# Petition for Writ of Certiorari — Lundy v. American Cyanamid Co. > Briefs, arguments, decisions, and more. URL: https://www.frixlaw.com/law-library/documents/brief%3Amicro_IA40386001_1176%3A1 ## Record - **Collection:** Supreme Court brief - **Document type:** Petition for Writ of Certiorari - **Published:** January 1, 2004 - **Citation:** 541 U.S. 990 ## Text Supreme Cau 031258 war » — 2004 Jn The Supreme Court of the Anited States ROY LEE LUNDY et al., Petitioners, V AMERICAN CYANAMID COMPANY, Respondent, and JOSEPH R. GRAHAM et al., Petitioners, V. AMERICAN CYANAMID COMPANY, Respondent. ON PETITION FOR WRIT OF CERTIORARI TO THE UNITED STATES COURT OF APPEALS FOR THE SIXTH CIRCUIT PETITION FOR WRIT OF CERTIORARI Marc S. Moller Counsel of Record Kreindler & Kreindler LLP 100 Park Avenue New York, New York 10017 (212) 687-8181 Counsel for Petitioners QUESTION PRESENTED Where a circuit court, in a case involving the violation of a federal statute, 42 U.S.C. § 262(d), and its implementing regulations, fails to apply and materially deviates from the controlling United States Supreme Court decision, Berkovitz v. United States, 486 U.S. 531 (1988), should not this Court grant a Writ of Certiorari to enforce the Congres- sional mandate, the regulatory process, and the rule of law enunciated by this Court? PARTIES TO THE PRCCEEDING IN THE SIXTH CIRCUIT The parties to Graham v. American Cyanamid Company (No. C-2-94-423 in the district court and No. 01-4175 in the Sixth Circuit), were Joseph R. Graham and Lisa A. Graham, as individuals, and Joseph R. Graham and Lisa A. Graham, as parents and next friend of Zachary A. Graham (a minor at the time of filing the action), as plaintiffs, and American Cyanamid Company, as defendant. The parties to Lundy v. American Cyanamid Company (No. C-2-94-425 in the district court and No. 01-4176 in the Sixth Circuit), were Roy Lee Lundy and Janet Lundy, as individuals, and Roy Lee Lundy and Janet Lundy as parents and next friend of Jason Lundy (a minor at the time of filing the action), as plaintiffs,-and American Cyanamid Company, as defendant. CORPORATE DISCLOSURE STATEMENT PURSUANT TO RULE 29.6 None of the parties plaintiff in the Graham and Lundy actions who seek certiorari is a corporate entity. \ sé TABLE OF CONTENTS QUESTIONS PRESENTED.............. i PARTIES TO THE PROCEEDING IN Wee CRPRE TE GOPURATED 6 we ec ees ii CORPORATE DISCLOSURE STATEMENT PURSUANT TO eee ii Rte SI GATEMATA once enwas iii TABLE OF AUTHORITIES............. vi TABLE OF CONTENTS TO THE a ee ere xii PETITION FOR WRIT OF CERTIORARI .. . 1 Soo 8G 8, | a 2 ar 2 STATUTES INVOLVED IN THE CASE... 2 STATEMENT OF THE CASE.......... 3 I kd vob te eee ea 8s 3 The Roles of the Division of Biologics Standards and the National Institutes of Health in Regulating Oral Poliovirus Vaccine.......... a ES 7 -ili- SOTY GUO. 6 ce es 7 PROCEEDINGS BELOW ............0.. 8 REASONS FOR GRANTING THE WRIT... 9 I. UNLESS AND UNTIL BERKOVITZ IS OVERRULED, THE SIXTH CIRCUIT’S AFFIRMANCE OF THE LOWER COURT CREATES AN IRRECONCILABLE CONFLICT WITH THIS COURT’S CONTROLLING ARTICULATION foe 8 Aree errs eee 9 A. Although Oral Polio Vaccine Is No Longer in Use in the United States, the Issues Raised by this Petition Are Not Moot, and the Issue of the Safety of this Vaccine Is a Matter of National Concern to the Public Health....... 19 B. The Regulatory Scheme And The Amendments Thereto. 20 II. THIS COURT SHOULD GRANT THE PETITION BECAUSE THE HOLDING OF THE SIXTH CIRCUIT DENIGRATES INTO OBLIVION NEUROVIRULENCE, THE CENTRAL UNDERPINNING OF THE ENTIRE FEDERAL OPV REGULATORY SCHEME. 23 -iV- III. THE POLIO VACCINE REGULATIONS HAVE NOT ERIE ARATE. cee es 27 ee RR 6 ee eee re ee eee 7 30 peg tk rer eee eee eee A thru E TABLE OF AUTHORITIES CASES Baker v. United States, 817 F.2d 560 FOUN Gs BFE os ik dwcko aun evcecn 1C, 20 Berkovitz v. United States, 486 U.S. 531 (1988) .......... Ta a 5 14, 15, 16, 17, 18, 20, 21, 24, 26, 27, 30 Berkovitz v. United States, 822 F.2d 1322 (3d Cir. 1987....... 9,10 Campagna v. American Cyanamid Compan , 337 N.J. Super. 530, 767 A.2d 996 (2001).............. 13, 14 General Motors Corp. v. Romein, wus U.S. 191 (1990)... ow ces 28 Griffin v. United States, 351 F. Supp. 10 (E.D. Pa. 1972), affd, 900 F.2d 1059 (3d Cir. 1974)....... 4 Gulla v. Straus, 154 Ohio St. 193, 93 N.E.2d 662 (1950) ............ 12 -vi- In R in lio Vacci ts Liabili Litigation, 743 F. Supp. 410 (D. Md. 1990) ("Sabin I"), 763 F. Supp. 811 (D. Md. 1991) ("Sabin II"), and 774 F. Supp. 952 (D. Md. 1991) ("Sabin III"), affd, 984 F.2d 124 (4th Cir. Picea 6, 8, 16, 20, 21, 22, 23, 25, 26, 27 Kaiser Aluminum & Chemical Corp. v. Bonjorno, 494 U.S. 827 (1990)..... 28 Loge v. United States, 662 F.2d 1268 (8th Cir. 1981), cert. denied, So0 U.B. 944 (1SGZ) ow wc 10, 20 Lundy & Graham v. American Cyanamid Company, 2000 WL 1911431 (E.D. Ohio, Dec. 3, 2003), affd, 350 F.3d 496 (6th Cir. 2003) passim STATUTES AND REGULATIONS yk oe | ren 2 ee as OP I 8 kk oe ke eee 2 Federal Tort Claims Act, 28 U.S.C. §§ 1346(b) and 2680(a)........... S ee ee a, 40, 11, 1S, &7 en SS a bode oa he ee 11 -Vli- 21 C.F.R. § 600.3(n) (2000) ........... eS A eS er er eee 21 C.F.R. § 601.4 (1987) .............. 21 C.F.R. §610.1 ...........005. Ri CHM. MGM... i 21 C.F.R. § 630.10(b)(2)(1987) ......... 21 C.F.R. § 630.10(b)(3), (4). 0.2... 21 C.F.R. § 630.10(b)(4).............. 21 C.F.R. § 630.16 (1987) ............ 21 C.F.R. § 630.16(b)(1) (1987)......... 21 C.F.R. §§ 630.110(b)(2)(ii) (1987)... .. 21 C.F.R. §§ 630.110(b)(4) (1987)....... AD CPM. Part TS, oo. 05 coke cea es 42 C.F.R. § 73.3 (Supp. 1964) ......... 42 C.F.R. § 73.5(a) (Supp. 1964) ....... 42 C.F.R. § 73.110(b)(2)............. 42 C.F.R. § 73.110(b)(2)(ii) 2... 2... 42 C.F.R. § 73.110(b)(3)............. 5, -Viii- 3 10, 11, 12 11,19 6,9, 10 11, 24 6 6 6,11, 19 42 C.F.R. 673. 110004)... ww ess 6 J eek 8 oo 2). eer te 6 Ee ee ee BE | eerrarne 8 7 eee fF Oe & © |. ew rer era 6 MCR SPR sic oe 6, 11 73 CPR. SD FRA chi hv ee eee 10 42 C.F .R. § 7S. TEST). oc ie ces 6 42 C.F.R. § 73.114(b)(1)(iili).... 2.2... 6 42 C.F.R. § 73.114(3)(i), (ii), (ili) ...... 6 eee Ae Sees eee eT 10 hat § Ree Bey ee ee ree 10 56 Fed. Reg. 21,418 et seq. (May 18, 1991) 24 Federal Rules of Civil Procedure Rule 56 2 MISCELLANEOUS Hearing Before the House Energy and Commerce Subcommittee on Human Rights and Wellness, Committee on Government Reform, Serial No. 108-85 a: ee eee eee ee oe 19, 22, 24 -1X- Hearing Before the House Energy and Commerce Subcommittee on Human Rights and Wellness, Committee on Government Reform, Nov. 13, 2003: Preventing Another SV40 Tragedy: Are Today’s Vaccine Safety Protocols Effective? Serial No. ___ (in press) ... FDA Docket No. 86N-0027 ........... L. Fuller, The Morality of Law, 51-62 (Yale U. Press 1977).............. Munzer, A Theory of Retroactive Le islation, 61Texas L.Rev. 425 (1982)......... Brock, Kelleher and Zlotnick: "Simian Virus 40 (SV40): A Possible Human Polyomavirus: Product Quality Control testing for the Oral Polio Vaccine," Developments in Biologic Standardization, 217-219 (1998).... Gazdar, A.F., Butel, J., and Carbone, M.: SV40 virus and human tumours, Nature Reviews Cancer, 2:957-964 (2002)................ Klein G, Powers A, Croce C., "Association of SV40 with human tumors," Oncogene, 21:1141-1149 Raat 20 24, 25 29 28 20 20 20 Se * The Institutes of Medicine Evaluation of Poliomyelitis Vaccines, The Nightingale Report, IOM Publication 77-02, re-published as Nightingale, E.O., Recommendations for a national policy on poliomyelitis vaccination, N. Engl J. Med, 1977; 297:249-253 3 Report by Immunization Safety Review Committee on Health Promotion and Disease Prevention of the Institute of Medicine, Immunization Safety Review SV40 Contamination of Polio Vaccine and Cancer, July 11-12, 2002 (102 pp), available at www.nap.educatalog/10534.html1/ (accessed Feb. 29, 2004)... 20 «Xi- TABLE OF CONTENTS TO THE APPENDIX Opinion of the Court of Appeals, 350 F.3d 496 6" Cir. 2003). cease... App. A Judgment of the Court of Appeals for the Sixth Circuit, filed December 3, 2003............ App. A at 37-38 Opinion of the lower court in Graham / Lundy v. American Cyanamid Company, 2000 WL 191 1431 (S.D.Ohio, Dec. 21, ers App. B Judgment in a Civil Case of the United States District Court for the Southern District of Ohio in Graham v. American Cyanamid ee aii App. B at 31-32 Judgment in a Civil Case of the United States District Court for the Southern District of Ohio in Lundy v. American Cyanamid os App. B at 33-34 42 UBS. GIGI oo coc. App. C Federal regulations governing live oral poliovirus vaccine, 42 C.F.R. Part 73, later re-numbered as 21 C.F.R. Part 630 (relevant portions) ....... App. D American Cyanamid Company submittals to FDA Docket No. 86N-0027 (extracts)........\. App. E -Xll- PETITION FOR A WRIT OF CERTIORARI Roy Lundy, his wife Janet Lundy, and his son, Jason Lundy respectfully seek a Writ of Certiorari to review the decision of the United States Court of Appeals for the Sixth Circuit, which, on December 3, 2003, affirmed a Summary Judgment Order and Judgment dismissing the action, issued by the United States Dis- trict Court for the Southern District of Ohio, entered on December 21, 2001. In this same petition, Zachary Graham, his mother Lisa Graham, and his father Joseph Graham respectfully seek a Writ of Certiorari to review the same decision of the United States Court of Appeals for the Sixth Circuit, which affirmed a Summary Judgment Order and Judgment dismissing the action, issued by the United States District Court for the Southern District of Ohio, entered on December 21, 2001. The Lundy and Graham actions were decided in a single decision by the trial court; that decision in turn, was affirmed by the Sixth Circuit in one decision. In the Lundy action, plaintiff Roy Lundy claimed that he contracted Type III paralytic poliomyelitis through contact with his recently-immunized infant son, Jason. The oral polio vaccine which was administered to his infant son had not been licensed, tested, and manufactured in accordance with the federal oral polio vaccine regulations. One of the particular batches of trivalent vaccine Jason may have received contained rejected and expired vaccine, as well as a monovalent pool that was more neurovirulent than the entire neurovirulence safety testing history of the reference standard as conducted by the manufacturer, Cyanamid. In the Graham action, plaintiff Zachary Graham’s parents claimed that their infant son contracted para- lytic poliomyelitis after ingesting 4 dose of Orimune vac- cine which was defective. The violations of the same federal regulatory scheme that was applicable to the Lundy case was applicable to Zachary Graham’s immu- nization. In both instances, the vaccine manufacturer failed to comply with the licensing, testing and manufacturing requirements for the vaccine at each stage of manufacture. OPINIONS BELOW , The opinion of the Court of Appeals (App. A)! and Judgment (App. A at 31) is reported at 350 F.3d 496 (6" Cir, 2003). The unpublished opinion of the lower court is available at 2000 WL 1911431 (S.D.Ohio 2000, Dec. 21, 2001) (App. B). The Judgment of the District Court appealed from in Graham (App. B at 31), and in Lundy (App. B at 33) are unreported. JURISDICTION The jurisdiction of this Court is invoked pursuant to 28 U.S.C. § 1254/1). STATUTES INVOLVED IN THE CASE The statutes involved are 28 U.S.C. § 1254(1), Federal Rules of Civil Procedure Rule 56, and 42 U.S.C. § | 262(d) (App. C). The regulations involved are the federal regulations governing live oral poliovirus vaccine, 42 C.F.R. Part 73, later re-numbered as 21 C.F.R. Part ye References to the Appendices which are bound in this volume are preceded with the section designations “App. A,” App. B.” etc.. a 630. Relevant portions of those regulations are set forth in Appendix E. STATEMENT OF THE CASE Background Since the introduction of oral polio vaccine in the United States in 1962 until its removal from sale in 1999, American Cyanamid/Lederle has been America’s major supplier of Sabin Oral Poliovirus Vaccine. Beginning in 1962, when it first applied for its license, until 1977, American Cyanamid/Lederle had approxi- mately 83% of the United States market. After 1977, it was the sole oral poliovaccine manufacturer in the United States until 1999, when Orimune was no longer recommended for pediatric immunization. At all times relevant to this petition, a completely safe alternative vaccine, the Salk vaccine, also known as inactivated polio vaccine (“IPV”), was available to the American public.’ 2 In 1977, the Institutes of Medicine issued a report known as the Nightingale Report, which found there was no benefit to the individual recipient of oral polio vaccine over immunization with inactivated polio vaccine. Cf. Lundy v. American Cyanamid Company, 350 F.3d at 499. The Sixth Circuit’s recitation of the properties of IPV and OPV and their differences is historically inaccurate and conflicts with both the Institutes of Medicine Report written in 1977, The Institutes of Medicine Evaluation of Poliomyelitis Vaccines, The Nightingale Report, IOM Publication 77-02, and all other scientifically correct descriptions, as can be found in the manufacturer’s own package insert beginning in the late 1980's. Me On Between 1979 and 1999, the sole source of paralytic poliomyelitis cases in the United States was the oral polio vaccine known as “Orimune,” the vaccine product manufactured by American Cyanamid Company / Lederle Laboratories. Once the nation’s pediatric regi- men was changed from oral polio vaccine to inactivated polic vaccine in 2000, not a single child or adult in the United States was thereafter afflicted with paralytic poliomyelitis, and no wild cases of polio have occurred. The Roles of the Division of Biologics Standards and the National Institutes of Health in Regulat- ing Oral Poliovirus Vaccine. Oral poliovirus vaccine, as every other vaccine utilized to immunize the population in order to protect the public health of the United States, was initially regulated not by the Food and Drug Administration (FDA), but by the Division of Biologics Standards (DBS), part of the United States Public Health Service. The FDA did not assume any responsibility for vaccines until 1972, when the DBS was found liable for releasing non- compliant oral polio vaccine. Griffin v. United States 351 F. Supp. 10 (E.D. Pa. 1972), aff'd, 500 F.2d 1059 (3d Cir. 1974). Poliovirus was a scourge to humans because of its capability to attack the nervous system and permanently destroy the capacity of particular nerve cells to relay through the spinal cord the electrical potentials which activate muscles. Thus, when public health officials geared up for use of a live virus vaccine in the United States, they proposed and adopted a set of highly detailed and stringent regulations which had as their goal to implement the best methods then known to science to insure that the neurovirulence of manufac- -4- tured vaccine would be at an acceptably safe level. To accomplish this goal, they specified a particular licen- sing, manufacture, and safety testing regimen from which manufacturers could not diverge if they wished to sell OPV. Lederle was one of only a handful of biologics manufacturers that decided to apply for an OPV license. During the period of American Cyanamid’s licensure, it and each of the other license applicants were required to submit to the government the test results demonstrating -- as a condition precedent to subsequent lawful manufacture of polio vaccine -- that its master seeds, production seeds, and/or intermediate seeds passed all regulatory safety requirements and that the manufac- turer’s test results for the final product, in the form in which it distributed it, also demonstrated that that product fully complied with the regulations. The record below demonstrated that Cyanamid did not perform the necessary tests and did not submit any seed test results with its Orimune license applications. Moreover, the consistent uncontradicted record testimony of Cyanamid’s personnel is that the vaccine manufacturer did not submit the test results. The vaccine manufacturer did not submit the test results for two reasons: first, most of the test results, had they been submitted, would have shown the applicant’s failure to comply with the regulations then in effect, such as that all of its seeds were contaminated with an adventitious agent (i.e., one from an extrinsic source) known as SV40, which had been shown to cause cancer in test animals and whose presence in the vaccine was prohibited explicitly by regulation. 