B

Scope of Liability Related to Pharmaceuticals Dispensed to Pregnant and Lactating Women

AUTHORS

Lauren Colton, Phil Katz, Katherine Kramer, and Megan Dorsch, Hogan Lovells US LLP, Consultants to the Committee, 2024

INTRODUCTION

The National Academies of Science, Engineering, and Medicine (NASEM) requested assistance with research regarding the potential scope of legal liability associated with drugs, biologics, or related medical devices prescribed to pregnant or lactating women. NASEM also asked that we identify, where applicable, any insights, patterns, or conclusions this legal landscape reveals, particularly with respect to the question of “What is the true legal risk associated with pharmaceutical products researched in, and dispensed to, pregnant and lactating women?”

RESEARCH METHOD

To address this research question, we consulted a variety of sources, including but not limited to legal research websites (e.g., Westlaw, Lexis), secondary sources (e.g., peer-reviewed literature, law review articles), and Internet sources to gather relevant case law. We did not limit our search to product liability actions but tailored our search terms to gather all potential case law related to drugs studied in or used by pregnant or lactating populations. We did not gather cases that did not have a publicly available court opinion. When the case law indicated substantial litigation surrounding a particular pharmaceutical product, we broadened our search basis in an effort to appraise the true breadth of litigation. For example, Internet, dockets, and secondary

sources may reveal the existence of settlements, the formation of multidistrict litigation (MDLs), and other legal activity surrounding a particular pharmaceutical product that the reported case law does not identify.¹

We then prepared tables to consolidate and synthesize the case law and other relevant legal liability information we identified on this topic. The “Legal Landscape Overview” is appended to this memorandum as “Appendix A.” The charts are divided by subtopic: (1) case law involving drugs used in lactating women; (2) case law involving drugs used “on-label” in pregnant women; (3) case law involving drugs used “off-label” in pregnant women; and (4) case law specifically involving medical malpractice claims. Each chart provides the case name (Case), relevant pharmaceutical product (Drug), a brief description of whether the labeling included any warnings or a contraindication for use in pregnant or lactating populations, to the extent this information is available (Labeling information), the type of plaintiff and specific injury alleged (Plaintiff/injury), the claims asserted by the lawsuit (Claims), a description of the case disposition and relevant holdings (Case description), and a Settlement/Verdict amount, if applicable. When there were a vast number of cases regarding a particular drug or area of liability, we provided a high-level summary of the litigation and a representative subset of cases (e.g., “DES Cases” and “Accutane Cases”).

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¹ We also collected a sample of lawsuits filed during the last year (Aug. 2022–2023). A senior research analyst pulled complaints from Courthouse News and Bloomberg Law using the following search terms:

• CN: (drug OR pharma! OR biologic! OR device) AND (pre-natal OR prenatal OR post-natal OR postnatal OR pregnancy OR pregnant OR breastfeeding OR “breast feeding” OR miscar!)
• BL: (pregnant OR pregnancy OR lactat! OR breastfeed! OR pre-natal OR post-natal OR post-partum OR postpartum OR miscar!) w/8 (drug OR pharma! OR biologic! OR device).

A review of the complaints for this time period revealed that the majority of recently filed lawsuits involved either DES or acetaminophen. We did not include these new lawsuits in our summary materials, for several reasons, including: (1) these lawsuits reflect patterns and redundancies already seen in the existing, reported case law; (2) reviewing and summarizing these materials, beyond confirming that they involved personal injury claims related to DES and acetaminophen, was not likely to lead to a new or different conclusion in our liability analysis; and (3) given the abundance of reported case law on this topic, we felt it was a better use of our resources to analyze existing precedent rather than cases that are in the very early stages of litigation.

The breadth of the research topic and the nature of product liability litigation do not lend themselves to certainty; we cannot warrant that we have identified all relevant cases or have a complete understanding of the legal landscape, particularly as it relates to unpublicized, undisclosed settlements. However, our findings did allow us to draw several conclusions regarding the legal risks and potential liabilities associated with pharmaceutical products used in pregnant and lactating populations as well as certain liability trends in this area (e.g., defenses, barriers to liability, the potential for long-tail liability or MDLs). Those conclusions are described in more detail below in Section C.

RESEARCH FINDINGS

Clinical Trial Liability

There is a dearth of case law in the clinical trial context related to pregnant and lactating populations. We were unable to find any reported case law in which a pregnant or lactating woman—or their children/grandchildren—filed suit against a drug manufacturer/designer, clinical trial sponsor, or any other entity for personal injuries related to their participation in a clinical trial or study.² Fear of liability is a regularly cited obstacle to the inclusion of pregnant women in clinical research,³ yet the case law (or the lack thereof) does not evidence a materially greater risk of liability with respect to pregnant/lactating women as compared to other participants in clinical trials, such as children—a

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² For completeness, we note that there are a few cases involving a medical experiment conducted by the University of Chicago and Eli Lilly & Company to determine the value of DES in preventing miscarriages. See Mink v. Univ. of Chicago, 460 F. Supp. 713 (N.D. Ill. 1978); Wetherill v. Univ. of Chicago, 570 F. Supp. 1124 (N.D. Ill 1983). DES was administered to over 1,000 pregnant women without their knowledge of the drug or consent to participate in the study. In Mink, the plaintiffs brought suit against the university and the manufacturer, seeking recovery on theories of battery, products liability, and breach of duty to notify plaintiffs that they had been given drug (medical malpractice). Although the court denied the defendants’ motion for summary judgment on the battery claim, the court granted the motion as to the plaintiffs’ other claims because no personal injury was alleged.

Additionally, we identified a qui tam suit, brought under the False Claims Act, against clinical trial sponsor of COVID-19 vaccine for administering the vaccine/placebo to pregnant women in violation of the clinical trial protocol. No injuries were alleged. See Appendix A, United States ex rel. Jackson v. Ventavia Research Group, LLC, No. 1:21-CV-00008, 2023 WL 2744394 (E.D. Tex. Mar. 31, 2023) (appeal pending).

