January February 2019 CBA Report

Similar to Wyeth, the question presented to the Supreme Court in Mensing was whether federal law — that is FDA’s oversight of generic drug labeling — preempted plaintiffs’ state law tort claim that the label for metoclopramide failed to provide an adequate warning about the risk of tardive dyskinesia. 8 In order to address this question, the court looked to the process of FDA approval of generic drugs. Generic drugs can obtain FDA approval by showing the drug is bioequivalent to an already approved FDA brand-name drug; generic manufacturers need not perform the numerous clin- ical trials conducted by the brand name manufacturer. 9 In terms of labeling, the manufacturer has to establish its labeling is the same as the approved brand name drug. Similar to Wyeth, plaintiffs argued the generic manufacturers could have changed their labels through the CBE-0 process. The court, however, giving defer- ence to FDA’s interpretation of the generic labeling regulations, held that a generic drug manufacturer can only change its label after the brand name manufacturer changes the label. Since the generic drug manufacturer could not avail itself of the CBE-0 process, plaintiffs’ state tort law claims were preempted by federal law. The court explained that while the generic manufacturers could have asked the FDA to prevail upon the brand name manu- facturer to change the label (ultimately resulting in a label change to the bioequiv- alent generic drug), such action was not an independent action by the generic drug manufacturer to satisfy its state law duties. “When a party cannot satisfy its state duties without the Federal Govern- ment’s special permission and assistance, which is dependent on the exercise of judgment by a federal agency, that party cannot independently satisfy those state duties for pre-emption purposes.” 10 The court held that plaintiffs’ state law tort claims for failure to warn were preempted by federal law. Despite the court’s holding in Wyeth that a drug “manufacturer bears respon- sibility for the content of its label at all times,” 11 the Mensing court lets generic drug manufacturers skirt around this responsibility. According to Mensing , a generic drug manufacturer is only “responsible for ensuring that its warning label is the same as the brand name’s.” 12 Essentially, the generic drug manufacturer can’t change the label unless the brand name manufacturer changes the label. Two years after the Mensing decision, the FDA proposed new regulations which would have allowed generic drug manu- facturers to change labels through the CBE-0 process. 13 However, the proposed regulations have met strong opposition particularly from manufacturers and distributors of generic drugs. 14 As a result, the FDA has never finalized the new regulations. 15 Generic drugs account for 89 percent of prescription drugs dispensed. 16 Yet, consumers of generic drugs cannot hold manufacturers liable for providing inadequate warnings about the poten- tially serious side effects of those drugs. As Justice Sotomayor declares in her Mensing dissent, a drug consumer’s right to compensation for inadequate warnings now turns on the happenstance of whether her pharmacists filled her prescription with a brand-name drug or a generic. . . . Even when consumers can request brand- name drugs, the price of the brand-name drug or the consumers’ insurance plans may make it impossible to do so. As a result, in many cases, consumers will have no ability to preserve their state-law right to recover for injuries caused by inade- quate warnings. 17 Pharmacists in Ohio are permitted to select a generally equivalent drug with notice to the patient that the generic is available at a lower or equal cost. 18 The only exception to this is if the prescribing physician gives specific directions to the pharmacist to “dispense as written” or “do not substitute.” 19 Although generic drugs may save consumers money, it comes at a cost. Consumers may want to think twice before substituting their brand name prescription drugs with generic drugs, particularly if there is no difference in price. Bailey is an attorney at Burg Simpson Eldredge Hersh Jardine. 1 21 U.S.C. § 355(j)(2)(A). 2 Wyeth v Levine , 555 U.S. 555 (2008). 3 Wyeth , 555 U.S. at 565. 4 Wyeth , 555 U.S. at 568. 5 Id. ; 21 CFR 314.70. 6 Wyeth , 555 U.S. at 571.The Supreme Court recently granted certiorari in Merck Sharp & Dohme Corp. v. Albrecht , No. 17-290, to further address the issue of what constitutes “clear evidence” that the FDA would not have approved a label change. 7 PLIVA, Inc. v. Mensing , 564 U.S. 604 (2011). 8 Mensing , 564 U.S. at 609. 9 Mensing , 564 U.S. at 612. 10 Mensing , 564 U.S. at 623-24. 11 Wyeth , 555 U.S. at 570-71. 12 Mensing , 564 U.S. at 613. 13 Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products, 78 Fed. Reg. 67,985 (Nov. 13, 2013). 