42 C.F.R. § 73.110(b)(3). Cyanamid had not demonstrated that it had successfully tested for and removed the SV40, a specific requirement for licensure pursuant to Si this Court’s Berkovitz opinion. Second, no tests were submitted for neurovirulence (see 42 CFR §§ 73.110(b)(2)(ii), 73.110(b)(4), 73.114(b)(1) (Supp. 1964); 21 CFR §§ 630.110(b)(2)(ii), 630. 110(b)(4), 630.16(b)(1) (1987)) (App. D) or markers (42 C.F.R. § 73.114(3)(i), (ii), (iii)), for any of the seeds utilized to license this oral poliovaccine product. The adventitious agent test results were not submitted for any of the seeds utilized to license this product. See 42 C.F.R. §§ 73.110 (b)(3), and 73.112, 113 and 114. ~ What testing was conducted, and what records do exist in regard to neurovirulence and markers, proved that both the licensing lots and the subsequent lots manufactured for distribution exceeded the neuro- virulence safety requirements and were more neuro- virulent than the “reference standard,” a vaccine provided to manufacturers by which safety testing results could be calibrated to a standard for maximally permissible acceptable neurovirulence. 42 C.F.R. §§ 73.114(b)(1)(iii); In re Sabin, infra, 763 F. Supp. at 815-817, 826-827, 829. Throughout the years Orimune was produced, American Cyanamid/Lederle assured the courts, the public, the medical profession, the state legislatures, and all others that it warranted that it had fully complied with each and every regulation in effect at each relevant time period. This promise and guarantee of compliance, prominently displayed in each of Cyana- mid’s Orimune advertisements, package inserts, and vaccine containers, was false. One of respondent’s Managers, who was in charge of communications with physicians, admitted that no physician would use a non- licensed vaccine and, more importantly, no vaccine manufacturer could or should be able to sell an unli- censed product. -6- During all times relevant herein, the regulations that were enacted in 1960 remained in full effect at the time that Roy Lundy, one of the petitioners herein, was paralyzed through contact with his recently immunized infant son, Jason, and when petitioner Zachary Graham, then a minor, was paralyzed by ingesting Orimune. Roy Lundy Roy Lundy is a wheelchair-bound contact polio victim of Type III poliovirus from Orimune which contained a neurovirulent component which exceeded the entire reference history of Lederle’s safety testing in comparison to the reference standard from 1962 to 1977, and thereafter, until 1999. One of the trivalent bulks that could have been administered to Roy’s son Jason came from rejected, expired vaccine, without knowledge of or permission from the FDA. Sale of such vaccine was strictly prohibited by the applicable regulations at the time Jason Lundy was vaccinated. Zachary Graham Zachary Graham is a lower-limb paralyzed direct recipient case of paralytic poliomyelitis. His case was evaluated by the Centers for Disease Control, and he was determined to be a vaccine-associated case of polio. There are no test results showing that the various seeds utilized in manufacture of Zachary’s final production seed passed all the required safety tests and, specifi- cally, neurovirulence and marker tests, which, by regul- ation, are utilized to judge the safety of the vaccine prior “to release. It was admitted below that the vaccine was eB beyond five tissue culture passages. Pursuant to the In re Sabin decision (763 F. Supp. at 813, 821 823), this Court’s Berkovitz decision (486 U.S. at 541, 544, 545 n.11), and the regulations then in effect (42 C.F.R. § 73.113(b)), Zachary Graham’s vaccine could not legally be sold. PROCEEDINGS BELOW Following several years of consolidated pretrial discovery in Graham and Lundy, in 1998 American Cyanamid filed two summary judgment motions. It sought to dismiss Jason Lundy’s product defect, negligence, breach of express warranty, and fraud claims and the dismissal of Roy Lundy’s fraud and punitive damages claim. Plaintiffs opposed the motions. The district court granted summary judgment on both motions on December 21, 2000, finding that defendant was entitled to summary judgment. Plaintiffs moved to amend judgment, which the court denied on September 28, 2001. On the same day, Cyanamid filed parallel motions in Graham. Plaintiffs opposed them. The district court granted summary judgment on both motions on December 21, 2000. Plaintiffs moved to amend judgment, which the court denied on September 28, 2001. Plaintiffs in both cases timely appealed. The Sixth Circuit affirmed the lower court, finding that -8- violation of licensing requirements and excessive vaccine neurovirulence did not cause the plaintiffs’ paralysis. The plaintiffs in each case then peti- tioned this Court for certiorari. REASONS FOR GRANTING THE WRIT i. UNLESS AND UNTIL BERKOVITZIS OVER- RULED, THE SIXTH CIRCUIT’S AFFIRMANCE OF THE LOWER COURT CREATES AN IRRECONCIL- ABLE CONFLICT WITH THIS COURT’S CONTROL- LING ARTICULATION OF THE LAW. Berkovitz v. United States, 486 U.S. 531 (1988), presented to this Court a polio victim’s claims against the United States, as licensor of the instant defendant, American Cyanamid Company, for non-compliant manufacture of Orimune live oral polio vaccine. In the district court action, the Western District of Pennsylvania had denied the government's motion to dismiss on discretionary function exception grounds, and the government appealed. In Berkovitz v. United States, 822 F.2d 1322 (3d Cir. 1987), the Court of Appeals correctly held that "[T]he duty to submit test data rests with the manufacturer.", (the point of error which Petitioners address to the Court in Lundy and Graham), citing 21 C.F.R. §§ 601.2, 610.1, 630.10(b)(4) (822 F.2d at 1330, n.6), but reversed the lower court's additional finding that the government was also liable. The Third Circuit based its reversal upon the discretion- ary function exception to the Tort Claims Act, 28 U.S.C. §§ 1346(b) and 2680(a). The Third Circuit's opinion stated: "It is therefore evident that looking at the [poliovirus vaccine] regula- tions as a whole, it is the manufacturer that is required -9- to perform the tests [set out in 42 C.F.R. §§ 73.114(b), 73.115, 73.117]." 822 F.2d at 1330 (emphasis supplied). Judge Higginbotham’s dissent, relying upon Baker v. United States, 817 F.2d 560 (9th Cir. 1987), and Loge v. United States, 662 F.2d 1268 (8th Cir. 1981), cert. denied, 456 U.S. 944 (1982), found that an additional and co-equal liability resided in the govern- ment. In language which was consistent with what this Court ultimately held, Judge Higginbotham agreed with his brethren as to the vaccine manufacturer, stating: "The regulations in this field place mandatory duties upon a drug manufacturer, such as Lederle, that seeks to obtain a federal license to market its drug product." 822 F.2d at 1332 (emphasis supplied). However, citing to the various regulatory requirements of 21 C.F.R. §§ 601.2(a), 630.10(b)(2), 630.10(b)(4), and 42 U.S.C. 262(d), he went further than the majority, adopting the position that the relevant statutes and regulations not only obligated Lederle, the licensee-applicant, to submit everything the regulations required, but also obligated the DBS to require submission of test results and review the same to measure whether there is full compliance. Id. at 1333. Denial of a license when test data failed to prove that the vaccine conformed with the mandatory require- ments -- which were the only applicable safety standards — was what this Court demanded. See 486 U.S. at 544, n.10, 548. If the manufacturer failed to submit the test results, the regulatory language imposed a non-discre- tionary duty on the regulator to insure that that manu- facturer had to be properly licensed to manufacture its vaccine. One hundred percent compliance was required. This Court reversed the Third Circuit and referenced with approval the broader reading of the -10- regulations articulated by the Eighth and Ninth Circuits, announcing what was assuredly intended to be the rule of law in regard to licensing and manufacture of all vaccines. The unanimous Supreme Court in Berkovitz, supra, stated: Under federal law, a manufacturer must receive a product license prior to marketing a brand of live oral polio vaccine. See 58 Stat. 702, as amended, 42 U.S.C. § 262(a). In order to become eligible for such a license, a manufacturer must first make a sample of the vaccine product. See 42 CFR § 73.3 (Supp. 1964); 21 CFR § 601.2 (1987). [FN7] This process begins with the selection of an original virus strain. The manufacturer grows a seed virus from this strain; the seed virus is then used to produce monopools, portions of which are combined to form the consumer-level product. Federal regula- tions set forth safety criteria for the original strain, see 42 CFR § 73.110(B)(2) (Supp. 1964); 21 CFR § 630. 10(b)(2)(1987), the seed virus, seed 42 CFR § 73.110(b)(3), (4) (Supp. 1964); 21 CFR § 630.10(b)(3), (4) (1987), and the vaccine monopools, see 42 CFR § 73.114 (Supp. 1964); 21 CFR § 630.16 (1987). Berkovitz v. United States, 486 U.S. at 541 (footnote omitted). Notwithstanding Berkovitz, the Sixth Circuit in the within matter found that there had been non- compliance with the licensing regulatory demands, but nevertheless, equated its proximate cause significance to Ry that of an individual who does not have a driver's license at the particular moment of an accident leading to injury, but who had a valid driver's license the day before the accident, and could get one the day after the accident. The Grahams also claim that the Orimune vaccine Zachary received was defective because American Cyanamid was not properly licensed to manufacture it. While they question whether certain testing procedures necessary for licensing occurred, they offer no evidence that the company did not in fact have a valid license to manufacture Orimune. As with their other claims, they also offer no evidence that any anomalies in American Cyanamid's license proximately caused Zachary's injuries. In Ohio, the absence of a valid or properly issued license does not by itself establish the proximate cause of an injury. Cf. Gulla v. Straus, 154 Ohio St. 193, 93 N.E.2d 662, 664 (1950). What the Sixth Circuit clearly misunderstood and failed to appreciate was the significance of the licensing requirements of vaccines in particular, a biological product which was mandated by many state legislatures to be administered to children throughout their early childhood years as a condition precedent to attending school. No legislator, physician, or public health official would have permitted the use of non-compliant or non- licensed vaccine. Stephen A. Szumski, Ph.D., was the associate director of Cyanamid’s Professional Medical Service Department from 1965 to 1982. While employed in that capacity, he chaired a Cyanamid committee which had the authority over the wording of Orimune’s $4. a Pe oa ee Mee a package inserts and the Physician’s Desk Reference annual insert. The testimony of this witness was relied upon by the New Jersey Appellate Division in reversing a lower court grant of summary judgment for Cyanamid on theories of failure to warn, strict liability, negligence, fraud, and punitive damages in Campagna v. American Cyanamid Company, 337 N.J.Super. 530, 767 A.2d 996 (2001): Dr. Szumski was also asked if he was aware that defendant's vaccine had failed certain safety tests (tests that were required under the federal regulations), would he have "notified the medical profession" if the medical profession had asked whether the vaccine could be administered? Dr. Szumski answered, "Well, I certainly would have told them not to use it." The plaintiffs attorney then read to Dr. Szumski the disputed warning statement concerning regulatory compliance from the package insert and Dr. Szumski testified that he thought physicians would believe that statement. When asked if the statement would constitute a "misrepresentation" or "lie" if defendant had released vaccine that did not comply with the regulations, Dr. Szumski replied, "Well, if they [defendant] say so and it wasn't so, then certainly I would believe it's a lie." On cross-examination by defen- dant's attorney, Dr. Szumski was asked "[ijf it was determined by the [FDA] that a 4%. technical violation of the regulations had no effect on the safety of the [Orimune OPV] vaccine, do you think it would be reasonable for [defendant] to rely on that?" Dr. Szumski answered, "Yes, [defendant] would take action and they probably wouldn't market it." Unsatisfied with this answer, defendant's attorney repeated the question and Dr. Szumski again replied: "([Defendant] would probably act on it [the FDA's determination] and not use the vaccine." Still unsatisfied, defendant's attorney repeated the question again, whereupon Dr. Szumski answered that defendant "would use their judgment" in relying on the FDA's determination. Finally, on redirect examination by the plaintiffs attorney, Dr. Szumski was asked, "Doctor, if in 1978 [Orimune OPV] did not technically comply with the regula- tions, if you were aware of that in 1978, | would you have informed physicians, hospitals, and other health care providers of that fact?" Defendant's attorney objected, and the plaintiffs attorney rephrased the question, asking "If it [Orimune OPV] did not technically comply with the regulations in 1978, would you have informed health care providers of that fact?" Dr. Szumski replied that, "[ilf it didn't comply with the regulations, it wouldn't have been on the market." Id. ,767 A.2d at 545-547. It is evident that this Court's holding in Berkovitz ata. was disregarded by the Sixth Circuit when it reviewed the Graham and Lundy appeals. This Court necessarily and implicitly ruled that if a vaccine manufacturer fails to submit any of the requisite safety tests of its license application, it cannot sell the product. If the manufac- turer succeeds in obtaining licensure because of the regulator’s failure to enforce regulatory requirements, neither the government nor the vaccine manufacturer can claim that a person injured does not have a valid damage claim. Any conduct which departs from what the regulations mandate is squarely prohibited. If the manufacturer-license applicant fails to submit the required safety test results, or if the sample of the oral polio vaccine product intended to be marketed fails the government’s own safety testing, or if the manufacturer failed to present proof as to the absence of adventitious agents, then the license application as presented must be rejected. Pursuant to the Public Health Service Act, 42 U.S.C. § 262(d), and the regulations enacted thereunder, neither the government nor the vaccine maker can permit the product to be sold. The Berkovitz Court held: A regulation similarly provides that "[a] product license shall be issued only upon examination of the product and upon a determination that the product complies with the standards prescribed in the regulations... ." 