In the Arkansas Reglan lawsuit of Fields v. Wyeth, the tardive dyskinesia lawyer representing Bettye Fields alleges that the black box warning Reglan has should have come sooner:
I.
INTRODUCTION
Plaintiff sued these defendants for their negligent acts, which proximately caused Plaintiff's injuries. This is a failure to warn case. Wyeth and Schwarz Pharma, Inc. claim that they cannot be liable for the warning they crafted, no matter how negligently, because they are neither the manufacturers nor suppliers of the drug Plaintiff ingested. Though they appear not to have manufactured the drug at issue here, Wyeth and Schwarz Pharma, Inc. should remain liable under claims of negligence, fraud and misrepresentation as they relate to failure-to-warn claims. Wyeth and Schwarz Pharma, Inc. are the manufacturers of name-brand Reglan(R), generically known as MCP. Ms. Fields took the generic form. MCP/Reglan(R), typically prescribed for gastroesophageal reflux disease, carries a significant risk of tardive dyskinesia, a severe drug side effect characterized by grotesque involuntary movements of the mouth, tongue, lips, and extremities, involuntary chewing movements, and a general sense of agitation, especially with extended use. Tardive dyskinesia is a terribly debilitating condition. Plaintiff contends that the various defendants failed to adequately warn of the risks of tardive dyskinesia associated with extended use of MCP/Reglan(R), that the drug, by whomever manufactured, ought to carry a black box warning of the risk of tardive dyskinesia with extended use. It was in fact the warning created and sponsored by Wyeth and Schwarz Pharma, Inc., the warning that the FDA approved, that, by law, the MCP consumed by Bettye Fields carried. In fact, as of February, 2009, MCP/Reglan(R) now carries, as mandated by the FDA, just such a “Black Box” warning.[FN1] As a result, Ms. Fields has suffered permanent, disabling and disfiguring injuries.
FN1. The newly required warning says that “Chronic treatment with [MCP] can cause tardive dyskinesia.... [MCP] therapy should routinely be discontinued in patients who develop signs or symptoms of tardive dyskinesia. There is no known treatment for tardive dyskinesia .... Prolonged treatment (greater than 12 weeks) ... should be avoided in all but rare cases....” See Exhibit A.
A designer who is not also the manufacturer should share the same duty in design and warning.
II.
PLAINTIFF'S STATEMENT OF UNDISPUTED FACTS
A. Relevant FDA Regulations
To better understand the liability in generic only cases, one must understand several basic regulations applicable to innovator and generic manufacturers. These regulations cover: (1) the initial approval of the label; (2) post-approval revisions to the label; and (3) post-approval pharmacovigilance.
1. Regulations Concerning Initial Approval of the Label
Pursuant to the Federal Food, Drug and Cosmetic Act (“FDCA”), the FDA regulates the manufacture, sale and labeling of prescription drug products. Among other responsibilities, the FDA ensures that drugs are safe and effective, 21 U.S.C. § 355(d) and § 393(b)(2)(B), and that they are properly labeled, i.e., not “misbranded.” Id. §§ 331(a)(b), and (k), 352 and 321(n).
Before marketing a prescription drug, a pharmaceutical manufacturer must obtain regulatory approval. For the innovator drug, the innovator must submit a New Drug Application (“NDA”). Id. § 355(a)-(i). The innovator must prove both safety and efficacy of the drug through extensive laboratory and clinical trials. Id. § 355(b)(1)(F). The FDA will deny the NDA if the innovator does not provide, among other things, “adequate tests . . . to show whether or not such drug is safe for use under the conditions prescribed, recommended, or suggested in the proposed labeling.” Id. § 355 (d)(1).
Once the NDA is approved, the innovator has the exclusive right to market the drug for a certain period of time. Once that exclusivity period has expired, other drug manufacturers may market generic versions of the innovator drug if such approval has been obtained under the FDCA.
As this Court is aware, the approval procedure for generic drugs was relaxed and abbreviated by the Drug Price Competition and Patent Term Restoration Act of 1984 (commonly known as the “Hatch-Waxman Amendments”), Pub. L. No. 98-417, 98 Stat. 1584 (1984). Before 1984, a generic manufacturer was required to submit its own NDA, which required the same proof required for an innovator drug. Since the adoption of these amendments, a generic manufacturer may chose to submit only an Abbreviated NDA, or “ANDA.” If this choice is made, then the generic manufacturer no longer has to submit independent evidence of safety or efficacy. Instead, it must only establish, among other things, that: (1) the generic drug generally has the same active ingredient as the brand name drug and is a “bio-equivalent” to the innovator drug, id. §355(j)(2)(A)(ii), (iv); and (2) the proposed label of the generic drug is “the same as” that of the innovator drug. Id. § 355(j)(2)(A)(v).
To establish that the label is the same, the generic manufacturer must also submit a side-by-side comparison of the previously approved innovator label and the proposed generic label. 21 C.F.R. § 314.94(a)(8)(iv). During initial approval, the only differences that are allowed are those that reflect a different manufacturer or a different “active ingredient” or “route of administration, dosage form, or strength” than the innovator drug. Id. § 314.93(b). Simply stated, the FDA will not approve an ANDA unless, the applicant demonstrates that the “labeling proposed for the [generic] drug is the same as the labeling approved for the listed drug.” 21 U.S.C. § 355(j)(2)(A)(v). Thus, initially, the generic manufacturer can provide no input to or diverge from the innovator's label in any pertinent way at the time of approval.
