H. (T.) v. NOVARTIS PHARMACEUTICALS CORPORATION

Amicus Curiae Brief of Public Citizen

Cal.December 15, 2016

SUPREME COURT COPY 5233898 IN THE SUPREME COURT OF CALIFORNIA T.H., A MINOR,ET AL., SUPREME COURT Plaintiffs and Appellants, F IL E D v. DEC 15 2016 Jorge Navarrete Clerk NOVARTIS PHARMACEUTICALS CORPORATION, g Defendant and Respondent. Deputy Review ofa decision of the Court of Appeal, Fourth Appellate District, Division One Case No. D067839 Application for Leave to File Brief as Amicus Curiae In Support of Plaintiffs-Appellants And Brief of Amicus Curiae Public Citizen, Inc. CHAVEZ & GERTLER LLP NANCEF. BECKER (SBN 99292) 42 Miller Ave. Mill Valley, CA 94925 415-381-5599 RECEIVED Of counsel: Allison M. Zieve a Public Citizen Litigation Group UEL 07 2016 1600 20" Street NW Washington, DC 20009 CLERK SUPREME COURT 202-588-1000 Attorneys for Amicus Curiae Public Citizen 5233898 IN THE SUPREME COURT OF CALIFORNIA T.H., A MINOR, ET AL., Plaintiffs and Appellants, Vv. NOVARTIS PHARMACEUTICALS CORPORATION, Defendant and Respondent. Review ofa decision of the Court of Appeal, Fourth Appellate District, Division One Case No. D067839 Application for Leave to File Brief as Amicus Curiae In Support of Plaintiffs-Appellants And Brief of Amicus Curiae Public Citizen, Inc. CHAVEZ & GERTLER LLP NANCEF. BECKER (SBN 99292) 42 Miller Ave. Mill Valley, CA 94925 415-381-5599 Of counsel: Allison M. Zieve Public Citizen Litigation Group 1600 20" Street NW Washington, DC 20009 202-588-1000 Attorneys for Amicus Curiae Public Citizen APPLICATION OF PUBLIC CITIZEN,INC., FOR LEAVETO FILE AMICUS CURIAE BRIEF IN SUPPORT OF PLAINTIFFS-APPELLANTS Public Citizen, Inc. respectfully requests leave to file the accompanying brief as amicus curiae in support of plaintiffs-appellants T.H., a minor, et al., addressing the question whether a patient should be able to hold the brand-name manufacturer accountable for injuries resulting from misrepresentations about the safety of a drug, when the patient took the generic form of the product. INTEREST OF AMICUS CURIAE | Public Citizen is a non-profit consumer advocacy organization with members and supporters nationwide, including nearly 19,000 in California. Since its founding in 1971, Public Citizen has assessed the safety and efficacy of drugs, provided information on drug safety to the public, and advocated before the Food and Drug Administration (FDA) for product labeling and regulation to reduce safety risks. In June 2013, a Public Citizen report compiled a list of drugs for which black-box warnings—the most serious contraindications and warnings—were added after a generic equivalent entered the market. Looking at a five-year period, the report identified 53 drugs for which a black-box warning calling attention to serious or life-threatening risks was added after generic market entry. The data underscore the public health imperative of requiring pharmaceutical companies to maintain active surveillance of safety, even after a drug is also marketed in generic form.! Public Citizen and its attorneys have participated, as amicus or appellate counsel, in many cases brought bypatients injured by drugs that carried inadequate warnings, including PLIVA, Inc. v. Mensing (2011) 131 S. Ct. 2567, and Conte v. Wyeth, Inc. (2008) 168 Cal.App.4th 89. ' Thereport is available at www.citizen.org/documents/2 138.pdf. 1 In PLIVA, the United States Supreme Court held that federal law preempts failure-to-warn claims against generic drug manufacturers because FDA regulations prohibit generic manufacturers from updating labeling except to mimic brand-namelabeling changes or as ordered by the FDA.Public Citizen responded by petitioning the FDAto allow generic drug manufacturers to revise product labeling through the procedures already available to brand-name manufacturers. In November 2013, the FDAgranted Public Citizen’s petition in part by issuing a proposedrule, 78 Fed. Reg. 67985 (Nov. 13, 2013). The FDA, however, has yet to issue a final rule. Until it does so, and unlike brand-name manufacturers, generic drug manufacturers cannot initiate safety updates to product labeling. Patients and physicians therefore depend on brand-name manufacturers to provide adequate warnings for both brand-name and generic drugs. Allowing patients to pursue misrepresentation claims against brand-name manufacturers for injuries caused by inadequate warningsis important as both an incentive to be vigilant about product safety and to provide accountability to patients. For this reason, this case thus has important implications for all Californians that go well beyond the interests of the parties. CERTIFICATION | No party’s counsel authored this brief in whole or in part, and no party or party’s counsel made a monetary contribution to fund the preparation or submission ofthis brief. No person orentity other than amici made a monetary contribution to the preparation or submissionofthis brief. Dated: December6, 2016 Respectfully submitted, CHAVEZ & GERTLER LLP PUBLIC CITIZEN,INC. By:NunPredn~ Nance F. Becker CERTIFICATE OF INTERESTED PARTIES Pursuant to California Rule of Court 8.208, proposed amicus Public Citizen, Inc. makes the following disclosure