Marcus v. Forest Labs., Inc. (In re Celexa & Lexapro Mktg. & Sales Practices Litig.), No. 14–1290.

• Court: U.S. Court of Appeals — First Circuit
• Writing for the Court: KAYATTA, Circuit Judge.
• Citation: 779 F.3d 34
• Parties: In re CELEXA AND LEXAPRO MARKETING AND SALES PRACTICES LITIGATION. Randy and Bonnie Marcus, on behalf of themselves and all other persons similarly situated, Plaintiffs, Appellants, v. Forest Laboratories, Inc. and Forest Pharmaceuticals, Inc., Defendants, Appellees.
• Decision Date: 20 February 2015
• Docket Number: No. 14–1290.

779 F.3d 34

In re CELEXA AND LEXAPRO MARKETING AND SALES PRACTICES LITIGATION.

Randy and Bonnie Marcus, on behalf of themselves and all other persons similarly situated, Plaintiffs, Appellants
v.
Forest Laboratories, Inc. and Forest Pharmaceuticals, Inc., Defendants, Appellees.

No. 14–1290.

United States Court of Appeals, First Circuit.

Feb. 20, 2015.

779 F.3d 35

R. Brent Wisner, with whom Baum, Hedlund, Aristei & Goldman, P.C. and Pendley, Baudin & Coffin, LLP were on brief, for appellant.

Edwin G. Schallert, with whom Debevoise & Plimpton LLP and Sugarman, Rogers, Barshak & Cohen, P.C. were on brief, for appellee.

Before LYNCH, Chief Judge, SELYA and KAYATTA, Circuit Judges.

Opinion

KAYATTA, Circuit Judge.

This appeal arises out of a putative class action against Forest Pharmaceuticals, the manufacturer of Lexapro, an antidepressant medication. Plaintiffs claim that Lexapro's FDA-approved drug label misleads California consumers by omitting material efficacy information, in violation of California's Consumer Legal Remedies Act (“CLRA”), Cal. Civ.Code § 1750 et seq., False Advertising Law (“FAL”), Cal. Bus. & Prof.Code § 17500 et seq., and Unfair Competition Law (“UCL”), Cal. Bus. & Prof.Code § 17200 et seq. The district court dismissed these claims, finding them barred by California's safe harbor doctrine. See In re Celexa & Lexapro Mktg. Sales Practices Litig. (Marcus v. Forest Labs., Inc.), No. 13–11343–NMG, 2014 WL 866571 (D.Mass. March 5, 2014). See generally Cel–Tech Commc'ns, Inc. v. L.A. Cellular Tel. Co., 20 Cal.4th 163, 182, 83 Cal.Rptr.2d 548, 973 P.2d 527 (1999) (outlining California's safe harbor doctrine).

Expressing no view on the California safe harbor doctrine's applicability here, we instead find that federal law impliedly preempts these claims because the Federal Food, Drug, and Cosmetic Act (“FDCA”), 21 U.S.C. § 301 et seq., prohibits Forest from independently changing its FDA-approved label as plaintiffs claim California law requires. See PLIVA, Inc. v. Mensing, –––U.S. ––––, 131 S.Ct. 2567, 2580–81, 180 L.Ed.2d 580 (2011). Therefore, we affirm the judgment dismissing the complaint.

I. Background

Lexapro belongs to a class of antidepressants known as selective serotonin reuptake inhibitors. Forest also manufactures Celexa, a drug with a chemical composition closely related to Lexapro. In 2002, the FDA first approved Lexapro to treat adults for depression. In 2008, Forest sought FDA approval for the use of Lexapro to treat major depressive disorder in adolescents.

A. FDA's Drug Approval Process

The FDA drug approval process is “onerous and lengthy.” Mut. Pharm. Co., Inc. v. Bartlett, ––– U.S. ––––, 133 S.Ct. 2466, 2471, 186 L.Ed.2d 607 (2013). The FDCA requires that drug manufacturers gain FDA approval prior to marketing or selling a drug in interstate commerce. See 21 U.S.C. § 355(a). To gain FDA approval,

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a drug manufacturer must submit either a new-drug application (“NDA”), for a new drug, or a supplemental new-drug application (“sNDA”), for a new treatment. See 21 C.F.R. § 314.1 et seq. NDAs and sNDAs are subject to the same approval requirements. See id. The NDA or sNDA must include “full reports of [all clinical] investigations which have been made to show whether ... such drug is effective in use.” 21 U.S.C. § 355(b)(1)(A). The FDA may only approve the drug if the NDA or sNDA provides “substantial evidence that the drug will have the effect it ... is represented to have.” Id. § 355(d)(5). As part of its showing that it has provided such substantial evidence, a manufacturer submits the results of “adequate and well-controlled investigations, including clinical investigations, by experts qualified by scientific training and experience to evaluate the effectiveness of the drug involved.” Id. § 355(d)(7).