42 CFR § 73.5(a)(Supp. 1964); see 21 CFR § 601.4 (1987). In addition, a regulation states that "[a]n application for license shall not be considered as filed" until the DBS receives the information and data regarding the product that the manufacturer is required to submit. 42 CFR § 73.3 (Supp. 1964); 21 CFR § 601.2 (1987). These statutory and at$. regulatory provisions require the DBS, prior to issuing a product license, to receive all data the manufacturer is required to submit, to examine the product, and to make a determination that the product complies with safety standards. Berkovitz, 486 U.S. at 542 (emphasis supplied). It is unquestionable that from the very earliest days of Orimune, American Cyanamid fully understood the importance of compliance with the regulations: in order to convince physicians, legislators, the parents of infants, and the public health community that its vaccine was safe, Lederle stated on each of its package inserts, and on each container of Orimune that was shipped from its plant, that it had fully complied with all of the regulations that were in effect at the time of release. See Lundy & Graham v. American Cyanamid Company, 2000 WL 1911431 at *5 (App. B). That express and affirmative warranty statement was false (see In_Re Sabin Oral Polio Vaccine Products Liability Litigation, 984 F.2d 124 (4th Cir. 1993), affg 743 F. Supp. 410 (D. Md. 1990) ("Sabin I"), 763 F. Supp. 811 (D. Md. 1991) ("Sabin II"), and 774 F. Supp. 952 (D. Md. 1991) ("Sabin III")) and flew directly in the face of what the vaccine manufacturer was required to do under the Public Health Act and under the regulations which were enacted pursuant to that Congressional mandate. Berkovitz v. Unit tates is the law of the land, and if this Court fails to grant certiorari, the Sixth Circuit's decision in these cases will conflict irreconcilably both with this Court's Berkovitz decision and the decisions of the circuits which have applie Berkovitz’ holdings and with the applicable era -16- tll statute, 42 U.S.C. § 262(d), not to mention the plain meaning of the text of the regulations themselves. In essence, the requirement to be properly licensed in order to sell a vaccine (or, in a more general sense, a drug) in the United States, which was the basis for this Court's discretionary function exception decision in Berkovitz, will have been abolished by the Sixth Circuit, notwith- standing the clear language of this Court and the authorizing statutes. The possibly unintended but inevitable conse- quence of allowing the Lundy and Graham decision to stand will be that in the future, a drug or vaccine manufacturer will be able to point to the Sixth Circuit decision and argue that whenever licensing require- ments may have been overlooked, ignored, omitted, performed improperly, or even falsified and resulted in injury or death, the government, and not the manufac- turer / licensee, is liable in damages for breach of that duty, and that Berkovitz, supra, does not in any way speak to liability which can result from failures or defalcations on the part of the manufacturer. To the contrary, Berkovitz confirmed that a regulatory system such as that which governed the oral polio vaccine involved here created a very calculated and deliberate additional layer of liability, over and above the vaccine manufacturer’s direct liability, which has never been diminished by this Court. Furthermore, in the face of the oral polio regulatory scheme, that direct liability was strict and absolute if the regulation was breached at any time or at any juncture. The failure of experts to cite peer-viewed studies to support their conclusions where there are unquestioned violations of the safety tests used to measure neurovirulence of the vaccine cannot be a basis to deny relief to paralyzed polio victims exposed to an unacceptably neurovirulent vaccine. si? Cyanamid’s failure to submit the safety test results can not be as the Sixth Circuit has determined -- that it is “only an issue of licensing” and, therefore, not important, much as failure to have a driver license is not a basis for liability in Ohio. Clearly, from the Pennsylvania District Court and Third Circuit decisions which were the predicate of what this Court ruled in Berkovitz, it was a given that the regulations at issue were addressed to the conduct of the manufacturer and governed the conduct of the manufacturer with at least as great consequence in their breach as attached to the government. This Court in Berkovitz did not alter in any manner that portion of the two Berkovitz decisions below which correctly articulated the law as it applied to the vaccine manufacturer. Petitioners respectfully submit that if that is the case, and if Berkovitz v. United States is to have any substantive meaning at all, this Court must re-affirm what it cogently proclaimed in Berkovitz , but the Sixth Circuit declined to accept: the obligation of the vaccine manufacturer, as well as the government, must fulfill the duties created and mandated by the duly promulgated regulatory system in effect at the time of the release of the product, which system had been subject to extensive public and industry comment. For this reason, we respectfully request this Court to grant the Writ of Certiorari so that this issue involving the duties of drug and vaccine manufacturers to comply under the federal regulations can be clarified for all time in regard to the licensing of this product. -18- A. Although Oral Polio Vaccine Is No Longer in Use in the United States, the Issues Raised by this Petition Are Not Moot, and the Issue of the Safety of this Vaccine Is a Matter of National Concern to the Public Health. The mootness doctrine does not apply here and is not an appropriate reason for the Court to deny certiorari in these cases. To the contrary, the extreme currency and the high importance of the Court's review of this matter can easily be ascertained by examining the Orimune-related public health issues currently being discussed and debated in the scientific community and in its peer-reviewed literature as a new public health issue of substantial concern. That issue is whether Orimune oral polio vaccine contained the carcinogenic simian virus adventitious agent, SV40, in violation of licensing provisions of the regulations which prohibited American Cyanamid from selling any Orimune which contained any adventitious agents. 42 C.F.R. § 73.110(b)(3) (renumbered as 21 C.F.R. § 630. 10(b)(3)) (App. D). There is presently litigation in the courts of California, New Jersey, and Texas which questions whether American Cyanamid truthfully told the world scientific community that its Orimune product was free of the cancer-causing agent SV40. The failure to comply with the licensing requirements mandating demonstra- tive proof that SV40 was not in any oral polio vaccine intended to be distributed and sold in the United States is now before those courts, before the international scientific community, and before Congress.° * See Sept. 10, 2003: Hearing Before the House Energy and Commerce Subcommittee on Human Rights and Wellness, Com-mittee on Government Reform, Serial No. 108-85, “SV-40 Virus: Has Tainted Polic Vaccine Caused An Increase in Cancer” (available full text at www.access.gpo.gov/congress/house / -19- B. The Regulatory Scheme And The Amend- ments Thereto. When Messrs. Lundy and Graham were paralyzed by the live virus in Orimune, the OPV regulations then in effect were basically the regulations that had been enacted in 1960. Those very regulations had been the subject matter of federal court decisions in Baker v. United States, 817 F.2d 560, 566 (9th Cir. 1987) (license may not issue unless vaccine manufacturer has submitted all the relevant test data), Berkovitz, and Loge v. United States, 662 F.2d 1268 (8th Cir. 1981), cert. denied, 456 U.S. 944 (1982), and thereafter, the In Re Sabin decisions cited supra. In 1991, following the District Court's decisions in In Re Sabin (“Sabin II”), the United States, at the behest of American Cyanamid, immediately changed the regulations to permit the legal sale of Orimune at a tissue culture passage greater than the five tissue culture passages the regulations had house07ch108. html (accessed 02/28/04); Hearing Before the House Energy and Commerce Subcommittee on Human Rights and Wellness, Committee on Government Reform, Nov. 13, 2003: “Preventing Another SV40 Tragedy: Are Today’s Vaccine Safety Protocols Effective?” Serial No. __ (in press); Report by Immunization Safety Review Committee on Health Promotion and Disease Prevention of the Institute of Medicine, Immunization Safety Review SV40 Contamination of Polio Vaccine and Cancer, Klein G, Powers A, Croce C. “Association of SV40 with human tumors” Oncogene, 21:1141-1149, 2002; Gazdar, A.F., Butel, J., and Carbone, M.,SV40 virus and human tumours, Nature Reviews Cancer, 2:957-964, 2002. Cf. American Cyanamid’s presentation and paper by Brock, Kelleher and Zlotnick: Simian Virus 40 (SV40): A Possible Human Polyomavirus: Product Quality Control testing for the Oral Polio Vaccine, Developments, Biologic Standardization, 217-219 (1998). 20. previously permitted. At Cyanamid's request following Sabin II, supra, the government re-designated what the "original strain material" would be considered to be for the Type III component of the trivalent vaccine. At that time and for many years before, the only OPV manufacturer in the United States was American Cyanamid, and the only oral polio vaccine sold was Orimune. American Cyanamid by that time realized that it could no longer utilize the seeds that it had been utilizing to produce its Type III trivalent component, because they had been shown to be highly neurovirulent in humans, and the Maryland District Court and the Fourth Circuit had so held. See In Re Sabin, supra, 763 F. Supp. at 817, 823 n.11, 827, 828, citing Berkovitz (at 827). See also Berkovitz, supra, 486 U.S. at 547. Even after the regulations were changed in 1991, that change, relating to tissue culture passages, | pertained solely to the Type III component; the regulatory agency was not asked to make changes to any other parts of the regulations, and it did not do so sua sponte. Accordingly, the Type I and Type II components, which were combined with the Type III to make the trivalent Orimune vaccine Jason Lundy and Zachary Graham received, all had to have passed the require- ments of the mandatory regulatory system. Not a single type* of polio vaccine ever satisfied the initial licensing requirements which were in effect in 1991 and which 4 There are three strains of wild poliovirus and, therefore, three types of vaccine are needed to confer human immunity. Shortly after introducing Orimune as three different monovalent vaccines, Cyanamid applied for and received permission to market a trivalent product, the only form of Orimune thereafter sold. cs A ine ilar Bric a wk remain in effect even today (see POINT III, infra), and the failure to submit the test results of all seeds continued with respect to the Type I and Type II vaccines utilized in the United States from the 1970s to 1999, when the last oral polio vaccine was distributed in the United States. American Cyanamid has been forced to admit to the same, and it is part of the Congressional record. Sept. 10, 2003 Hearing, Report Serial No. 108-85, at 231-232 (Request for Admissions Nos. 9 and 10). The 1991 change in regulations did no more than make prospectively permissible and "acceptable" under the amended regulations a Type III vaccine component that was at the seventh tissue culture passage from the original seed. If, forexample, Zachary Graham had been a plaintiff in the In Re Sabin Multi District Litigation, he would have been entitled to judgment either against the United States or against American Cyanamid, just as were the actual In Re Sabin plaintiffs, in whose favor judgment was entered and affirmed, because Zachary’s paralysis had occurred prior to 1991. The subsequent removal of the regulations in 1996 (see 350 F.3d at 514) pertained to all vaccines, not merely oral poliovirus vaccine. In any event, it was unrelated to the initial licensing requirements applicable to every manufacturer-applicant for a vaccine license. This change indicated that the regulator, in order to fulfill the congressional mandate, agreed with this Court and its holding that the license and the tests conducted to procure that license was the measuring rod used to determine the safety of the product. The word standard was further defined in 1996 to constitute “ . specifications and procedures applicable to an establishment or to the manufacture or release of products, which are prescribed in this subchapter or established in the biologics license application 7. Ee i ne a a a Te ee EE See A. eee, designed to insure the continued safety, purity and potency of such products.” 