³ Anna C. Mastroianni et al., Research with Pregnant Women: New Insights on Legal Decision-Making, 47 Hastings Ctr. Rep. 38 (2017), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533594/ (author’s manuscript at 7).

similarly sympathetic population.⁴ Indeed, the tort system poses unique challenges to all research participants because they must show that they did not “assume the risk” through the informed consent process.⁵ Further, “injured research participants are also often injured by unforeseen risks that are not anyone’s fault and so fall outside the tort system entirely.”⁶

Thus, scholars posit that the fear of liability is fueled in part by uncertainty. The “paucity of relevant and easily accessible precedents of approved research with pregnant women that might serve as a guide through regulatory pathways” means that the legal decision makers advising clients at each stage of the development process “have scant knowledge of what others in the same or similar position are doing.”⁷ Moreover, regulatory ambiguities surrounding Subpart B of the Department of Health and Human Services regulations,⁸ including how the regulatory definition of “minimal risk” should be interpreted, whether “minimal risk” applies equally to all phases of pregnancy, and regulatory inconsistencies regarding the biological father’s role in the informed consent process also factor into legal considerations that may result in the exclusion of pregnant women from clinical research.⁹

Despite the lack of legal precedent in this area, several potential claims may arise if a study participant (mother/lactating woman) and/or her child is injured as a result of clinical trial conduct. Based on our experience and expertise, potential claims are most likely to be asserted against the drug manufacturer and/or clinical trial sponsor and often include strict liability, negligence, and/or inadequate informed consent.¹⁰

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⁴ The absence of case law may also reflect, to some extent, differences in the compensation systems for injuries resulting from clinical trials and FDA-approved products. Although U.S. laws do not require research sponsors or institutes to compensate human research subjects who experience a research-related injury, some institutions and research sponsors may agree to cover medical expenses if a research related injury occurs. See 21 C.F.R. § 50.25(a)(6) & 45 C.F.R. § 46.116 (requiring an explanation of whether compensation for research-related injuries is available for studies involving more than minimal risk). One study, albeit somewhat dated, estimated that about one half of research participants enrolled in research at medical schools have their medical bills for research-related injuries covered. Michael K. Paasche-Orlow & Frederick L. Brancata, Assessment of Medical School Institutional Review Board Policies Regarding Compensation of Subjects for Research-Related Injury, 118 AM. J. MED. 175, 177 (2005).

⁵ Elizabeth R. Pike, Recovering from Research: A No-Fault Proposal to Compensate Injured Research Participants, 38 Am. J.L. & Med. 7, 23–24 (2012).

⁶ Id. at 24.

⁷ Mastroianni et al., supra note 3, at 7 (author’s manuscript).

⁸ Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research, 45 C.F.R. §§ 46.201–46.207 (2001).

⁹ Mastroianni et al., supra note 3, at 5-7 (author’s manuscript).

¹⁰ Original authors provided a court transcript.

Generally, clinical trial claims tend to be based on the allegations that the participant was not adequately warned of the risks associated with the experimental product, was not an appropriate candidate for the study, or that the study was not designed appropriately.¹¹ Breach of contract claims are also often asserted based on the compensation provision of informed consent documents. Employing risk mitigation measures throughout the clinical trial process, such as instituting a robust and comprehensive informed consent process and ensuring that safety and efficacy are demonstrated in preclinical and animal studies before instituting research in human populations, can mitigate the risk of litigation. Examples of mitigation strategies include:

• Include clear statements in the informed consent regarding the known risks and the potential for unknown risks to assist with the defense to lack of informed consent cases and to support the assumption of risk defense. Also, consistent with FDA regulations, the consent document should be updated regularly as new safety information is obtained about the investigational product.
• Ensure that the Investigator’s Brochure documents the known and potential risks associated with the investigational product to support the learned intermediary defense to a litigation claim.
• State in the clinical trial agreement with the investigator and in the informed consent document that the investigator is not an agent of the sponsor to preserve the sponsor’s defense to a claim for lack of informed consent, which is consistent with the regulatory framework requiring the investigator to obtain consent. Such a statement may also support the defense to a negligence claim that the sponsor owed no duty to the study participant.
• State in the informed consent that the investigational product will be provided only during the course of the study, that there is no commitment to provide the investigation product after the study has concluded and that the sponsor may stop the trial at any time for any reason to protect against expanded access claims.
• State in the informed consent that the investigational product is being provided during the study free of charge and is not otherwise available to the study participant in the stream of commerce to provide documentary evidence to support the defense to a strict liability that such a cause of action is not appropriate for a product that is not in the stream of commerce.

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¹¹ Clinical trial precedent—outside the of the pregnancy/lactation space—includes a line of “expanded access” cases involving claims for continued access to an experimental treatment after the study has ended. We have not detailed those cases here but are willing to provide additional information if those cases are of interest.

• State in the informed consent that the document is not a contract between the sponsor and the study participant to protect against breach of contract claims.
• Define clearly the definition of the medical expenses for which the sponsor will be responsible in the event of an injury and make clear that the injury must be directly related to the administration of the investigational product to preserve the lack of causation defense.

Lactating Women—Post Market Liabilities

We identified a number of personal injury lawsuits brought against drug manufacturers for injuries experienced by lactating women. However, the cases all related to the same drug: Parlodel, a lactation inhibitor,¹² and the injuries alleged (e.g., stroke and seizure) were suffered by the lactating women ingesting the drug (see Table B-1). We did not identify any cases alleging an injury to a child caused by consumption of a drug present in breast milk.