2. Regulations Concerning the Post-Approval Revisions to the Label
Once the NDA is approved, an innovator may revise its labels in two ways. First, it may submit a proposed labeling change to the FDA for prior approval. In this situation, the innovator submits information and support for the proposed revision and awaits the FDA's approval. This is by far the most common approach used by innovators to effect labeling changes. Second, the innovator may add or strengthen a warning statement in a label without prior FDA approval. 21 C.F.R. § 314.70(c)(6)(iii)(A). To do so, the manufacturer must make a supplemental submission to the FDA about the proposed change along with a full basis for the change. Id. § 314.70(c). If the FDA does not reject the submission within 30 days, the innovator may distribute the drug with the new labeling. The FDA, however, may choose to reject the proposed labeling change even after that date, and may order the manufacturer to cease distribution of the drug with the revised labeling. Id. § 314.70(c)(7).
As this Court is also aware, if a generic manufacturer believes that new safety information should be added to its label, an ANDA holder can “add to” or “strengthen” the warnings in their label. This action would then trigger a process whereby the FDA would decide whether the labeling for both the generic and innovator drug should be revised. 57 Fed. Reg. 17,961 (Apr. 28, 1992). See also Wyeth v. Levine, _____ U.S. _____, 129 S.Ct. 1187 (2009).
3. Regulations Concerning Pharmacovigilance
Following FDA approval to market a drug, both the innovator and generic manufacturer are subject to continuing obligations to monitor, analyze and report adverse effects associated with the drug. See 21 U.S.C. § 355(k); 21 C.F.R. §§ 314.80, 314.81, 314.98. All defendants were required to keep records of and report adverse effects associated with the use of their drug regardless of whether they are “considered drug related.” 21.C.F.R. §§ 314.80(a), (c), 314.98(a). For “serious and unexpected” adverse events, all defendants were required to submit a report within 15 days after learning of the adverse event and investigate these events. Id. § 314.809(c)(1). All defendants were also required to review the published literature relating to their drugs. See id. §§ 314.80(b), (d), 314.81(b)(2). Published literature and other information must be reported to the FDA in annual and special reports. See id. § 314.80.
B. MCP Label Facts
Reglan(R), also known as MCP, was initially marketed in the United States by A.H. Robins Co. (Robins) and later sold by Wyeth, Robins' successor, to Schwarz. Reglan(R) was first approved in 1979, by the FDA, for the treatment of diabetic gastroparesis; and subsequently approved in 1984 for the treatment of gastroesophageal reflux disease (GERD) (commonly known as “heartburn”). Appx., pp 125-133. Upon the expiration of the patent exclusivity, several drug companies began manufacturing generic versions of Reglan(R), also known as MCP (including Wyeth). The other Defendants are such generic MCP manufacturers.
It has been known for decades in the scientific community that MCP crosses the blood-brain barrier and causes central nervous system side effects, like tardive dyskinesia (a type of extrapyramidal movement disorder). Although the condition is rarely fatal, severe TD is extremely disabling, and there is no known cure. Physicians are most familiar with tardive dyskinesia through the experience of other older neuroleptic drugs, such as Thorazine and Haloperidol. These drugs were once widely prescribed and used in the treatment of psychosis until it became clear, by the late 1970s, that an extremely high percentage of patients exposed to neuroleptics on a long-term basis - about 1 in 4 - were developing tardive dyskinesia.[FN2] (Appx., pp 001-089.). The wisdom of prescribing a neuroleptic drug having the potential to induce tardive dyskinesia for minor illnesses, such as heartburn, was debatable even at the time Reglan(R) was first approved in 1984. At that time, however, Reglan(R) was the only drug approved for the treatment of heartburn. In response to increasing case reports of tardive dyskinesia in the published medical literature, the FDA mandated class-wide warnings for all neuroleptic drugs, including Reglan(R) because of its neuroleptic characteristics.[FN3] In 1989, Drs. L. Miller and J. Jankovic published a paper where they reviewed the available published scientific literature and identified 1,031 patients with MCP-induced EPS and concluded that MCP manufacturers' estimates of a 1/500 frequency for MCP-induced movement disorders was inaccurate. (See above footnote, Id.) Nevertheless, the 1/500 frequency ratio has been on the Reglan(R)/MCP label since 1984 and is still on the label, generic and brand-name, today. ( Id.)
FN2. Yassa & Jeste, “Gender Differences In Tardive Dyskinesia: A Critical Review of the Literature,” Schizophrenia Bull. 18 (4): 701-15 (1992).
FN3. See L. Miller and J. Jankovic, “Metoclopramide-Induced Movement Disorders: Clinical Findings With a Review of the Literature,” Arch. Intern. Med. 149:2486, 2489 (1989).
The FDA only approved MCP for short-term use (4-12 weeks). Even though the MCP label specifically quantified the dosage associated with the 1/500 ratio, the label also did not qualify the duration of therapy. As reflected in the literature, as MCP long-term drug therapy, defined as greater than 12 weeks duration, became popular (to treat minor gastrointestinal complaints, such as heartburn), the incidence of tardive dyskinesia increased.[FN4]
FN4. R. Stewart, et al, “Metoclopramide: An Analysis of Inappropriate Long-Term Use in the Elderly” Annals of Pharmacotherapy 26:977,978 (1992).
By the early 1990s, peer-reviewed medical literature established that MCP's 1/500 risk for tardive dyskinesia or extrapyramidal reactions ratio were significantly higher than previously thought. Thus, the risk/benefit analysis for MCP had substantially changed after initial FDA approval. For instance, in other MCP litigation, Dr. Frederick Wilson, testified:
Q: Just so I'm absolutely clear on your answer - - are you telling me that it is your opinion, as Wyeth's medical monitor for Reglan, that Reglan should not be prescribed in long-term therapy for GERD, because its side effects are too dangerous, and because its efficacy in long-term use has never been established?