regarding persons orentities havinga financial or otherinterest in the outcome of the proceedingthat the justices should consider in determining whether to disqualify themselves: Thereare no interested persons or entities who must be identified pursuant to Rule 8.208. . Dated: December6, 2016 Respectfully submitted, CHAVEZ & GERTLER LLP PUBLIC CITIZEN,INC. AAVAxcpNe ch“, Nance F. Becker Attorneysfor Public Citizen, Inc. 5233898 IN THE SUPREME COURT OF CALIFORNIA T.H., A MINOR,ET AL., Plaintiffs and Appellants, Vv. NOVARTIS PHARMACEUTICALS CORPORATION, Defendant and Respondent. Review ofa decision of the Court of Appeal, Fourth Appellate District, Division One Case No. D067839 Brief of Amicus Curiae Public Citizen, Inc. CHAVEZ & GERTLER LLP NANCEF. BECKER (SBN 99292) 42 Miller Ave. Mill Valley, CA 94925 415-381-5599 Of counsel: Allison M. Zieve Public Citizen Litigation Group 1600 20" Street NW Washington, DC 20009 202-588-1000 Attorneys for Amicus Curiae Public Citizen TABLE OF CONTENTS INTRODUCTION AND SUMMARYOF ARGUMENT|... cccccccccccccceeee. 1 ARGUMENT 00.0. cccccceseesctessesesesesesesessscsssssssssssevevasecesausssasssassesevecsesesees 3 I. Safety concerns often do not cometo light until years after a drug first comes on the market, and only brand-name manufacturers can promptly update labelingin light ofnewly Ciscovered risks. .........eesccsessscssesessscssesssssesecssssacecescssssstsssesesesecscsesees 3 If. | Brand-name manufacturers can easily foresee that physicians and patients will rely on the brand-namelabeling, regardless of whether a patient’s prescriptionisfilled with a generic drug............ 7 Il. Novartis’s position, if adopted, would putpatients atrisk.............. 10 CONCLUSION1.00. cceccccsscnesesseessesesesesesencscssssssscssssssuevectesserssasesssssveseceeses 13 CERTIFICATE OF COMPLIANCE.......c.ccccccccssssssesssssessesssesssesssesecececeeees 14 PROOF OF SERVICE 0.0... ccccccscscscessssescssesseerevees seseeseeseetseeesecesentsesaeesscesses 15 TABLE OF AUTHORITIES Pages Cases Conte v. Wyeth, Inc., (2008) 168 CalApp.4th 89 oieccsssssssesesesssesssesssesasssssssscstsesessvesessarsetescececcececccc. 8 Garcia v. Superior Court, (1990) 50 Cal.3d 728 ooo eeesssssesssssssssescseecscscsvsessecassuacsesssssesssassesesesecseseesecececececcec, 9 Huck v. Wyeth, Inc., (Lowa 2014) 850 N.W.2d 353 o.u..cesessssssesssescsesessessecarestacsssrssssesesesevesercesseseseecececcece, 8 PLIVA, Inc. v. Mensing, (2011) 131 S.Ct. 2567 ooeeccesessssesesesssesesesessesssseacssaessvasssssssasacsetesesecesseserececceces 6, 8 Randi W. v. Muroc Joint Unified School District, (1997) 14 Cal.4th 1066 oooececeecsessesssesesescsssssscsrenssssssssssesssesssevevssesseetesceseseseecs. 9 IH. v. Novartis Pharms. Corp., (2016) 245 Cal.App.4th 589 oo. cccccsssssssssscssssscssssscesessesssssssssssssecesessresseeceecsssececces. 8 Wyeth v. Levine, (2009) S55 U.S. 555 woecccessssectesesesessssesesessesvssessacssevassusssesesssesasecsssesceressececececeeece,4 Wyeth, Inc. v. Weeks, (Ala. 2014) 159 S0.3d 649 oo. sccsessssssssssssesesssesssassesssssssssessevecessersassecetsesecesecsesees, 9 Federal Statutes and Regulatory Materials 21 ULS.C. § 352(£)(2) coececccscescsesecseesesessessssessssssssessseeesesssssescausesssassvassssssssresesecseevecsescesecesecce. 5 21 U.S.C. § 355 veececcssesesssssscsesssessseseesessesssssesssesssssssesesscstsuseesasasasasssusuessssvesausecererecesccceceees 3 Drug Price Competition and Patent Term Restoration Act of 1984, Pub.L. No. 98-417, 98 Stat. 1585.0... cccccsesssescscsesssscsessesscssauscsssesssesesevescetecesecceseecee. ] 21 CAPAR. § 201.57(C)(G)(i) eee eecssesessssessessssesseessesesesssessessuavesessasssusssesesessesecetsucceesecceeescee, 5 21 CAPAR. § 314.70 ceceecesesesessssssescsessssssesesesssssssesssrevessssasssasessssevassesesessueseeseecscecccs, 6 21 CAFAR. § 314.70(D) oo.ceee eccceesesesessssssesesessssssdacsesssssssssearsseusecavasssesuasasasseseseeseceesceces 6, 12 21 CAFLR. § 314. 70(C)ceccccecseccscssessestenesesesesessesesesessssscsessveseesauasasasasacessasasesevereeseseeececeecee. 6 21 CAFR. § 314.70(C)(6)Gii)(A)...ce eececccsescescsesesesecsessscstssesssesusassvasssessesessesesevecceseescsecccccee. 6 21 CABAR. § 314.71(D)ceceeceecssssessessssessscsecsesesesessssescscsussusesasasasavssssuesagseeseseeceseeesccecccec, 6 21 CAPLR. § 314.800)...eeeeeseesssesessessescsesesssssscsestscsusesaesasasscavsssseusaapsesesssceseseeccccceces. 5 21 CAFLR. § 314.94(a)(8)(ii)oeeceseeeeesesesssssenscsessessesssacsesesassvassssses sessesesevereeececsecceecec, 6 il 21 CFR. § 314.105(C)...ceecscsssssssscccccssssssevsessssnnssssssssssusevscsassusssssusssstisecsstiveceesceeesseeeeeeeece 6 21 CAFR. § 314.108(b)(5)..cscccsssssevsssssssssssssssusssessssssesssssstesassssissssssssueceessestseeeceeeceecceceee 12 78 Fed.Reg. 67985 (Nov. 13, 2013)...ssssssssssssesssscsssssssssessssesesssitesseseeeeeeseeeeeeeeeeeeocoeeccc 17 State Statutes Ala. Code § 6-5-530 ..c.ccccecsecssssssesssssssssssesesessssesssssssssscavsvacarsassassssesssaverescescesesseseecececeececg 9 Cal. Bus. & Prof. Code § 4073.0... ccccssssssssssssesssesseeessssseessesacscasssssesssasesescesseceseseeeececeeecece. 