Earlier, I posted the second brief filed by Gladys Mensing in her Metoclopramide lawsuit.  Here’s the opening brief.  It gives an even better overview of the history of Metaclopramide litigation and the link between Tardive Dyskinesia and Metoclopramide.  Metoclopramide is of course the generic version of the prescription drug Reglan.

There are many lawsuits in state and federal court filed on behalf of people who acquired movement disorders such as Tardive Dyskinesia and Tardive Dystopia after using Reglan or Metoclopramide for long periods of time.  If you think you may have a movement disorder, and you’ve been using Reglan or Metoclopramide for longer than 12 weeks, contact me and I’ll put you in touch with a Reglan attorney who will investigate whether you may have a potential Metoclopramide lawsuit.

SUMMARY OF THE CASE AND REQUEST FOR ORAL ARGUMENT

Appellant Gladys Mensing developed tardive dyskinesia, a serious neurological movement disorder, as a result of her long-term use of the drug metoclopramide, the generic version of the prescription drug Reglan. She sued the manufacturers of the generic metoclopramide she had ingested for failure to provide adequate warnings of the risks of using metoclopramide. She also sued the manufacturers of Reglan for tortious misrepresentation.

The district court ruled that Ms. Mensing's claims against the manufacturers of generic metoclopramide are preempted by the federal Food, Drug & Cosmetic Act (FDCA) and FDA regulations regarding generic drugs. The court also ruled that Ms. Mensing could not sue the manufacturers of Reglan, because under Minnesota law drug companies owe no duty to persons who do not take their product. This appeal followed.

Appellant requests oral argument of 30 minutes per side. This case presents two important legal issues of first impression in this court: the preemptive effect of FDA regulation of generic drugs on state tort liability and the liability of name-brand drug companies for misrepresentations that foreseeably result in physical injury to third parties.[FN1]

    FN1. Appellant is today filing a motion to certify this second question to the Minnesota Supreme Court pursuant to Minnesota Statues §480.065. If that motion is granted, Appellant suggests that only 20 minutes per side will be needed for argument on the issue of federal preemption.

TABLE OF CONTENTS

SUMMARY OF THE CASE AND REQUEST FOR ORAL ARGUMENT … i

TABLE OF AUTHORITIES … v

JURISDICTIONAL STATEMENT … 1

STATEMENT OF ISSUES … 2

STATEMENT OF THE CASE … 3

STATEMENT OF FACTS … 4

Regulatory History of Metoclopramide … 5

The Risks of EPS Associated with Use of Metoclopramide … 8

FDA Regulation of Generic Drugs … 8

SUMMARY OF ARGUMENT … 11

ARGUMENT … 13

I. Appellant's Failure-to-Warn Claims Against the Manufacturers of Generic Metoclopramide Are Not Preempted Under the FDCA … 13

A. Standard of Review … 13

B. Introduction … 13

C. The District Court Ignored the Strong Presumption that Appellant's State Tort Claims Are Not Preempted … 17

D. There Is No Conflict Between Ms. Mensing's Claims and the FDA's Regulation of Generic Drugs … 20

1. FDA requires all drug manufacturers to update label warnings to reflect current knowledge about a drug's risks … 21

2. A generic manufacturer can add or strengthen label warnings without prior FDA approval through a “changes being effected” supplement … 23

3. A generic manufacturer can employ other means to warn of its product's risks … 30

4. Appellant's failure-to-warn claims complement and advance the purposes and objectives of congress … 34

5. This Court should not defer to pronouncements by the FDA under the Bush Administration regarding preemption … 37

II. Name-Brand Manufacturers Schwarz and Wyeth Are Liable for Their False and Misleading Statements … 41

A. Standard of Review … 41

B. Introduction … 41

C. The District Court Erred in Granting Summary Judgment on Ms. Mensing's Intentional Fraud Claims … 42

1. Schwarz and Wyeth are liable for fraud regardless of whether they produced the product that caused Ms. Mensing's injuries … 42

2. Flynn is not to the contrary … 44

D. The District Court Erred in Granting Summary Judgment on Ms. Mensing's Negligent Misrepresentation Claim … 46

1. Schwarz and Wyeth owed a duty of care … 46

2. The name-brand Appellees failed to establish any basis for immunity … 49

3. The Minnesota Supreme Court would likely recognize a negligent misrepresentation tort based on Restatement §311 if squarely presented with the question … 51

E. The Minnesota Supreme Court Would Follow Conte, not Foster … 54

CONCLUSION … 57

TABLE OF AUTHORITIES

Cases

62 Cases, More or Less, Each Containing Six Jars of Jam v. United States, 340 U.S. 593 (1951) … 35

Albertson v. Chicago, M., St. P. & P. R. Co., 64 N.W.2d 175 (Minn. 1954) … 52

Altria v. Good, 128 S.Ct. 538 (2008) … 19

Auer v. Robbins, 519 U.S. 452 (1997) … 39

Barnhill v. Teva Pharmaceuticals USA, Inc., No. 06-0282-CB-M, 2007 U.S.Dist. LEXIS 44718 (S.D. Ala. Apr. 24, 2007) … 2, 25, 27, 29

Bates v. Dow Agrosciences, LLC, 544 U.S. 431 (2005) … 14, 17, 19, 36

Bell v. Lollar, 791 N.E.2d 849 (Ind. App. Ct. 2003) … 24, 29

Block v. Wyeth, Inc., No. 3:02-CV-1077, 2003 WL 203067 (N.D. Tex. Jan. 28, 2003) … 29

Bonhiver v. Graff, 248 N.W.2d 291 (Minn. 1976) … 51

Bonito Boats, Inc. v. Thunder Craft Boats, Inc., 489 U.S. 141 (1989) … 18

Bowen v. Georgetown University Hospital, 488 U.S. 204 (1988) … 39

Bursch v. Beardsley & Piper, a Division of Pettibone Corp., 971 F.2d 108 (8th Cir. 1992) … 55, 56

Busterud v. Farrington, 31 N.W. 360 (Minn. 1887) … 43

Canada by and through Landy v. McCarthy, 567 N.W.2d 496 (Minn. 1997) … 56

Carter v. Arkansas, 392 F.3d 965 (8th Cir. 2004) … 13

Chevron, U.S.A., Inc. v. Natural Resources Defense Council, Inc., 467 U.S. 837 (1984) … 38

Christensen v. Harris County, 529 U.S. 576 (2000) … 39

Clark v. Pfizer, Inc., 2008 Phila. Ct. Comm. PI. LEXIS 74 (Phila. Ct. Com. Pl. Mar. 14, 2008) … 49, 50

Clark v. Rental Equipment Co., 220 N.W.2d 507 (1974) … 53

Conte v. Wyeth, 85 Cal. Rptr. 3d 299 (Cal. Ct. App. 2008), review denied (Jan. 21, 2009) … passim

Cozza v. Culinary Foods, Inc., 723 N.E.2d 1199 (Ill. App. Ct. 2000) … 54

Davis v. Board of County Commissioners of Dona Ana County, 987 P.2d 1172 (N.M. Ct. App. 1999) … 53

Demahy v. Wyeth, Inc., 586 F. Supp. 2d 642 (E.D. La. 2008) … passim

Desiano v. Warner-Lambert, 467 F.3d 85 (2d Cir. 2006), aff'd sub nom. Warner-Lambert v. Kent, 128 S.Ct. 31 (2007) … 18