21 C.F.R § 600.3(n) (2000) (emphasis supplied). The regulations were still to be followed, because the license requirements demanded it. From 1996 until the last day on which it manufactured Orimune, American Cyanamid continued the identical test regimen it had used to produce the Lundy and Graham doses. The requirements remained the same -- notwithstanding what the Sixth Circuit erroneously stated -- both in the statutory scheme and in actual practice. Il. THIS COURT SHOULD GRANT THE PETITION BECAUSE THE HOLDING OF THE SIXTH CIRCUIT DENIGRATES INTO OBLIVION NEUROVIRULENCE, THE CENTRAL UNDERPINNING OF THE ENTIRE FEDERAL OPV REGULATORY SCHEME. The Sixth Circuit incongruously determined that notwithstanding American Cyanamid's failure to comply with the neurovirulence test standards (In re Sabin, 763 F. Supp. at 813, 815, 817 n.7, 818, 820, 822, 826, 827, 828 n.17, 829), and even though the neurovirulence of the vaccine was higher than the reference standard allowed, the Sixth Circuit stated that that did not relate to an increase in the risk to an individual recipient. 350 F.3d at 509-510, 511-512. The Sixth Circuit quoted this Court in part (350F.3d at 510), but failed to follow and apply the entire statement of this Court. The Sixth Circuit quoted the first sentence of this Court’s description of neurovirulence, but then completely ignored and omitted the Court’s next statement, which was that neurovirulence is the barometer by which one can determine whether administration of the vaccine will 24. result in vaccinees contracting paralytic poliomyelitis. This Court stated the following in regard to neuro- virulence: Neurovirulence is the capacity of an infec- tious agent to produce pathologic effects on the central nervous system. In this context, it refers to the vaccine's ability to cause paralytic poliomyelitis. The neuro- virulence of a vaccine product is tested by injecting the product into monkeys. The product meets the neurovirulence criterion only if a specified number of the animals survive and a "comparative analysis" demonstrates that the neurovirulence of the vaccine product "does not exceed” the neurovirulence of a reference product previously selected by the agency. 42 CFR §73.114(b)(1)(iii) (Supp.1964); 21 CFR § 630. 16(b)(1)(iii) (1987). Berkovitz, supra, 486 U.S. at 542. Such a position is irreconcilable under the plain language of the regulations and under the holding of Berkovitz v. United States, because the inescapable and anomalous conclusion which the Sixth Circuit's findings compel is that there was no purpose served by the regulations. See Report, Serial No. 108-85, supra, at 228-233, 240, 248. As the record below amply demonstrated from Cyanamid's own business records (Cyanamid filings in FDA Docket No. 86N-0027, the public record of a formal rulemaking), the so-called "change" in the tests that occurred in 1991 (56 Fed. Reg. 21,418 et seq. (May 8, -24- a Nena 1991)), had been fought by American Cyanamid in at least seven separate submittals to the FDA extending from 1984 through and after 1991. FDA Docket No. 86N-0027 (pertinent portions reproduced in App. E) reflects not the support for amendment "relaxing" the regulatory requirements, as one would anticipate from the position Cyanamid took in the court below, but rather the total opposition of the defendant below to any government attempt to amend the neurovirulence test protocol to broaden the range of test results which the regulations would accept as associated with a "safe" lot of vaccine. Cyanamid adopted this position notwith- standing that every FDA scientist involved in the rule- making effort had concluded that the newer method of calculating the test results was a better method of insuring public safety. The In Re Sabin Court deter- mined the following in 1991 in regard to American Cyanamid’s willingness to utilize the new and safer method: In 1986 DBS did seek extensive amend- ments for the purpose of adopting the WHO regulatory scheme in the United States. Under the WHO regulations (of which, incidentally, Dr. Elisberg is a strong proponent) only intraspinal need to be conducted and type 3 lots are to be compared to a type 3 reference history. Opposed by Lederle, the proposed amend- ments failed. 763 F. Supp. at 821 n.10. In the new test protocol proposed by the FDA and opposed by Cyanamid, the test performed was identical to what it had been, as was the degree (scored on a 0 - 4 "grade" scale) of any observed simian test animal 26. lesion, as was the method by which the calculation was to be performed. The only difference lay in what reference standard would be used, how one would compare the test results, and on what materials the tests would be conducted. At the behest of American Cyanamid, however, the regulations ultimately continued to allow the vaccine manufacturer (in this instance, American Cyanamid, which had already assumed OPV monopoly- supplier status) to utilize none other than the identical method it had utilized from 1960 up to that point. After 1977, when the last of the OPV licensees competing with Lederle closed up shop under the intense economic pressure that Lederle's methods of marketing to pediatricians and other physicians created, no other vaccine manufacturer ever again sought licensure in the United States for the production of oral polio vaccine. By preserving the regulations to require both the intrathalamic and intraspinal tests be conducted, as originally set forth in the regulations, Lederle realized its goal of excluding other biological firms from OPV market competition. The only other manufacturer did not per- form the intrathalamic test. Lederle now had the best of ali worlds: it would continue to present regulatorily- unacceptable vaccine lots to the releasing agency, and if they were approved for release -- whether rightly or wrongly -- that simply translated into that much more sellable product and profit for Cyanamid. It was, in fact, precisely that wrongful approval under Berkovitz which resulted in the government being held liable by the Fourth Circuit in the In Re Sabin Multi District Litigation. See 984 F.2d 124, 128 (4th Cir. 1993). "= OR Sei hee Fa Ts wa a DAT Se teil Ty By 1991, American Cyanamid knew from its lengthy production experience history that it could not comply with the new amendments were the government to enforce them, and conversely, that its competition, Connaught Laboratories, could not comply with the existing regulations, which the government was failing to enforce against Cyanamid. Therefore, by fighting any change until 1991, American Cyanamid accomplished its goal of keeping the competition out, while retaining the opportunity provided by government non-enforcement to continue to violate the neurovirulence regulations through monovalent pool test results that exceeded the entire history of testing on the reference standard. Cyanamid had convinced the FDA by that late date in American production of OPV that if the government would suddenly begin enforcing the regulations as the words of the regulation required, the results from the vaccine production of the nation's only OPV supplier would constitute an admission that the government had been violating, and continued to violate, the require- ments this Court set out in Berkovitz. III. THE POLIO VACCINE REGULATIONS HAVE NOT BEEN ABOLISHED. The Sixth Circuit and the district court both found that the “removal” of all safety regulations in 1996 proved the contention of American Cyanamid that the regulations were useless. This Court has in the past issued opinion after opinion stating the importance of enforcing the regulations applicable at the time of operative events which flow from the regulations. There is no legal precedent in the sefety regulatory system for the approach the Ohio Southern District court and the circuit court used to determine the standard of conduct which would control rights of recipients of drugs and/or vaccines and questions of the public health. Eo American Cyanamid argued successfully below that its non-compliance with the regulations was excused by the amendment to the five tissue culture safety rule in 1991 (one of the bases for the Grahams’ claim) -- and thereafter, as the Sixth Circuit Court of Appeals found at the behest of American Cyanamid -- the obsolete regulations were all abolished in 1996. 350 F.3d at 514. This retroactive application of regulatory amendments to an operative event giving rise to a cause of action runs counter to the jurisprudence of this Court and of this country. Justice Scalia has stated that the presumption against retroactive legislation is deeply rooted in our jurisprudence and embodies a legal doctrine centuries older than our Republic. Elementary considerations of fairness dictate that individuals should have an opportunity to know what the law is and to conform their conduct accordingly; settled expectations should not be lightly disrupted. For that reason, the “principle that the legal effect of conduct should ordinarily be assessed under the law that existed when the conduct took place has timeless and universal appeal.” Kaiser Aluminum & Chemical Corp. v. Bonjorno, 494 U.S. 827, 842-844, 855-856, (1990) (Scalia, J., concurring). Ina free dynamic society, creativity in both commercial and artistic endeavors is fostered by a rule of law that gives people confidence about the legal consequences of their actions. See, also, General Motors Corp. v. Romein, 503 U.S. 181, 191, (1992) (“Retroactive legislation presents problems of unfairness that are more serious than those posed by prospective legislation, because it can deprive citizens of legitimate expectations and upset settled transactions”); Munzer, A Theory of Retroactive Legisla- tion, 61 Texas L.Rev. 425, 471 (1982) (“The rule of law _. is a defeasible entitlement of persons to have their behavior governed by rules publicly fixed in advance”); -28- a Or A lala ene HOO! Be Maa LE TID IGA AN BOBO ob o Vidteear detiint Beek a ARLEN OM NTR Nha ee a ee — L. Fuller, The Morality of Law, 51-62 (Yale U. Press 1977). Even if it were the case that the regulations were no longer in effect, we respectfully submit that does not change the obligation of the vaccine manufacturer at the time of the occurrences in question. However, the regula- tions were not amended and were not made obsolete; as to Orimune, they were the rule of law which every physician and every parent relied on to insure that their children were not exposed to an unlicensed or unsafe product. This Court should grant the writ so as to put to rest whether safety regulations can be made “obsolete” nearly two decades after the individuals exposed to the product governed by those regulations have suffered paralysis which the regulations were intended to prevent. This Court’s grant of certiorari will put an end to Cyana- mid’s fiction that the OPV regulations were rendered obsolete. They were not: all that occurred was a structural streamlining of the existing regulations under which all vaccines (one of which was the oral polio vaccine) no longer needed to be regulated through individually promulgated regulations, because the word “standards” in the definitions of the Food and Drug Act was expanded to incorporate the original licensing process: (n) The word standards means specifi- cations and procedures applicable to an establishment or to the manufacture or release of products, which are prescribed in this subchapter or designed to insure the continued safety, purity and potency of such products. -29- 21 C.F.R. § 600.3(n) (2000) (emphasis supplied). The regulators saw the wisdom of this Court’s reliance on the licensing requirements in Berkovitz and once again emphasized as central to the process the same points which the Sixth Circuit ignored. The regulators understood that the tests necessary to secure a license were the best barometer by which to judge the product. If this Court fails to grant certiorari and allows the Sixth Circuit’s opinion to stand, every future litigant will be misled to believe that licensing serves no safety purpose, that the regulations’ requirements of submis- sion of safety testing data is optional for licensing a vaccine, and that even if the data are non-conforming to the standards (now, the license), it does not matter. Such an outcome is in direct conflict with the Congressional mandate, this Court’s opinions, and now, even the regulator’s own determination to make licensure the barometer by which to measure safety. CONCLUSION For all the reasons stated herein, the Petition for Writ of Certiorari should be granted. DATED: March 1, 2004 Marc S. Moller (MM-1231) Kreindler & Kreindler LLP 100 Park Avenue New York, New York 10017 (212) 687-8131 Counsel for Petitioners and Counsel of Record +. mat ta 7 Stanley P. Kops 102 Bala Avenue 7 Bala Cynwyd, Pennsylvania 19004 (610) 949-9999 Counsel for Petitioners SSA RTP ‘aa. ; f 4 4 | ; i j ; % 4 ——— —— United States Court of Appeals, Sixth Circuit. Joseph R. GRAHAM, et al., Plaintiffs-Appellants, v. AMERICAN CYANAMID COMPANY, Defendant- Appellee. Roy Lee Lundy, et al., Plaintiffs-Appellants, v. American Cyanamid Company, Defendant- Appellee. Nos. 01-4175, 01-4176. Argued: Aug. 1, 2003. Decided and Filed: Dec. 3, 2003. Reported at 350 F.3d 496 Before: DAUGHTREY, MOORE, and SUTTON, Circuit Judges. i | j i | y 3 : | 4 OPINION SUTTON, Circuit Judge. he ee nS ee Joseph Graham and Roy Lee Lundy, along with several members of their families, challenge the district court's order granting summary judgment to American Cyanamid Company on a series of fraud and product liability claims. American Cyanamid manufactures Orimune, which is an oral polio vaccine. Plaintiffs allege that the use of Orimune in one instance and the exposure to it in another caused a family member to contract polio. App. A- 1 Seeking compensation for these injuries, both sets of plaintiffs filed fraud claims against American Cyanamid, asserting that the company publicly represented Orimune as licensed, manufactured, tested and released in accordance with FDA regulations, when in fact the Orimune vaccines at issue (according to plaintiffs) did *499 not comply with FDA standards. The Graham plaintiffs separately brought strict liability and negligent failure-to- warn claims against American Cyanamid. Both sets of plaintiffs also filed derivative claims for loss of consortium and punitive damages. The district court granted American Cyanamid's motion for summary judgment on all claims. We AFFIRM. I. BACKGROUND A. Polio and the Orimune Vaccine. Poliomyelitis (or polio) is a disease of the central nervous system that causes illness, paralysis and in some instances death. It affected thousands of individuals in this country during the first half of the twentieth century. See Dorothy M. Horstmann, Poliovirus (Poliomyelitis), in 2 Textbook of Pediatric Infectious Diseases 1186, 1189-90 (Ralph D. Feigin & James D. Cherry, eds., 1981). At its height between 1951 and 1955, polio led to 21,000 cases of paralysis per year in the United States. See id. That this scourge did not continue through the second half of the twentieth