9 Treatises Restatement (Second) of Torts § 310, at 103 ..c.cccccesesessssescscstsrsscscssecsssessecsecseececscesececec. 8 Restatement (Second) of Torts § 311, comment b, at 106... .ecccccccccccccececcccccocececececccccce. 7,9 Restatement (Third) of Torts (2016) § 18(a) .....ccccscsssssessssscscscscsesssssesessesscsesesececseseseeeeecc, 8 Miscellaneous A Critical Examination ofthe FDA’s Efforts to Preempt Failure-to- Warn Claims, David A. Kessler & David C. Vladeck, 96 Geo.L.J. 461 (2008) weeeeeesesessecseessssseseecssessssssecssssssscsssssssesesessesececesececesececeees 5 ASPE Issue Brief: Expanding the Use ofGeneric Drugs, HHS(Dec. 2010), https://aspe.hhs.gov/basic-report/ expanding-use-Qeneric-Grugs..........cccssssscscscssscscsesescarscscsssssssessesesesecececececeeeceececececeecs Brief of the Am. Med. Ass’net al. as Amici Curiae Supporting Resp’ts, 2011 WL 794118, PLIVA, Inc. v. Mensing (2011) 131 S. Ct. 2567 (Nos. 09-993, 09-1039, 09-1501)....cccccsescsssessssstssssssecesesssssseseeseteceerecesesececsecececece. 3 Declining Medicine Use and Costs: For Better or Worse?, IMSInstitute for Healthcare Informatics (May 2013), http://static.correofarmaceutico.com/docs/2013/05/20/ USALEPOTt.Pdf... eee eseeseecssesssssssesssesesescseeescaesesvssesesesessssesasassussusasavsssssseasaversvesecsceeecees 2 Draft Guidance, Updating ANDA Labelingafier the Marketing Applicationfor the Reference Listed Drug Has Been Withdrawn, FDA (July 2016), http://www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatoryInformation/Guidances/ UCM10240.pdf oo.ecceeecsessssssscsssseecsssesesescstassssresesasssssssesseseesesecececesececeececes 6, 112 Drug Product Selection: Legal Issues, ThomasP. Christensenetal., 41 J. Am. Pharm.Ass’n 868 (2001)......c:cccccssssssessssescesssessssecsssecsecetecececeeeececeeccececces ] iil as “d e Drug Safety: FDA Has Begun Efforts to Enhance Postmarket Safety, But Additional Actions Are Needed, GAO (Nov. 2009), http://www.gao.gov/assets/300/298135.pdf.....cccccessssccsesesscssssssesesesersecescececeecescees, 5 Drug Safety: Improvement Needed in FDA’s Postmarket Decision- making and Oversight Process, GAO (Mar. 2006), http://www.gao.gov/new.items/d06402.pdf.......cccccssceesesescssscscssesecececcecececececcecece. 5 Evaluation ofFDA safety-related drug label changes in 2010, Jean Lester, etal., 22 Pharmacoepidemiology and Drug Safety 302 (2013)....eccscccsccseccsssesesseseseces4,10 Guidancefor Industry, Distributing Scientific and Medical Publications on Unapproved New Uses—RecommendedPractices, FDA (Feb. 2014), http:/Awww.fda.gov/downloads/drugs/guidance complianceregulatoryinformation/guidances/ucm387652.pdf .....cccccccccccssssecessessons 12 Guidancefor Industry, Revising ANDA Labeling Following Revision ofthe RLD Labeling, FDA (May 2000), http://www.fda.gov/downloads/Drugs/GuidanceCompliance RegulatoryInformation/Guidances/ucm072891 pdf .oo..ceeccccccccccececececcecececececccceececes, 6 High-Risk Series: An Update, GAO (Feb. 2011), http://www.gao.gov/assets/320/3 15725.pdf.......ccsscccssecesescscssssseseseeeceeees sisesetseesoeens4 High-Risk Series: An Update, GAO (Feb. 2015), http://www.gao.gov/assets/670/668415.pdf......ccccccceccscsesesesssscssesesececeescececececececees.4 How Increased Competition From Generic Drugs Has Affected Prices and Return in the Pharmaceutical Industry, Congressional Budget Office (1998), https://www.cbo.gov/sites/default/files/105th-congress-1997- 1998/reports/pharm.pdf...eeccccsssssesssssesesssssesesssesesssesscesssssssasssesesecececececesecececese. I Prescription Drugs, Products Liability, and Preemption ofTort Litigation, Catherine D. DeAngelis & Phil B. Fontanarosa, 300 J. Am. Med. Ass’n 1939 (2008).....ccccscsssssssesessecesecsssesssstssecseseceesesecseecececececee. 3 Research and Development in the Pharmaceutical Industry, Congressional Budget Office (2006), https://www.cbo.gov/sites/default/files/cbofiles/ftpdocs/ 76XX/d0C7615/10-02-drugr-d.pdf.......cesccsesssesssesessscsesesestsesesessesssseesecsececevececeecesces.2 State Generic Substitution Laws Can Lower Drug Outlays Under Medicaid, William H.Shrank et al., 29 Health Affairs 1383 (July 2010) oo.eeesecsesseeesesesssesessesesescsesescssssssscavacsesesstesvassaasassesesesseesececesecececee. I Timing ofNew Black Box Warnings and Withdrawalsfor Prescription Medications, Karen E.Lasser, et al., 287 J. Am. Med. Ass’n 2215 (2002)......ccssssssssssesssssssserssssesssssessssssesececceetececeseceeees4 iv The Use ofMedicines in the United States: Review of2010, IMSInstitute for Healthcare Informatics (Apr. 201 1), https://www.imshealth.com/files/web/IMSH%20Institute/ Reports/The%20Use%200f%20Medicines%20in%20the%20 United%20States%202010/Use_of_Meds_intheU.S._ Review_Of_2010.pdf... eecccsssssssssssseescssssscssstsvesssassssssscssssssssevesesisecseessecesessececee. 2 INTRODUCTION AND SUMMARY OF ARGUMENT The primary issue presented in this case—whether brand-name drug manufacturers can be held liable for injuries caused by inadequately labeled generic drugs—is of significant and growing importance to patients. Following passage of the Drug Price Competition and Patent Term Restoration Act of 1984, Pub. L. No. 98-417, 98 Stat. 1585, commonly referred to as the Hatch-Waxman Amendments,sales of generic drugs have grown dramatically, fundamentally reshaping the pharmaceutical market. The increased availability of generic drugs has made many prescription drugs more affordable for patients. In 1983, only 35 percent of top-selling drugs with expired patents had generic equivalents; by 1998, nearly all did.’ And when generics compete, they typically capture a significant part of market share and profit As of 2010, 90 percent of prescriptions for drugs with generic versions were filled with generics rather than brand-name drugs*—a development spurred by state laws authorizing pharmacists to substitute generic drugs when filling prescriptions.’ Somestates have gone further and now mandate generic substitution where available.’ From 2009 through 2012, generic prescriptions’ share of the prescription drug market ' How Increased Competition From Generic Drugs Has Affected Prices and Return in the Pharmaceutical Industry, Congressional Budget Office, p. xii (1998), https://www.cbo.gov/sites/default/files/105th- congress-1997-1998/reports/pharm.pdf. * See Research and Development in the Pharmaceutical Industry, Congressional Budget Office, pp. 16-17 (2006), https://www.cbo.gov/sites/ default/files/cbofiles/ftpdocs/76xx/doc76 15/10-02-drugr-d.pdf. * ASPE Issue Brief: Expanding the Use of Generic Drugs, HHS,pp. 3-4 (Dec. 2010), https://aspe.hhs.gov/basic-report/expanding-use-generic- drugs. 4 See Drug Product Selection: Legal Issues, Thomas P. Christensen et al., 41 J. Am. Pharm. Ass’n 868 (2001). > State Generic Substitution Laws Can Lower Drug Outlays Under Medicaid, William H.Shrank et al., 29 Health Affairs 1383 (July 2010). 1 increased to 84 percentofall U.S. prescriptions.° In 2010, generics captured more than 80 percent of the market within six months of expiration of a brand-name’s patent (as compared to 55 percentin 2006).’ Despite these market changes, the law places responsibility for labeling firmly on brand-name manufacturers. Generic drug manufacturers cannotinitiate labeling updates; the labeling of generic drugs must mirror that of the brand-name products. A patient’s reliance on the brand-name labeling, regardless of whether the patient took the branded orthe generic version of the drug, is thus intended by the regulatory scheme. In light of this unusual fact—that one manufacturer is required to copy the safety information provided by another—patients should be able to hold brand- name drug manufacturers accountable for injuries resulting from misrepresentations aboutthe safety of their drugs, even if those injuries are caused by a generic version of the drug. As discussed below, allowing patients to do so makessense undertraditional tort law principles and as a matter of policy. ARGUMENT I. Safety concerns often do not cometo light until years after a drug first comes on the market, and only brand-name manufacturers can promptly update labeling in light of newly discoveredrisks. Before a manufacturer can market a drug in the United States, it must obtain FDA marketing approval. 21 U.S.C. § 355. Although the FDA 6 Declining Medicine Use and Costs: For Better or Worse?, IMS Institute for Healthcare Informatics (May 2013), http://static.correofarma ceutico.com/docs/2013/05/20/usareport.pdf; The Use of Medicines in the United States: Review of 2010, IMSInstitute for Healthcare Informatics, pp. 11, 15, 22 (Apr. 2011), https://www.imshealth.com/files/web/IMSH% 20Institute/Reports/The%20Use%200f%20Medicines%20in%20the%20 United%20States%202010/Use_ofMedsintheU.S.Reviewof2010. pdf (IMS 2011 Report). 7IMS2011 Report, supra note6, at p. 21. 2 evaluates the drug’s safety and effectiveness for its intended use before granting approval, the importance ofpost-approval monitoring for ensuring drug safety is well-recognized. Asan article in the Journal ofthe American Medical Association explained: Even though the evaluation of new drugs and devices is technically rigorous, the current approach of basing drug approval decisions on clinical trials of efficacy that include relatively small numbers ofpatients virtually guarantees that the full risks and complete safety profile of these drugswill not be identified at the time of approval. Rather, the full safety profile and effectiveness only manifest as each drugis used in the wider population of patients who are less carefully selected than participants in clinicaltrials.® The limitations in pre-approval testing are especially salient when a drug’s significant adverse effects are relatively rare or have long latency periods—forms of risk that the FDA approval process is not designed to uncover. Examples of drugs whose substantial risks were only discovered post-approval abound in the medicalliterature.” A 2013 article authored jointly by three FDA staff members and two academics reported that “[t]he most critical safety-related label changes, boxed warnings and contraindications, occurred a median 10 and 13 years after drug approval (and the range spanned from 2 to 63 years after approval).”!