A: Today, as we sit here, and with the other drugs that are currently on the market, I would agree with that.
See Wilson deposition at p. 66, Appx., pp 134-143.
Moreover, two formal epidemiological studies published in peer-reviewed journals in the early 1990s specifically addressed the prevalence of tardive dyskinesia in MCP exposed patients. The article published by Linda Ganzini, et al., entitled “ The Prevalence of Metoclopramide-Induced Tardive Dyskinesia and Acute Extrapyramidal Movement Disorders,” Arch. Intern. Med. 153:1469, 1471 (1993). Dr. Ganzini's study found that the frequency of tardive dyskinesia among her patients that were treated with MCP was over 29%, or at a frequency of about 1 in 4 - a prevalence that was 100 times higher than reported in the text of the MCP label. (See Id). A second epidemiological study (closely replicating Ganzini's) found that 27% of patients treated with MCP contracted tardive dyskinesia. (See Id. n. 6)
These same studies also found that diabetic patients exposed to MCP faced a particularly higher risk of developing tardive dyskinesia, and typically developed more severe forms of the disease than non-diabetic patients exposed to the drug. (See Gazini, fn 6). Nevertheless, the MCP label makes absolutely no reference to the particularly higher risk of tardive dyskinesia in this patient population of diabetics taking MCP.
Despite the availability of medical literature, Schwarz/Wyeth did not report either study to the FDA; did not make any changes in their MCP label, and did not call the FDA's attention to the epidemiological data contained in these articles. No one at Schwarz/Wyeth appears to have read these articles, despite their duty to do so, because it is reasonable to assume that if Schwarz/Wyeth had read the articles, then Schwarz/Wyeth would have reported the important safety information to the FDA, and Schwarz/Wyeth has not produced or offered any such evidence to support that they had actually done so. Had they reported this, then the labeling would have been changed well before it was prescribed to Plaintiff, avoiding her injuries.
C. Schwarz/Wyeth Are Responsible For Reglan(R) Warnings
Schwarz/Wyeth does not dispute that Wyeth was responsible for the original NDA and that the two have been continuously responsible for warnings submitted to the FDA. Moreover, regulations actually allow a manufacturer to add to or strengthen warnings without prior FDA approval. 21 C.F.R. § 314.70(c)(6)(iii)(A). Nor do they dispute that they are responsible for Reglan(R) warnings. See Wyeth v. Levine, _____ U.S. _____, 129 S.Ct. 1187 (2009). They dispute that they are responsible for anyone's reliance on those same warnings, warnings they submitted to the FDA and that accompany bioequivalent versions of Reglan(R) manufactured by someone else.
III.
SUMMARY JUDGMENT STANDARD
Summary judgment is appropriate when “there is no genuine issue as to any material fact and... the moving party is entitled to a judgment as a matter of law.” Fed R.Civ.P. 56(c). Once the moving party demonstrates the absence of a genuine issue of material fact, “[t]he non-moving party must thereafter produce specific facts demonstrating a genuine issue of fact for trial.” Pierce v. Commonwealth Life Ins., Co., 40 F.3d 796, 800 (6th Cir. 1994). A fact is “material” only if its resolution will affect the outcome of the lawsuit. Anderson v. Liberty Lobby, Inc., 477 U.S. 242, 248 (1986). In deciding the motion, all inferences from, and ambiguities in, the underlying facts are to be resolved in favor of the party opposing summary judgment. Minter v. Great Am. Ins. Co., 423 F.3d 460, 465 (5th Cir. 2005).
Summary judgment should only be granted if the non-moving party has failed to make a sufficient showing on an essential element of its case with respect to which it has the burden of proof. Hellstorm v. United States Dep't of Veterans Affairs, 201 F.3d 94, 97 (2nd Cir. 2000). However, on summary judgment, the non-moving party should not be “railroaded” into his offer of proof in opposition. Id. at 201 F.3d at 97; accord Trebor Sportswear Co. v. The Ltd. Stores, Inc., 865 F.2d 506, 511 (2nd Cir. 1989).
IV.
LAW AND ARGUMENT
A. Arkansas Law is Consistent With A Drug Originator's Liability For Its Warnings Though the Warnings Accompany a Bioequivalent Drug
Schwarz/Wyeth rely on Arkansas law to make the claim that a non-manufacturer cannot be held liable. They rely on several cases to the effect that there must be evidence of proximate cause to establish product liability. But this is not controversial.[FN5] The key to both duty and proximate cause here is “foreseeability.” See Shannon v. Wilson, 329 Ark. 143, 150-152, 947 S.W.2d 349, 352 - 353 (1997).
FN5. E.g., Ashley County, Ark. v. Pfizer, Inc., 552 F.3d 659, 668 (8th Cir. 2009) (Manufacturer of cold medicine too attenuated from the plaintiff Counties' costs of incarceration and law enforcement connected to criminal use of the cold medicine to make methamphetamine); National Bank of Commerce of El Dorado, Arkansas v. Dow Chemical Co., 165 F.3d 602, 607 (8th Cir. 1999) (Plaintiffs' evidence that pesticide at issue was sold at Henley's feed store and came in a glass or metal container. However, during discovery Dow and United produced uncontroverted evidence that Henley's Feed Store has neither sold nor stocked Spectracide Dursban Indoor and Outdoor Insect Control and that it was never formulated or distributed in a metal or glass container); Rogers v. Armstrong World Industries, Inc, 744 F.Supp. 901, 905 (E.D.Ark. 1990) (mere presence of a toxic substance at a plaintiff's workplace, without evidence of exposure, is not enough); Chavers v. General Motors Corp., 349 Ark. 550, 562, 79 S.W.3d 361, 369 (2002) (where Plaintiff in mesothelioma case contended he was injured by exposure to the defendant's asbestos containing products, he was required to show that it was defendants' asbestos-containing products that he used.).
