In re Zofran (Ondansetron) Prods. Liab. Litig.
| Decision Date | 05 February 2019 |
| Docket Number | MDL No. 1:15-md-2657-FDS |
| Parties | IN RE: ZOFRAN (ONDANSETRON) PRODUCTS LIABILITY LITIGATION This Document Relates to: All Actions |
| Court | U.S. District Court — District of Massachusetts |
MEMORANDUM AND ORDER ON DEFENDANT'S MOTION FOR SUMMARY JUDGMENT BASED ON FEDERAL PREEMPTION
This is a multi-district litigation ("MDL") proceeding arising out of product-liability claims that the use of the drug Zofran
(ondansetron ) by pregnant women caused birth defects in their children. Defendant GlaxoSmithKline LLC ("GSK") has moved for summary judgment based on federal preemption—in substance, that state-law claims of failure to provide an adequate warning label are preempted by federal law. For the following reasons, the motion will be denied.
is an anti-emetic—that is, a drug that prevents or treats nausea or vomiting. It was initially approved by the Food and Drug Administration in 1991 for the prevention of nausea and vomiting induced by chemotherapy or radiation therapy and post-operative nausea and vomiting.
was not approved, and never has been approved, for the prevention of nausea and vomiting in pregnancy. Nonetheless, Zofran has been prescribed off-label to pregnant women for many years. According to plaintiffs, that widespread practice was due in large part to unlawful marketing practices by GSK that sought to promote off-label usage.
At some point, the FDA became aware that Zofran
was being prescribed to pregnant women in significant numbers. In 2010, the FDA requested that the GSK provide supplemental information concerning the safety of Zofran when used during pregnancy. In response, GSK provided an analysis of the then-available safety data. The FDA did not require any labeling changes. In 2013, a citizen petition requested that the FDA revise the Zofran label to indicate an increased risk to fetal safety if ingested during pregnancy. The FDA rejected that request. In 2015, the current manufacturer of Zofran, Novartis, submitted a proposed label change to provide, among other things, a warning that use in pregnancy could cause harm to the fetus and is not recommended. That, too, was rejected.
In short, whether Zofran
poses a risk to fetal safety has been considered, and rejected, by the FDA on multiple occasions since the drug's initial approval. Even today, it is not contraindicated for use during pregnancy, and its label contains no enhanced form of warning for such use. Indeed, the current label states that "[a]vailable data do not reliably inform the association of Zofran and adverse fetal outcomes."
Plaintiffs nonetheless contend that ingestion of Zofran
during pregnancy in fact causes birth defects, that the label should contain such a warning, and that GSK's failure to provide such a warning should result in tort liability under state law. Plaintiffs contend that the FDA's initial approval of Zofran in 1991, and its subsequent rejection of label changes, were based on incomplete information—essentially, because GSK withheld certain data from the FDA and made material misrepresentations. GSK denies that it withheld information and contends that any state-law failure-to-warn claims are preempted by federal law.
The potential preemption issue arises out of a clash between federal regulation of prescription drugs and state-law product-liability principles. By federal law, the FDA closely regulates the labeling of drugs, including warning labels; as a general matter, a drug label may only be created or changed with FDA approval. That creates an obvious tension with state laws, which generally permit recovery for failure to provide an adequate warning, but which assume that a manufacturer is free to provide such warnings as it sees fit.
There is, however, a process under federal law—called the "changes being effected," or "CBE," process—that permits a drug company to change a label unilaterally, based on certain "newly acquired information" concerning its safety, subject to later FDA approval. Because of the existence of the CBE process, the Supreme Court has held that a drug company can in fact add safety information to its label without FDA approval. See Wyeth v. Levine , 555 U.S. 555, 570-71, 129 S.Ct. 1187, 173 L.Ed.2d 51 (2009). As a result, a drug company may prove that federal law preempts state law only if it can show by "clear evidence" that the FDA would have rejected the warning that plaintiffs contend state law required. Id. at 571, 129 S.Ct. 1187.
Here, there is little doubt that the FDA would have rejected plaintiffs' proposed warning: it in fact did reject it, at least in substance. But plaintiffs contend that GSK's failure to make complete disclosures to the FDA means that the agency's decisions were not fully informed, and therefore a finding of federal preemption is precluded.