Ehlis v. Shire Richwood, Inc., 367 F.3d 1013 (8th Cir. 2004) … 41

Ellis v. Lindmark, 225 N.W. 395 (Minn. 1929) … 56

Federal Labor Relations Authority v. United States Department of Navy, 966 F.2d 747 (3d Cir. 1992) … 38

Fjellman v. Weller, 7 N.W.2d 521 (Minn. 1943) … 47

Florenzano v. Olson, 387 N.W.2d 168 (Minn. 1986) … 51, 54

Flynn v. American Home Products Corp., 627 N.W.2d 342 (Minn. Ct. App. 2001) … 44, 45, 49

Foster v. American Home Products Corp., 29 F.3d 165 (4th Cir. 1994) … passim

Gade v. National Solid Wastes Management Ass'n, 505 U.S. 88 (1992) … 27

Gaetke v. Ebarr Co., 263 N.W. 448 (Minn. 1935) … 43

General Insurance Co. of America v. Lebowsky, 252 N.W.2d 252 (M inn. 1977) … 53

Globetti v. Sandoz Pharms. Corp., No. CV 98-TMP-2649-S, 2001 19160 (N.D. Ala. Mar. 5, 2001) … 35

Gonzales v. Oregon, 546 U.S. 243 (2006) … 38, 39

Good Samaritan Hospital v. Shalala, 508 U.S. 402 (1993) … 40

Hanberry v. Hearst Corp., 81 Cal. Rptr. 519 (Cal. Ct. App. 1969) … 51

Hollerman v. F.H. Peavey & Co., 130 N.W.2d 534 (Minn. 1964) … 53

Holthusen v. United States, 498 F. Supp. 2d 1236 (D. Minn. 2007) … 47

In re Minnesota Breast Implant Litigation, 36 F. Supp. 2d 863 (D. Minn. 1998) … 45

Inwood Laboratories, Inc. v. Ives Laboratories, 456 U.S. 844 (1982) … 48

Isler v. Burman, 232 N.W.2d 818 (Minn. 1975) … 52

Iverson v. Johnson Gas Appliance Co., 172 F.3d 524 (8th Cir. 1999) … 42

Kellogg v. Wyeth, No. 2:07-cv-82, 2008 WL 5272715 (D. Vt. Dec. 17, 2008) … passim

Kelly v. Wyeth, No. 03-3314F, 2007 WL 1302589 (Mass. Super. Ct. Apr. 12, 2007) … 29, 31

Kelly v. Wyeth, No. 03-3314F, 2007 WL 3407466 (Mass. Super. Ct. Oct. 23, 2007) … 29

Knapp v. Hanson, 183 F.3d 786 (8th Cir. 1999) … 13

Laisure-Radke v. Par Pharmaceutical, No. C03-365RSM, 2006 WL 901657 (W.D. Wash. Mar. 29, 2006) … 2, 24, 29

Larson v. Wasemiller, 738 N.W.2d 300 (Minn. 2007) … 43, 54

Lehman v. Hansord Pontiac Co., 74 N.W.2d 305 (Minn. 1955) … 44

Levine v. Wyeth, 944 A.2d 179 (Vt. 2006), cert. granted, 128 S.Ct. 1118 (2008) … 14

M.H. v. Caritas Family Services, 488 N.W.2d 282 (Minn. 1992) … 57

Maryland v. Louisiana, 451 U.S. 725 (1981) … 17

Mattingly v. Sportsstuff, Inc., No. 07-cv-0403-MJR, 2007 WL 2410105 (S.D. Ill. Aug. 23, 2007) … 51

McKenney v. Purepac Pharmaceutical Co., 83 Cal. Rptr. 3d 810 (Cal. Ct. App. 2008), review denied (Jan. 14, 2009) … 22

McNeil v. Wyeth, 462 F.3d 364 (5th Cir. 2006) … 5, 41

Medtronic, Inc. v. Lohr, 518 U.S. 470 (1996) … 17, 19

Merrell Dow Pharmaceuticals, Inc. v. Oxendine, 649 A.2d 825 (D.C. 1994) … 14

Metrpolitan Life Insurance Co. v. Massachusetts, 471 U.S. 724 (1985) … 17

Molloy v. Meier, 679 N.W.2d 711 (Minn. 2004) … 2, 46, 47

Mulder v. Parke Davis & Co., 181 N.W.2d 882 (Minn. 1970) … 47

Mulroy v. Wright, 240 N.W. 116 (Minn. 1931) … 47, 51, 52

Perry v. Novartis Pharmaceutical Corp., 456 F. Supp. 2d 678 (E.D. Pa. 2006) … 31, 32

Plutshack v. University of Minnesota Hospitals, 316 N.W.2d 1 (Minn. 1982) … 53

Rice v. Norman Williams Co., 458 U.S. 654 (1982) … 15, 27

Rice v. Santa Fe Elevator Corp., 331 U.S. 218 (1947) … 17, 20

Richey v. Philipp, 259 S.W.3d 1 (Mo. Ct. App. 2008) … 53

Richfield Bank & Trust Co. v. Sjogren, 244 N.W.2d 648 (1976) … 43, 45

Riegel v. Medtronic, Inc., 128 S.Ct. 999 (2008) … 38, 40

Rottinghaus v. Howell, 666 P.2d 899 (Wash. Ct. App. 1983) … 51

Securities Exchange Commission v. Capital Gains Research Bureau, Inc., 375 U.S. 180 (1963) … 44

Sharp v. Leichus, No. 2004-CA-0643, 2006 WL 515532 (Fl. Cir. Ct. Feb. 17, 2006) … 29

Sheeks v. American Home Products Corp., No. 02-CV-337 (D. Ct. Col. Jun. 17, 2005) … 29