century is a credit tu the work of several scientists. In 1955, Dr. Jonas Salk developed the first widely successful vaccine against polio. Derived from a dead polio virus, the Salk vaccine is known as an inactivated polio vaccine ("IPV") and was licensed for production and use in the United States in 1955. See In re Sabin Oral Polio Vaccine Prods. Liab. App. A -2 Litig., 743 F.Supp. 410, 412 (D.Md.1¢90) ("Sabin I"). The vaccine decreased the incidence of polio but did not eradicate it. Between 1958 and 1961, for example, nearly 19,000 cases of the disease were still reported in the United States. Id. Thirteen thousand people became paralyzed by the disease, and more than 1,000 people died from it during this period. Id. At the same time that Dr. Salk was developing his vaccine, Dr. Albert Sabin began working on an oral polio vaccine ("OPV") made from attenuated strains of the polio virus. The Sabin OPV, unlike the Salk IPV, is produced from a live polio virus that has been weakened but not killed. " 'Like all vaccines cultivated from live viruses,' " such as those used for smallpox and yellow fever, " 'OPV creates immunity by inducing a mild infection in the recipient.' " United States v. St. Louis Univ., 336 F.3d 294, 295 (4th Cir.2003) (quoting Stuart v. Am. Cyanamid Co., 158 F.3d 622, 625 (2d Cir.1998)). OPV has several advantages over IPV. OPV is less expensive and requires only a single dosage, while IPV requires three inoculations and a follow-up booster shot. OPV is administered orally, commonly on a sugar cube, while IPV must be injected by a hypodermic needle. The interaction of the live virus in OPV with the immune system confers lifetime immunity, while IPV requires periodic re-administration. See generally Sabin I, 743 F.Supp. at 412. And OPV creates "herd immunity," because an individual who has not received the vaccine can obtain immunity by contact with someone who has been vaccinated. Id. Individuals who have been immunized with IPV, by contrast, may still serve as carriers of the wild polio virus and may pass it on to others even though they themselves have been immunized. Id. App. A - 3 = OPV, however, also has several inherent risks in view of the way it--and all vaccines developed from live viruses--work. The live but weakened viruses of OPV grow in the intestinal tract of the vaccinated individual. They eventually trigger the production of antibodies, which in turn make the individual immune to the disease after thirty days. On rare occasions, however, the virus reproduced in the vaccinee's intestinal tract reverts to the virulent *500 form. When this occurs, vaccinated individuals or persons coming in close contact with them during the thirty-day period may contract polio. Unvaccinated adults may take two precautions to avoid the risk of contracting polio: (1) alternative vaccination with IPV prior to contact with the vaccinee; or (2) avoidance of contact with the vaccinee for one month, during which time live polio viruses are being shed from the intestinal tract of the vaccinee. In 1958 and 1959, epidemiologists. conducted a series of field trials on the use of OPV. See Sabin I, 743 F.Supp. at 412-13. On the basis of these tests, the Surgeon General in 1960 determined that OPV was suitable for use in the United States, and it soon became the most widely used of the polio vaccines. Id. The Federal Government granted licenses to three manufacturers to make live polio vaccines from the strains developed by Dr. Sabin. American Cyanamid purchased strain material that Sabin had developed, and its Lederle Laboratories division received one of the three authorized licenses from the Division of Biologic Standards ("DBS") of the National Institutes of Health to manufacture and sell OPV. The polio virus has three types--types I, II and III-- and different vaccines address each of them. Some vaccines address just one type of polio, and one vaccine App. A-4 OO RR TANTS I A RS on we RIA ANNs OT aN NS SNR ts iat Neer ow ed ei eddy Sa NE is designed to prevent all three types of polio. American Cyanamid first produced "monovalent" vaccines, which contain just one of the three types of polio virus vaccine. In 1963, however, the Federal Government granted American Cyanamid a license to make and distribute a "trivalent" vaccine, which contains all three types of polio virus vaccine. Since then, American Cyanamid has distributed a trivalent OPV product under the name Orimune. The production of Orimune proceeds in several stages. Manufacturers initially obtain wild polio virus and attenuate its neurovirulent properties by passing it through animal hosts. What results is a "strain," which in small portions is then injected into monkey kidney cell cultures. This process, known as a "tissue culture passage," leads to the growth of more virus and the creation of vaccine "seeds." Small portions of this seed material are frozen periodically and again injected into monkey kidney cell cultures to create "pools" of vaccine for each of the three types of polio manufactured. Each monopool contains a single type of vaccine and is given a designation indicating the type of vaccine and the number of the pool (e.g., 3-442 is a type II vaccine from monopool 442). Monopools for each of the vaccine types are then blended together to make a trivalent bulk "lot" that is used to fill vials. The trivalent bulk lot is given a seven-digit number and letter, such as 2054-532A. The prefix (2054) designates Orimune dosage, and the suffix (532) represents the sequential number for the trivalent bulk of that dose. The final letter (A) designates the particular filling of the final product from its trivalent bulk lot. After packaging, the manufacturer gives each lot of final containers a six-digit control number, then ships the lots to physicians, pharmacies, hospitals and clinics for use. The product is not sold directly to patients. In the late 1970s, American Cyanamid explored App. A - 5 the possibility of obtaining a new type III seed to replace the seed it had been using to make most of the type III component of Orimune since the mid-1960s. At the time, another manufacturer, Pfizer, Ltd., had taken one of the "Sabin Original" strains and cloned it to create a seed known as "Sabin Original Rederived." In 1981, American Cyanamid obtained some of the Sabin Original Rederived type III seed and started using it in Orimune production. *501 Since 1977, American Cyanamid has been the sole supplier of OPV in the United States. The annual number of cases of polio in this country has steadily declined since the widespread use of OPV. By the 1980s, fewer than twenty-five vaccine-associated cases of paralytic polio in the United States were being reported yearly, a number that dropped to an average of ten per year in the 1990s. The ten-per-year figure represents one case for every 2.6 million doses of vaccine distributed. Sabin I, 743 F.Supp. at 412 n. 3. B. Federal Regulation of Polio Vaccine Production and Testing in the United States. In view of the health and safety risks of polio vaccines, the Federal Government regulates the manufacture and distribution of them in a variety of ways. In 1961, the DBS adopted regulations governing the issuance of manufacturing licenses and the approval and release of OPV. See 21 C.F.R. §§ 630.10-.18 (1974) (formerly codified at 42 C.F.R. §§ 73.110-.118 (Supp.1964)). To obtain a _ license authorizing manufacture from the Secretary of the Department of Health, Education and Welfare under these regulations, drug manufacturers must prove that their product conforms to regulations covering all phases of the manufacturing process--beginning with the original Sabin strains of vaccine (the only strains approved in the App. A - 6 United States) and ending with the doses administered to patients. See generally 42 U.S.C. §§ 262. Under these regulations, tests must be performed on the vaccine during various stages of production as a condition not only for licensing but also for the release of each monopool and the filling of the product. See Federal Food, Drug and Cosmetic Act, 21 U.S.C. §§§§ 301 et seq.; 21 C.F.R. §§§§ 200 et seg. (1977); Public Health Act, 42 U.S.C. §§ 262. Certain regulations are addressed solely to manufacturers of OPV. See 21 C.F.R. §§8§ 630.10-17; Berkovitz ex rel. Berkovitz v. United States, 486 U.S. 531, 541, 108 S.Ct. 1954, 100 L.Ed.2d 931 (1988). Others are addressed specifically to the Federal Government. See, e.g., 21 C.F.R. §§§§ 600.3 et seq., 630.17(e). To distribute any dose of Orimune, American Cyanamid thus had to obtain a license from the government and allow the government to test each batch of vaccine before releasing it for use. The regulations in effect in the 1970s required that vaccine monopools be tested in monkeys for neurovirulence before they could be used for production of vaccine. See 21 C.F.R. §§ 630.16(b)(i)-(ii). "Neurovirulence is the capacity of an infectious agent to produce pathologic effects on the central nervous system." Berkovitz, 486 U.S. at 543 n. 9, 108 S.Ct. 1954. In performing tests for neurovirulence, samples of each monopool are injected at different dilutions into the brain stems of thirty monkeys and into the spinal cords of at least fifteen other monkeys. After these injections, the monkeys are sacrificed and their spinal and brain tissues are microscopically examined by qualified pathologists who conduct a "comparative evaluation" of the monopool being tested relative to identical tests performed on samples of a "Reference Attenuated Poliovirus" provided by the FDA. See 21 C.F.R. §§ App. A - 7 630.16(b)(iii). The evaluation examines: (a) the number of animals showing lesions characteristic of poliovirus infection, (b) the number of animals showing lesions other than those characteristic of poliovirus infection, (c) the severity of the lesions, (d) the degree of dissemination of the lesions, and (e) the rate of occurrence of paralysis not attributable to the mechanical injury resulting from inoculation trauma. *502 Id. A given monopool passes the neurovirulence test "if a comparative analysis of the test results demonstrates that the neurovirulence of the test virus pool does not exceed that of the Reference Attenuated Poliovirus." Id. Among the FDA regulations governing these neurovirulence tests at this time were a "consistency of manufacture" regulation and a "tissue culture passage” regulation. The "consistency of manufacture" regulation required that no lot of vaccine be released "unless each monovalent pool contained therein is one of a series of five consecutive pools of the same type, each having been manufactured by the same procedures, and each having met the criteria of neurovirulence for monkeys prescribed in §§ 630.16(b)(1)...." Id. §§ 630.17(b). The "tissue culture passage" regulation required that all polio "[vjirus in the final vaccine shall represent no more than five tissue culture passages from the original strain...." Id. §§ 630.13(a). Over time, the FDA modified its regulations governing the manufacture, testing and release of OPV, prompting disagreements over how the regulations should be interpreted. Some of these disagreements resulted in lawsuits under the Federal Tort Claims Act ("FTCA") between the Federal Government and individuals allegedly injured by the vaccine. In 1981, the App. A- 8 FDA's Bureau of Biologics assured American Cyanamid that the vaccine produced from the Pfizer seed, though rederived from the Sabin Original, did not violate the "tissue culture passage" regulation. However, several FTCA plaintiffs argued generally that the Federal Government had failed to interpret its regulations correctly and as a result had released an excessively neurovirulent Orimune vaccine, which violated the "tissue culture passage" regulation. See Sabin I, 743 F.Supp. at 410; In re Sabin Oral Polio Vaccine Prods. Liab. Litig., 763 F.Supp. 811 (D.Md.1991), affd, 984 F.2d 124 (4th Cir.1993) ("Sabin II"); Griffin v. United States, 500 F.2d 1059 (3d Cir.1974). Similar claims were brought against vaccine manufacturers. See Jones v. Am. Cyanamid Co., 139 F.3d 890, 1998 WL 116171 (4th Cir. Mar.17, 1998); Am. Cyanamid Co. v. St. Louis Univ., 336 F.3d 307 (4th Cir.2003). In 1991, a federal district court judge in Maryland ruled that vaccine from seed 45B165 was, in fact, more than five tissue culture passages beyond the Sabin original strain and that the FDA had violated 21 C.F.R. §§ 630.13(a) by approving that seed for use. See Sabin II, 763 F.Supp. at 813. The same district court, however, expressly found that Orimune made from this seed was both safe and effective: [M]y finding that regulatory violations occurred does not imply that the public health is or has been endangered in any respect. According to the undisputed record, the OPV used in the United States has always been 'state of the art’ vaccine and the OPV program has resulted in the virtual eradication of wild poliovirus in the Western Hemisphere. App. A -9 ¢ ; 7 s 2 Id. After characterizing the country's OPV program as "perhaps the most successful public health program in history," id., the court held that the FDA's only error with respect to seed 45B165 was in not "amend{[ing] ... the regulations" to allow the Pfizer seed to be the "starting point" for counting tissue culture passages-- something that "would clearly be proper and in the public interest." Id. at 825. The Fourth Circuit affirmed this judgment. See In re Sabin Oral Polio Vaccine Prods. Liab. Litig., 984 F.2d 124 (4th Cir.1993). As a result of the Sabin decisions, the FDA amended its polio vaccine regulations. See *503 Additional Standards for Viral Vaccines; Poliovirus Vaccine Live Oral, 56 Fed.Reg. 21,418, 21,422 (May 8, 1991). It amended 21 C.F.R. §§ 630.13(a) to provide that "[vjirus in the final vaccine shall represent no more than five tissue culture passages from the original strain or no more than five tissue culture passages from a virus clone derived from one of the first five tissue culture passages of the original strain." Id. at 21,433. At the same time, the agency repealed and amended several other regulations, including the "consistency of manufacture" regulation. In doing so, the FDA determined that, based on extensive experience with the vaccine in the field, the repealed regulations did not impact vaccine safety. See id. at 21,431. C. Graham v. American Cyanamid Co. Zachary Graham was born on May 2, 1984. On July 3, 1984, his mother, Lisa Graham, took him to one of the offices of Delaware Family Practice, P.C. to receive an Orimune polio vaccine. The vaccine dose came from lot 739-472, which was derived from seed 45B165. The type III component of this lot was manufactured from monopool 3-486. App. A - 10 At Ae PE at The dose of Orimune that Zachary Graham received contained the following warning from American Cyanamid: ADVERSE REACTIONS: Paralytic disease following the ingesting of live poliovirus vaccines