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The FDA recently released draft guidance concerning the labeling of biosimilar products (analogous in the biologic context to generic drugs). It’s called, not surprisingly “Labeling for Biosimilar Products Guidance for Industry.” Here’s a link to it on the FDA’s website.

When we think of bioequivalence, we think of generic drugs, and more specifically generic drug preemption under PLIVA v. Mensing, 131 S. Ct. 2567 (2011), and its progeny. Generic preemption, as we’ve discussed many times, depends on the impossibility of making an immediate change to a product (including its labeling) as required by state law, where the same change necessitates prior approval by the FDA under federal law. So we took a look at the guidance to see whether biosimilar products were likely to enjoy the same protection from state-law product liability.

It doesn’t look that way.Continue Reading FDA Biosimilars Guidance Not Conducive To Preemption

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A lot of firms have already expended a lot of ink discussing the proposed memorandum of settlement filed on March 8, 2016 in Amarin Pharma’s First Amendment litigation against the FDA Here’s a link to Reed Smith’s. We’ll try not to be repetitive of what everybody else has been saying. Four points that we haven’t seen elsewhere:

Agreement to be “bound”

Sure, the FDA has “agreed to be bound,”− but to what? The phraseology preserves agency options:

Defendants agree to be bound by the Court’s conclusion that Amarin may engage in truthful and non-misleading speech promoting the off-label use of Vascepa and, under United States v. Caronia, 703 F.3d 149 (2d Cir. 2012), such speech may not form the basis of a prosecution for misbranding.

Proposed Amarin Settlement, first numbered paragraph. In the first clause, the FDA simply binds itself to a “conclusion” regarding “speech promoting the off-label use of Vascepa” (the drug in question). That’s very case specific.

The second clause, however, is capable of a different meaning. In that clause, the FDA binds itself to the conclusion that “under [Caronia], such [truthful and non-misleading] speech may not form the basis for misbranding.” By its terms, this second conclusion is not tied to the facts of the Amarin case. It looks like a general agreement to be bound, broad enough to be invoked by other companies. Maybe it is; maybe it isn’t, but anyone who might later seek to argue that the FDA is collaterally estopped by the decision in Amarin Pharma, Inc. v. FDA, 119 F. Supp. 3d 196 (S.D.N.Y. 2015) – to the extent that’s even possible under United States v. Mendoza, 464 U.S. 154, 162-63 (1984), something that would take more time to examine than we have at the moment − can find support in this clause. In any event, since courts rather than the FDA now have the last word on the First Amendment question, any limitation that the FDA might try to put on this concession will end up being litigated.

Continue Reading Examining The Amarin/FDA Off-Label Promotion Settlement

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On New Years’ Eve, the FDA released an interesting, and unsettling, proposed guidance indicating that it has plans to go public with what are essentially regulatory guesses, based on what it calls “emerging signals” that might suggest medical device risks.  The formal title of the proposed guidance is “Public Notification of Emerging Postmarket Medical Device Signals.”  It’s not final, and there is currently open a 60-day comment period that closes March 4, 2016.
Basically the FDA is proposing to make public statements about possible device risks (and can drugs be far behind?) if the “emerging signals” meet the following criteria of “proof” – quotation marks intended:

  1. the information represents a new, potentially causal association, or a new aspect of a known association (e.g., increased rate or severity of event or reduced benefit), between a medical device and one or more adverse events or clinical outcomes;
  2. the available information is reliable and supported by sufficient strength of evidence; and
  3. the information could have important clinical implications for patient management decisions and/or could it significantly alter the known benefit-risk profile of the device.

Proposed Guidance at 6 (emphasis added).  The guidance cautions, however, that such “information has not been fully analyzed, validated or confirmed, and . . . the Agency does not yet have specific recommendations.”  Id. at 4.  Further, the communications that the FDA is proposing “may lack certainty about the significance of the information.”  Id.Continue Reading FDA Proposing Regulatory Shots in the Dark

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We just read on 360 this morning that the FDA has again postponed its schedule for finalizing the generic drug labeling changes (the so-called “Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products” rule) it proposed two years ago in order to overturn Supreme Court precedent recognizing preemption in generic drug product liability…

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Not quite two years ago, we posted about how, under Wyeth v. Levine, 555 U.S. 555 (2009), and subsequent Supreme Court cases, private plaintiffs can’t make claims that so-and-so should have warned about such-and-such with respect to the off-label use of a prescription medical product.  That’s because the FDA zealously guards its authority over warnings concerning off-label uses and does not allow such warnings unless the Agency specifically says so.  That’s crystal clear for drugs.  21 C.F.R. §§201.57(c)(6)(i), 21 C.F.R. §201.80(e).  It’s a little more roundabout for devices (which we explained in that post), but for now, we’re talking about drugs.  Bottom line − since off-label warnings aren’t something a manufacturer can do unilaterally under the CBE regulation, a la Levine, any tort claim demanding such warnings is preempted.