The Parlodel litigation is notable for two related reasons. First, the cases demonstrate differing applications of the evidentiary standard for the admissibility of expert testimony set forth in the Supreme Court’s landmark Daubert decision.¹³ Consistent with our broader observations, cases where the court denied the manufacturer’s dispositive motion were more likely to settle. Therefore, such jurisdictional differences—where courts in different jurisdictions apply the Daubert standard inconsistently—can make it harder for sponsors to predict the risk of liability. Second, and relatedly, the litigation sheds light on the potential legal effect of adverse administrative actions. In the years leading up to the Parlodel litigation, serious adverse event reports caused FDA first to encourage manufacturers to include a warning in their labeling and alert doctors to the potential hazards of using the drug for lactation suppression, and later, to initiate withdrawal proceedings for this indication for Parlodel based on the agency’s conclusion that the possible risks outweighed the utility

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¹² The following search terms were used to collect case law and secondary sources from Westlaw: “breastfeeding” or “lactation/ing”, “drug,” and “malpractice,” “clinical trial,” “liability,” or “consumer protection.” Based on these searches and supplemental internet searches, the only litigation identified with respect to lactating persons involved the drug Parlodel.

¹³ Many cases were decided in Sandoz’s favor on summary judgment motions on the basis that testimony offered by plaintiffs’ expert witnesses lacked critical indicia of scientific reliability as set forth in the Supreme Court’s Daubert to establish causation. See Stephen Otero & Melissa Roberts Levin, “JAWS” Attacks On The Daubert Trilogy: A Case Study: The Parlodel^®Litigation, Troutman Sanders LLP, https://www.troutman.com/a/web/257/art-otero-levin2.pdf for a comprehensive summary of the Parlodel litigation.

of the drug in lactating women.¹⁴ In declining to admit expert testimony based in part on FDA’s risk-benefit determination, a number of courts noted that the FDA’s risk-utility standard is lower than the standard of proof required in tort actions.¹⁵ On the other hand, a minority of courts found the determination to be a reliable source of evidence.¹⁶

Pregnant Women—Post Market Liabilities

We found copious case law associated with pregnant women’s use of pharmaceutical products, both on- and off-label, during various phases of their pregnancy (see Tables B-2,B-3). We refer to these cases as “post-market” liabilities herein because the pharmaceutical product was ingested after it was on the market versus during the clinical study phase of its development. These post-market cases involve pharmaceutical products prescribed for pregnancy-related conditions (e.g., Zofran—morning sickness) and for general ailments nonspecific to pregnancy (e.g., Zoloft—antidepressant). The overwhelming majority of these cases share the following characteristics:

• Personal injury lawsuits;
• Filed against the drug manufacturer or other entity involved in the chain of distribution (e.g., hospital and pharmacy);¹⁷
• The pregnant woman ingested the drug in utero, and the drug subsequently caused injury to the woman’s child;
• The injury alleged is a birth defect, of varying types;
• The plaintiffs consist of either the child, the mother, or both individuals; and
• Common causes of action include violation of state consumer protection law, negligence, breach of warranty, failure to warn, fraud and strict liability.

And, as demonstrated by the below sub-sections of this Memorandum, the majority of the case law involving a pregnant woman’s post-market

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¹⁴ See 60 F.R. 3403 (Jan. 17, 1995). Note that Parlodel is an FDA-approved drug doctors still prescribe today for multiple other uses.

¹⁵ See, e.g., Siharath v. Sandoz Pharmaceuticals Corp., 131 F. Supp.2d 1347, 1366 (N.D. Ga. 2001); Glastetter v. Novartis Pharmaceuticals Corp., 107 F. Supp.2d 1015 (E.D. Mo. 2000), aff’d 252 F.3d 986, 990-91 (8th Cir. (per curiam), petition for reh’g and reh’g en banc denied (8th Cir. 2001).

¹⁶ See, e.g., Brasher v. Sandoz Pharma. Corp., 160 F. Supp. 2d 1291 (N.D. Ala. 2001) (medical causation); see also Brasher v. Sandoz Pharma. Corp., 2001 WL 36403362 (N.D. Ala. Sept. 21, 2021) (denying summary judgment motion); Globetti v. Sandoz Pharma. Corp., 111 F. Supp. 2d 1174 (N.D. Ala 2000) (holding the same on the issue of medical causation).

¹⁷ The viability of claims against entities other than manufacturers is fact-specific and certain entities, such as pharmacies, may have only a limited duty to patients. See Moore ex rel. Moore v. Memorial Hosp. of Gulfport, 825 So.2d 658 (Miss. 2002); see also infra note 29.

ingestion of a pharmaceutical product can be categorized as: (1) product liability claims, or (2) medical malpractice claims.

1. Products liability and related claims.¹⁸ As demonstrated by Tables B-2 and B-3, defendant-manufacturers are often successful in dismissing personal injury claims by filing dispositive legal motions (e.g., motions to dismiss or motions for summary judgment) on theories of preemption or lack of medical causation (Daubert motions).¹⁹ As to preemption, defendants have successfully argued that manufacturers lack the ability to add certain warning to an approved product label, where there is insufficient evidence to trigger a manufacturer’s ability to add plaintiff’s desired warning, or where sufficient evidence is available, FDA considered all available safety information associated with the drug at the time of the injury and clear evidence shows that FDA would not have permitted the plaintiff’s desired warning.²⁰ In such cases, courts have found the warning contained in the product labeling to be adequate, as a matter of law.²¹ On the other hand, where new evidence or analyses indicate that the manufacturer knew or should have known of an increased risk of injury that warranted a stronger warning

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¹⁸ Cases were collected using various combinations of advanced search terms on Westlaw (e.g., “pregnan!” AND “drug” OR “pharm!”). Using broad searches, we then filtered the cases by case type to extricate products liability suits from the results. We also reviewed secondary sources.

¹⁹ Although less common, several cases were also dismissed and/or judgment was granted in favor of the defendant, based on the learned intermediary doctrine. In these cases, the defendant would argue that the manufacturer had fulfilled its duty of care when it provided all necessary information to the prescribing physician, who is ultimately responsible for informing the patient of the risks and benefits associated with use of the drug. See, e.g., Martin by Martin v. Ortho Pharmaceuticals, 661 N.E.2d 352 (Ill. 1996); Hunt by Hunt v. Hoffman-La Roche, Inc., 785 F. Supp. 547 (D. Md. 1992) (granting defendant’s motion for summary judgment under learned intermediary doctrine, concluding that manufacturer warned prescribing doctor of risks associated with Accutane); see also Moore ex rel. Moore v. Memorial Hosp. of Gulfport, 825 So.2d 658 (Miss. 2002) (granting motion for summary judgment and extending the learned intermediary doctrine to the pharmacy).