The legal framework for considering preemption claims is muddy at best. Among other things, there is considerable debate as to such basic matters as the required standard of proof and the appropriate roles of the judge and jury. The United States Supreme Court recently granted a writ of certiorari in an FDA preemption case, presumably to clarify some of those issues. See In re Fosamax , 852 F.3d 268 (3d Cir. 2017), cert. granted sub nom. Merck Sharp & Dohme Corp. v. Albrecht , ––– U.S. ––––, 138 S.Ct. 2705, 201 L.Ed.2d 1095 (2018).
In the meantime, this Court is required to consider the matter under the existing framework, without the benefit of that guidance, and notwithstanding the fact that the applicable principles as determined by this Court may eventually prove to be erroneous. Under the existing legal framework, as this Court understands and interprets it, the basic factual question underlying preemption—that is, whether the FDA would have rejected the label had it been presented with the evidence plaintiffs contend was withheld—must be resolved by a jury.
Accordingly, and for the following reasons, the motion of GSK for summary judgment based on preemption will be denied.
Unless otherwise noted, the following facts are undisputed.
Under federal law, a drug company may not market or sell a new pharmaceutical drug without the approval of the Food and Drug Administration. 21 U.S.C. § 355(a). To obtain that approval, the company (which is referred to as the "sponsor") must submit a New Drug Application ("NDA") to the FDA. (Id. ). An NDA must provide comprehensive information about the drug, including its formulation, the proposed labeling, and scientific data about its safety and efficacy. Id. § 355(b)(1)(F) ; 21 C.F.R. §§ 314.50(d)(5)(viii), 201.57(a).
Not surprisingly, FDA regulations require that an NDA fully disclose all "pertinent" safety information. See, e.g. , 21 C.F.R. §§ 314.50 (); 314.50(d)(5)(vi)(A) (requiring "an integrated summary of all available information about the safety of the drug product, including pertinent animal data[ and] demonstrated or potential adverse effects of the drug"); 312.50 ( that "[s]ponsors are responsible for ... providing [investigators] with the information they need to conduct an investigation properly ... and ensuring that FDA and all participating investigators are promptly informed of significant new adverse effects or risks with respect to the drug").
The sponsor's duty to make full disclosure continues beyond the initial submission of its NDA. See, e.g., id. §§ 314.50(d)(5)(vi)(B) (); 312.33 (requiring annual reports for investigational NDAs that include "[a] list of the preclinical studies {including animal studies} completed or in progress during the past year and a summary of the major preclinical findings," and, "[i]f the study has been completed, or if interim results are known, a brief description of any available study results").
The FDA approval process is "onerous and lengthy." Mutual Pharm. Co. v. Bartlett , 570 U.S. 472, 476, 133 S.Ct. 2466, 186 L.Ed.2d 607 (2013). The FDA will approve a drug only if the NDA demonstrates that the drug (1) is "safe for use," (2) "will have the effect it purports or is represented to have," and (3) is accompanied by labeling that is neither "false [n]or misleading in any particular." 21 U.S.C. §§ 355(c)(1)(A), (d).
The FDA does not only approve the drug and its intended use; it also approves the exact text of the label. Id. § 355 ; see Wyeth , 555 U.S. at 568, 129 S.Ct. 1187. With one exception, noted below, the sponsor may not alter the label in any respect without the approval of the FDA. Wyeth , 555 U.S. at 565, 129 S.Ct. 1187.
After approval of a drug, the FDA retains the authority to require changes to the label to reflect new information concerning its safety and efficacy. 21 U.S.C. § 355(o)(4) ; 21 C.F.R. § 314.93. Nonetheless, a "central premise of federal drug regulation [is] that the manufacturer bears responsibility for the content of its label at all times." Wyeth , 555 U.S. at 570-71, 129 S.Ct. 1187. The manufacturer is "charged both with crafting an adequate label and with ensuring that its warnings remain adequate as long as the drug is on the market." Id. at 571, 129 S.Ct. 1187.
There are two ways in which a manufacturer can seek to change the warnings on a drug label. See In re Celexa & Lexapro Mktg. & Sales Practices Litig. , 779 F.3d 34, 37 (1st Cir. 2015) (citing 21 C.F.R. § 314.70(b)(2), (c)(6) ).
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