The remedy is to file a citizen’s petition asking the FDA to impose such a warning.

A former colleague recently passed along an example of how such a petition can crash and burn, making preemption even more likely in any civil litigation.  Earlier in the same year (2013) we wrote our post, one James P. Reichmann filed a citizen’s petition concerning the drug ondansetron asserting that it was used off-label for relief of morning sickness (“nausea and vomiting during pregnancy,” or “NVP”) and that the FDA should require warnings (and some other stuff) about birth defects.  The FDA therefore opened up Docket No. 2013-P-0048.  The FDA took its time because the petition “raise[d] complex issues requiring extensive review and analysis by Agency officials.”Continue Reading The Ghost of Bendectin – Exorcized by the FDA?

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Today we discuss a couple of developments involving (actually or potentially) the application of the First Amendment to the FDA’s increasingly battered prohibition against truthful promotion of off-label use.

First, we’ve mentioned Pacira Pharmaceuticals v. FDA before as the latest First Amendment follow-up action to Amarin Pharma, Inc. v. FDA, ___ F. Supp.3d ___, 2015 WL 4720039 (S.D.N.Y. Aug. 7, 2015).  What we have for you now are the two industry-side amicus briefs filed in support of Pacira’s First Amendment motion against the FDA.  This one was filed by PhRMA, and this one was filed by something called the Medical Information Working Group, which is a consortium consisting of Amgen, Bayer, Boehringer, Lilly, Genentech, GSK, J&J, Novartis, Novo Nordisk, Pfizer, and Sanofi.  Impressive lineup.  And to think we can remember when nobody was willing to take on the FDA about truthful off-label promotion for fear of retaliation….  What a difference a few wins make.

We’ve read through the two amicus briefs and we heartily recommend them to anyone interested in bringing the FDA’s reign of (t)error in this area to long-overdue end.  Briefly, the MIWG brief makes the following points:  (1) the FDA’s ban is an “ambiguous tangle of regulations, nonbinding guidance documents, and severe enforcement practices”; (2) pharmaceutical promotion is First Amendment protected speech under Sorrell v. IMS Health, Inc., 131 S. Ct. 2653 (2011); (3) truthful off-label promotion provides valuable information to physicians and patients alike; (4) what FDA claims is “misbranding” is the same information it has pledged in other contexts to “work hard to address”; (5) Pacira’s speech is really on-label promotion that the FDA has attempted to suppress through an improperly crabbed reading of the drug’s intended use; (6) off-label use is legal, common-place, medically valuable, and sometimes the medical standard of care; (7) more truthful speech about off-label use is better than less; (8) the FDA’s ban unconstitutionally discriminates on the basis of both speaker and content; (9) the basis for the FDA’s ban is unconstitutionally vague and ambiguous; (10) FDA’s “safe harbors” are arbitrary and constitutionally inadequate; (11) the FDA has taken inconsistent positions on what off-label promotion is allowed; (12) the FDA has never even defined “promotion”; (13) the FDA’s vagueness and contradictory policies chills protected speech − truthful pharmaceutical promotion; and (14) because of this chilling effect there is both standing and justiciability.Continue Reading First Amendment Notes: Amicus Briefs In Pacira & Application of IMS v. Sorrell

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Here are a couple of non-litigation related matters that we thought our readers need to know about.

First, the FDA.  We’ve pointed out before that the FDA’s “intended use” regulations for drugs (21 C.F.R. §201.128) and devices 21 C.F.R. §801.4) both contain the following potentially disturbing language:

[I]f a manufacturer knows, or has knowledge of facts that would give him notice that a device introduced into interstate commerce by him 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 to which the article is to be put.

This language has the potential, if the FDA wanted to, to allow the prosecution of a drug or device manufacturer for an “adulterated”/”misbranded” product (for not having “adequate labeling”), merely because that manufacturer KNEW ABOUT off-label use of its products – forget promotion (truthful or otherwise). Fortunately, the FDA generally has not read this language literally.  Instead it requires prior agency approval of warnings about risks peculiar to off-label uses (we discussed that here).Continue Reading The FDA Tiptoes – and Congress Splashes Into – the 21st Century

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The FDA may be in for a lot of this.  In the wake of Amarin’s preliminary injunction win, another pharmaceutical company has brought a First Amendment challenge to the FDA’s restriction of off-label promotion.  Last year, the FDA issued a warning letter claiming that Pacira Pharmaceuticals, Inc. had engaged in false and misleading promotion and…

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“Jurisfiction” is a word coined by Jasper Fforde, author of the Tuesday Next series, one of the more sophisticated set of children’s works that has come to populate this post-Harry Potter era.  To be very brief, Jurisfiction is the fictional police force for BookWorld, one of Fforde’s fictional universes.  Tuesday is a Jurisfiction agent (sometimes rather more than that).