Silkwood v. Kerr-McGee Corp., 464 U.S. 238 (1984) … 18, 19

Skidmore v. Swift & Co., 323 U.S. 134 (1994) … 39, 40

Smith v. Brutger Cos., 569 N.W.2d 408 (Minn. 1997) … 2, 53, 55

Thomas v. Winchester, 1852 WL 4748 (N.Y. Jul. 1852) … 18

United States v. Dotterweich, 320 U.S. 277 (1943) … 35

United States v. Mead Corp., 53 3 U.S. 218 (2001) … 38, 39, 40

United States v. Sullivan, 332 U.S. 689 (1948) … 35

Witczak v. Pfizer, Inc., 377 F. Supp. 2d 726 (D. Minn. 2005) … 27, 35

Wuebker v. Wilbur-Ellis Co., 418 F.3d 883 (8th Cir. 2005) … 17, 20, 41

Statutes

21 U.S.C. §321 … 14

21 U.S.C. § 352(f)(2) … 2, 9, 12, 26

21 U.S.C. § 355-1 … 33

21 U.S.C. § 355(a) … 8

21 U.S.C. § 355(b) … 5, 8

21 U.S.C. § 355(d) … 8

21 U.S.C. § 355(j) … 5, 9

21 U.S.C. § 355(j)(2)(A)(iv) … 48

21 U.S.C. § 355(j)(2)(A)(v) … 24, 25, 28

21 U.S.C. § 355(o)(4) … 29

21 U.S.C. § 355(o)(4)(1) … 30

35 U.S.C. § 154 … 56

35 U.S.C. § 156 … 5 6

Minn. Stat. § 151.21 (2005) … 42, 48

Minn. Stat. § 480.065 (2008) … ii

Minn. Stat. § 604.01 (2008) … 56

Pub. L. No. 110-85, 121 Stat. 823 (2007) … 16, 29, 30, 33

Pub. L. No. 87-781, 76 Stat. 780 (1962) … 14

Pub. L. No. 98-417, 98 Stat. 1585 (1984) … 57

Regulations

21 C.F.R. § 10.85(d) (2005) … 38

21 C.F.R. § 201.56 (2005) … 9

21 C.F.R. § 201.57 (2005) … 9

21 C.F.R. § 201.57(e) (2005) … 10, 12, 21, 39

21 C.F.R. § 201.80(e) (2008) … 11, 21, 30, 34

21 C.F.R. § 314.150 (2005) … 27

21 C.F.R. § 314.150(b)(10) (2005) … 27

21 C.F.R. § 314.70(a) (2005) … 23

21 C.F.R. § 314.70(b) (2005) … 10, 31

21 C.F.R. § 314.70(c) (2005) … passim

21 C.F.R. §314.70(c)(2) (1993) … 28

21 C.F.R § 314.70(c)(6)(iii)(A) (2005) … 10, 23

21 C.F.R. § 314.97 (1993) … 28

21 C.F.R. § 314.97 (2005) … 16, 24, 39

44 Fed. Reg. 37434 (Jun. 26, 1979) … 11

57 Fed. Reg. 17950 (Apr. 28, 1992) … 22, 27, 28

63 Fed. Reg. 66378 (Dec. 1, 1998) … 36

71 Fed. Reg. 3922 (Jan. 24, 2006) … 10, 48

73 Fed. Reg. 16313 (Mar. 27, 2008) … 33

73 Fed. Reg. 2848 (Jan. 16, 2008) … 25, 37

Other Authorities

108 Cong. Rec. 21,083 (1962) … 14

Adler, Robert S. & Mann, Richard A., Preemption and Medical Devices: The Courts Run Amok, 59 Mo. L. REV. 895 (1994) … 18

Center for Drug Evaluation and Research, NDAs: Dear Healthcare Professional Letters, MANUAL OF POLICIES AND PROCEDURES (July 2, 2003) … 33

Colacicco v. Apotex, Inc., No. 06-3107, Brief of the United States as Amicus Curiae (3d Cir. Dec. 28, 2006) … 21, 37

Hearings on S. 1944 Before a Subcommittee of the Committee on Commerce, S. 1944, 73d. Cong., 2d Sess. 400 (1933) … 18

Kessler, David A. & Vladeck, David C., A Critical Examination of the FDA's Efforts to Preempt Failure-to-Warn Claims, 96 GEO. L.J. 461 (2008) … 36

Minn. Dist. Judges Association, MINN. PRAC.: JURY INSTRUCTION GUIDES-CIVIL (5th ed. 2006) … 56

Porter, Margaret J., The Lohr Decision: FDA Perspective and Position, 52 FOOD & DRUG. L.J. 7 (1997) … 36

Restatement (First) of Torts § 311 (1934) … 54

Restatement (Second) of Torts § 310 (1965) … 43

Restatement (Second) of Torts § 311 (1965) … 51

Restatement (Second) of Torts § 440 (1965) … 56

Restatement (Second) of Torts § 549 (1977) … 44

Restatement (Second) of Torts § 552 (1977) … 47

JURISDICTIONAL STATEMENT

Jurisdiction in the district court was based on diversity of citizenship under 28 U.S.C. §1332. This appeal is from a final judgment disposing of all claims, establishing jurisdiction in this Court under 28 U.S.C. § 1291. The trial court entered final judgment for defendants on October 28, 2008, and Appellant filed a timely notice of appeal on November 26, 2008.

STATEMENT OF ISSUES

1. Whether the district court erred in holding that the FDCA preempts Appellant's claims for personal injuries caused by generic drug manufacturers' failure to warn?

Kellogg v. Wyeth, No. 2:07-cv-82, 2008 WL 5272715 (D. Vt. Dec. 17, 2008).

Demahy v. Wyeth, Inc., 586 F. Supp. 2d 642 (E.D. La. 2008).

Barnhill v. Teva Pharms. USA, Inc., No. 06-0282-CB-M, 2007 U.S.Dist. LEXIS 44718 (S.D. Ala. Apr. 24, 2007).

Laisure-Radke v. Par Pharm., Inc., No. C03-365RSM, 2006 WL 901657 (W.D. Wash. Mar. 29, 2006).

21 U.S.C. §352(f)(2).

2. Whether name-brand prescription drug manufacturers owe a duty of care under Minnesota law to consumers of materially identical, generic equivalents, when it is reasonably foreseeable that physicians will rely on the name-brand companies' labeling in prescribing the bioequivalent generic product?

Conte v. Wyeth, 85 Cal. Rptr. 3d 299 (Cal. Ct. App. 2008), review denied (Jan. 21, 2009).

Smith v. Brutger Cos., 569 N.W.2d 408 (Minn. 1997).

Molloy v. Meier, 679 N.W.2d 711 (Minn. 2004).

STATEMENT OF THE CASE

This is a personal injury action brought by Appellant Gladys Mensing for injuries caused by her long-term ingestion of metoclopramide. Mensing sued the manufacturers of the generic metoclopramide she had taken for failure to warn of the risks of long-term metoclopramide use. She also sued the manufacturers of Reglan for fraud and negligent misrepresentation.

All defendants filed motions to dismiss or for summary judgment. On June 17, 2008, the district court issued a memorandum opinion and order dismissing Ms. Mensing's claims against defendants Actavis Elizabeth, LLC (Actavis) and Pliva, Inc. (Pliva) on grounds of federal preemption. App. 282a-299a. On October 27, 2008, the district court granted motions for summary judgment filed by all remaining defendants,[FN2] on grounds of federal preemption in the case of the remaining manufacturers of generic metoclopramide, and on grounds of no duty of care under Minnesota law for the manufacturers of Reglan. This appeal followed.

    FN2. Appellant had voluntarily dismissed original defendants Alpharma, Inc. and Purepac Pharmaceutical Co. after establishing that neither had manufactured any of the generic metoclopramide she had taken. App. 306a. The Court's October 27, 2008, opinion was subsequently amended on October 30, 2008, to correct a minor error. Appellant has included the amended opinion in the Appendix and Addendum.

STATEMENT OF FACTS

In March 2001, Gladys Mensing's physician prescribed the drug Reglan to treat her diabetic gastroparesis. App. 29a. The active ingredient in Reglan is metoclopramide, which is available in both branded and generic forms. In prescribing metoclopramide for Ms. Mensing, her physician relied on the labeling for Reglan. App. 30a. Reglan was manufactured and distributed by Appellee Wyeth, Inc. (Wyeth) from approximately 1989 through 2001, and thereafter through 2005 by Appellee Schwarz Pharma, Inc. (Schwarz) (collectively, “name-brand appellees”). App. 313a

In accordance with Minnesota law, Ms. Mensing's pharmacy filled her prescriptions with generic metoclopramide. The generic metoclopramide was manufactured and/or distributed by, inter alia, appellees Actavis, Pliva, Teva Pharmaceuticals USA, Inc. (Teva), UDL Laboratories, Inc. (UDL), and Wyeth (collectively, “generic appellees”).[FN3]

    FN3. During the period between 1995 and 2001, Wyeth manufactured and sold both name-brand Reglan and also a generic version of metoclopramide. App. 313a.