B. Recent Case Law, Law Involving These Same Defendants, Adopts Originator Drug Warning Liability
Plaintiff cites Conte v. Wyeth, Inc., 168 Cal.App.4th 89, 85 Cal.Rptr.3d 299, 08 Cal. Daily Op. Serv. 13,931 (2008). Conte found against these defendants on just these issues. Conte held that there is nothing out of the ordinary about imposing liability on the originator of the warning. This principle is “rooted in common sense and California common law. We are not marking out new territory by recognizing that a defendant who authors and disseminates information about a product manufactured and sold by another may be liable for negligent misrepresentation where the defendant should reasonably expect others to rely on that information and the product causes injury, even though the defendant would not be liable in strict products liability because it did not manufacture or sell the product.” 2008 WL 4823066 at *6. This fits the Arkansas standard that foreseeability defines the scope and limit of duty. See Shannon, supra.
Conte found “the conclusion inescapable that Wyeth knows or should know that a significant number of patients whose doctors rely on its product information for Reglan(R) are likely to have generic metoclopramide prescribed or dispensed to them.” Id at *9. “In the absence of ‘overriding policy considerations ... foreseeability of risk [is] of ... primary importance in establishing the element of duty.’ As a classic opinion states: ‘The risk reasonably to be perceived defines the duty to be obeyed.’ ” Id., quoting Dillon v. Legg, 68 Cal.2d 728, 739, 69 Cal.Rptr. 72, 441 P.2d 912, 29 A.L.R.3d 1316 (1968), in turn quoting Palsgraf v. Long Island R.R. Co., 248 N.Y. 339, 344, 162 N.E. 99 (1928). “As the foreseeable risk of physical harm runs to users of both name-brand and generic drugs, so too runs the duty of care, and Wyeth has not persuaded us that consideration of other factors requires a different conclusion.” Conte, 2008 WL 4823066 at *9. “We hold that Wyeth's duty of care in disseminating product information extends to those patients who are injured by generic metoclopramide as a result of prescriptions written in reliance on Wyeth's product information for Reglan(R).” Id.
C. Arkansas Law of Duty/Proximate Cause
Arkansas law is essentially similar to California's regarding duty and proximate cause. “The ultimate test in determining the existence of a duty to use due care is found in the foreseeability that harm may result if care is not exercised.” Shannon, 329 Ark. at 150, 947 S.W.2d at 352. Generally proximate causation is a question of fact . Stacks v. Arkansas Power & Light Co., 299 Ark. 136, 138-139, 771 S.W.2d 754, 756 (1989). Further, “[t]o constitute negligence, an act must be one from which a reasonably careful person would foresee such an appreciable risk of harm to others as to cause him not to do the act, or to do it in a more careful manner.” Ethyl Corp. v. Johnson, 345 Ark. 476, 481, 49 S.W.3d 644, 648 (2001) (quoting Wallace v. Broyles, 331 Ark. 58, 961 S.W.2d 712 (1998). While “negligence in the air” does not give rise to liability, “[t]he question, however, is not whether a defendant could have reasonably foreseen the exact or precise harm that occurred, or the specific victim of the harm.” Coca-Cola Bottling Co. of Memphis, Tennessee v. Gill, 352 Ark. 240, 254, 100 S.W.3d 715, 724 (2003), citing Wallace v. Broyles, supra. “It is only necessary that the defendant be able to reasonably foresee an appreciable risk of harm to others.” Id. Coca-Cola Bottling Co. explains, in Palzgraf fashion, the contours of duty with reference to Jordan v. Adams, 259 Ark. 407, 533 S.W.2d 210 (1976). In Jordan, Adams sued for injuries sustained when Jordan, enraged by an argument that he had with a man who was talking to his female companion, threw her purse across a crowded bar dining room, causing a pistol inside the purse to discharge and hit Adams in the leg. Jordan argued that Adams was not a foreseeable plaintiff, because he did not know that the pistol was inside the purse when he threw it. Jordan held “if the act is one which the party in the exercise of ordinary care ought to have anticipated was likely to result in injury to others, then such person is liable for the injury proximately resulting therefrom although he may not have foreseen the particular injury which did happen.” Jordan, 259 Ark. at 411, 533 S.W.2d at 212.
Here, Wyeth/Schwarz, as Conte held, “knows or should know that a significant number of patients whose doctors rely on its product information for Reglan(R) are likely to have generic metoclopramide prescribed or dispensed to them.” Under Arkansas law of negligence, Wyeth/Schwarz had a duty to Bettye Fields to see that Reglan(R) (and thus the generic versions) carried appropriate warnings.
D. Concept That a Designer Or Originator Remains Liable For Products Manufactured By Another Has Long Been Recognized
The concept that a designer or originator remains liable, under certain conditions, for products manufactured by another has long been recognized. Because a “manufacturer, as well as all suppliers of a product, also has a duty to inform users of hazards associated with the use of its products...,[t]here is no reason to distinguish a designer, who has intimate knowledge of a designed product, from a retailer, wholesaler or manufacturer.” Alm v. Aluminum Co. of America, 717 S.W.2d 588, 591 (Tex. 1986), citing RESTATEMENT (SECOND) OF TORTS § 388 (1965); additional citation omitted, italic added.