° This conclusion is consistent with an earlier study’s findingthat “[olnly half of 8 Prescription Drugs, Products Liability, and Preemption of Tort Litigation, Catherine D. DeAngelis & Phil B. Fontanarosa, 300 J. Am. Med. Ass’n 1939, 1939 (2008). ? See, e.g., Brief of the Am. Med. Ass’n et al. as Amici Curiae Supporting Resp’ts, 2011 WL 794118, PLIVA, Inc. v. Mensing (2011) 131 S. Ct. 2567 (Nos. 09-993, 09-1039, 09-1501), at 12-17 (discussing examples of fenfluramine, propoxyphene, ibuprofen, terbutaline sulfate, and metoclopramide). "© Evaluation of FDA safety-related drug label changes in 2010, Jean Lester, et al., 22 Pharmacoepidemiology and Drug Safety 302, 304 (2013). newly discovered serious [adverse drug reactions] are detected and documented in the Physicians’ Desk Reference within 7 years after drug approval.”!! Because safety risks are commonly not identified until long after a drug comes on the market, and indeed after generic versions of the drug come on the market, ongoing monitoring and labeling updates are crucial for safe use of medications. Yet as the Supreme Court recognized in Wyeth v. Levine (2009) 555 U.S. 555, “[t]he FDA has limited resources to monitor the 11,000 drugs on the market, and manufacturers have superior access to information about their drugs, especially in the postmarketing phase as new risks emerge.” Jd. at 578-79 (footnote omitted). It has therefore been “a central premise of federal drug regulation that the manufacturer bears responsibility for the content ofits label at all times ... [and] ensuring that its warnings remain adequate as long as the drug is on the market.”Jd. at 570-71. The need for manufacturersto play a significant role is heightened by funding and staff shortages at the FDA that have prompted the Government Accountability Office (GAO) repeatedly to express concern about post-approval drug safety monitoring.’ NT.iming of New Black Box Warnings and Withdrawals for Prescription Medications, Karen E. Lasser, et al., 287 J. Am. Med. Ass’n 2215, 2218 (2002). * See, e.g., High-Risk Series: An Update 271, GAO (Feb. 2015), http://www.gao.gov/assets/670/668415.pdf (expressing concern that FDA lacks resources to adequately inspect drug manufacturingfacilities); High- Risk Series: An Update 116-17, GAO (Feb. 2011), http://(www.gao.gov/ assets/320/315725.pdf (‘FDA staff have expressed concern about their ability to meet a growing postmarket workload, with some maintaining that their premarket responsibilities are considered a higherpriority.”); Drug Safety: FDA Has Begun Efforts to Enhance Postmarket Safety, But Additional Actions Are Needed, GAO (Nov. 2009), http://www.gao.gov/ assets/300/298135.pdf; Drug Safety: Improvement Needed in FDA’s Postmarket Decision-making and Oversight Process, GAO (Mar. 2006), http://www.gao.gov/new.items/d06402.pdf; see also A Critical 4 To ensure the post-approval safety of their drugs, manufacturers must “promptly review all adverse drug experience information obtained or otherwise received by the [manufacturer] from any source, foreign or domestic, including information derived from commercial marketing experience, post-marketing clinical investigations, postmarketing epidemiological/surveillance studies, reports in the scientific literature, and unpublished scientific papers.” 21 C.F.R. § 314.80(b). To ensure that labeling is kept up to date as information accumulates, FDA regulations require that the labeling of both brand-name and generic drugs “must be revised to include a warning abouta clinically significant hazard as soon as there is reasonable evidence of a causal association with a drug; a causal relationship need not have been definitely established.” Jd. § 201.57(c)(6)(i) (implementing 21 U.S.C. § 352(f)(2), which provides that a drug lacking “adequate warnings” is misbranded). Yet the FDA significantly restricts generic manufacturers’ ability to do so, in ways that absolve those manufacturers of responsibility for labeling updates and that reinforce the brand-name manufacturers’ responsibility. | Brand-name manufacturers, who market drugs approved through the new drug application (NDA) process, may seek review and approval of revised labeling by filing a supplemental application. Jd. § 314.70. A supplemental application mustsatisfy all regulatory requirements that apply to original applications. See id. § 314.71(b). Although somelabel changes require prior FDA approval—obtained through a “prior approval supplement,” id. § 314.70(b)—other changes are brought to FDA’s Examination of the FDA’s Efforts to Preempt Failure-to-Warn Claims, David A. Kessler & David C. Vladeck, 96 Geo. L.J. 461, 485 (2008) (noting that “[rJesource constraints have been especially acute with the agency’s post-marketing surveillance efforts” and that two-thirds of FDA doctors and scientists “worry that the FDA is not adequately monitoring the safety of drugs once they are on the market”). 