²⁰ See, e.g., In re Zofran (Ondansetron) Products Liab. Litig., 541 F. Supp. 3d 164 (D. Mass. 2021), aff’d by In re Zofran (Ondansetron) Products Liab. Litig., 57 F.4th 327 (1st Cir. 2023). For a more thorough discussion of how courts have applied FDA preemption doctrine following the Supreme Court’s decision in Merck v. Albrecht, 139 S. Ct. 1668, 1672 (2019), see generally Jamie Kendall et al., FDA Preemptions and Albrecht’s Progeny, 76 FOOD & DRUG L.J. 579 (2022). The paper analyzes many of the birth defects-related cases cited in this analysis and Appendix A.

²¹ See, e.g., Zamfirova v. AMAG Pharmaceuticals, Inc., 2021 WL 2103287 (D.N.J. May 25, 2021), Clark v. Hoffman-La Roche, Inc., 2006 WL 1374516 (Super. Ct. N.J. May 2, 2006), Willis v. Abbott Laboratories, 2017 WL 5988215 (W.D. Ky. 2017).

1. under FDA’s Changes Being Effected regulations,²² courts have rejected dispositive motions.²³ Defendants are also successful in dismissing claims where plaintiffs’ expert witnesses could not identify sufficiently reliable evidence to support causation—i.e., proof that the drug can actually cause the injury alleged (general causation) or did cause the alleged injury in that particular case (specific causation).²⁴ The success of both defenses often hinges on the scientific evidence before the Court—the existence of robust data demonstrating the safety/efficacy of the drug, data to support the adequacy of the warnings on the label, and/or the absence of data supporting a link between the drug and the injury alleged²⁵ can be determinative. The fact that science is critical to the defense of these claims is not surprising.
2. Medical malpractice claims.²⁶ Fewer reported cases involved claims asserted against practitioners. Some cases were brought against practitioners individually,²⁷ though, we identified a number examples where claims were asserted against the drug

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²² 21 C.F.R. § 314.70(c)(6)(iii)(A).

²³ See, e.g., Kiker v. SmithKline Beecham Corp., 2026 WL 8189286 (S.D. Ohio Dec. 15, 2016); Anderson v. Janssen Pharmaceuticals, Inc., No. 2330 EDA 2014, 2016 WL 2909234 (Pa. Super. Ct. May 11, 2016).

²⁴ See, e.g., Zamfirova v. AMAG Pharmaceuticals, Inc., 2021 WL 2103287 (D.N.J. May 25, 2021), Clark v. Hoffman-La Roche, Inc., 2006 WL 1374516 (Super. Ct. N.J. May 2, 2006); Willis v. Abbott Laboratories, 2017 WL 5988215 (W.D. Ky. 2017).

²⁵ Lawsuits involving pregnant women’s ingestion of Accutane (see Appendix A, Table 2, pp. 12-13) demonstrate that the defendant can prevail in these lawsuits even if there is data supporting a link between the drug and injury alleged. In fact, general causation (evidence that Accutane can cause the injury alleged) is often a foregone conclusion in these lawsuits because Accutane’s teratogenic effects were well-documented when the drug received FDA approval. The Accutane label included a black-box warning disclosing the high risk of birth defects since 1984. Therefore, courts frequently ruled in favor of the defendant-manufacturer in Accutane birth defect suits because the warnings were deemed “adequate” as a matter of law.

Similarly, the court may rule on a dispositive motion where the injury alleged is not of the same type known to be associated with a drug.

²⁶ Cases were collected using advanced search terms (+“medical malpractice” AND +”birth defect” [or] +“pregnancy” AND +“drug” as well as specific drugs commonly involved in litigation, e.g., Accutane) and reviewing secondary sources.

²⁷ See, e.g., Dyson v. Winfield, 113 F. Supp. 2d 35 (D.D.C. 2000), judgment aff’d, 21 Fed. Appx. 2 (D.C. Cir. 2001) (case against manufacturer); Dyson v. Winfield, 2d 44 (D.D.C. 2000) (case against practitioner); Hunt by Hunt v. Hoffman-La Roche, Inc. 785 F. Supp. 547 (D. Md. 1992) (discussing an earlier case brought against practitioners); Muhammad v. Abbott Labs., Inc., 203 N.E.3d 1001 (Ill. App. Ct., 1st Dist., 4th Div. 2022) (discussing an earlier case brought against practitioners, where $18.5 million was awarded in damages). These examples may suggest that more cases are brought against practitioners than reflected in the case law.

1. manufacturer and practitioners as co-defendants.²⁸ Here, different claims were asserted against each defendant—i.e., products liability with respect to the manufacturer and negligence with respect to the practitioner.²⁹

Of note, expert medical testimony is necessary to establish the physician’s standard of care—that is, courts have not permitted plaintiffs to use a drug’s prescribing information (and the Physician’s Desk Reference [PDR]) to establish the standard of care. Warnings are generally admissible when accompanied by expert testimony, but the drug’s labeling is not considered conclusive evidence of a violation of the standard of care.³⁰ To hold otherwise would undermine physician discretion to act in the patient’s best interest, including by prescribing products off-label. Nevertheless, failure to provide warnings or to adhere to strict prescription guidelines may be strong evidence of a breach of the standard of care.³¹

Further, a common fact pattern in the medical malpractice cases we found involved physicians who failed to properly diagnose a plaintiff’s pregnancy before prescribing a drug contraindicated for pregnant women and/or failed to warn the pregnant person of the risk of birth defects associated with a particular drug product.³² Like in products liability cases, plaintiffs must establish medical causation in medical malpractice cases.³³ To that end, plaintiffs are much more likely to meet their burden of proof in such cases where it is well established that the drug ingested causes birth defects (e.g., Accutane, Provera).