has been, on rare occasion, reported -in individuals receiving the vaccine ... and in persons who were in close contact with vaccinees. The vaccine viruses are shed in the vaccinee's stools for at least 6 to 8 weeks as well as via the pharyngeal route. Most reports of paralytic disease following ingestion of the vaccine or contact with a recent vaccinee are based on epidemiological analysis and temporal association between vaccination or contact and the onset of symptoms. Most | authorities believe that a _ causal 2 relationship exists. “a dest BA UCR Sipe LEE Mi aA The risk of vaccine-associated paralysis is extremely small for vaccinees, } susceptible family members and other close personal contacts. However, prior to administration of the vaccine, the attending physician should warn or specifically direct personnel acting under his authority to convey the warnings to the vaccinee, parent, guardian, or other responsible person of the possibility of vaccine-associated paralysis. The Centers for Disease Control report that during the years 1969 through 1980 approximately 290 million doses of [ JOPV were App. A - 11 distributed in the United States. In the same 12 years, 25 "vaccine-associated" and 55 "contact vaccine-associated" paralytic cases were reported. Twelve other "vaccine-associated" cases have been reported in persons (recipients and contacts) with immune _ deficiency conditions. These statistics do not provide a satisfactory basis for estimating these risks on a per person basis. When the attenuated vaccine strains are to be introduced into a household with adults who have not been adequately vaccinated or whose immune status cannot be determined, the risk of vaccine-associated paralysis can be minimized by giving these adults three doses of IPV a month apart before the children receive ORIMUNE. The CDC reports that no paralytic reactions to IPV are known to have occurred since the 1955 cluster of poliomyelitis cases caused by vaccine that contained live polioviruses that had escaped inactivation. The Immunization Practices Advisory Committee of the U.S. Public Health Service states: "Because of the overriding importance of ensuring prompt and complete immunization of the child *504 and the extreme rarity of OPV- associated disease in contacts, the Committee recommends the administration of OPV to a child regardless of the poliovirus-vaccine status of adult household contacts. This is the usual App. A - 12 —E (ee) Som be ed cE practice in the United States. The responsible adult should be informed cf the small risk involved. An acceptable alternative, if there is strong assurance that ultimate, full immunization of the child will not be jeopardized or unduly delayed, is to immunize adults according to the schedule outlined above before giving OPV to the child.” In addition to this warning, Lisa Graham signed an "Important Information" consent form provided by the Ohio Department of Health. It stated that she understood the risks and benefits associated with OPV and had been given an opportunity to ask questions about OPV that were answered to her satisfaction. The form also stated: "[O]nce in about every 4 million vaccinations, persons who have been vaccinated or who come in close contact with those who have recently been vaccinated are permanently crippled and may die. Even though these risks are low, they should be recognized." And the form made known the availability of IPV as an alternative polio vaccine with "no known risk of causing paralysis." On July 26, 1984, Zachary Graham began experiencing fever, irritability, lethargy and general weakness. He was admitt«-d to Grady Memorial Hospital in Delaware, Ohio, wher oe remained until July 29, 1984. The Centers for Disease Control in Atlanta diagnosed Zachary with Type III poliomyelitis caused by the Orimune vaccine that he had received earlier in the month. As a result of the illness, Zachary Graham became permanently disabled in his lower extremities. The Grahams initially filed a petition in the United States Court of Federal Claims on September 27, 1990, seeking compensation under the "no fault" provisions of \ App. A - 13 the National Vaccine Injury Compensation Act, 42 U.S.C. §§§§ 300aa-10 et seq. (Supp. 1990). Because his paralysis occurred before the Act's effective date of October 1, 1988, however, it limited the amount of compensation Zachary could receive for his injuries to $30,000. 42 U.S.C. §§ 30Qaa-15(b). Graham's family thereafter filed a motion to dismiss their petition voluntarily, which the United States Court of Federal Claims granted on December 10, 1993. On May 10, 1994, Zachary's parents, Joseph and Lisa Graham, filed this action against American Cyanamid in the Southern District of Ohio (Eastern Division) on behalf of Zachary, who was then a minor. Their complaint sought compensatory and punitive relief under a variety of state-law theories: (1) strict products liability; (2) fraud; (3) negligence; (4) breach of implied warranty of merchantability; (5) breach of implied warranty of fitness; and (6) breach of express warranty. D. Lundy v. American Cyanamid Co. On March 24, 1977, Janet Lundy took her young son, Jason, to an office of the Jackson County Combined General Health District for a routine check-up. There, Dr. Carl Greever gave Jason a dosage of Orimune for immunization from polio. On April 19, 1977, Jason's father, Roy Lee Lundy, began experiencing fever, headaches, diarrhea, myalgia, malaise and general weakness. After a brief stay at Mercy Hospital in Portsmouth, Ohio, Roy's doctors transferred him to The Ohio State University Hospital in Columbus. About a week later, he was diagnosed with type III poliomyelitis, which led to permanent paralysis. *505 Roy's doctors advised him that the probable source of the disease was the Orimune vaccine given to App. A - 14 Jason, which likely had been transmitted to him through close contact with-his son. Jason Lundy's vaccine came from lot 480- 277 or lot 483-269. The type III component of Orimune in lot 480-277 was manufactured from a mixture of monopools 3-427 and 3-436. The type III component in lot 483-269 was manufactured from a single monopool--3-437. The evidence does not establish which lot was responsible for the Orimune vaccine that Jason ingested. The Lundys allege that they did not suspect that American Cyanamid had acted wrongfully until they saw a television program on vaccine-induced cases of polio on September 27, 1985. After viewing this program, the family initially attempted to recover for their injuries in state court. 1. State Court Action On March 13, 1987, Lisa and Roy Lee Lundy filed an action in the Franklin County Court of Common Pleas against (1) Lederle Laboratories, a Division of American Cyanamid, (2) the Board of Health of the Jackson Combined General Health District and (3) Dr. Carl Greever. See Lundy v. Lederle Laboratories, Div. of Am. Cyanamid Co., 54 Ohio App.3d 192, 561 N.E.2d 1027 (1988). Roy Lee Lundy sought compensatory and punitive relief under a variety of theories: (1) negligence; (2) failure to obtain informed consent from the plaintiffs; (3) failure to warn; (4) breach of implied warranties of merchantability and fitness; (5) strict liability; and (6) breach of express warranties. Janet Lundy separately filed a claim for loss of consortium. The Franklin County Court of Common Pleas eventually granted motions to dismiss on behalf of all | defendants. The Ohio Court of Appeals for the Tenth | District affirmed these decisions. App. A - 15 In November 1990, the Lundy plaintiffs filed a petition in the United States Court of Federal Claims seeking compensation under the National Vaccine Injury Compensation Act, 42 U.S.C. §§ 300aa-10 et seq. On March 11, 1994, the Lundys voluntarily withdrew their petition in view of the limited size of the award authorized by the Act. See 42 U.S.C. §§ 300aa-15(b). 2. Federal Court Action On May 10, 1994, Roy, Janet and Jason Lundy filed this action in federal court in the Southern District of Ohio (Eastern Division), naming American Cyanamid as the only defendant. They sought compensatory and punitive relief under the following state-law theories of liability: (1) strict products liability; (2) fraud; (3) negligence; (4) breach of implied warranty of merchantability; (5) breach of implied warranty of fitness; and (6) breach of express warranty. Janet and Jason Lundy each filed independent loss-of-consortium claims. American Cyanamid filed a motion for judgment on the pleadings, arguing that all of the claims were barred by res judicata (due to the prior state-court action) and the statute of limitations. With the exception of Roy's fraud claim and Jason's loss-of-parental- consortium claim, the district court dismissed each of the other claims as barred by res judicata on September 29, 1995. The two remaining Lundy claims’ were consolidated with the Graham plaintiffs' claims. On July 15, 1998, after considerable discovery, American Cyanamid filed separate motions for summary judgment against the Lundy plaintiffs and the Graham plaintiffs. *506 E. The District Court's Decision App. A - 16 On December 21, 2000, the district court granted American Cyanamid's motions for summary judgment against the Grahams and Lundys. As to the Lundys, the court held that they had failed to submit sufficient evidence to raise a triable issue that the alleged fraudulent representations made by American Cyanamid in the package insert regarding compliance were in fact false. It further concluded that the plaintiffs had failed to submit any admissible evidence that the alleged violations had any impact on the safety of the Orimune dose that Jason Lundy received. As to the Grahams, the court concluded that they had abandoned their fraud claim by failing to respond to American Cyanamid's summary judgment motion on the claim. It dismissed the Grahams' strict liability claim, concluding that Orimune was unavoidably unsafe. And it dismissed the Grahams' negligent failure-to-warn claim, concluding that the Orimune warnings and "Important Information" sheet provided to Zachary Graham and his mother were adequate and reasonable as a matter of law. On the basis of these rulings, the court held that the derivative nature of Jason Lundy's consortium claim and each claim for punitive damages required these claims to be dismissed as a matter of law as well. (While the district court labeled the entry disposing of all of these claims a "final judgment," neither the record nor the docket sheet reveals what happened to the three warranty claims filed by the Graham plaintiffs in their complaint. Because the Grahams do not address these claims on appeal and because the district court purported to dismiss all claims, we do not address them here.) The district court denied the Graham and Lundy plaintiffs’ motions for reconsideration, and these consolidated appeals followed. II. DISCUSSION App. A - 17 The customary rules for reviewing a summary- judgment decision apply. We give de novo review to the district court's decision. Sperle v. Mich. Dep't of Corr., 297 F.3d 483, 490 (6th Cir.2002). A decision granting summary judgment is proper where no genuine issue of material fact exists and the moving party is entitled to judgment as a matter of law. Fed.R.Civ.P. 56(c). And in considering such motions, we give all reasonable factual inferences to the nonmoving party. Matsushita Elec. Indus. Co. v. Zenith Radio Corp., 475 U.S. 574, 587, 106 S.Ct. 1348, 89 L.Ed.2d 538 (1986). Our jurisdiction over these state-law claims rests on the diversity of citizenship of the parties. All of the Graham and Lundy plaintiffs are residents of Ohio. American Cyanamid, incorporated in Maine, maintains its principal place of business in New Jersey. See 28 U.S.C. §§ 1332. In this setting, we sit in effect as another court of the forum state, in this case Ohio, and therefore must apply its choice-of-law rules. See Muncie Power Prods., Inc. v. United Tech Auto., Inc., 328 F.3d 870, 873 (6th Cir.2003). In this instance, the parties agree that those choice-of-law rules indicate that Ohio substantive law governs this claim. All three of the tort claims in this case represent a variation on a common theme. Whether labeled fraud, strict liability, or negligent failure to warn, all three claims turn on the theory that there is a proximate connection between the alleged violations of the FDA's neurovirulence rules and the safety of the Orimune vaccine. Because we conclude that plaintiffs have failed to establish a triable issue of fact on this central point and because we conclude that each of these tort claims otherwise fails as a matter of law, we agree with the *507 District Court that the claims must be summarily App. A - 18 dismissed. A. FRAUD We begin by addressing the one claim common to both sets of plaintiffs. The Grahams and Lundys each allege that American Cyanamid acted fraudulently by representing that Orimune was licensed, manufactured, tested and released in accordance with FDA regulations when in fact it did not comply with FDA standards. To establish a cognizable claim of fraud under Ohio law, a claimant must prove the following six elements: "(a) a representation or, where there is a duty to disclose, a concealment of fact, (b) which is material to the transaction at hand, (c) made falsely, with knowledge of its falsity, or with such utter disregard and recklessness as to whether it is true or false that knowledge may be inferred, (d) with the intent of misleading another into relying upon it, (e) justifiable reliance upon the representation or concealment, and (f) an injury proximately caused by the reliance." Russ v. TRW, Inc., 59 Ohio St.3d 42, 570 N.E.2d 1076, 1083 (1991). The elements of the claim are conjunctive, and accordingly all of them must be shown. See Schwartz v. Capital Sav. & Loan Co., 56 Ohio App.2d 83, 381 N.E.2d 957, 959 (1978). Both in the district court and here, the parties have vigorously contested many of these elements. Did the company in fact violate certain FDA regulations in manufacturing Orimune--specifically, the "tissue culture passage" and "consistency of manufacture” regulations? Were American Cyanamid's regulatory representations inaccurate? Did plaintiffs justifiably rely upon any of these representations? Were the _ representations material to product safety? And, even if all of plaintiffs’ allegations are true, did the alleged regulatory violations App. A - 19 proximately cause these injuries? Because we conclude that the plaintiffs have failed as a matter of law to present admissible evidence of proximate cause, we address this issue and this issue (with one minor exception) alone. Under Ohio law, plaintiffs bear the burden of establishing that American Cyanamid's alleged misrepresentation of Orimune's regulatory compliance proximately caused their injuries. See Burr v. Bd. of County Comm'rs, 23 Ohio St.3d 69, 491 N.E.2d 1101, 