Ignacuinos v. Boehringer Ingelheim Pharm. Inc.

• Decision Date: 06 August 2021
• Docket Number: August Term, 2020,Docket No. 20-3643
• Citation: 8 F.4th 98
• Parties: Carl IGNACUINOS, on Behalf of Himself and Others Similarly Situated, Pamela Davis, on Behalf of Herself and Others Similarly Situated, Plaintiffs-Appellants, v. BOEHRINGER INGELHEIM PHARMACEUTICALS INC, Defendant-Appellee.
• Court: U.S. Court of Appeals — Second Circuit

8 F.4th 98

Carl IGNACUINOS, on Behalf of Himself and Others Similarly Situated, Pamela Davis, on Behalf of Herself and Others Similarly Situated, Plaintiffs-Appellants,

v.BOEHRINGER INGELHEIM PHARMACEUTICALS INC, Defendant-Appellee.^*

Docket No. 20-3643

August Term, 2020

United States Court of Appeals, Second Circuit.

Submitted: April 30, 2021

Decided: August 6, 2021

C.K. Lee, Lee Litigation Group, PLLC, New York, NY, for Plaintiffs-Appellants Carl Ignacuinos and Pamela Davis.

James T. Shearin, Pullman & Comley, LLC, Bridgeport, CT; Shankar Duraiswamy, Emily S. Ullman, Covington & Burling LLP, Washington, DC, for Defendant-Appellee Boehringer Ingelheim Pharmaceuticals, Inc.

Before: LOHIER and BIANCO, Circuit Judges, and ABRAMS, District Judge.^**

Lohier, Circuit Judge:

Plaintiffs-Appellants Carl Ignacuinos and Pamela Davis appeal from a September 25, 2020 judgment of the United States District Court for the District of Connecticut (Underhill, J. ), which dismissed their putative class action claims contained in a third amended complaint against Defendant-Appellee Boehringer Ingelheim Pharmaceuticals, Inc. The plaintiffs asserted various state law claims for injuries caused by the alleged deceptive marketing or defective design and manufacture of Boehringer Ingelheim's metered-dose inhaler. The District Court dismissed the complaint in its entirety, holding that the plaintiffs’ claims were preempted by federal law. On appeal, the plaintiffs challenge only the dismissal of their design and manufacturing-related claims. For the reasons set forth below, we AFFIRM the judgment of the District Court.

BACKGROUND

For the purpose of resolving this appeal, we accept as true the following allegations in the third amended complaint. See Mirabilio v. Reg'l Sch. Dist. 16, 761 F.3d 212, 213 (2d Cir. 2014).

Boehringer Ingelheim manufactures Combivent

Respimat, a metered-dose inhaler that is prescribed to alleviate symptoms of chronic obstructive pulmonary disease (COPD). The Combivent Respimat inhaler, which the Food and Drug Administration (FDA) approved in 2011, consists of an inhaler equipped with a mouthpiece (Respimat) and a cartridge, which contains the medication itself (Combivent ). The product's label recommends a dose of "one inhalation four times a day, not to exceed six inhalations in 24 hours," and it represents that the product will deliver 120 metered doses (i.e., 120 "puffs"). App'x 12–13. The inhaler locks and will not spray any more medication after 120 doses have been dispensed. In 2016 the FDA approved an updated version of the labeling of the product, including "Instructions for Use" that noted the possibility that "[t]he dose indicator on the [inhaler] [may] reach[ ] zero too soon" under certain circumstances involving user error. App'x 80.

The plaintiffs were prescribed Combivent

to alleviate their COPD symptoms. They allege, however, that the Combivent inhalers deliver significantly fewer than the labeled 120 doses, and that they were physically and economically injured as a result. The plaintiffs therefore seek to hold Boehringer Ingelheim liable under Connecticut, Florida, and Indiana state law for alleged design or manufacturing defects that caused the failure to deliver the labeled number of doses.¹

The District Court dismissed both sets of claims as preempted by federal law. This appeal followed.

DISCUSSION

We review the District Court's dismissal of the plaintiffs’ claims de novo. See Dolan v. Connolly, 794 F.3d 290, 293 (2d Cir. 2015). To determine whether the claims are preempted, "we start with the basic principle that under the Supremacy Clause of the Constitution, state and local laws that conflict with federal law are without effect." UnitedHealthcare of N.Y., Inc. v. Lacewell, 967 F.3d 82, 91 (2d Cir. 2020) (cleaned up); see Gibbons v. Bristol-Myers Squibb Co., 919 F.3d 699, 708 (2d Cir. 2019). The Food, Drug, and Cosmetics Act (FDCA) authorizes the federal Government to regulate the manufacture, labeling, and sale of pharmaceuticals. 21 U.S.C. § 301 et seq. ; see Gibbons, 919 F.3d at 707. Design and manufacturing defect claims that a drug manufacturer has breached its duties under state law are preempted by federal law if the manufacturer would require prior FDA approval to comply with those duties. See Gibbons, 919 F.3d at 708. Conversely, the same state claims may proceed if the manufacturer could have acted unilaterally without prior FDA approval. See id.; PLIVA, Inc. v. Mensing, 564 U.S. 604, 620, 131 S.Ct. 2567, 180 L.Ed.2d 580 (2011) (citing Wyeth v. Levine, 555 U.S. 555, 573, 129 S.Ct. 1187, 173 L.Ed.2d 51 (2009) ) (explaining that "impossibility" preemption applies when a private party cannot "independently do under federal law what state law requires of it").