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²⁸ E.g., Ambrosini v. Labarraque, 966 F.2d 1464 (D.C. Cir. 1992); Vaccaro v. Squibb Corp., 418 N.E.2d 386 (N.Y. 1980) (bringing claims against manufacturer, physician, and hospital); Baker v. St. Agnes Hosp. 70 A.D.2d. 400 (N.Y. App. Div. 1979) (also asserting claims against manufacturer, Eli Lilly).

²⁹ It is worth mentioning that physicians (and hospitals) are unlikely to face strict product liability claims as retailers or other distributors. See Lars Noah, This Is Your Products Liability Restatement on Drugs, 74 Brooklyn L. Rev. 839 (2009).

³⁰ See Spensieri v. Lasky, 723 N.E.2d 231 (N.Y. Ct. App. 1999) (“[t]he purposes behind [drug labeling] render its content ill-suited to serve as prima facie evidence of a standard of care,”)

³¹ See Hogle v. Hall By and Through Evans, 916 P.2d 814 (Nev. 1996).

³² See, e.g., McClendon v. Williams, 110 So.3d 216 (La. Ct. App., 2d. Cir., 2013), rev’d by McClendon v. Williams, 126 So.3d 1270 (La. 2013); Hogle v. Hall By and Through Evans, 916 P.2d 814 (Nev. 1996); Lynch v. Bay Ridge Obstetrical & Gynecological Assoc., 532 N.E.2d 1239 (N.Y. Ct. App. 1988); Hogle v. Hall By and Through Evans, 916 P.2d 814 (Nev. 1996).

³³ See, e.g., R.R. By and through Stowell v. Dandade, 2017 WL 2117386 (N.M. Ct. App. Apr. 25, 2017) (excluding untested and unsupported medical testimony); Davis v. United States, 2015 WL 11142426 (N.D. Ga. Mar. 31, 2015) (rejecting plaintiff’s “damaged sperm” theory); Serigne v. Ivker, 808 So.2d 783 (La. App. Ct., 4th Cir., 2002) (dismissing the case due to a lack of expert testimony on the issue of causation, despite evidence that the physician breached the standard of care by prescribing phenobarbital to a pregnant person).

Potential for Long-Tail Liability and Mass Litigation

The Legal Landscape Overview (Appendix B-1) evidences the Plaintiffs’ Bar’s clear preference for birth defect claims. The unborn child is a highly sympathetic plaintiff. Because certain harms can take years to manifest in the child—and the statute of limitations does not start to run until the child reaches the age of majority (i.e., often age 18, in many states)—this creates a longer window of time for plaintiffs to file suit against a culpable party. This is often referred to as “long-tail” liability. “A long-tail claim involves tortious or other liability-creating conduct that causes latent bodily injury or property damage that then manifests itself only many years after the harm-causing conduct occurred.”³⁴ Long-tail claims often involve a massive number of claimants, in part because it is easier to spot a pattern emerging when there is a larger number of parties suffering the same kind of harm.³⁵ There are several notorious mass tort cases in which there was a long-tail between a pregnant woman’s exposure to a drug and her child’s manifestation of a birth defect. Those cases involve the drugs thalidomide, Bendectin, and diethylstilbestrol (DES), described briefly below:

• Thalidomide: Thalidomide was a morning sickness drug that entered the market in the 1950s in several foreign countries, including but not limited to Germany, the United Kingdom, Australia, Japan, Canada, and Norway. The drug was banned in most countries by 1961 when within just a few years of the drug being on the market approximately 10,000 children were born with phocomelia (a rare congenital birth defect that causes limb reduction anomalies).³⁶ Thalidomide-exposed children suffered a variety of injuries, including developmental disabilities, kidney malformations, and ocular anomalies, among others.³⁷ In 1961, two independent clinicians confirmed that thalidomide caused severe birth defects in children, and “[t]he evidence that thalidomide causes birth defects is now undoubted.”³⁸ Fortunately, thalidomide was never FDA approved for use in pregnant women in the United States, and litigation in countries outside of the United States spanned decades.

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³⁴ Kenneth S. Abraham, The Long-Tail Liability Revolution: Creating the New World of Tort and Insurance Law, 6 U. Penn. J.L. & Pub. Aff. 346, 348 (2021).

³⁵ Id. at 357.

³⁶ James Kim & Anthony Scialli, Thalidomide: The Tragedy of Birth Defects and the Effective Treatment of Disease, 122 Toxicological Sciences 1, 1 (2011).

³⁷ Id. at 3.

³⁸ Neil Vargesson, Review, Thalidomide-Induced Teratogenesis: History and Mechanisms, 105 Wiley Birth Defects Rsch 141, 141–42. (2015).

• Bendectin: This FDA-approved morning sickness drug was prescribed to over 35 million American women between 1956 and 1983, before it was withdrawn from the market.³⁹ Concerns about a possible link between Bendectin and birth defects resulted in over 2,000 claimants filing suit against the manufacturer, Merrell Dow Pharmaceuticals.⁴⁰ In 1984, Merrell Dow offered to settle the majority of these claims (for $120 million) and ceased sales of Bendectin because the costs of litigation were too high. The court did not approve the settlement, and a trial was held for 818 Bendectin cases in federal court in Ohio. After hearing the evidence, the jury decided in favor of Merrell and found that plaintiffs failed to establish that Bendectin was a proximate cause of human birth defects.⁴¹ Unlike thalidomide, no causal link between Bendectin and birth defects was ever scientifically established.⁴² Possibly a testament to Bendectin’s safety, in 2013, the FDA approved a rebranded version of Bendectin, Diclegis, for use in the treatment of “nausea and vomiting of pregnancy in women who do not respond to conservative management.”⁴³ We were unable to find any reported litigation involving Diclegis, despite Bendectin’s litigious history.
• DES: DES is a synthetic estrogen that was approved for treatment of miscarriage, preterm labor, and related pregnancy complications. It was widely prescribed to pregnant women between 1940 and 1971.⁴⁴ In 1971, an article in the New England Journal of Medicine reported a possible correlation between DES and clear cell adenocarcinoma of the vagina and cervix in girls and young women who were prenatally exposed to DES.⁴⁵ DES has been linked to a variety of reproductive cancers, fertility problems, and related medical conditions in woman who ingested DES, offspring of mothers who ingested DES in utero (“DES daughters”), and even

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³⁹ Betsy J. Grey, Book Review, Michael D. Green, Bendectin and Birth Defects: The Challenges OF Mass Toxic Substances Litigation 83 (1996).