Indeed Alm has been applied in just these circumstances. A federal Court held in a Thimersol case against Eli Lilly that:
It is undisputed that Lilly did not manufacture the thimerosal that was administered to Jordan Easter as part of his vaccine regimen. However, plaintiffs allege that for many years, Lilly, as the original designer of thimerosal, distorted published medical literature and deceived health regulators and physicians about the safety of thimerosal. They further allege that Lilly's misrepresentations were relied upon by physicians, health regulators, and other thimerosal manufacturers which led to the widespread use of thimerosal in vaccines.
Easter v. Aventis Pasteur, Inc., 2004 WL 3104610, 8 (E.D.Tex. 2004). The Court distinguished another Texas case, holding that it concerned “a mere product concept which was unlicensed and which was different from the final modified ... product that injured the plaintiff.” Id. It then noted that the thimerosal at issue did not deviate from Lilly's original design. Id. Indeed, as a bioequivalent, it could not have. Moreover “ Alm is analogous to this case. Lilly developed the design for thimerosal, used thimerosal in vaccines, licensed thimerosal to other manufacturers, and after its patent expired, knew that other manufacturers had copied its thimerosal design for use in vaccines.” Id. Therefore, “Lilly was in the best position to know about the potentially harmful effects of thimerosal, to warn others about them, and even, as plaintiffs allege, to conceal them as well.” Id. As here, the Easters alleged “that ... Lilly promoted thimerosal as being non-toxic while concealing research findings which showed that it was indeed toxic.” This led the Court to conclude that “Lilly, as a designer, has a duty to develop a safe design for thimerosal. Also, Lilly's design of and intimate knowledge about thimerosal also gives rise to a duty to inform users of hazards associated with the use of thimerosal.” Id.
The same facts are present here. Schwarz/Wyeth, as the originators and primary manufacturers have an ongoing duty, under Arkansas law, to provide an adequate warning. They have an ongoing duty under the above FDA regulations. They are also in the best position to do so. Indeed federal regulation dictates the same result.
D. Wyeth and Schwarz are Liable in “Generic Only” Cases
Plaintiff alleged the simple and basic common law elements of fraud and misrepresentation against Wyeth and Schwarz. SEE RESTATEMENT (SECOND) OF TORTS § 311 (negligent misrepresentation involving risk of physical harm to another); 388 (above). The basic elements of these claims are met because, first, Wyeth and Schwarz owed a duty to the intermediary Doctor and/or the injured plaintiff to provide an accurate label. See Wyeth v. Levine, _____ U.S. _____, 129 S.Ct. 1187 (2009). Second, the label contained false and/or misleading statements because Wyeth and Schwarz provided false and misleading information to physicians, the medical community and/or patients in its label and marketing materials for Reglan(R). Third, the prescribing physician and/or plaintiff relied on the misstatements in the label in prescribing and/or using the generic drug. Finally, such reliance was justified. Since the innovator and the generic drug are the same, such reliance is foreseeable and expected.
1. Genuine Issues Of Material Fact Exists As To Whether Schwarz/Wyeth Breached Their Duty And Whether The Breach Of That Duty Could Foreseeably Caused Plaintiff's Injuries
Genuine issues of material fact exist as to whether the information disseminated by Schwarz/Wyeth, whether through the Physician's Desk Reference, through aggressive marketing campaigns, promotional materials, or otherwise, was materially false, incomplete and misleading. (See e.g. Axel Olsen and Frederick Wilson's (Wyeth Corporate Executives) admitting inadequacies and inaccuracies of risk of TD, attached as Appx. pp 001-0013 & pp 0014-0021.)
Schwarz/Wyeth were the voluntary disseminators and promulgators of the official metoclopramide labeling and body of knowledge relating to the safety and efficacy of Reglan and had a heightened duty under the FDA regulations to exercise reasonable care to ensure that the information is accurate and not misleading; that they owe a duty to any patient whose physician would reasonably rely upon the information in prescribing medicine, regardless of whether the pharmacy filled the prescription with a generic instead of the brand name drug that was prescribed. Schwarz/Wyeth breached this duty when they voluntarily promulgated and disseminated false and misleading information as to the risks of tardive dyskinesia.
2. Schwarz/Wyeth Promulgated and Distributed Inaccurate and Inadequate Warnings: Schwarz/Wyeth knew the Risk of Contracting Tardive Dyskinesia was Substantially Greater Than Reported
The estimates of the risks for tardive dyskinesia among patients treated with metoclopramide are much greater than what is implied by the statements made in the WARNINGS section of the RLD's official metoclopramide labeling. The official labeling states that:
“Extrapyramidal symptoms, manifested primarily as acute Dystonic reactions occur in approximately 1 in 500 patients treated with the usual adult dosages of 30 to 40 mg/day of metoclopramide.”
Furthermore, in the official labeling, under the warning for “Tardive Dyskinesia,” no risks or prevalence estimates are provided, but the claim is made that: “it is impossible to predict which patients are likely to develop the syndrome.”[FN6] Not only is this claim inconsistent with the vast amount of literature discussing drug- induced tardive dyskinesia but also the quantitative implication of the warning is unclear. This warning language used in the official labeling [promulgated and disseminated by Wyeth] is misleading. It implies that the risks of tardive dyskinesia are extremely low - purportedly less than 1 in 500. However, this is directly contradicted by the scientifically available literature.
FN6. As noted above, recent changes to the label mandated by the FDA correct this.
Wyeth knew that the warning to prescribing physicians and consumers were profoundly underestimated the actual risks of tardive dyskinesia. Wyeth knew about these increased risks as early as 1989, but chose not to update the official labeling. See e.g. Jankovic, et al. and Ganzini, et al., “The Prevalence of Metoclopramide-Induced Tardive Dyskinesia and Acute Extrapyramidal Movement Disorders,” Arch. Intern. Med. 153:1469, 1471 (1993) (finding that the frequency of tardive dyskinesia among her patients treated with metoclopramide was over 29% or about 1 in 4 - a prevalence that was 100 times higher than reported in the text of official metoclopramide monograph-Wyeth's labeling) Id. at p. 1473.