1105 (1986); Cohen v. Lamko, Inc., 19 Ohio St.3d 167, 462 N.E.2d 407, 409 (1984). See also Picklesimer v. Baltimore & O.R. Co., 151 Ohio St. 1, 84 N.E.2d 214 (1949) (noting that ordinary element of proximate cause applies where plaintiff has alleged fraud); Restatement (Second) of Torts §§ 557A cmt. a (noting that ordinary rules of legal cause govern fraudulent misrepresentation cases involving physical harm). To show proximate cause, the Grahams and Lundys must demonstrate that the fact allegedly misrepresented--compliance with the FDA regulations--caused their harm. See Gaines Uv. Preterm-Cleveland, Inc., 33 Ohio St.3d 54, 514 N.E.2d 709, 712 (1987) (holding that misstatement by doctor could have caused plaintiffs physical injuries in action for fraud). That is to say, was the plaintiffs’ contraction of polio a "natural and probable" (i.e. reasonably foreseeable) consequence of the alleged noncompliance with the regulations? See Strother v. Hutchinson, 67 Ohio St.2d 282, 423 N.E.2d 467, 471 (Ohio 1981); Pfirsch v. Hall-Omar Baking Co., 6 Ohio App.2d 108, 216 N.E.2d 626, 628 (1966). In view of the technical and scientifically complex nature of this inquiry, only Daubert-qualifying expert testimony may satisfy it. See Daubert v. Merrell Dow Pharms., 509 U.S. 579, 113 S.Ct. 2786, 125 L.Ed.2d 469 (1993); cf Berdyck v. Shinde, 66 Ohio St.3d 573, 613 N.E.2d 1014, 1022 (1993). App. A - 20 battens ie omisna nasa *508 The Fourth Circuit recently addressed the issue of proximate cause in a similar context in American Cyanamid Co. v. St. Louis University, 336 F.3d 307 (4th Cir.2003). In that case, St. Louis University sued American Cyanamid, seeking contribution for a state- court judgment arising from vaccine- related injuries suffered by one of its patients. St. Louis University claimed that the Orimune vaccine violated the FDA "tissue culture passage" and "consistency of manufacture" neurovirulence regulations. In doing so, however, the university failed to produce expert testimony establishing that a polio vaccine violating these FDA regulations was any more likely to cause injury than a fully compliant vaccine. "[I]n analyzing the element of proximate cause in claims against Cyanamid," the district court initially explained, "the focus must be on whether the plaintiff can prove that it was a defect in the OPV that resulted in his injury, not simply ... whether he had been exposed to OPV derived from a seed that had been improperly approved in violation of the regulatory process." St. Louis Univ. v. United States, 182 F.Supp.2d 494, 500 (D.Md.2002). Applying Missouri law, the district court held that a "violation of the OPV regulations is not sufficient to prove the element of proximate cause in a context ... where a plaintiff must prove that it is more likely than not that it was excessive neurovirulence in a dose of vaccine that caused him to contract polio." Id. at 501. The Fourth Circuit affirmed, holding that St. Louis University "presented no expert testimony showing that [the patient] would not have contracted polio or would have contracted a less severe case of polio had he been given a vaccine complying with the neurovirulence regulations." 336 F.3d at 310. Today's case parallels St. Louis University in many App. A - 21 ways. It involves the same defendant, the same Orimune vaccine, the same FDA regulations, the same allegations of non-compliance and the testimony of two of the same experts--Drs. Almond and Steinman. A different state's law applies, to be sure--here Ohio law, there Missouri law. St. Louis University of course comes from a different Circuit. And some differences in the evidence and apparently in the nature of the tort claims exist as well. But in the end we see the issue in much the same way St. Louis University did. Under Ohio law, as under Missouri law, plaintiffs must show that American Cyanamid's alleged misrepresentation of Orimune's regulatory compliance proximately caused their injuries. Because the Grahams and Lundys have not made out a tenable claim of proximate cause in this respect (and more specifically because they have not produced expert testimony that supports this claim), their claims must be dismissed as a matter of law. As in St. Louis University, Drs. Almond and Steinman did not satisfy the proximate cause requirement in either a general or a specific manner. They did not show as a general matter that American Cyanamid's alleged regulatory noncompliance increased the risk that the Orimune vaccine would cause polio in recipients or those in close contact with recipients, beyond the inherent risk long known to be associated with OPV. Plaintiffs’ statistician, Dr. Krieger, attempted to perform a statistical analysis to determine if one could "predict based on the [neurovirulence test] results of the lot whether somebody [i]s more likely or less likely to get polio from that particular lot, if it were released." Krieger Dep. at 18 (testifying in Campagna v. Am. Cyanamid Co., 767 A.2d 996 (2001)). But he did not find a correlation or any study supporting the existence of such a correlation. Id. App. A - 22 *509 Plaintiffs and their experts do not fare any better in discussing the alleged violation of specific neurovirulence regulations. They initially claim, for example, that the vaccines at issue violate the "tissue _culture passage” regulation. At the time of manufacture, this regulation required the vaccines to be no more than five tissue culture passages from the Sabin original strain, see 21 C.F.R. §§ 630.13(a), on the theory that more than five tissue culture passages would increase monkey neurovirulence. The Lundys cite a single article, published in 1961, to support their claim of a causal connection between monkey neurovirulence and the likelihood of vaccine- associated paralytic polio. See R. Murray, Standardization, Licensing, and Availability of Live Polio Vaccine, 175 J.A.M.A. 843 (1961). While the article states that "[n]eurovirulence for monkeys ... has some correlation with safety in man," it equivocates on the extent of that relationship, noting that "many strains exist which, while causing evidence of infection in monkeys, apparently cause no discernible disease in man." Id. at 845. In the end, the article fails to address whether a causal connection between monkey neurovirulence and paralytic polio exists and indeed never references tissue culture passage. No less importantly, the Lundys offer no studies, data or expert testimony establishing any such connection. When questioned about compliance with the 1984 "tissue culture passage” regulation, it is true, Dr. Almond opined that Orimune exceeded the permissible tissue culture passage limits. At the same time, however, he called the regulation "daft" and in need of change, and did not opine that failure to comply with the regulation would lead to a more dangerous vaccine. More specifically, Dr. Almond testified as follows about the regulation: App. A - 23 A. [T]he move to Pfizer seed was a sensible development and a desirable development. But in light of that development and in light of the decision to do it, the maintaining of a regulation which said you couldn't be more than five passages away from [the original strain] was daft. It should have been changed. Q. They should have amended the regulation? A. They should have amended the regulation. Q. Now, if they had amended the regulation-- A. Before giving it to Zachary? Q. Yes. A. That would have been fine. Almond Dep., June 9, 1998, at 171-72. Some seven months after this deposition and six months after American Cyanamid filed its motion for summary judgment, Dr. Almond executed a new affidavit to "explain" his previous references to the "daft" regulation. Almond Aff., Jan. 14, 1999, 9 7. In that affidavit, he claims that American Cyanamid was "daft" in not seeking to have the regulation amended before producing Orimune from the Pfizer seed. Id. As the district court noted, however, "a party cannot create a factual issue by filing an affidavit which contradicts earlier deposition testimony after a motion for summary judgment has been made. If an affidavit is untimely and inconsistent with prior discovery responses, it is inadmissible and should not be considered." Graham v. Am. Cyanamid Co., 2000 WL 1911431, slip op. at 18 (S.D.Ohio Dec.21, 2000). See Hughes v. Vanderbilt Univ., 215 F.3d 543, 549 (6th Cir.2000). No less importantly, Dr. Almond's affidavit never contradicts his deposition testimony that the FDA should have changed its regulation. In 1991, when the FDA did amend this regulation, App. A - 24 it expressly recognized the absence *510 of any correlation between observed monkey neurovirulence and the risk of vaccine-associated paralytic polio. No single vaccine lot has been associated with an increased incidence of poliomyelitis. The lots that have been identified as associated with a case of paralytic poliomyelitis have had typically low scores when tested by FDA and the manufacturer for neurovirulence in monkeys. 56 Fed.Reg. at 21,420. With respect to the now-repealed "tissue culture passage" regulation, in short, plaintiffs have not established that this alleged regulatory nencompliance increased the risk that the Orimune vaccine would cause polio in recipients or those in close contact with recipients. Plaintiffs also contend that the vaccines at issue, and more specifically the relevant monopools comprising Orimune's type III component of the vaccine, did not meet the "consistency of manufacture" regulation. As noted, this regulation required manufacturers (at the time of production) to demonstrate the genetic stability of the seed and the regularity of its manufacturing processes through the production of five consecutively and properly manufactured monovalent pools. See 21 C.F.R. §§ 630.17(b) ("each monovalent pool ... [must be] one of a series of five consecutive pools of the same type, each pool having been manufactured by the same procedures, and each having met the criteria of neurovirulence for monkeys...."). Again, however, plaintiffs have not produced evidence showing that a monopool that failed to satisfy the 1984 "consistency of manufacture” regulation would be more App. A - 25 likely to cause vaccine-associated polio than one that satisfied the requirement. When asked whether there was a scientific basis for concluding that the "consistency of manufacture" requirement was linked with product safety, Dr. Almond testified that "there is a scientific argument that you can make which would support such a conclusion ... | am not saying that is the right conclusion." Almond Dep., April 20, 1998, at 144- 45. Almond added that he was not aware of any study supporting this theory. Id. This testimony does not suffice to create a material dispute of fact. An admissible expert's opinion, it is clear, "must be supported by more than subjective belief and unsupported speculation...." McLean v. 988011 Ontario Ltd., 224 F.3d 797, 800-01 (6th Cir.2000) (quotations and citations omitted). Nor did Dr. Steinman fill this gap. He testified that he was "not aware of any data one way or the other" showing that a violation of this regulation poses a higher risk of causing vaccine-associated paralytic polio than one satisfying the requirement. He testified: MR. DONOVAN: Q: You understand and acknowledge that live oral polio vaccine poses a risk of vaccine- associated polio? MR. KOPS: Objection. THE WITNESS: Yes. MR. DONOVAN: Q: Whether it complies with the regulations in your view or it does not comply? THE WITNESS: A: Absolutely, yes. Steinman Dep., June 23, 1998, at 113. The FDA's view of the former "consistency of manufacture" regulation echoes this view. In 1991, it amended and expanded the regulation in an attempt to make it more applicable to product safety. App. A - 26 The former’ consistency requirements were based on the premise that the failure of a monovalent virus pool to meet neurovirulence requirements could be the result of a manufacturing deficiency.... [N]o criteria were provided to link the history of performance of monovalent *511 virus pools with the continued qualification of the seed virus. Long experience has shown that the failure of a monovalent virus pool, produced from an acceptable seed virus, is usually unrelated to deficiencies in the manufacturing process, but is usually due instead to test variability.... The revised methodology is at least as stringent as the former consistency requirements in detecting neurovirulence problems related to manufacturing defects, while having the added benefit of providing a statistical means for monitoring the continued qualification of a seed virus by evaluating its ability to consistently produce monovalent pools of acceptable neurovirulence.... [T]hese requirements provide assurances of consistency ... while actually reducing the likelihood that a seed virus will be rejected on the basis of test variability unrelated to genetic stability. 