⁴⁰ Id.

⁴¹ In Re Richardson-Merrell, Inc. Bendectin Products Liability Litigation, 624 F. Supp. 1212 (S.D. Ohio 1985); see also Richard Goldberg, Scientific Evidence, Causation and the Law—Lessons of Bendectin (Debendox) Litigation, 4 Med. L. Rev. 32 (1996).

⁴² Id. at 36.

⁴³ Dicelegis, NDA Approval Letter, https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2013/021876Orig1s000ltr.pdf.

⁴⁴ Nat’l Cancer Inst., Diethylstilbestrol (DES) Exposure and Cancer, https://www.cancer.gov/about-cancer/causes-prevention/risk/hormones/des-fact-sheet.

⁴⁵ National Academies of Sciences, Engineering, & Medicine, Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies, vol. 1, 238 (Anna Mastroianni et al. ed) (1994).

• third-generation populations.⁴⁶ It is estimated that several million pregnant women ingested DES over a 25-year period, resulting in an estimated 1,000+ individual or class-action products liability lawsuits against the pharmaceutical companies that manufactured DES.⁴⁷ The majority of the cases were filed in the 1980s/1990s, decades after the exposure. Yet, further demonstrative of the “long-tail” liability risk, new DES cases are still being filed today,⁴⁸ and plaintiffs’ firms still advertise DES lawsuits on their websites.⁴⁹

Other than DES, these litigations are not described or included in Appendix A because the swell of litigation occurred, and largely resolved, decades ago.⁵⁰ We included a sampling of DES cases in Appendix B-1 because DES litigation is ongoing to this day. And, as described in the table, DES litigation demonstrates two “long-tail” liability themes: (1) the potential for litigation initiated by third-generation plaintiffs (“DES granddaughters” who experienced injuries from their grandmother’s ingestion of DES in utero); and (2) the difficulty identifying a culpable defendant (the manufacturer responsible for supplying the drug that injured a particular plaintiff), where there are numerous defendants manufacturing the same drug over an extended period of time.⁵¹

Although the thalidomide, Bendectin, and DES cases are largely “cautionary” tales⁵² in terms of liability, history has a tendency to repeat itself. For example, today, we still see “mass” litigations, particularly multidistrict litigations (MDLs), involving pharmaceutical products

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⁴⁶ DES cases can be found at Appendix B-1.

⁴⁷ See Women and Health Research, supra note 45, at 239.

⁴⁸ See supra note 1; see, e.g., Lalor v. Eli Lilly & Co. Complaint, 1:22cv6872 (E.D.N.Y. Nov. 10, 2022).

⁴⁹ See, e.g., Napoli Shkolnik PLLC, DES Daughters and Serious Injury, https://www.napolilaw.com/practice-areas/diethylstilbestrol-des/.

⁵⁰ See Appendix A, pp. 10–12.

⁵¹ WOMEN AND HEALTH RESEARCH, supra note 45, at 239.

⁵² Yet, there are several long-lasting positive impacts the thalidomide and Bendectin litigations had on drug safety and liability regimes. The thalidomide tragedy was said to “completely change[] the way drugs are tested.” Vargesson, supra note 38, at 141. For example, thalidomide demonstrated that there are species differences in drug reactions, and today, drug screening policies now incorporate several species and in vitro tests. Id. at 142. Thalidomide also led to “universal” testing of all drugs for teratogenicity and resulted in more rigorous procedures for drug licensing. See Peter J Lachmann, The penumbra of thalidomide, the litigation culture and the licensing of pharmaceuticals, QJM: AN INTERNATIONAL JOURNAL OF MEDICINE 105, no. 12 (2012): 1179-1189. Meanwhile, the Bendectin litigation resulted in the landmark case, Daubert v. Merrell-Dow Pharmaceuticals Inc., which introduced a more rigorous standard for admitting scientific evidence based on the relevance and reliability of such evidence. See Goldberg, supra note 41, at 48-50. As demonstrated in Appendix A, numerous defendant-manufacturers have since prevailed on birth defect lawsuits involving pregnant women’s ingestion of a pharmaceutical product, using the Daubert precedent.

ingested by pregnant women. An MDL is a type of civil procedure in the federal court system that is used when multiple lawsuits are pending against the same defendant or set of defendants and the lawsuits share common factual/legal issues. Appendix A demonstrates that there have been several recent MDLs involving birth defect injuries suffered as the result of a pregnant woman’s ingestion of the following drugs: Depakote, Zofran, and Zoloft.⁵³ Over 700 of the Zofran and Zoloft MDL lawsuits were dismissed, and judgment was entered on behalf of the defendant manufacturers, on issues of preemption or general causation.⁵⁴ However, these defense “wins” in MDL cases come at a high cost to the drug manufacturer (i.e., time, money, resources, reputational burden), perhaps confirming that stakeholders’ fear of liability in developing and marketing drugs towards pregnant women is not entirely unfounded.⁵⁵

CONCLUSION

The legal landscape associated with pharmaceutical products researched in and dispensed to pregnant and lactating women reveals several key themes. Most notably, the case law does not corroborate stakeholders’ fear that including pregnant or lactating women in clinical studies will result in significant litigation risk. At the very least, there is no indication that the legal risk of including pregnant or lactating women in clinical studies exceeds the risk drug manufacturers and clinical trial sponsors typically assume when conducting human trials on any pharmaceutical product.