In fact, Wyeth affirmatively ignored the literature as evidenced by its own internal memorandum, Appx., pp 154-157. This documents evidences that Wyeth decided to take “no action” to report findings to the FDA. Despite its affirmative duty under the FDA regulations to do so.
Despite the presence of overt safety signals, the Schwarz/Wyeth failed to report these profoundly important safety signals detected in the literature that would indicate that metoclopramide was associated with substantially increased risk of a serious side effect, greater than previously known to prescribing physicians. See also, L. Miller and J. Jankovic, at 149:2486, 2489 (1989) and Ganzini, et al., 1993.
E. Genuine Issues of Material Fact Exist As To Whether It Was Foreseeable that the Official Metoclopramide Monograph was relied upon by Plaintiff's Treating Physician or Individuals Responsible for Teach Plaintiff's Physician, whether through presentations, seminars or the like, about the safety and efficacy of Reglan
Plaintiff's doctor prescribed REGLAN(R). Plaintiff's pharmacy filled the prescription with generic metoclopramide as required by the generic laws in the State of Arkansas. Plaintiff alleges that in ordering the REGLAN(R) prescription, her doctors relied upon the body of knowledge disseminated and promulgated by Wyeth and, subsequently, Schwarz Pharma, in which they touted Reglan as a safe and effective treatment for Plaintiff's ailments, and promoted Reglan for long-term use. This is a reasonable assumption, as evidenced by the very fact that Wyeth paid to put the official metoclopramide labeling into the body of knowledge through the Physicians Desk Reference publication.
In publishing a warning in the PDR and in package inserts, Wyeth sought to warn physicians concerning the use of its product. It was in the best position to know exactly what it was communicating to the doctors. If that warning is insufficient and a patient is harmed by the insufficient warning, the patient may have a cause of action against Wyeth though the patient never had any personal relationship with Wyeth.
Wyeth knew the PDR was a national circulation that physicians as well as teachers rely upon as an authoritative source for information about prescription drugs. Wyeth must argue, in light of Alm, that it was not foreseeable that a physician would rely upon the PDR and will argue that the doctors here did not rely on said reference material. But, why then, would Wyeth pay money to publish the official labeling into the PDR(R) If physicians and teachers did not rely on the publication as an authoritative source. If the official labeling, published in the PHYSICIAN'S DESK REFERENCE is inaccurate as to risks of tardive dyskinesia, then the physician or teacher relying on that publication has not been adequately warned. Wyeth was the one primarily responsible for warning the learned intermediary, and did so insufficiently and inadequately. It is entirely foreseeable that a patient could be injured from a drug that the physician would not have ordinarily prescribed had the true dangers been known.
F. Genuine Issues of Material Fact Exists as to whether Schwarz/Wyeth Did (And Still Do) Owe A Duty To Both Plaintiff And To Other Defendants
As this Court is aware, RLD status was conferred upon Wyeth, and therefore had heightened duties because it is the RLD holder's labeling language that is, and will be, primarily relied upon, by all persons who wish to manufacture metoclopramide.
FDA regulations provide that the RLD official labeling shall be “revised to include a warning as soon as there is reasonable evidence of an association of a serious hazard with a drug[.]” See 21 C.F.R. § 201.57(e); see also 21 C.F.R. 314.70(b)(2)(v) (requiring label to be in approved form.) Necessary label changes are proposed by either the RLD holder [here Schwarz/Wyeth] and/or the generic company. See generally id. §§ 314.70, 314.71, 314.97; see also id. at § 314.70(c)(6)(iii)(A), (C)2; see also 44 Fed. Reg. 37434, 37447 (1979) (revised warnings may be made by various means, including labeling changes and “Dear Doctor Letters”). Under the regulations, both Schwarz/Wyeth and the generic manufacturer have an individual and joint duty to trigger a label change if a serious hazard or signal in the marketplace is associated with the use the drug. Id. See C.F.R. § 201.57 (e) mandating labeling change as soon as there is reasonable evidence that a drug is associated with a serious hazard; (See also 21 C.F.R. § 314.70(C)(6)(iii)(c)) promulgating procedure to “add or strengthen” warning to increase safe use of drug.) (emphasis added) See 21 C.F.R. § 314.80(b); See also e.g. 21 U.S.C. § 352(a), 21 U.S.C. § 355 (j)(2)(A)(iii) and (iv) and (4); 21 U.S.C. 314.80, 314.105(d) (promulgating individual and joint duty upon RLD holder and generic to individually and jointly conduct pharmacovigilance activities, including reviewing adverse event drug event reports, including those obtained from the post marketing experience found in the scientific literature, and to report that literature and safety information in their Annual reports to the FDA.) Id. Schwarz/Wyeth, once their NDA was approved many years ago, still have to comply with the FDA post-marketing safety and reporting requirements - 21 C.F.R. § 314.80 and 21 C.F.R. § 314.81, as long as they continue to be the NDA/RLD holder. Those duties under these FDA regulations only terminate if they decide to withdraw their NDA, and thus, no longer serve as the RLD holder. Schwarz/Wyeth had not withdrawn the specific NDA at issue in this lawsuit for metoclopramide.