5 attention at the time the applicant makes the change through a “changes being effected” (CBE) supplement. Jd. § 314.70(c). CBE supplements are authorized for, among other things, “[c]hanges in the labeling to reflect newly acquired information ... [t]o add or strengthen a contraindication, warning, precaution, or adverse reaction for which” there is reasonable evidence ofa causal association. Id. § 314.70(c)(6)(iii)(A). | The United States Supreme Court, deferring to the FDA’s interpretation of the existing regulation, has held that the CBE processis not available to generic manufacturers. PLIVA, Inc. v. Mensing (2011) 131 S.Ct. 2567, 2575. Instead, in most cases, generic drug manufacturers can make safety updates only after approval of a CBE supplement submitted by the brand-name manufacturer for that product or when ordered to by the FDA.” Thisrestriction follows from the generalrule that the labeling of the generic product must generally be “the same as the labeling of” the corresponding brand-namedrug. 21 C.F.R. § 314.94(a)(8)(iii); see also id. § 314.105(c). As a result, brand-name manufacturers—and only brand- name manufacturers—have the responsibility for updating labeling to provide adequate warnings, even after generic versions of the brand-name drug are on the market. Il. Brand-name manufacturers can easily foresee that physicians and patients will rely on the brand-namelabeling, regardless of whethera patient’s prescriptionis filled with a generic drug. Asexplained above, current FDA regulations allow the brand-name company to make safety updates without prior FDA approval, but prohibit 8 Guidance for Industry, Revising ANDA Labeling Following Revision ofthe RLD Labeling, FDA, p. 5 (May 2000), http://www. fda.gov/ downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ ucm072891.pdf; see also Draft Guidance, Updating ANDA Labeling After the Marketing Application for the Reference Listed Drug Has Been Withdrawn, FDA (July 2016), http://www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatoryInformation/Guidances/UCMS 10240.pdf. 6 the generic company from making safety updates except to mimic the brand-namelabeling revision or as instructed by the FDA. See 78 Fed.Reg. 67985, 67988 (Nov. 13, 2013). As Novartis acknowledges, even after generics come on the market, the brand-name manufacturer has an “ongoing responsibility to monitor the drug safety and labeling,” Novartis Reply Br. 33, while the generic manufacturer lacks control over the safety information in its product labeling. Amicus Public Citizen has advocated that this system should be changedto allow generic companiesto initiate safety updates. However, as the regulatory scheme currently exists, the responsibility for safety labeling remains squarely with the brand-name manufacturer. For this reason, a patient’s (and physician’s) reliance on the brand- namelabeling is not only foreseeable—whetherthe patient takes the brand- nameor the generic form ofthe drug—it is inevitable and expected. Andin light of the brand-name manufacturer’s responsibility for maintaining the adequacy of the drug’s labeling, it is not surprising that patients who suffered injury after taking a generic drug that had inadequate safety warnings have sometimes sought to hold the brand-name manufacturer accountable. At least some such lawsuits do not seek to hold the brand- name company responsible under strict products liability theory; some cases, including this one, are premised on a negligent failure to warn or intentional misrepresentation. As explained in the Restatement (Second) of Torts, “one who negligently gives false information to anotheris subject to liability for physical harm caused by action taken by the otherin reasonable reliance upon such information, where such harm results ... to such third persons as the actor should expect to be put in peril by the action taken.” Restatement (Second) of Torts (1965) § 311(1)(b), at 106. See also id. § 310 at 103 (imposes similar liability for knowing misrepresentations); Restatement (Third) of Torts (2016) § 18(a) (defendant may fail to exercise 7 reasonable care by failing to warn if “(1) the defendant knowsor has reason to know:(a) of that risk; and (b) that those encountering the risk will be unawareof it; and (2) a warning might be effective in reducing the risk of harm”). This traditional understanding of a misrepresentation claim provides strong support forthe plaintiffs’ position here. In Conte v. Wyeth, Inc. (2008) 168 Cal.App.4th 89, the Court of Appealheld that a negligent misrepresentation claim against a brand-name manufacturer for injury caused whenthe patient took the generic equivalent was proper in light of the relationship between branded and generic drug labeling. The United States Supreme Court’s subsequent decision in PLIVA reinforces Conte’s strong foundation. And the Court of Appeal’s decision in this case correctly adopted Conte’s reasoning. As the court acknowledged, whether or not the facts alleged “can be proven remains to be seen, but is not the issue before us. Accepting these facts as true ... they are sufficient to establish foreseeability and a connection between the alleged injuries and the harm.” 7:H. v. Novartis Pharms. Corp. (2016) 245 Cal.App.4th 589, 605-06. As Novartis points out (at 32 n.11), several federal appellate courts, predicting how the issue would be resolved under state laws ofstates other than California, have held to the contrary. Only two state Supreme Courts have authoritatively addressed the issue under the laws of their states, however. In one, Huck v. Wyeth, Inc. (owa 2014) 850 N.W.2d 353, the state court held that