In contrast, as revealed by our Legal Landscape Overview, there is no paucity of case law in the post-market space. The true legal risk associated with drugs dispensed to pregnant women is best assessed by reviewing this post-market case law. Product liability lawsuits, particularly birth defect claims, comprise the majority of the case law in Appendix A. Compared to pharmaceutical product liability litigation generally, products liability cases involving pregnant women reveal similar risks (e.g., latent injuries, potential for MDLs) and similar defenses (e.g., preemption and causation) that hinge on the drug’s safety and efficacy data, the drug’s labeling/warnings, and the scientific record before the Court. Although children injured in utero are particularly sympathetic plaintiffs and may present a more significant long-tail liability risk than other plaintiffs, the cases we found can, in many ways, be analogized to the pharmaceutical litigation landscape overall.

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⁵³ See Appendix B-1. Although it is outside the scope of the committee’s domain, we also note that there is MDL in the Southern District of New York involving acetaminophen. Id. at 17-20.

⁵⁴ See Appendix B-1.

⁵⁵ Mastroianni et al., supra note 3, at 7 (author’s manuscript).

APPENDIX B-1

TABLE B-1 Summary of Lawsuits Brought by Lactating/Breastfeeding Women¹

¹ The following search terms were used: “breastfeeding” or “lactation/ing,” “drug,” and “malpractice,” “clinical trial,” “liability,” or “consumer protection.” Based on these searches, the only litigation identified with respect to lactating persons involved the drug Parlodel.

² See The Pharma Letter, Sandoz Faces Parlodel Lawsuits In USA, Aug. 21, 1994, https://www.thepharmaletter.com/article/sandoz-faces-parlodel-lawsuits-in-usa.

³ See human drugs: New drug applications—Sandoz Pharmaceuticals Corp.; approval withdrawn, 59 FR 44337 (Aug. 23, 1994)

⁴ Id.

⁵ Id.

⁶ Id.

⁷ Id.

⁸ See 60 F.R. 3403 (Jan. 17, 1995). Note that Parlodel is an FDA-approved drug doctors still prescribe today for a variety of uses.

⁹ There appears to be approximately 65-70 cases cited on Westlaw. However, there may be more litigation that is not reflected in online databases.

¹⁰ See The Pharma Letter, Sandoz Faces Parlodel Lawsuits In USA, Aug. 21, 1994, https://www.thepharmaletter.com/article/sandoz-faces-parlodel-lawsuits-in-usa.

¹¹ Jurisdictional differences with respect to the Parlodel litigation exist. Most notably, Alabama found expert testimony, excluded in other jurisdictions, to pass muster under Daubert, and the case proceeded to trial (Brasher v. Sandoz Pharmas. Corp.). Commentators have noted that the Parlodel litigation demonstrates that “[a]pplication of the Daubert standard to differential diagnosis testimony has engendered particular disagreement and confusion in the federal courts over the past several years” and observed that “the admissibility of clinical medical evidence has a tremendous impact on the course of product liability litigation and is therefore a determination that should be undertaken carefully.” Just What the Doctor Ordered: The Admissibility of Differential Diagnosis in Pharmaceutical Product Litigation, 5 VAND. L. REV. 1227, 1229 (2003).

TABLE B-2 Summary of Lawsuits Brought Against Manufacturers for Injuries Suffered from Pregnant Women’s On-Label Use of a Drug

¹² Other class actions lawsuits involving allegations that AMAG misrepresented the effectiveness of Makena were transferred to New Jersey. See, e.g., Barnes v. AMAG Pharmaceuticals, Inc. 2020 WL 759121 (W.D. Mo. Feb. 14, 2020).

¹³ The majority of jurisdictions do not recognize an exception to the learned intermediary doctrine for manufacturers of contraceptive. However, a minority of jurisdictions do recognize such exception. See Martin, 661 N.E.2d at 356 (collecting cases).

¹⁴ 21 C.F.R. § 310.501.

¹⁵ A number of settlements and jury verdicts have favored plaintiffs based on allegations of improper use of Pitocin (e.g., excessive doses). See Miller & Zois, Maryland Malpractice: Pitocin Settlements and Verdicts, https://www.millerandzois.com/medical-malpractice/birth-injuries/pitocin-birth-injury/pitocin-birth-settlement-maryland/ for examples.

¹⁶ It is unclear whether any settlements were reached. However, the manufacturer claimed that it had only been able to confirm the sale of one defective pack to a patient. More than 100 women say birth control mix-up led to unplanned pregnancies, CBS News (Nov. 12, 2015), https://www.cbsnews.com/news/women-sue-drug-company-claiming-defective-birth-controls-led-to-unplanned-pregnancies/.

¹⁷ Other cases involving Provera/Depo-Provera include Ambrosini v. Labarraque, 966 F.2d 1464 (D.C. Cir. 1992) (bringing actions against manufacturer and prescribing physician).
See also Am. L. Prod. Liab. 3d, Product Citator § 127 (May 2023 Update) (collecting cases)

¹⁸ Sullivan v. Aventis, Inc., 2015 WL 4879112 (S.D.N.Y. Aug. 13, 2015) (granting and denying motion to dismiss in part); Morgan v. Christman, 1990 WL 137405 (D. Kan. July 20, 1990) (denying defendant physician’s motion for summary judgment) (also listed in Table 4); Lust By and Through Lust v. Merrell Dow Pharmaceuticals, Inc., 89 F.3d 594 (9th Cir. 1994) (holding that the district court was justified in concluding that plaintiff’s causation expert’s testimony did not meet the Daubert standard for admissibility).

¹⁹ New York has since reversed course, at least in the case of a medical malpractice claim, allowing a mother to recover for damages under a theory of negligent infliction of emotion distress. See generally Alicia A. Ellis, Better Late Than Never: New York Finally Closes the “Gap” in Recovery Permitted for Negligent Infliction of Emotional Distress in Prenatal Medical Malpractice Cases, 80 St. John’s L. Rev. 725 (2006).

²⁰ National Academies of Sciences, Engineering, & Medicine, Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies, vol. 1, 238 (Anna Mastroianni et al. ed) (1994).