Thus, any or all of the defendants could and should have revised the official metoclopramide labeling to warn about the serious and increased hazards of tardive dyskinesia associated with the drug. Indeed, all defendants must revise their labeling whenever there is reasonable evidence of an association between the drug and a serious hazard. Schwarz/Wyeth had a duty to exercise ordinary care in the dissemination of its warning, and was under a heightened duty to warn of the true risks of tardive dyskinesia and could do so without running afoul of, and indeed, as specifically contemplated by FDA regulations. A breach of these duties by defendants gives rise to the imposition of state common law liability for failure to warn, despite or in addition to the existence of FDA regulation. It is now clear that FDA approval is not a shield to liability in state tort cases. Wyeth v. Levine, _____ U.S. _____, 129 S.Ct. 1187 (2009).
G. Schwarz/Wyeth Owe a Common Law Duty to Plaintiff
Negligent misrepresentation is actionable in Arkansas. It is of course true that fraud requires proof of five elements: (1) a false representation of a material fact; (2) knowledge that the representation is false or that there is insufficient evidence upon which to make the representation; (3) intent to induce action or inaction in reliance upon the representation; (4) justifiable reliance on the representation; (5) damage suffered as a result of the reliance. Tyson Foods, Inc. v. Davis, 347 Ark. 566, 66 S.W.3d 568 (2002).
The Arkansas Supreme Court has said that “we have many times held fraud even in the complete absence of any moral wrong or evil intention. Cardiac Thoracic & Vascular Surgery, P.A. Profit Sharing Trust v. Bond, 310 Ark. 798, 840 S.W.2d 188 (1992) (quoting Davis v. Davis, 291 Ark. 473, 725 S.W.2d 845 (1987)).” Riley v. Hoisington, 80 Ark. App. 346, 353, 96 S.W.3d 743, 748 (2003). That the misrepresentations are knowably false is enough. “Representations are considered to be fraudulent when made by one who either knows them to be false, or, not knowing, asserts them to be true.” Miskimins v. City Nat. Bank of Fort Smith, 248 Ark. 1194, *1204, 456 S.W.2d 673, 679 (Ark. 1970), citing Fausett & Co. v. Bullard, 217 Ark. 176, 229 S.W.2d 490; Maurice v. Chaffin, 219 Ark. 273, 241 S.W.2d 257. “It may involve a mere mistake of fact.” Miskimins, citing Kersh Lake Drainage District v. Johnson, 203 Ark. 315, 157 S.W.2d 39.
Even though Plaintiff may not have ingested a Wyeth product, Wyeth still owed her a duty not to negligently misrepresent the safety of the Reference Listed Drug, Reglan, because it was certainly foreseeable that the warnings for Reglan and metoclopramide products would, at least initially, follow the Referenced Listed Drug label warnings. Thus, it was foreseeable that a patient like Plaintiff would be injured by Wyeth and Schwarz's misrepresentations.
Wyeth, and later Schwarz Pharma, had a duty to use ordinary care to ensure that information they provided, both as the manufacturer and the RLD holder (NDA sponsor) was accurate and adequate. Failure to do otherwise is a breach of their duty to exercise ordinary care towards the citizens of the State of Arkansas who ingest metoclopramide, whether generic or name brand.
H. Restatement Duty
Furthermore, under the Restatement of Torts and Arkansas Common Law, Wyeth and Schwarz Pharma had a duty toward plaintiff's physician who reasonably relied upon the information disseminated and promulgated in the body of knowledge and was negligent because they failed to correct inaccuracies and inadequacies that they created in that body of knowledge. § 310 of the Second Restatement addresses intentional misrepresentations and states that:
an actor who makes a misrepresentation is subject to liability to another for physical harm which results from an act done by the other or a third person in reliance upon the truth of the representation, if the actor
(a) Intends his statement to induce or should realize that it is likely to induce action by the other or a third person, which involves an unreasonable risk of harm to the other, and
(b) Knows
(i) That the statement is false, or
(ii) That he has not the knowledge which he professes.
RESTATEMENT OF TORTS, 2D, § 310 (2d ed. 1965). § 311 provides:
(1) One who negligently gives false information to another is subject to liability for physical harm caused by action taken by the other in reasonable reliance upon such information, where such harm results
(a) to the other, or
(b) to such third persons as the actor should expect to be put in peril by the action taken.
(2) Such negligence may consist of failure to exercise reasonable care
(a) in ascertaining the accuracy of the information, or
(b) in the manner in which it is communicated.
RESTATEMENT OF TORTS, 2D, § 311 (2d ed. 1965). As the Restatement puts it, such a duty extends to any person who, in the course of an activity which is in furtherance of his own interests, undertakes to give information to another, and knows or should realize that the safety of the person or others may depend on the accuracy of the information. Similarly Wyeth and Schwarz, in the course of their business, disseminated misleading warning information and false labeling when they knew or should have known that the safety of patients depended on the accuracy of their information.
In an analogous situation, “[T]he absence of a duty to speak does not entitle one to speak falsely.” Garcia v. Superior Court, 50 Cal.3d 728, 734-35, 789 P.2d 960, 963-64 (1990), cited in Conte. The Garcia case involved the duty of a parole officer to reveal truthful information to a potential victim of a parolee's dangerous propensities that were known to the officer. Even though there was no duty to speak, the court said that under RESTATEMENT OF TORTS, 2D, § 311 (2d ed. 1965), there was a legal duty when someone chooses to speak to convey truthful information when the speaker should be aware that the listener will likely rely on the information given in deciding what to do.
This same duty was found in Friedman v. Merck & Co., 107 Cal.App.4th 454, 477, 131 Cal. Rptr. 2d 885, 902 (2003), to justify a cause of action against a drug manufacturer for negligent misrepresentations as the result of false information being produced about the risk of contracting tuberculosis. “The rule stated in this Section may also apply where the information given is purely gratuitous, and entirely unrelated to any interest of the actor, or any activity from which he derives benefit.” RESTATEMENT OF TORTS, 2D, § 311, comment c (2d ed. 1965); Friedman, supra, 107 Cal.App.4th at 478, 131 Cal. Rptr. 2d at 902.