14 Interestingly, even the Ohio Public Employees Retire- ment System submitted a comment in opposition to the proposed regulations. 15 Since the new regulations were proposed, Scott Gottlieb, M.D. has been appointed FDA Commissioner. Dr. Gottlieb has been quoted as stating,“FDA needs to bear more responsibility for updating the labels of old generic drugs and can take on that rule, rather than foisting it onto generic drug makers in a way that will not [ ] increase generic costs and expose them to the same sort of failure to warn suits that plague branded companies, . . .” Zachary Brennan, FDA’s Punt on Finalizing the Generic Drug Labeling Rule: Experts Debate , http://www.raps.org/regulatory-focus ™/news- articles/2016/5/fda’s-punt-on-finalizing-the-generic- drug -labeling-rule-experts-debate. 16 Association for Accessible Medicines, Generic Drug Access & Savings in the U.S . (2017). 17 Mensing , 564 U.S. at 643-644. 18 ORC § 4729.38. 19 ORC § 4729.38. F or consumers who suffer an adverse reaction to a prescrip- tion drug, the ability to hold the drug manufacturer responsible for their injuries may turn on whether the drug was a brand name drug or generic drug. While the U.S. Food and Drug Administration (FDA) requires generic drug manufacturers to establish their drug is bioequivalent and has the same thera- peutic effect as the brand name drug, 1 the liability of generic and brand name manufactures for failure to warn of an adverse effect of its drug are not equal. Such results may appear illogical, but it’s the current law of the land. In Wyeth v. Levine, the United States Supreme Court addressed the liability of a brand name drug manufacturer for failure to warn. 2 In Wyeth , Ms. Levine sought treatment at a health clinic for a migraine. She was given Phenergan, a brand name drug manufactured by Wyeth, via IV-push injection. When Ms. Levine received Phenergan, which causes gangrene if it enters a patient’s arterial blood, it reached her arterial blood. Unfortunately Ms. Levine, a professional musician, developed gangrene and ulti- mately had to undergo amputation of her arm below the elbow. She filed suit against Wyeth asserting the label for Phenergan was inadequate because it failed to instruct clinicians to use the IV-drip method of administration rather than the riskier IV-push method. After the trial court denied Wyeth’s motion for summary judgment and a verdict was rendered for Ms. Levine, Wyeth ulti- mately appealed to the Supreme Court. The question presented to the Supreme Court was whether federal law— that is FDA’s oversight of drug labeling — preempted Ms. Levine’s state law tort claim that the label failed to provide an adequate warning about the dangers of administering Phenergan using the IV-push method. 3 The court did not agree with Wyeth’s assertion that it was impossible for it to comply with both federal labeling requirements and state law tort duties. FDA regulations permit a manufacturer to update its label before receiving FDA’s approval if the change is done to “add or strengthen a contra- indication, warning, precaution, or adverse reaction’ or to ‘add or strengthen an instruction about dosage and administration that is intended to increase the safe use of the drug product.” 4 This method of changing a warning label is commonly referred to as the “changes being effected” (CBE-0) regulation. 5 Although a CBE-0 label change eventually gets reviewed by FDA, the process allows manufacturers to provide important safety information immediately to prescribing physicians rather than waiting on an overburdened government agency to provide its review many months later. The court held that Wyeth could have changed the Phenergan label through the CBE-0 method and “absent clear evidence that the FDA would not have approved a change to Phen- ergan’s label, … it was not impossible for Wyeth to comply with both federal and state requirements.” 6 Just two years after Wyeth , the Supreme Court addressed the liability of a generic drug manufacturer for failure to warn. In PLIVA, Inc. v. Mensing , plaintiffs Mensing and Demahy were prescribed Reglan for the treatment of gastroesophageal reflux disorder. 7 Both plaintiffs received generic Reglan (metoclo- pramide) from their pharmacists. After taking the drug for several years, both women developed tardive dyskinesia, an involuntary neurologic movement disorder. Plaintiffs filed suit against the generic drug manufacturers for failing to warn that long term use of metoclopramide could cause tardive dyskinesia. Brand Name Drug or Generic Drug Generic May Foil Your Client’s Failure To Warn Case By Melanie S. Bailey Write for the CBA Report! Share your knowledge and expertise and grow your personal brand by becoming a CBA Report author. Contact CBA Director of Communications Aris Taylor for more details at ataylor@cincybar.org. 8 l January/February 2019 CBA REPORT www.CincyBar.org www.CincyBar.org January/February 2019 CBA REPORT l 9 Feature Article Feature Article