2017 WL 127731, at *5 (Ky. App. Jan. 13, 2017); Angeles v. Medtronic, Inc., 863 N.W.2d 404, 411 (Minn. App. 2015); McCormick v. Medtronic, Inc., 101 A.3d 467, 490 (Md. App. 2014).  But see Ramirez v. Medtronic Inc., 961 F. Supp.2d 977, 991 (D. Ariz. 2013) (the one outlier case we mentioned above).

The conduct plaintiff complains of − how defendants are promoting and marketing to physicians the off-label use of the [product] − is governed by the FDCA.  To determine whether said conduct is improper would require reliance on the requirements of the FDCA.   Further, even the concept of “off-label use” is a creature of the FDCA, is defined by the FDCA, and is not a part of [state] substantive law.

Caplinger, 921 F. Supp.2d at 1219-20.

Thus, whether preemption is express or implied, claims based on off-label promotion are not some kind of magic formula for making preemption disappear. The same principles still apply.  Within the confines of the various preemption regimes applicable to innovator drugs, generic drugs, PMA medical devices, and non-PMA medical devices, we expect plaintiffs to challenge the validity of particular statements made in off-label promotion to the same extent as they can (or cannot) challenge the validity of particular on-label statements.  In certain situations there could be liability, but it’s simply incorrect to posit that, by the mere fact of off-label promotion, there will be “more” liability than would otherwise exist.

The article, and the questionable statements, keep going.  Next comes a claim that the learned intermediary rule is “undercut” by truthful off-label promotion.  Again, we don’t see how.  The promotional statements are still directed to prescribing physicians.  We’re not aware of any groundswell for direct-to-consumer off-label promotion.  As long as the prescriber is the recipient of information about an off-label use, we don’t see any weakening of the learned intermediary rule.  The law should remain as it has been – “to get around the [learned intermediary] defense, a product liability plaintiff must now show that a different warning would have changed a prescribing physician’s decision.” (statement in article).

Finally, the article speculates that legal – that is to say, truthful – off-label promotion could somehow limit preemption with respect to generic drugs. We’ve already dispatched the argument that First Amendment protection makes generic preemption disappear, so here we’ll simply reiterate that FDA pre-clearance (the basis for Mensing/Bartlett preemption under the already discussed “independence principle”) is would be perfectly constitutional, as a reasonable time, place, and manner regulation, of generic drug free speech as it is of free speech generally, as the Amarin settlement demonstrates.

Otherwise, allegations of off-label use have not prevented broad application of generic preemption.  Stephens v. Teva Pharmaceuticals, U.S.A., Inc., 70 F. Supp.3d 1246, 1250-51 (N.D. Ala. 2014); Rojas v. Teva Pharmaceuticals USA, Inc., 920 F. Supp.2d 772, 780 (S.D. Tex. 2013); Whitener v. PLIVA, Inc., 2012 WL 1995795, at *4 (E.D. La. June 4, 2012). Kellogg v. Wyeth, 2012 WL 368658, at *4-5 (D. Vt. Feb. 3, 2012).  Once the FDA recognizes truthful off-label promotion as legal, there will be even less basis for attacks on generic preemption.  After all, the promotional materials would still qualify as “labeling” under the FDA’s and the courts’ broad definition of that term.  E.g., 21 C.F.R. §202.1(1)(2); Holmes v. Hospira, Inc., 2013 WL 12132046, at *10 (C.D. Cal. Jan. 10, 2013) (“FDA’s broad definition of labeling” “encompasses nearly every conceivable form of communication with medical professionals”).

The FDCA’s “sameness” requirement for generic drugs explicitly applies to “labeling.” 21 U.S.C. §§355(j)(2)(A)(v), 355(j)(4)(G).  “Sameness” would thus extend to off-label promotion of generic drugs.  That may create other complications with respect to off-label promotion in generic context, but legalization of truthful off-label promotion shouldn’t have any effect on the scope of generic preemption with respect to generic drugs as long as “sameness” is complied with.  Moreover, preemption under Buckman would preclude plaintiffs from invoking lack of “sameness” as some sort of cause of action against truthful off-label promotion.  Truthful off-label promotion isn’t a state law tort, whether it’s the “same” as something else or not.  “[T]here is no state-law duty to abstain from off-label promotion.” Aaron, 2016 WL 5242957, at *12 (applying Buckman).

[T]here is no state law duty to abstain from off-label promotion.  Off-label promotion itself exists only as a creation of the FDCA scheme.  A state law cause of action cannot rest solely on . . . off-label promotion. . . .  [E]ven the concept of ‘off-label use’ is a creature of the FDCA, is defined by the FDCA.”

Martin v. Medtronic, Inc., 32 F. Supp.3d 1026, 1038 (D. Ariz. 2014) (numerous internal citations and quotation marks omitted).  Thus, a suit alleging lack of sameness as a tort in the off-label promotion context would assert only a supposed FDCA violation (of sameness), and Buckman is 100% clear that private plaintiffs cannot enforce the FDCA.

In sum, we believe that the Bloomberg article’s prediction of “more” liability in the event of the demise of the FDA’s ban on truthful off-label promotion is simply the other side’s wishful thinking.  There will be some liability, just as there now is for on-label statements and promotion, but legalization isn’t going to have much effect, if any, on preemption.  To the extent legalization has any effect, both precedent (we cite cases; the article doesn’t) and common-sense suggests that such effect will be positive from a defense perspective.  The biggest thing that legalization will do is eliminate the other side’s arguments that defendants are acting illegally despite telling the truth.  The demise of “you broke the law” arguments can only be beneficial to the defense.

DISCLAIMER: Because of the generality of this update, the information provided herein may not be applicable in all situations and should not be acted upon without specific legal advice based on particular situations.

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