Ms. Mensing took the metoclopramide as prescribed for approximately four years, from March 2001 until March 2005. Ms. Mensing's long-term use of metoclopramide, as prescribed, resulted in her overexposure to the drug, which caused her to develop tardive dyskinesia, a severe, Parkinson's-like neurological disorder. App. 29a-31a.

Regulatory History of Metoclopramide

Reglan was approved by the FDA in 1980 and, five years later, generic drug manufacturers, including the generic appellees, began to obtain approval for generic versions of metoclopramide.[FN4] The warnings about tardive dyskinesia and other extrapyramidal symptoms (EPS) on the metoclopramide label were not revised from the time of that approval through the time when Ms. Mensing stopped taking the drug in 2005.

    FN4. The labeling used for Reglan was approved by the FDA as part of a “New Drug Application” (NDA) under FDCA §505(b), 21 U.S.C. § 355(b), and the labeling for the generic appellees' metoclopramide products was approved as part of an “Abbreviated NDA” (ANDA) under FDCA §505(j), 21 U.S.C. §355(j).

The FDA approved metoclopramide for use “for two to eight weeks … for the relief of symptoms associated with acute and recurrent diabetic gastric stasis” and as “short-term (4 to 12 weeks) therapy for adults with symptomatic, documented gastroesophageal reflux who fail to respond to conventional therapy.” App. 261a-262a. Despite these limitations, Appellant alleges that the name-brand appellees actively promoted the idea that long-term use was both safe and effective. App. 31a, 34a. As a result, many doctors prescribed metoclopramide for much longer periods. See McNeil v. Wyeth, 462 F.3d 364, 369 (5th Cir. 2006) (Wyeth's own data showed that 84 percent of patients were using Reglan long-term; 32 percent of patients in one study had been taking metoclopramide for more than one year). The generic appellees were aware of this widespread long-term use, but took no steps to discourage the practice. App. 35a-36a. It was not until July 2004, after Ms. Mensing had been taking metoclopramide for over three years, that the FDA approved a request by Schwarz to add a sentence to the “Indications and Usage” section of the Reglan label: “Therapy should not exceed 12 weeks in duration.”

The labels for Reglan and generic metoclopramide repeatedly assert that EPS, including tardive dyskinesia, are quite rare. The “Clinical Pharmacology” section of the label states: “Like the phenothiazines and related drugs, which are also dopamine antagonists, metoclopramide produces sedation and may produce extrapyramidal symptoms, although these are comparatively rare (See WARNINGS).” App. 260a. The “Warnings” section of the label elaborates:

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. These usually are seen during the first 24 to 48 hours of treatment with metoclopramide, occur more frequently in pediatric patients and adult patients less than 30 years of age and are even more frequent at higher dosages.

App. 261a.[FN5]

    FN5. The “Warnings” section identifies tardive dyskinesia, “a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements,” as one of the EPS that may develop in patients treated with metoclopramide, but suggests that it will occur far less frequently than the far more readily treatable acute dystonic reactions, which the label identifies as the “primar [y]” “manifest[ation]” of EPS. Id.

The “Adverse Reactions” section of the label reiterates this characterization:

Extrapyramidal Reactions (EPS)

Acute dystonic reactions, the most common type of EPS associated with metoclopramide, occur in approximately 0.2% of patients (1 in 500) treated with 30 to 40 mg of metoclopramide per day.

Id.[FN6]

    FN6. Again, tardive dyskinesia is identified as a possible adverse reaction, but one that will occur in far fewer patients than the 1 in 500 who will experience acute dystonic reactions. Id.

Despite mounting evidence that the risks of EPS in general and tardive dyskinesia in particular were much greater than reflected in the product label, particularly when patients took metoclopramide for extended periods, no manufacturer of metoclopramide ever proposed to the FDA that the warnings on metoclopramide's label should be changed to reflect that greater risk. As a result, the FDA never considered, let alone rejected as unsubstantiated, any stronger warnings for the drug. Nor did any manufacturer of metoclopramide ever take any steps to alert health care professionals or patients that metoclopramide's labeling significantly understated the risks of tardive dyskinesia and other EPS. App. 35a-40a.

The Risks of EPS Associated with Use of Metoclopramide

Unfortunately, the risk that patients taking metoclopramide at the usual dosage will experience tardive dyskinesia and other EPS is much greater than was reflected on the label. No scientific evidence of any sort reliably supports the 1 in 500 claim on the metoclopramide label. App. 262a. The actual incidence of all EPS in metoclopramide patients is many times greater, and the specific incidence of tardive dyskinesia in metoclopramide patients is also far greater than 1 in 500. Indeed, the prevalence of tardive dyskinesia among patients exposed to metoclopramide for six months or longer is as much as 20 percent, 100 times greater than 1 in 500. App. 35a.

FDA Regulation of Generic Drugs

All prescription drugs marketed in this country must first be approved by the FDA. To obtain permission to market a brand new product, a drug company must first submit an NDA for the FDA's review and approval. 21 U.S.C. §355(a), (b). An NDA must include information about the clinical trials that demonstrate the safety and effectiveness of the product, proposed labeling, and other information. Id. §§355(b), (d). FDA approval includes approval of the labeling, which must identify, inter alia, contraindications, warnings, precautions, and adverse reactions. 21 C.F.R. §§201.56, 201.57 (2005).[FN7]

    FN7. A number of regulations relevant to this case have been revised or redesignated after the time period during which Appellant took metoclopramide. This brief refers to the regulations in effect between 2001 and 2005, noting subsequent changes where relevant.

Once a new drug loses patent protection, a drug company may seek permission to market a generic version of an NDA-approved drug by submitting an ANDA. 21 U.S.C. §355(j). Generic manufacturers do not need to show independent evidence of safety and efficacy; they need only establish that their product is bioequivalent to the reference listed drug. Id. In the ANDA, the labeling proposed for the generic product must be the same as the labeling approved for the listed drug in all relevant respects. Id. §355(j)(2)(A)(v).

Once the ANDA is approved, generic manufacturers become subject to most of the same statutory and regulatory responsibilities as manufacturers of NDA-approved drugs. Drug companies must ensure that their product labels remain current, lest they be deemed misbranded. 21 U.S.C. §352(f)(2) (“A drug … shall be deemed to be misbranded … unless its labeling bears … such adequate warnings against use … where its use may be dangerous … as are necessary for the protection of users”). In particular, all drug manufacturers have an obligation to revise their labels “to include a warning as soon as there is reasonable evidence of an association of a serious hazard with a drug; a causal relationship need not have been proved.” 21 C.F.R. §201.57(e) (2005);[FN8] see Kellogg v. Wyeth, 2008 WL 5272715, at *4 (D. Vt. Dec. 17, 2008) (“The obligation to revise a label to include a warning as soon as there is reasonable evidence of an association of a serious hazard with a drug applies to both generic and listed drug manufacturers.”) (citation omitted).