such a claim was a products liability claim under Iowa law, not a negligent-misrepresentation claim, and under Iowa law a products liability claim can be brought only against the product seller or supplier. Jd. at 369, 371. In the other, the Supreme Court of Alabama rejected the notion that a misrepresentation claim is a species of products liability claim. Wyeth, Inc. v. Weeks (Ala. 2014) 159 So.3d 649, 675. That court held that the brand-name manufacturer could be held liable for 8 misrepresentation in an action brought by a patient who wasinjured by the generic versionofits drug. Id. at 670.4 Here, the plaintiffs’ misrepresentation claims are not properly deemed products liability claims under California law. See Randi W. y. Muroc Joint Unified School Dist. (1997) 14 Cal.4th 1066, 1077; Garcia v. Superior Court (1990) 50 Cal.3d 728, 735 (citing Restatement (Second) of Torts § 311, comment b, at 106). The reasoning of the Iowa court therefore is not pertinent here. As the Court of Appeal’s decision in Conte indicates, California law is fully consistent with the statement in Weeks that “{a] brand-name manufacturer could reasonably foresee that a physician prescribing a brand-name drug (or a generic drug) to a patient wouldrely on the warning drafted by the brand-name manufacturer evenif the patient ultimately consumed the generic version of the drug.” 159 So.3d at 670. Moreover, courts that have rejected recognition of a state-law misrepresentation claim in this context have failed to appreciate the unique elements of drug regulation—such as the requirement that generics use the brand-namelabeling, the bar against generic manufacturers updating except in response to a brand-name update or FDA order (and, ontheflip side, the brand-name manufacturers’ ability to update safety warnings promptly, without prior FDA approval), and state substitution laws requiring or, as in California pursuant to Cal. Bus. & Prof. Code § 4073, permitting pharmacists to fill prescriptions with generic versions where available. In addition, each of the federal court decisions looks to the tort law of the state | in which the claim arose, not to California law. Only two cases—Conte and the decision below—address California law. Both offer strong support for the conclusion that, under California law, a misrepresentation claim can be ‘4 After intense lobbying by the pharmaceutical industry, the State of Alabamalater enacted a statute superseding that decision, see Ala. Code § 6-5-530 (2015). brought against the brand-name manufacturer in the circumstancesofthis case, because a brand-name drug manufacturer can reasonably foresee that its labeling will be relied on by patients and physicians using both the brand-name and generic forms ofthe drug. III. Novartis’s position, if adopted, would put patientsat risk. If accepted, Novartis’s plea to be exempt from accountability for labeling for which it is solely responsible would exacerbate a dangerous safety gap. “[Mlost critical safety-related label changes” are made years after the drug’s initial approval, “underscoring the importanceofpersistent and vigilant postmarket drug safety surveillance.” Evaluation of FDA safety-related drug label changes in 2010, supra note 10, at 304. And the majority of labeling changesareinitiated by the brand-name manufacturers, not the FDA.Jd. at 303. Becausecritical safety information may cometo light after entry of the generic onto the market, and because the generic manufactureris limited to mimicking the brand-namelabeling, if the brand- name manufacturer does not continue actively to monitor and propose safety updates, patients are at risk. Declaring that “[t]he federal regulatory scheme dependsin part upon the continued presence of brand name drug manufacturers in the market after the end of the exclusivity period,” Novartis argues that holding brand- name manufacturers accountable for misrepresentations to patients injured by generic formsoftheir drugs will encourage manufacturers to pull brand- name drugs from the marketplace after generic equivalents become available. Novartis Reply Br. 32. Novartis warns that this consequence would “leav[e] the public with no NDA [new drug application] holder with ongoing responsibility to monitor the drug safety and labeling.” Jd. at 33. Novartis is correct that withdrawal of an NDA relieves the brand- name manufacturer of responsibility for labeling updates goingforward. Id. at 3. The manufacturers’ “ongoing responsibility” while the NDA is in 10 effect, however, does patients little good if those manufacturers have no accountability for failing to fulfill that responsibility.’