When does a drug manufacturer need FDA approval, and when can it act unilaterally without approval? The relevant FDA regulation, 21 C.F.R. § 314.70, makes clear that a manufacturer must obtain prior FDA approval for any "major" changes to the design and manufacturing of already-approved drug products, but not for "moderate" or "minor" changes. See 21 C.F.R. § 314.70(b) – (d) ; see also Mut. Pharm. Co. v. Bartlett, 570 U.S. 472, 477, 133 S.Ct. 2466, 186 L.Ed.2d 607 (2013) ("Once a drug—whether generic or brand-name—is approved, the manufacturer is prohibited from making any major changes[.]" (citing 21 C.F.R. § 314.70(b)(2) )). The question presented on appeal is whether the changes necessary to cure the Combivent

inhaler's alleged defects qualify as "major" under § 314.70(b).

We start with "major" changes, which § 314.70(b) defines as follows:

(b) Changes requiring supplement submission and approval prior to distribution of the product made using the change (major changes).

(1) A supplement must be submitted for any change in the drug substance, drug product, production process, quality controls, equipment, or facilities that has a substantial potential to have an adverse effect on the identity, strength, quality, purity, or potency of the drug product as these factors may relate to the safety or effectiveness of the drug product.

(2) These changes include, but are not limited to:

(i) Except those described in paragraphs (c) and (d) of this section, changes in the qualitative or quantitative formulation of the drug product, including inactive ingredients, or in the specifications provided in the approved [drug application]; ...

(vi) Changes in a drug product container closure system that controls the drug product delivered to a patient ...."

21 C.F.R. § 314.70(b). Section 314.70(b)(1) thus tells us how to identify changes that require FDA pre-approval: A change in drug design or manufacturing requires pre-approval if it has a "substantial potential to have an adverse effect." And § 314.70(b)(2) provides a specific but non-exhaustive list of "[t]hese changes."

The provisions that define "moderate" and "minor" changes have a similar structure. They first broadly define a category of changes with "moderate" or "minimal" potential to have an adverse effect. Id. § 314.70(c)(1), (d)(1). They then list specific categories of qualifying changes. Id. § 314.70(c)(2), (d)(2).

On appeal, the plaintiffs argue that a manufacturer must show that a change has a "substantial potential to have an adverse effect" under § 314.70(b)(1) to qualify as "major," even if the change is specifically listed in § 314.70(b)(2). Here, the plaintiffs submit, Boehringer Ingelheim failed to show that the proposed modifications to the inhaler's design or manufacture would have a substantial adverse effect.

We have not previously addressed the argument that a change listed in § 314.70(b)(2) must also separately be proven to have a "substantial potential to have an adverse effect" to qualify as a "major" change. But we agree with the First Circuit in holding that "if a change fits under any of the categories listed in section (b)(2), that change necessarily constitutes a ‘major’ change requiring FDA pre-approval," regardless of whether the defendant has shown a substantial potential for an adverse effect. Gustavsen v. Alcon Lab'ys, Inc., 903 F.3d 1, 11 (1st Cir. 2018).

As the First Circuit explained, there are three principal reasons for this interpretation and for rejecting the plaintiffs’ proposed reading of the regulation. First, section (b)(2)’s non-exhaustive list of qualifying changes is provided "in a heading of the same level as the broad definition in section (b)(1) (rather than in section (b)(1) itself, or as perhaps in a hypothetical section (b)(1)(i))." Id. at 10–11. That (b)(2) is not a subpart of (b)(1) "makes it unlikely that the ‘changes’ in (b)(2) are a subcategory of the changes in (b)(1)." Id. at 11. Second, under the plaintiffs’ reading, "whether a change is major or moderate would depend in every case on a separate determination of the qualitative magnitude of the change," which the Supreme Court has never "previously read these regulations to ... require[.]" Id. at 11 (citing Wyeth, 555 U.S. at 568, 129 S.Ct. 1187 ); see Bartlett, 570 U.S. at 477, 133 S.Ct. 2466. And third, "the categories later defined in section (b)(2) do not map easily onto the types of changes identified in (b)(1)," such that much of the regulatory language in section (b)(2) would not "have any meaning under [the plaintiffs’] reading." Gustavsen, 903 F.3d at 11.

We would add to the First Circuit's compelling analysis only that the authorizing statutory language of 21 U.S.C. § 356a(c)(2) provides that "a major manufacturing change is a manufacturing change that is determined by the [FDA] to have substantial potential to adversely affect the ... safety or effectiveness of a drug." The FDA's decision to refer to a particular product modification in 21 C.F.R. § 314.70(b)(2) ’s list of major changes tells us that it considers the modification's potential to have an adverse effect to be substantial per se. See Supplements and Other Changes to an Approved Application, 69 Fed. Reg. 18,728,...