Similarly, Wyeth and Schwarz negligently gave false information about the risks inherent in name brand MCP to the general public, generic makers, doctors, and Plaintiff. This false information reflected Wyeth and Schwarz's failure to accurately state risks it knew or should have known actually existed.
Here, Wyeth and Schwarz, in the course of their business, had a duty to use due care in formulating MCP warnings which they knew would be relied upon by doctors, patients and generic manufacturers. And, they failed to do so. Wyeth and Schwarz had knowledge of such reliance because they knew it was highly likely that a prescription for brand name MCP written in reliance on Wyeth or Schwarz's product information would be filled with generic MCP. Likewise, it is eminently foreseeable that a doctor might prescribe generic MCP in reliance on Wyeth and Schwarz's representations about name brand MCP.
It is reasonable to assume that had treating doctors been aware of the true risks (100 times greater risk of TD not warned about) associated with metoclopramide, it is more likely than not, that he would not have made the decision to prescribe the drug to Plaintiff. By intentionally or negligently failing to adequately report the increased risks and frequency of Tardive Dyskinesia associated with the use of metoclopramide, Wyeth and Schwarz Pharma deprived the doctors, Plaintiff, and/or members of the medical community from receiving adequate and complete safety information about the risks, associated with this dangerous drug to Plaintiff.
I. Foster v. American Home Products And Its Progeny Are Not Applicable
Schwarz/Wyeth rely heavily on Foster v. American Home Products Corp., 29 F.3d 165, 167 (4th Cir. 1994) and its progeny, to avoid accountability. Schwarz/Wyeth attempt to avoid accountability for the false and misleading information promulgated and distributed by them by arguing that they did not manufacturer the product Plaintiff ingested. Not only is this argument improper under Arkansas law, because Schwarz/Wyeth is the original designer bound to exercise due care to foreseeable victims, this argument is flawed because (1) so long as Schwarz/Wyeth are the NDA sponsors (RLD holder) they remain primarily responsible for the warnings in the official metoclopramide labeling; See 21 U.S.C. § 355; 21 CFR §314.50, 21 CFR §201.57, 21 CFR §314.80 & 21 CFR §314.81; (2) so long as Schwarz/Wyeth knowingly distribute inaccurate and inadequate information, and that information is reasonably relied upon by learned intermediaries in making treatment decisions, Schwarz/Wyeth are liable for the injuries caused because it is foreseeable their information would be relied upon; (3) so long as Schwarz/Wyeth fail to correct the misinformation distributed in the stream of commerce they remain liable to Plaintiff; (4) as long as Schwarz/Wyeth are primarily responsible for promulgating and distributing the warnings, it should be responsible for injuries caused by the inadequacy of those warnings. These all fit the above Arkansas law.
Moreover, even if Foster were applicable, it erroneously concluded that the information disseminated by defendants could not reasonably be relied upon because the information disseminated only pertained to the manufacturer's product. Id. at 170-171. This is incorrect and overlooks the fact that the information promulgated and distributed by the NDA/RLD sponsor is the safety information in the drug labeling that is relied upon for all drugs whether generic or name brand. It is not only reasonable, but expected, physicians, pharmacists and patients will rely upon information distributed in the official metoclopramide labeling by the NDA/RLD holder, whether by publication into a reference book, a package insert or promotional materials. In the current claim in this lawsuit, the official metoclopramide labeling and other information, including marketing information, was written and published by Schwarz/Wyeth and this misinformation did not properly disclose the increased risks and frequency of the dangers of Tardive Dyskinesia to Plaintiff's prescribing physician.
Conte rejected Foster for these reasons, saying further, “the Foster court first criticized the plaintiffs' negligent misrepresentation claim as an attempted end-run around the requirements of product liability law and, specifically, the requirement that the plaintiff must prove the defendant made the injurious product.” 2008 WL 4823066 at *10. In Conte, as here, Wyeth “maintains that Conte's action is an attempt to ‘evade ... black-letter [law]’ by labeling product liability claims as causes of action for negligent and intentional misrepresentation.” Id. But as Conte explained, “we do not agree that a suit based on a theory of negligent or intentional misrepresentation is governed by rules developed under the distinct doctrine of strict products liability law. Just because a products liability claim arising from an injury might lie against other parties ... does not mean that Wyeth has no potential liability for a negligent or intentional tort.” Id.
V.
ORIGINATOR LIABILITY COMPORTS WITH ARKANSAS PRODUCT LIABILITY LAW
The Arkansas statute on product liability appears to encompass warnings cases.[FN7] But relative to Wyeth and Schwarz, the harm is caused by the negligent warning itself. This gives rise to a negligent failure to warn claim as described above, based upon the duty imposed as a consequence of the Hatch Waxman Act, under which Wyeth and Schwarz know or should know that generic makers, doctors and patients will rely on their warnings.
FN7. ARK. CODE ANN. § 16-116-102(5)
VI.
CONCLUSION
Plaintiff is not simply suing Wyeth and Schwarz Pharma as “manufacturers” of a drug, but is suing them as corporate citizens of the State of Arkansas, and as the designer of this product and its warning, and seeks to hold them accountable for their negligent and fraudulent acts which caused her injuries pursuant to Arkansas law. Thus, Plaintiff respectfully requests that this Court deny Wyeth and Schwarz Pharma, Inc.'s motion for summary judgment.
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