²¹ Two “DES granddaughters” claimed that their premature births and related disabilities were caused by damage to their mothers’ reproductive organs from DES exposure in utero. See, e.g., Lyons v. Premo Pharmaceuticals Labs, Inc., 406 A.2d 185 (N.J. 1979); see also Enright v. Eli Lilly & Co., 570 N.E.2d 198 (N.Y. 1991) (dismissing plaintiff’s personal injury claims—fraud, breach of warranty, strict liability, and negligence—against the DES manufacturer because extending liability to a third generation would unreasonably stretch traditional tort concepts beyond manageable bounds and potentially inhibit the creation or availability of important prescription drugs); Sorrells v. Eli Lilly and Company, 737 F. Supp. 678 (D.D.C. 1990) (granting defendant’s motion to dismiss plaintiff’s strict liability and negligence claims because the “law of Maryland at this time does not extend defendant’s duty to the unborn granddaughter of a mother who ingested DES.”).

²² National Academies of Sciences, Engineering, & Medicine, WOMEN AND HEALTH RESEARCH: ETHICAL AND LEGAL ISSUES OF INCLUDING WOMEN IN CLINICAL STUDIES, vol. 1, 238 (Anna Mastroianni et al. ed) (1994).

²³ Jury Awards $42.3 Million To Women in Drug Lawsuit, The Associated Press (Jan. 9, 1994), https://www.nytimes.com/1994/01/09/nyregion/jury-awards-42.3-million-to-women-in-drug-lawsuit.html.

²⁴ See e.g., Gianvito v. Premo Pharma. Labs., Inc., 19 N.Y.3d 812 (N.Y. 2012), aff’g 93 A.D.3d 546 (N.Y. App. Div. 1 2012) (declining to adopt “market share” theory of liability under New Jersey law where plaintiffs failed to identify the manufacturer of DES they consumer).

²⁵ Hunt by Hunt v. Hoffman-La Roche, Inc., 785 F. Supp. 547 (D. Md. 1992) (granting defendant’s motion for summary judgment under learned intermediary doctrine, concluding that manufacturer warned prescribing doctor of risks associated with Accutane). The plaintiff also filed suit against the prescribing doctor. Id. at 549 & n.3.

²⁶ There is jurisdictional variation on whether a wrongful birth suit is recognized.

²⁷ Earlier cases that went to trial resulted in mixed jury verdicts. See Michelle Llamas, Depakote Lawsuits, Drugwatch (Nov. 4, 2022), https://www.drugwatch.com/depakote/lawsuits/; see e.g., Barron v. Abbott Laboratories, 529 S.W.3d 795 (Mo. 2017) (discussed below)

²⁸ See Am. L. Prod. Liab. 3d, Treatise, § 89.81 (May 2023 Update) for other cases involving injuries due to in utero exposure to Depatoke; see, e.g., Hutchens v. Abbott Laboratories, Inc., 2017 WL 5622688 (N.D. Ohio 2017) (denying plaintiff’s motion for a new trial after the jury unanimously found in the defendant’s favor); Rheinfrank v. Abbott Laboratories, Inc., 199 F. Supp. 3d 749 (S.D. Ohio 2015) (granting defendant’s motion to dismiss plaintiff’s failure-to-warn claim on preemption grounds); Muhammad v. Abbott Labs., Inc., 203 N.E.3d 1001 (Ill. App. Ct., 1st Dist., 4th Div. 2022) (reversing grant of summary judgment on grounds of judicial estoppel because physician’s negligence does not automatically relieve a drug manufacturer of liability for failure to warn).

²⁹ Other cases involving Zoloft include: J.C. by and through Michelle C. v. Pfizer, Inc. 814 S.E.2d 234 (W.V. 2018) (holding that expert testimony was required to support claim that label for drug failed to adequately warn of risks of use during pregnancy and affirming the grant of summary judgment to Pfizer); Bealer v. Hoffman-LaRoche, Inc., 729 F. Supp. 43.

³⁰ See also Gurley v. Janssen Pharmaceuticals, Inc., 113 A.3d 238 (Pa. Super. Ct. 2015) (affirming $11 million jury verdict, awarded based on the finding that manufacturer failed to adequately warn of the risk of birth defects; the appellate court agreed that the claim was not preempted because the defendant could have unilaterally changed its label warnings per FDA’s Changes Being Effected regulations); Czimmer v. Janssen Pharmaceuticals, Inc., 122 A.3d 1043 (Pa. Super. Ct. 2015) (affirming $4.2 million jury verdict).

TABLE B-3 Summary of Lawsuits Against Manufacturers for Injuries Suffered from Pregnant Women’s Off-Label Use of Drugs

³¹ See also Nate Raymond, GSK Defeats 425 Lawsuits Alleging Zofran Causes Birth Defects, Reuters (June 1, 2021), https://www.reuters.com/legal/litigation/gsk-defeats-425-lawsuits-alleging-zofran-causes-birth-defects-2021-06-01/.

³² The risk of liability on this expansive theory of duty is likely unique to California. See Anand Agneshwar & Jocelyn Wiesner, T.H. v. Novartis Pharmaceuticals Corp., Top Food and Drug Cases, 2017 & Cases to Watch, 2018, Food & Drug L. Inst., https://www.fdli.org/2018/07/t-h-v-novartis-pharmaceuticals-corp/. Other jurisdictions have generally declined to hold brand-name manufacturers liable for injury caused by products other than their own.

TABLE B-4 Summary of Lawsuits Against Practitioners for Injuries Suffered from Pregnant Women’s Use of Drugs

³³ The court noted that the plaintiff’s credibility was seriously undermined at trial

³⁴ See also Nichols v. Central Merchandise, Inc., 817 P.2d 1131 (Kan. Ct. App. 1991) (granting summary judgment in favor of defendant pharmacy on the basis that under learned intermediary doctrine, the pharmacy and its pharmacist owed no duty to warn customer of potential side effects of drug prescribed by customer’s treating physician).

³⁵ Note that claims against the manufacturer were dismissed because it met its duty to warn the prescribing physician.

³⁶ Note on wrongful life claims: courts differ on whether to recognize such claims. Cf. Bruggeman v Schimke (1986) 239 Kan 245, 718 P2d 635 (rejecting all damages for “wrongful life.”).

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