“Jurisfiction,” unfortunately, is also something we see in our line of work, sometimes making us wonder whether the likes of Emperor Zhark, the Red Queen, and Pinky Perkins may have aliases who serve in the all-too-real judicial branches here in the States.  Jurisfiction is shorthand for a decision that gets a legal issue totally bollixed  – perhaps applying the UltraWord to the issue – allowing the user to control the plot, garbling it, and ultimately making all precedent useless.

We recently ran across a shining example of jurisfiction in the discussion of FDA warning letters found in Mihok v. Medtronic, Inc., ___ F. Supp.3d ___, 2015 WL 4722847 (D. Conn. Aug. 10, 2015).  Here’s what Mihok held on that subject:

The Complaint is rooted in FDA Warning Letters which state that [defendant] failed to comply with the CGMP regulations. . . .  While perhaps not dispositive on the issue, the FDA’s conclusions and interpretations of its own regulations are likely to receive a considerable degree of deference.  See, e.g., Conroy v. Dannon Co., Inc., No. 12 CV 6901(VB), 2013 WL 4799164, at *6 (S.D.N.Y. May 9, 2013) (stating that the FDA’s interpretations of its own regulations promulgated under title 21 “are ‘controlling unless plainly erroneous or inconsistent with the regulations’ or there is any other reason to doubt that they reflect the FDA’s fair and considered judgment”) (citing and quoting PLIVA, Inc. v. Mensing, ––– U.S. ––––, ––––, 131 S.Ct. 2567, 2575, 180 L.Ed.2d 580 (2011)); Dorsey v. Housing Auth. of Baltimore City, 984 F.2d 622, 632 (4th Cir. 1993) (finding district court abused its discretion in refusing to consider regulatory agency’s assessment of defendant’s compliance with agency regulations and noting that the district “court should welcome [the agency’s] appraisal of [the defendant’s] compliance with regulations, given its concern for deference to agency interpretations of its own regulations”). Indeed, it is precisely when a court is called upon to interpret the regulations, i.e., when they are ambiguous, and where their application to facts raises complex issues, that the court is most likely to defer to the FDA’s prior determinations.  See Wilson v. Frito-Lay N. Am., Inc., 961 F. Supp.2d 1134, 1142 (N.D. Cal. 2013) (noting that “an agency’s informal interpretation of its own ambiguous regulation is [typically] controlling” but declining to give “deference to two warning letters that the FDA sent” because neither party to the case “contended that the FDA regulations . . . [w]ere ambiguous, and the Court d[id] not find that they [we]re”); James T. O’Reilly, et al., 1 Food & Drug Admin. §4:56 (4th Ed. 2015) (“The FDA is allowed great deference in the interpretations of its own regulations…. The more complex the issue, the more scope is likely to be given for the FDA to draw the interpretations.”).

As to deference, Defendants cite a non-binding case, Schering-Plough Healthcare Prods., Inc. v. Schwarz Pharma, Inc., 547 F. Supp.2d 939 (E.D. Wisc. 2008), for the proposition that “a warning letter from the FDA is not considered a final agency action,” and contend that, as a result, “Plaintiffs’ allegations … raise legal questions as to the potential effects of various actions by a federal agency … [which] should be decided in a federal forum.”  The Second Circuit has not taken a position on whether an FDA Warning Letter is considered a final agency action.  Even if it is not, such letters may still be entitled to deference.  See Cmty. Health Ctr. v. Wilson-Coker, 311 F.3d 132, 138 (2d Cir. 2002) (“[E]ven relatively informal [agency] interpretations, such as letters from regional administrators, warrant respectful consideration” where the statute at issue is complex and the regulatory agency possesses “considerable expertise”) (citations and quotations omitted).  Regardless, they may serve as evidence of regulatory violations.  Gelber v. Stryker Corp., 788 F. Supp.2d 145, 155–56 (S.D.N.Y. 2011) (finding plaintiffs who provided FDA Warning Letters as evidence of violations of FDA regulations stated claims for manufacturing defects).

Mihok, 2015 WL 4722847, at *5-6 (citations not omitted, for once).  Under this analysis, there being no undecided FDA-related issue, Mihok was remanded to state court.Continue Reading Warning Letters and Jurisfiction

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