    FN8. In 2006, the FDA issued amended labeling regulations for prescription drugs. 71 Fed. Reg. 3922 (Jan. 24, 2006). That rulemaking, which became effective on June 30, 2006, redesignated §201.57(e) as 21 C.F.R. §201.80(e) and it remains the regulatory standard for drugs labeled under the old labeling rules, such as metoclopramide. 71 Fed. Reg. at 3988, 3996. A virtually identical requirement applies to drugs labeled under the new regulation. 21 C.F.R. §201.57(c)(6) (2008) (“In accordance with §§314.70 and 601.12 of this chapter, the labeling must be revised to include a warning about a clinically significant hazard as soon as there is reasonable evidence of a causal association with a drug; a causal relationship need not have been definitely established.”). 71 Fed. Reg. at 3990.

There are two procedures for applying for a labeling change: a Prior Approval Supplement, required for “Major Changes,” 21 C.F.R. §314.70(b), and a Changes Being Effected (CBE) Supplement for “Moderate Changes,” 21 C.F.R. §314.70(c), under which a manufacturer may proceed with the change upon notification to the agency, unless the FDA disapproves. Pursuant to regulation, labeling changes to “add or strengthen a contra-indication, warning, precaution, or adverse reaction,” may be made through the CBE process. 21 C.F.R §314.70(c)(6)(iii)(A) (2005). FDA regulations are clear that these procedures are equally applicable to supplement applications filed by generic manufacturers. 21 C.F.R. §314.97 (2005).

Even before a product label can be revised, drug companies may warn health care professionals by other means, such as a “Dear Doctor” letter, whenever possibly harmful adverse effects associated with use of the drug are discovered. 44 Fed. Reg. 37434, 37447 (Jun. 26, 1979).

Thus, the label is not fixed as of the date of FDA approval. Nor should it be: drugs receive initial approval based upon very limited clinical trials and there is a substantial likelihood that new risks, complications, and contraindications will only be identified or confirmed after the drug has been prescribed more widely. For this reason, a company's obligation to provide physicians and patients with up-to-date warnings and precautions continues as long as the product is being marketed and prescribed to patients. 21 C.F.R. §§201.57(c)(6), 201.80(e) (2008).

SUMMARY OF ARGUMENT

Taken together, the district court's two rulings leave Gladys Mensing, and any other person injured by an inadequately labeled generic drug, without legal remedy. That is not, and should not be, the law and the decisions below should be reversed.

The lower court's ruling that Ms. Mensing's claims against the generic appellees are preempted ignores the strong presumption against preemption and grants undue deference to the Bush FDA's views on this issue. Generic drugs, just like their name brand equivalents, must have adequate label warnings to protect their users, 21 U.S.C. §352(f)(2), and generic companies must revise their labels “to include a warning as soon as there is reasonable evidence of an association of a serious hazard with a drug” 21 C.F.R. §201.57(e) (2005). The generic appellees could have strengthened their warnings without prior FDA approval under 21 C.F.R. §314.70(c), they could have sought FDA approval for a labeling change, or they could have notified health care professionals, such as Ms. Mensing's doctor, by other means, but they chose not to do so. Ms. Mensing's state tort claims do not conflict with, but rather complement, the federal regulation of generic drugs and therefore are not preempted. Statements by the Bush FDA to the contrary are not entitled to judicial deference.

The district court also erred in dismissing Ms. Mensing's claims against the name-brand appellees for fraud and negligent misrepresentation on the ground that they owed no duty of care to users of generic metoclopramide. Ms. Mensing alleged that these companies made intentional misrepresentations about the risks of metoclopramide on which her physician reasonably relied, resulting in her injury. These allegations, which are as yet uncontested, satisfy all of the elements for a claim of fraud under Minnesota law. Ms. Mensing likewise alleged all of the elements of a claim for negligent misrepresentation; because it was reasonably foreseeable that her doctor would rely on the name-brand appellees' material misrepresentations about metoclopramide in prescribing the drug to Ms. Mensing, these companies both owed and breached a duty under Minnesota law. It is simply irrelevant to these tortious misrepresentation claims that Ms. Mensing was injured as a result of ingesting generic metoclopramide rather than Reglan.

ARGUMENT

I. Appellant's Failure-to-Warn Claims Against the Manufacturers of Generic Metoclopramide Are Not Preempted Under the FDCA.
A. Standard of Review.

The district court granted defendants' motions to dismiss all of Ms. Mensing's claims against the generic appellees on grounds of federal preemption. This Court “review[s] the district court's grant of a 12(b)(6) motion to dismiss de novo, ‘taking all facts alleged in the complaint as true.’ ” Carter v. Arkansas, 392 F.3d 965, 968 (8th Cir. 2004) (quoting Knapp v. Hanson, 183 F.3d 786, 788 (8th Cir. 1999)). A motion to dismiss should be granted only if it appears “beyond doubt” that the plaintiff can prove no set of facts that would entitle her to relief. Id.
B. Introduction.

In its June 17, 2008 decision, the court below decided that all of Ms. Mensing's claims against the manufacturers of generic metoclopramide were impliedly preempted, because they “actually conflict[ed] with federal law.” App. 286a. The court noted that implied conflict preemption can arise either “when compliance with both federal and state regulations is a physical impossibility, or when state law stands as an obstacle to the accomplishment and execution of the full purposes and objectives of Congress,” id., and held that Ms. Mensing's claims must be dismissed under both strands of implied conflict preemption doctrine. App. 297a-299a.[FN9]

    FN9. It is not at all clear whether the second form of conflict preemption, obstacle preemption, is even applicable to preemption claims involving prescription drugs, because of anti-preemption language added to the FDCA in the 1962 Drug Amendments: “Nothing in the Amendments made by this Act to the Federal Food, Drug, and Cosmetic Act shall be construed as invalidating any provision of State law which would be valid in the absence of such amendments unless there is a direct and positive conflict between such amendments and such provision of State law.” Drug Amendments of 1962, Pub. L. No. 87-781, ¶ 202, 76 Stat. 780, 793 (1962) (1962) (emphasis added) (incorporated in the U.S. Code as a note under 21 U.S.C. §321). At least one court has held that this language precludes claims of obstacle preemption. See Levine v. Wyeth, 944 A.2d 179 (Vt. 2006) (“This amendment essentially removes from our consideration the question of whether common-law tort claims present an obstacle to the purposes and objectives of Congress.”), cert. granted, 128 S.Ct. 1118 (2008); see also Merrell Dow Pharms., Inc. v. Oxendine, 649 A.2d 825, 828 n.3 (D.C. 1994) (citing 108 Cong. Rec. 21,083 (1962)) (explaining that the “direct and positive conflict” language has been understood to reflect Congress' intent, as expressed in the legislative history, that federal law should not preempt broadly in fields such as food and drug law where states have stronger laws and tort causes of action).

    In any event, several justices of the Supreme Court have clearly stated that obstacle preemption is increasingly disfavored. See Bates v. Dow Agrosciences, LLC, 544 U.S. 431, 459 (2005) (Thomas, J., joined by Scalia, J., concurring in judgment in part and dissenting in part) (stating that the Supreme Court is becoming “increasing[ly] reluctan[t] to expand federal statutes beyond their terms through doctrines of implied pre-emption. This reluctance reflects that pre-emption analysis is not ‘[a] freewheeling judicial inquiry into whether a state statute is in tension with federal objectives,’ but an inquiry into whether the ordinary meanings of state and federal law conflict”) (quoting Gade v. Nat'l Solid Wastes Mgmt. Ass'n, 505 U.S. 88, 111 (1992) (Kennedy, J., concurring in part and concurring in judgment)) (other citations omitted). See also Gade, 505 U.S. at 110 (Kennedy, J.) (“Our decisions establish that a high threshold must be met if a state law is to be pre-empted for conflicting with the purposes of a federal Act. Any conflict must be ‘irreconcilable.’ ”) (quoting Rice v. Norman Williams Co., 458 U.S. 654, 659 (1982)).