56 Fed.Reg. at 21,430-31. On this record, plaintiffs have not shown a connection between this regulation and product safety. Attempting to fill this evidentiary gap, the Grahams and Lundys make a series of arguments to the effect that the alleged violations of these regulations App. A - 27 establish negligence per se and to the apparent effect that proximate cause on this fraud claim accordingly need not be shown. But the invocation of this tort doctrine by itself, whether in the context of a negligence claim or a fraud claim, does not excuse the claimant from showing that the regulation at issue has a tenable and provable connection to public safety. See, e.g. Merchants Mutual Ins. Co. v. Baker, 15 Ohio St.3d 316, 473 N.E.2d 827, 828 (1984) ("Negligence per se does not equal liability per se. Simply because the law may presume negligence from a person's violation of a statute or rule does not mean that the law presumes that such negligence was the proximate cause of the harm inflicted."); see also Chambers v. St. Mary's School, 82 Ohio St.3d 563, 697 N.E.2d 198, 201 (1998) (noting that negligence per se requires a showing of proximate cause). In this instance, the alleged violations relate to regulations that no longer are in existence, that the FDA believes did not affect public safety and that plaintiffs’ experts have not been able to show affected public safety. Plaintiffs offer no example of a court (in Ohio or elsewhere) that has concluded that the invocation of "negligence per se " may fill this evidentiary gap. We doubt such a case exists, and at all events reject this argument as a matter of law. Plaintiffs do not gain any more traction by turning to the 1991 Sabin case and other cases arising from challenges to the 1984 neurovirulence regulations. These decisions did not involve the liability of private manufacturers for regulatory violations, but rather concerned the actions of the FDA in interpreting and applying its regulations. Sabin itself, moreover, concludes that the regulatory violations did not affect product safety: "[T]he scientists who established and implemented the OPV program ... consistently acted in the public interest as they reasonably perceived it to be. App. A - 28 They made judgments on extremely difficult questions which, strictly from the standpoint of public health, appear to be entirely proper.... [M]y finding that regulatory violations occurred does not imply that the public health is or has been endangered in any respect." Sabin II, 763 F.Supp. at 813. What is more, Judge Motz, who presided over Sabin II, presided over the recent case between St. Louis University and American Cyanamid. See St. Louis Univ., 182 F.Supp.2d at 494. There, Judge Motz concluded that the plaintiffs failure to prove, via expert testimony, that a regulatory violation increased the risk of paralysis meant that it could not prove any such violation by American *512 Cyanamid proximately caused the vaccinee's paralysis. See id. at 500-03. A similar flaw exists here. The Lundys further allege that expired and rejected materials were included in Jason's vaccine. American Cyanamid's experts confirmed that when a trivalent product's potency is not sufficient to reach the FDA criteria for potency, it must be re-bulked. That is to say, the manufacturer combines vaccine t’:at may not qualify for use by itself in order to reach F_4-regulated potency levels and must do so without violating anc*her FDA regulation. The Lundy (and Graham) experts ain did not offer a tenable basis for concluding tha. re- bulking vaccine potency with expired or rejected material negatively affects product safety. In the end, as in St. Louis University, plaintiffs have not met their burden of proximately linking their allegations of regulatory non-compliance with these undisputed and indisputably-severe injuries. That evidentiary gap is particularly significant in this medical setting. All vaccines produced from live viruses, as this one is, carry the paradoxical risk of inducing the very disease that the vaccine strives to prevent. In the App. A - 29 absence of expert testimony showing that these alleged regulatory violations made Orimune more unsafe than it otherwise would have been, a rational trier of fact could rule for plaintiffs only on the basis of conjecture, not a legitimate set of inferences drawn from admissible evidence. On this record, it remains unknowable whether plaintiffs’ injuries stemmed from an avoidable defect in the product or unavoidable bad luck. That the 1984 regulations upon which these claims rest have since been repealed and that the FDA has concluded that compliance with these regulations did not decrease the incidence of vaccine- associated paralytic polio cement this conclusion. Unable to establish a connection between these regulations and product safety, plaintiffs also necessarily come up short in showing that the representations at issue were material. For if plaintiffs cannot show that the alleged misrepresentations affected product safety, they cannot show that they were material. All things considered, the fraud claims in both cases must be summarily dismissed. ' B. STRICT LIABILITY The Grahams separately claim that they have presented a triable issue of fact on their strict-liability claim. For many of the same reasons that their fraud claim fails, however, this claim fails as well. (The Lundys, recall, brought strict-liability and failure-to- warn claims in state court and lost; when they filed the same claims here, the district court rejected them on res judicata grounds; those decisions have not been appealed.) Ohio has adopted §§ 402A of the Restatement (Second) of Torts (1965) as the standard for strict App. A - 30 liability. See Temple v. Wean United, Inc., 50 Ohio St.2d 317, 364 N.E.2d 267, 271 (1977). It says: (1) One who sells any product in a defective condition unreasonably dangerous to the user or consumer or to his property is subject to liability for physical harm thereby caused to the ultimate user or consumer, or to his property, if (a) the seller is engaged in the business of selling such a product, and (b) it is expected to and does reach the user or consumer without substantial change in the condition in which it is sold. . (2) The rule stated in Subsection (1) applies although (a) the seller has exercised ail possible care in the preparation and sale of his product, and *513 (b) the user or consumer has not bought the product from or entered into any _ contractual relation with the seller. Restatement (Second) of Torts §§ 402A. To establish strict liability under Ohio law, plaintiffs must produce expert testimony that the defect at issue "proximately caused the[ir] claimed injuries." State Farm Fire & Cas. Co. v. Chrysler Corp., 37 Ohio St.3d 1, 523 N.E.2d 489, 494 (1988). See Ohio Rev.Code Ann. §§ 2307.73(A)(2). Against this legal backdrop, the Grahams argue that American Cyanamid is strictly liable for Zachary's App. A - 31 injuries. Specifically, they claim that Orimune was defective because it violated several FDA regulations: (1) the "tissue culture test"; (2) the "consistency of manufacture test"; and (3) the FDA's licensing requirements. They further argue that the warning accompanying the Orimune dose Zachary received was inadequate. The Grahams’ strict-liability claim fails for the same reason that their fraud claim fails and for the same reason that the Fourth Circuit recently rej ected identical claims in American Cyanamid Co. v. St. Louis University, 336 F.3d at 307. They have not been able to show that the alleged regulatory violations--non-compliance with the "tissue passage culture" and "consistency of manufacture" regulations--proximately caused Zachary Graham's illness. Just as the expert testimony relied upon by the Grahams and Lundys did not show proximate cause in support of their fraud claims, the same expert testimony fails to do so here. In the absence of admissible evidence of proximate cause, the Grahams' _ product defect claim under the 1984 "tissue culture passage” and "consistency of manufacture” regulations fails as a matter of law. The Grahams also claim that the Orimune vaccine Zachary received was defective because American Cyanamid was not properly licensed to manufacture it. While they question whether certain testing procedures necessary for licensing occurred, they offer no evidence that the company did not in fact have a valid license to manufacture Orimune. As with their other claims, they also offer no evidence that any anomalies in American Cyanamid's license proximately caused Zachary's injuries. In Ohio, the absence of a valid or properly issued license does not by itself establish the proximate cause of an injury. Cf. Gulla v. Straus, 154 Ohio St. 193, App. A « 32 93 N.E.2d 662, 664 (1950). Plaintiffs also argue that the defense under Ohio law for "unavoidably unsafe" drugs is not available to American Cyanamid because the company allegedly violated FDA regulations. See White v. Wyeth Labs., 40 Ohio St.3d 390, 533 N.E.2d 748, 752 (1988) ("a manufacturer of an unavoidably unsafe product may not be held strictly liable for injuries caused thereby, provided that the product was’... properly prepared, and accompanied by proper directions and warning ...' ") (quotation omitted); Restatement (Second) of Torts §§ 402A, cmt. k (recognizing that certain products exist that cannot be made completely safe for their intended use and, when properly prepared, and accompanied by proper directions and warnings, are not defective, nor unreasonably dangerous). The availability of this defense, however, does not come into play in this instance, because plaintiffs have failed to establish their affirmative case by showing a causal relationship between the asserted defect--alleged regulatory violations--and Zachary's injury. See St. Louis Univ., 336 F.3d at 311 n. 4. C. NEGLIGENT FAILURE TO WARN The Graharns independently bring a negligent failure-to-warn claim. See*514 Crislip v. TCH Liquidating Co., 52 Ohio St.3d 251, 556 N.E.2d 1177, 1181-82 (1990). The claim has three elements, each of which must be satisfied: (1) a duty to warn against reasonably foreseeable risks; (2) breach of this duty; and (3) an injury that is proximately caused by the breach. See Briney v. Sears, Roebuck & Co., 782 F.2d 585, 587 (6th Cir.1986). Under Ohio law, the manufacturer of a prescription drug discharges its duty to warn about risks regarding prescription drugs if the manufacturer App. A - 33 : : H adequately warns the patient's doctor of those risks. See Ohio Rev.Code Ann. §§ 2307.76(C). When a plaintiff alleges that the warning given toa prescribing physician is inadequate, the plaintiff must prove his claim through expert medical testimony. See, e.g., Jones v. Roche Labs., 84 Ohio App.3d 135, 616 N.E.2d 545, 547 (1992). As with the Grahams’ other claims, this one too founders on the shoal of proximate cause. Even if we grant that the warning American Cyanamid offered was in some way inadequate, which appears not to be the case, see supra (reprinting warnings); see also Kearl v. Lederle Labs., 172 Cal.App.3d 812, 818-19, 834-36, 218 Cal.Rptr. 453 (holding that an "Important Information" statement identical to the one Lisa Graham signed adequately informed the plaintiff of the reasonably foreseeable risks associated with OPV as a matter of ° law), the Grahams have not shown that this inadequacy proximately caused Zachary's injuries. See Seley v. G.D. Searle & Co., 67 Ohio St.2d 192, 423 N.E.2d 831, 838 (1981). To the extent plaintiffs complain that the warning failed to acknowledge the alleged regulatory violations, they again have not shown that regulatory non-compliance in this instance had a bearing on product safety. To the extent plaintiffs mean to complain that the warning should have noted that IPV is the preferred polio vaccine, the record contradicts that claim. The scientific community agreed long ago that "IPV and OPV are both effective in preventing poliomyelitis, [but] OPV is the vaccine of choice for primary immunization of children in the United States when the benefits and risks for the entire population are considered." Recommendation of the Advisory Committee on Immunization Practices 2 (1982). This was largely because of “its ease of administration (oral instead of injected), App. A- 34 expected long lasting immunity, and the production of bowel immunity." E.O. Nightingale, Recommendations for a National Policy on Poliomyelitis Vaccination, 287 N.E. J. Med. 249-53 (1977). See also Report of Committee on Infectious Diseases 208, 209 (1982); Institute of Medicine, An Evaluation of Poliomyelitis Vaccine Policy Options 28 (1988). Mass vaccination with IPV also has had little impact on polio outbreaks. In contrast, wide use of OPV brought an end to any cases of paralytic polio caused by naturally circulating polio virus in the United States in 1979 and in the Western Hemisphere in 1991. Centers for Disease Control, Poliomyelitis Prevention in the United States: Updated Recommendations of the Advisory Committee on Immunization Practices (ACIP), Morbidity & Mortality Weekly Report, May 19, 2000, at 1, 5. In 1996, the FDA recognized the wide use of OPV as so successful that it officially revoked OPV regulations on the express ground that they were now "obsolete or no longer necessary to achieve public health goals." Revocation of Certain Regulations, Biological Products, 61 Fed.Reg. 40,153, 40,153 (Aug. 1, 1996). D. DERIVATIVE CLAIMS Jason Lundy's claim for loss of parental consortium and the Grahams’ and Lundys' claims for punitive damages are derivative *515 in nature. A derivative cause of action may not provide greater relief than that available under the primary cause of action. See Lynn v. Allied Corp., 41 Ohio App.3d 392, 536 N.E.2d 25, 36 (1987). Having dismissed plaintiffs’ respective causes of action for fraud, strict liability, and negligent failure-to-warn as a matter of law, we must dismiss these derivative claims as well. Ill, CONCLUSION App. A «35 For the foregoing reasons, we AFFIRM. App. A - 36 UNITED STATES COURT OF APPEALS FOR THE SIXTH CIRCUIT Nos. 01-4175; 014176 FILED DEC - 3 2003 LEONARD GREEN, Clerk No. 01-4175 JOSEPH R. GRAHAM, et al., Plaintiffs - Appellants, V. AMERICAN CYANAMID COMPANY, Defendant - Appellee. No. 01-4176 ROY LEE LUNDY, et al., Plaintiffs - Appellants, Vv. AMERICAN CYANAMID COMPANY, Defendant - Appellee. Before: DAUGHTREY, MOORE, and SUTTON, Circuit Judges. App. A - 37 JUDGMENT On Appeal from the United States District Court for the Southern District of Ohio at Columbus. THIS CAUSE was heard on the record from the district court and was argued by counsel. IN CONSIDERATION WHEREOF, it is ORDERED that the judgment of the district court is AFFIRMED. ENTERED BY ORDER OF THE COURT Leonard Green Leonard Green, Clerk ~ App. A - 38 United States District Court, S.D. Ohio, Eastern Division. Joseph R. GRAHAM, et al., Plaintiffs, Vv. AMERICAN CYANAMID COMPANY, Defendant. Roy Lee LUNDY, et al., Plaintiffs, AMERICAN CYANAMID COMPANY. Defendant. Nos. C-2-94-423, C-2-94-425. Dec. 21, 2000. [Reported at 2000 WL 1911431] OPINION AND ORDER SMITH, District Judge [*1] Plaintiffs Roy Lee Lundy and Zachary Graham assert state law claims alleging that they became permanently disabled by a polio vaccine (named "Orimune") that was manufactured by defendant American Cyanamid Co. Jason Lundy, as a child of Roy Lee Lundy, brings a derivative claim for loss of parental consortium based on product defect and failure to warn. This matter is before the Court on defendant's motion for summary judgment in each case. For the reasons herein, the Court grants defendant's motion for summary judgment in both cases. [FN1] FN1. The Court also denies plaintiffs' motion of May 18, 1999 that seeks a stay of disposition of App. B- 1 defendant's summary judgment motion, a "Bratka" hearing, and an order of the U.S. Marshall to seize all of defendant's records concerning the production, manufacture, and testing of Orimune between 1972 and 1984 (Doc. 188). I. BACKGROUND Poliomyelitis and the Orimune Vaccine Polio is a disease of the central nervous system. In 1955, Dr. Jonas Salk developed a vaccine against polio. Dr. Salk's vaccine was an inactivated polio vaccine ("IPV") derived from a dead polio virus. The Salk vaccine decreased the incidence of polio but did not eradicate it. While Dr. Salk was developing his IPV, which had to be injected, Dr. Albert Sabin, among others, was working on an oral polio vaccine ("OPV"). The OPV, unlike the IPV, is produced from live polio virus that is weakened, but not killed. OPV has advantages over IPV. First, OPV is less expensive and requires only a single dose, as [Text truncated at 120,000 characters. The full text is on the page linked above.] --- Source: Frix Law Library, https://www.frixlaw.com/law-library/documents/brief%3Amicro_IA40386001_1176%3A1. Public record. Not legal advice.