In its evaluation of an NDA or sNDA, the FDA has discretion to determine that data from “one adequate and well-controlled clinical investigation,” along with other “confirmatory evidence,” are “sufficient to establish effectiveness.” Id.; see 21 C.F.R. § 314.105(c) (“[The] FDA is required to exercise its scientific judgment to determine the kind and quantity of data and information an applicant is required to provide for a particular drug to meet the statutory standards.”) The FDA will not approve a drug if the NDA or sNDA lacks “substantial evidence that the drug will have the effect it purports or is represented to have.” 21 U.S.C. § 355(d)(5).

The drug manufacturer must also submit “the labeling proposed to be used for such drug.” Id. § 355(b)(1)(F) ; 21 C.F.R. § 314.50(c)(2)(i). The application must include the proposed label's text “with annotations to the information in the [drug application] that support the inclusion of each statement [on the label].” 21 C.F.R. § 314.50(c)(2)(i). In order to approve an NDA or sNDA, the FDA must determine, “based on a fair evaluation of all material facts,” that the proposed label is not “false or misleading in any particular.” 21 U.S.C. § 355(d)(7) ; 21 C.F.R. § 314.125(b)(6). After approval, the manufacturer may distribute the drug without violating federal law as long as it uses the FDA-approved label. See 21 U.S.C. §§ 331(c), 333(a), & 352(a), (c).

In an effort to secure FDA approval to sell Lexapro for the treatment of major depressive disorder in adolescents, Forest submitted to the FDA the results of four studies: Celexa Study 94404, Celexa Study 18, Lexapro Study 15, and Lexapro Study 32. Celexa Study 94404 and Lexapro Study 15 showed no efficacy. Celexa Study 18 and Lexapro Study 32 found positive efficacy that was statistically significant, but only barely so. In March 2009, the FDA nevertheless approved the sale of Lexapro to treat major depressive disorder in adolescents based on a finding that substantial evidence supported the efficacy of that use. In making this finding, the FDA “extrapolate[d] on the basis of a previously reviewed positive study with [Celexa ],” along with the positive statistical efficacy results from Lexapro Study 32. As required by the FDCA, in approving the sNDA, the FDA made a specific finding that Lexapro's label was not “false or misleading in any particular.” 21 U.S.C. § 355(d)(7) ; 21 C.F.R. § 314.125(b)(6). That approved label included the following:

Clinical Studies, Major Depressive Disorder—Adolescents

The efficacy of Lexapro as an acute treatment for major depressive disorder in adolescent patients was established in an 8–week, flexible-dose, placebo-controlled study that compared Lexapro 10–20 mg/day to placebo in outpatients

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12 to 17 years of age inclusive who met DSM–IV criteria for major depressive disorder. The primary outcome was change from baseline to endpoint in the Children's Depression Rating Scale—Revised (CDRS–R). In this study, Lexapro showed statistically significant greater mean improvement compared to placebo on the CDRS–R.

The efficacy of Lexapro in the acute treatment of major depressive disorder in adolescents was established, in part, on the basis of extrapolation from the 8–week, flexible-dose, placebo-controlled study with racemic citalopram [i.e., Celexa ] 20–40 mg/day. In this outpatient study in children and adolescents 7 to 17 years of age who met DSM–IV criteria for major depressive disorder, citalopram treatment showed statistically significant greater mean improvement from baseline, compared to placebo, on the CDRS–R; the positive results for this trial largely came from the adolescent subgroup.

Two additional flexible-dose, placebo-controlled MDD studies (one Lexapro study in patients ages 7 to 17 and one citalopram [Celexa ] study in adolescents) did not demonstrate efficacy.

Although maintenance efficacy in adolescent patients has not been systematically evaluated, maintenance efficacy can be extrapolated from adult data along with comparisons of escitalopram pharmacokinetic parameters in adults and adolescent patients.

B. Changing The Label

There are two ways pertinent to this lawsuit in which a manufacturer of a brand name prescription drug can change the drug's label. First, the default rule is that a manufacturer must secure FDA approval for a proposed change prior to distributing the product with the changed label. 21 C.F.R. § 314.70(b)(2)(v)(A). Second, under what is known as the Changes Being Effected (“CBE”) regulation, id. § 314.70(c)(6)(iii), a manufacturer can make certain types of changes to its label, without prior FDA approval, by sending the FDA a “supplement submission.”

To make a change under the CBE regulation, the manufacturer must satisfy at least two requirements. First, the change must “reflect newly acquired information.” Id.; see also id. § 314.3(b) (defining “newly acquired information”). Second, the change must be for the purpose of accomplishing at least one of the five following objectives:

(A) To add or strengthen a contraindication, warning, precaution, or adverse reaction for which the

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