That ruling was in error and must be reversed. As explained in further detail below, it would not have been impossible under federal law for the generic manufacturers to strengthen the warnings on their product labels, nor would it have frustrated Congress' purposes with regard to generic drugs. There can be no doubt that the generic appellees could have provided stronger warnings about the risk of EPS and tardive dyskinesia posed by prolonged exposure to metoclopramide without running afoul of FDA regulations. Indeed, contrary to the district court's conclusion, they could have altered their labeling to strengthen warnings without prior FDA approval. Alternatively, there is no dispute that the generic companies could have-but did not-seek FDA approval for such a change. Moreover, even while awaiting agency approval, the generic companies could have provided health care professionals such as Ms. Mensing's physicians with stronger warnings by other means, such as by issuing a “Dear Doctor” letter. Because they failed to take any of these steps, despite the fact that the warnings on their labels were inadequate, they can be held liable to Ms. Mensing for failure to warn under Minnesota law.[FN10]

    FN10. The district court did not distinguish among Ms. Mensing's various causes of action against the generic appellees, treating them all as failure-to-warn claims. App. 284a (“at the core of all of Plaintiff's claims is the basic assertion that Actavis and Pliva failed to adequately warn”). By contrast, considering the identical issue, the U.S. District Court for the District of Vermont thought it necessary to distinguish between claims sounding in failure to warn and those for breach of express and implied warranties, claims also advanced by Ms. Mensing here. App. 42a-44a. The latter, the Vermont court said, “are not based on failure to provide adequate warnings of the risks of long-term use of metoclopramide, and are not in any event preempted by the FDA's drug labeling regulations.” Kellogg v. Wyeth, 2008 WL 5272715, at *5 (D. Vt. Dec. 17, 2008). This is an independent ground for overturning the dismissal of those particular claims.

In reaching its erroneous conclusion, the district court disregarded the strong presumption against preemption that should guide judicial analysis in this area. And the court granted far too much deference to the views of the FDA under the Bush administration: views that had changed from prior administrations and that were flatly inconsistent with existing regulations, see 21 C.F.R. §314.97, and with the clear intent of Congress as expressed in recently enacted legislation. See Section 901, Food and Drug Administration Amendments Act of 2007, Pub. L. No. 110-85, 121 Stat. 823, 924 (2007) (FDAAA).[FN11]

    FN11. These views may also no longer reflect the position of the present administration; the Obama FDA has not yet announced its views regarding FDA preemption of state tort claims.

C. The District Court Ignored the Strong Presumption that Appellant's State Tort Claims Are Not Preempted.

Before turning to the substance of these arguments, it is important to emphasize that, because federal preemption of state law disturbs the balance in our federalist system, preemption analysis always begins with a “basic presumption against pre-emption.” Bates v. Dow Agrosciences, LLC, 544 U.S. 431, 449 (2005); Maryland v. Louisiana, 451 U.S. 725, 746 (1981) ( “Consideration under the Supremacy Clause starts with the basic assumption that Congress did not intend to displace state law.”) (citation omitted); see also Wuebker v. Wilbur-Ellis Co., 418 F.3d 883, 887 (8th Cir. 2005).

The presumption against preemption is heightened in this case for three reasons. First, the presumption is “particularly [strong] in those [cases] in which Congress has ‘legislated… in a field which the States have traditionally occupied.’ ” Medtronic, Inc. v. Lohr, 518 U.S. 470, 485 (1996) (quoting Rice v. Santa Fe Elevator Corp., 331 U.S. 218, 230 (1947)); see also Wuebker, 418 F.3d at 887 (“states have traditionally regulated manufacturers of poisonous substances… through tort law”) (citation omitted). “The States traditionally have had great latitude under their police powers to legislate as ‘to the protection of the lives, limbs, health, comfort and quiet of all persons,” Metro. Life Ins. Co. v. Massachusetts, 471 U.S. 724, 756 (1985) (citation omitted), and, historically, have employed common law liability as “the bedrock of state regulation” in this area. Desiano v. Warner-Lambert, 467 F.3d 85, 86 (2d Cir. 2006), aff'd sub nom., Warner-Lambert v. Kent, 128 S.Ct. 31 (2007).

Second, “[t]he case for federal pre-emption is particularly weak where Congress has indicated its awareness of the operation of state law in a field of federal interest, and has nonetheless decided to ‘stand by both concepts and to tolerate whatever tension there [is] between them.’ ” Bonito Boats, Inc. v. Thunder Craft Boats, Inc., 489 U.S. 141, 166-67 (1989) (quoting Silkwood v. Kerr-McGee Corp., 464 U.S. 238, 256 (1984)). State tort actions against pharmaceutical manufacturers have existed for more than a century. See, e.g., Thomas v. Winchester, 1852 WL 4748, *1 (N.Y. Jul., 1852) (“A dealer in drugs and medicines, who carelessly labels a deadly poison as a harmless medicine, and sends it so labeled into market, is liable to all persons, who, without fault on their part, are injured by using it as such medicine in consequence of the false label.”). Congress was well aware of these suits when it enacted the FDCA. In fact, Congress decided not to include a private right of action for damages in the FDCA on the grounds that it was unnecessary, because a “common-law right of action … exists” in state law. Adler & Mann, Preemption and Medical Devices: The Courts Run Amok, 59 Mo. L. REV. 895, 924 & n.130 (1994) (internal quotations omitted) (quoting Hearings on S. 1944 Before a Subcomm. of the Comm. on Commerce, U.S. Senate, 73rd Cong., 2d Sess. 400, 403 (1934)).

Finally, where preemption would deprive an injured person of a remedy, there is a greater burden on the party seeking preemption “to convince [the court] that Congress intended that result.” Lohr, 518 U.S. at 487. This is especially so if the federal act does not provide an alternate form of relief. Id. (“It is, to say the least, ‘difficult to believe that Congress would, without comment, remove all means of judicial recourse for those injured by illegal conduct.’ ”) (quoting Silkwood, 464 U.S. at 251); Bates, 544 U.S. at 449 (“If Congress had intended to deprive injured parties of a long available form of compensation, it surely would have expressed that intent more clearly.”); Kellogg v. Wyeth, 2008 WL 5272715, at *6 (“It is unlikely that Congress by its silence intended the Hatch-Waxman Amendments to accord generic drug manufacturers virtual immunity from tort liability.”) (citation omitted)).