° Looking backward, though, the NDA withdrawal wouldnotrelieve the manufacturer of liability under California law,if (similar to the facts in this case) the labeling were inadequate at the time the brand-name company withdrew and theinjured patient’s reliance on that labeling were foreseeable. In any event, no evidence supports the speculation that a rule allowing brand-name manufacturers to be held liable for injuries caused by generic versions of their products would cause brand-name manufacturers to change their behavior. Already, brand-name manufacturers sometimes withdraw their NDAsandstop selling their product when, because of the generic market share, the brand-nameproduct is no longer profitable. In fact, the FDA recently issued a draft guidance addressing this specific situation. See Updating ANDA Labeling after the Marketing Applicationjor the Reference Listed Drug Has Been Withdrawn, supra note 13 (discussing labeling changes after the brand-name product has withdrawn from the market). But the brand-name manufacturer keeps its product on the market as long asit is profitable to do so, because the manufacturer makes money only if it sells products. This common-sensepoint is true from the time the brand-name product first enters the market through an NDA:The brand- name manufacturer faces a potential fortort liability for injuries caused by failure to warn from thetimeit first places its product on the market, but that potential does not deter it from marketing its product, as long as the product remainsprofitable. '° The brand-name manufacturerretains responsibility for “necessary revisions to update product labeling” even if it has stopped selling the product, until such time as the NDA has been withdrawn. Draft Guidance, Updating ANDA Labeling After the Marketing Application for the Reference Listed Drug Has Been Withdrawn, supra note 13, at 3 n.6. 11 Novartis takes its argument a step further, suggesting that “[t]he withdrawal of NDAsalso will impede further innovations through which brand manufacturers with strong research and development programs can investigate established drug products for additional therapeutic purposes.” Novartis Reply Br. 33. This notion fails to take account of the regulatory scheme. A brand-name manufacturer must seek a supplemental approval from the FDA for each additional use for whichit intendsto sell a drug. 21 C.F.R. §314.70(b); Guidance for Industry, Distributing Scientific and Medical Publications on Unapproved New Uses—Recommended Practices, FDA, 3 & n.9 (Feb. 2014) (stating that Food, Drug, and Cosmetic Act and FDA regulations “prohibit manufacturers from introducing new drugs... into interstate commerce for any intended use that FDA has not determined to be safe and effective” and providing citations).'° And a manufacturer will have a three-year period of exclusivity to market a drug for a new approved use, beginning on the date of the additional approval. 21 C.F.R. § 314.108(b)(5). Given the incentives other laws provide for researching new uses, a rational manufacturer is not going to stop pursuing a promising supplemental use simply because a generic equivalent is now beingsold for the original use. CONCLUSION For the foregoing reasons and the reasons stated in T.H.’s Answer Brief on the Merits, the decision below should be affirmed. Dated: December6, 2016 Respectfully submitted, CHAVEZ & GERTLER LLP PUBLIC CITIZEN,INC. By:LV)4 afrecl_ NanceF. Bécker '® The guidanceis available at http://www.fda.gov/downloads/drugs /guidancecomplianceregulatoryinformation/guidances/ucm387652.pdf. 12 CERTIFICATE OF COMPLIANCE As required by California Rules of Court, rule 8.520(€)(1), I certify that, according to the word-count feature in Microsoft Wérd, this Brief of Amicus Curiae Public Citizen, Inc. contains word 3,574, including footnotes, but excluding any content identified in rule 8.520(c)(3). Dated: December6, 2016 By: WincePreck~~ NanceF. Bécker 13 PROOF OF SERVICE I, the undersigned, say: I am over 18 years of age, employed in the County of Marin, California, and not a party to the subject cause. My business address is Chavez & Gertler LLP, 42 Miller Ave., Mill Valley, California 94941. On December 6, 2016, I served a true and correct copy of the attached Application for Leave to File Brief as Amicus Curiae In Support of Plaintiffs-Appellants And Brief of Amicus Curiae Public Citizen, Inc. on the interested parties in this action addressed to each by U.S. Mail. I am readily familiar with the business' practice for collection and processing of correspondence for mailing with the United States Postal Service. I know that the correspondence is deposited with the United States Postal Service on the same day this declaration was executed in the ordinary course of business. I know that the envelope was sealed and, with postage thereon fully prepaid, placed for collection and mailing on this date, following ordinary business practices, in the United States mail at Mill Valley, California. Erin M. Bosman BenjaminI. Siminou Julie Y. Park THORSNES BARTOLOTTA MCGUIRE MORRISON & FOERSTER LLP LLP 12531 High BluffDrive 2550 Fifth Avenue, 11th Floor San Diego, CA 92130-2040 San Diego, California 92103 ic G. Lasker n. Joan M. Lewis Katharine R. Latimer AN DIEGO COUNTY SUPERIOR HOLLINGSWORTH LLP COURT 1350 I Street NW 330 West Broadway Washington, DC 20005 San Diego, CA 92101 Leslie A. Brueckner Get ofthe Court PUBLIC JUSTICE, PC “FOURTH DISTRICT COURT OF APPEAL 555 12th Street, Suite 1230 Division One Oakland, California 94607 750 B Street, Suite 300 San Diego, CA 92101 I declare under penalty of perjury that the foregoing is true and correct, and this declaration was executed at Mill Valley, California, on December6, 2016. ~ oo (Ignice Taheny | 14