The district court gave lip service to the presumption, App. 290a, but then asserted that “the presumption against preemption is not always appropriate,” at least in “the context of conflict preemption.” Id. The Supreme Court disagrees. In an important preemption decision handed down this past December, the Court observed: “When addressing questions of express or implied preemption, we begin our analysis ‘with the assumption that the historic police powers of the States [are] not to be superseded by the Federal Act unless that was the clear and manifest purpose of Congress.’ ” Altria v. Good, 128 S.Ct. 538, 543 (2008) (quoting Rice v. Santa Fe, 331 U.S. at 230); see also Wuebker, 418 F.3d at 887 (applying presumption to issue of implied conflict preemption).[FN12]

    FN12. See also Kellogg v. Wyeth, 2008 WL 5272715, at *6 n.5. After noting that the district court in this case “apparently declined to apply the presumption against preemption,” the Kellogg court “[r]espectfully” disagreed with that decision: “It is precisely where Congress has not included an express statement concerning the preemptive effect of its enactment that courts must be mindful that they do not lightly tread on the historic powers of the states to protect the health and welfare of their citizens, and apply the presumption.” Id. (citation omitted).

D. There Is No Conflict Between Ms. Mensing's Claims and the FDA's Regulation of Generic Drugs.

There is no direct conflict between the FDA's regulation of generic drugs and the remedy sought in Appellant's suit. In fact, state tort liability for inadequate warnings complements and furthers the objectives of the federal regulatory scheme. Both FDA regulations and Minnesota law require drug companies to provide adequate warnings of significant dangers posed by their products. The generic appellees could have avoided liability to Ms. Mensing by providing physicians with accurate warnings about metoclopramide's risks and by applying to the FDA for a labeling change to reflect those heightened warnings.[FN13]

    FN13. Cf. Kellogg v. Wyeth:

    At the times relevant to this litigation, under the regulations then in force, a generic manufacturer having new information about the hazards of a drug could have availed itself of the CBE process, could have sought FDA approval for a change in the drug labeling, could have provided health care professionals with stronger warnings, or could have elected not to act and to accept the risk of tort liability should an injured plaintiff prevail on her suit.

    2008 WL 5272715, at *7.

1. FDA requires all drug manufacturers to update label warnings to reflect current knowledge about a drug's risks.

As the FDA has recognized, “drug labeling does not always contain the most current information and opinion available to physicians about a drug because advances in medical knowledge and practice inevitably precede formal submission of proposed new labeling by the manufacturer and approval by the FDA.” 44 Fed. Reg. 37434, 37435 (Jun. 26, 1979). Therefore, FDA regulations place the onus on drug manufacturers-both name brand and generic-to strengthen label warnings as soon as possible: “the 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; a causal relationship need not have been proved.” 21 C.F.R. §201.57(e) (2005) (emphasis added). As the FDA stated in an amicus brief, it is “the manufacturer [that] has an obligation to seek FDA approval for a labeling change, in order to add a warning of the new potential hazard.” Colacicco v. Apotex, Inc., No. 06-3107, Brief of the United States as Amicus Curiae (Colacicco amicus), at 7 n.3 (3d Cir. Dec. 28, 2006) (citing 21 C.F.R. §201.80(e)).[FN14]

    FN14. Curiously, the decision below never acknowledges a drug manufacturer's federal statutory and regulatory obligation to update label warnings.

There can be no question that this obligation to strengthen warning labels applies to manufacturers of generic drugs. In the 1992 rulemaking notice promulgating final rules to implement the Hatch-Waxman Amendments, the FDA explicitly stated: “An ANDA applicant who believes the labeling for a proposed drug product should differ from that approved for the reference listed drug should contact the FDA to discuss whether labeling for both generic and listed drugs should be revised.” 57 Fed. Reg. 17950, 17957 cmt. 20 (Apr. 28, 1992). This obligation to strengthen warnings continues after an ANDA is approved: “After approval of an ANDA, if an ANDA holder believes that new safety information should be added, it should provide adequate supporting information to the FDA, and FDA will determine whether the labeling for the generic and listed drugs should be revised.” 57 Fed. Reg. at 17961 cmt. 40; see also Kellogg v. Wyeth, 2008 WL 5272715, at *4 (“The obligation to revise a label to include a warning as soon as there is reasonable evidence of an association of a serious hazard with a drug applies to both generic and listed drug manufacturers.”); McKenney v. Purepac Pharm. Co., 83 Cal. Rptr. 3d 810, 818 (Cal. Ct. App. 2008), review denied (Jan. 14, 2009) (citing above language from 1992 Federal Register and concluding: “We, therefore, see no reason to distinguish between original or ‘listed’ drugs and their generic equivalents for federal preemption purposes.”).
2. A generic manufacturer can add or strengthen label warnings without prior FDA approval through a “changes being effected” supplement.

Contrary to the conclusion of the court below, App. 292a, a generic manufacturer can add or strengthen label warnings without prior FDA approval. 21 C.F.R. §314.70(c), which is applicable to both name brand and generic drug manufacturers, authorizes manufacturers to make “Moderate Changes” to their labels upon notification to the FDA through a Changes Being Effected (“CBE”) Supplement. Normally, labeling changes to strengthen warnings are handled through the CBE supplement process. Section 314.70(c) expressly authorizes manufacturers to file a CBE supplement

(A) To add or strengthen a contraindication, warning, precaution, or adverse reaction;

(B) To add or strengthen a statement about drug abuse, dependence, or over-dosage;

(C) To add or strengthen an instruction about dosage and administration that is intended to increase the safe use of the drug product; [and]

(D) To delete false, misleading, or unsupported indications for use or claims of effectiveness

21 C.F.R. §314.70 (c)(2)(iii)(A-D) (2005).

This regulation, permitting manufacturers to strengthen label warnings unilaterally, applies to all “approved application[s],” 21 C.F.R. §314.70(a), and does not except or exempt manufacturers of generic drugs. See, e.g., Foster v. Am. Home Prods. Corp., 29 F.3d 165, 170 (4th Cir. 1994) (“generic manufacturers … [are] permitted to add or strengthen warnings and delete misleading statements on labels, even without prior FDA approval”); Bell v. Lollar, 791 N.E.2d 849, 854 (Ind. App. Ct. 2003) (21 C.F.R. §314.70(c)(2)(i) “provides that once an NDA or ANDA has been approved, the applicant may make changes to the label [to add or strengthen a warning] without FDA approval”); Laisure-Radke v. Par Pharm., Inc., No. C03-365RSM, 2006 WL 901657, at *5 (W.D. Wash. Mar. 29, 2006) (“once a generic drug manufacturer holds an approved ANDA for a particular product, it can add or strengthen a contraindication, warning, precaution or adverse reaction at any time without prior FDA approval.”). Indeed, a separate regulation, 21 C.F.R. §314.97, directs generic manufacturers to comply with section 314.70 “regarding the submission of supplemental applications and other changes to an approved abbreviated application”.

Despite this, the district court rejected the proposition that “FDA regulations require both name brand and generic manufacturers to strengthen warning labels post-approval.” App. 292a. The court based its conclusion, in substantial part, on 21 U.S.C. §355(j)(2)(A)(v), the provision of the Hatch-Waxman Act that requires an applicant for an ANDA to submit information to show “that the labeling proposed for the new drug is the same as the labeling approved for the listed drug,” as well as to FDA statements that refer back to this statutory obligation. Id.

There are at least three problems with this argument. First, and most importantly, the district court's conclusion simply cannot be squared with the clear, unambiguous language of 21 C.F.R. §§314.70(c) and 314.97. Section 314.70(c) expressly authorizes manufacturers to employ the CBE process to strengthen label warnings and section 314.97 unambiguously instructs generic manufacturers to comply with section 314.70 “regarding the submission of supplemental applications and other changes to an approved abbreviated application.” See Demahy v. Wyeth, Inc., 586 F. Supp. 2d 642, 651 (E.D. La. 2008) (under §314.97, “generic manufacturers should be able to unilaterally change their labels after initial ANDA approval”). The opinion below never even cites section 314.97.[FN15]

    FN15. The district court does accurately cite two instances in which the FDA under the Bush administration made statements to the effect that generic drug manufacturers could not utilize the CBE supplement procedure to strengthen their warning labels, one in the amicus brief submitted in the Colacicco case, and the other in the supplementary section of a notice of proposed rulemaking, 73 Fed. Reg. 2848, 2849 n.1 (Jan. 16, 2008). App. 296a-297a. As explained in Part I.D.5., infra, these statements are not entitled to any deference from the court, because they are flatly inconsistent with the unambiguous language of FDA regulations.

Second, 21 U.S.C. §355(j)(2)(A)(v), and much of the regulatory language the court cites, App. 292a-294a, by their terms apply only to the generic manufacturer's original ANDA, submitted to gain initial market approval, not to post-approval labeling supplements. Accord Barnhill v. Teva Pharms. USA, Inc., No. 06-0282-CB-M, 2007 U.S. Dist. LEXIS 44718, at *8 (S.D. Ala. Apr. 24, 2007) (21 U.S.C. §355(j)(2)(A)(v) and regulatory comments cited by generic manufacturer “address labeling requirements necessary for initial approval, not changes to labels for approved ANDA's”). Under the statutory scheme established by the Hatch-Waxman Act, it makes sense to require manufacturers of generic products to conform their label to that of the reference listed drug in the initial application: the whole point of the ANDA process is to limit initial FDA review to the issue of bioequivalence, without reopening issues of safety and efficacy regarding the listed product, in order to speed the entry of bioequivalent generic drugs into the market. Once the ANDA has been approved, however, the agency examination required to evaluate a proposed new warning will be the same, whether the request comes from a name brand or generic manufacturer. And generic manufacturers, just like their name brand competitors, are subject to the same statutory requirement that their labels, “for the protection of users,” bear adequate warnings against any use dangerous to health. 21 U.S.C. §352 (f)(2).[FN16]

    FN16. Cf Demahy v. Wyeth, Inc., 586 F. Supp. 2d at 649 (“Neither party disputes the fact that a generic drug must have the ‘same’ label as the name brand pioneer drug at the time of an initial ANDA application. The crucial question … is whether a generic drug that has already been approved via the ANDA process can change its label to include new or different warnings without FDA approval”) (emphasis in original).

Finally, the district court relied on a regulation that permits-but does not require-the FDA to seek to withdraw approval of an ANDA upon a determination that “the labeling for the drug product… is no longer consistent with that for the listed drug,” 21 C.F.R. §314.150(b)(10), as evidence that generic companies could not initiate CBE labeling changes. App. 293a. But that reliance was misplaced. As explained in Barnhill, “the purpose of this regulation was not to prevent a generic manufacturer from improving or strengthening its warnings. It was, instead, to ensure that the FDA could require a generic manufacturer ‘to modify its labeling to match labeling changes in the reference listed drug.’ ” Barnhill, 2007 U.S. Dist. LEXIS 44718, at *12-*13 (quoting 57 Fed. Reg. at 17970). Once one company successfully petitions the FDA to strengthen its warning label through the CBE process, others will be obliged to follow suit. Presumably, the FDA would not invoke its permissive authority under section 314.150 during the temporary transition of all manufacturers' products to a newer, strengthened warning. Indeed, neither the district court nor any of the generic manufacturers have been able to cite to even one instance where the FDA has revoked approval of an NDA or ANDA based on strengthened warnings added through the CBE process. Cf. Kellogg v. Wyeth, 2008 WL 5272715, at *7 (“there is no evidence that FDA has proposed to withdraw approval for a generic drug because its manufacturer sought to strengthen a label warning. A hypothetical or potential conflict is insufficient to warrant preemption.”) (citing Rice v. Norman Williams Co., 458 U.S. 654, 659 (1982)); Witczak v. Pfizer, Inc., 377 F. Supp. 2d 726, 731 (D. Minn. 2005) (declining to find irreconcilable conflict based on “assumptions of what the FDA would have done if defendant had unilaterally strengthened its warning label”)).[FN17]

    FN17. The court in Demahy, rejecting a generic manufacturer's claim of preemption, found it significant that 21 C.F.R. §314.150 uses the phrase “consistent with” the labeling for the listed drug, not “the same as.” In that court's view, this phrasing was broad enough to permit a generic label to “include[] additional warnings that do not appear on the name brand label,” without running a risk that its ANDA approval might be withdrawn. 586 F. Supp. 2d at 654.

    The Demahy court found additional support for its conclusion that generic drug companies can make unilateral changes in their label warnings from a comment in the 1992 final rulemaking notice requiring generic drug companies to submit periodic reports to FDA even if they have not “initiated any labeling changes.” 57 Fed. Reg. at 17965, cmt. 53. The court observed that “[t]his comment … clearly contemplates that a generic manufacturer with ANDA approval may initiate labeling changes.” 586 F. Supp. 2d at 653 (emphasis in original).

The majority of courts to consider the issue have concluded that manufacturers of generic drugs may invoke the CBE supplement process to strengthen their warning labels. The leading decision was rendered by the U.S. Court of Appeals for the Fourth Circuit in Foster v. American Home Products Corp., 29 F.3d 165 (4th Cir. 1994). After citing both 21 C.F.R. §§314.70(c)(2) and 314.97 (1993), the court decided that “generic manufacturers … [are] permitted to add or strengthen warnings and delete misleading statements on labels, even without prior FDA approval.” Id. at 170. The court rejected the argument that 21 U.S.C. §355(j)(2)(A)(v) bars generic manufacturers from strengthening their label warnings:

The statutory scheme governing premarket approval for drugs simply does not evidence Congressional intent to insulate generic drug manufacturers from liability for misrepresentations made regarding their products, or to otherwise alter state products liability law. Manufacturers of generic drugs, like all other manufacturers, are responsible for the representations they make regarding their products.

Foster, 29 F.3d at 170. Most other courts to consider the issue have reached the same conclusion. See, e.g., Kellogg, 2008 WL 5272715, at *12-*13; Demahy, 586 F. Supp. 2d at 648-49; Barnhill, 2007 U.S. Dist. LEXIS 44718; Kelly v. Wyeth, No. 03-3314F, 2007 WL 1302589 (Mass. Super. Ct. Apr. 12, 2007), and 2007 WL 3407466 (Mass. Super. Ct. Oct. 23, 2007) (denying cross-motions for reconsideration); Laisure-Radke, 2006 WL 901657, at *3; Sharp v. Leichus, No. 2004-CA-0643, 2006 WL 515532, at *7 (Fl. Cir. Ct. Feb. 17, 2006) (citing Sheeks v. Am. Home Prods. Corp., No. 02-CV-337 (D. Ct. Col. Jun. 17, 2005)); Block v. Wyeth, Inc., No. 3:02-CV-1077, 2003 WL 203067, at *1 n.1 (N.D. Tex. Jan. 28, 2003); Bell v. Lollar, 791 N.E.2d 849 (Ind. App. Ct. 2003).

Any doubt about the correctness of these rulings was resolved by Congress last year when it enacted FDAAA, Pub. L. No. 110-85, 121 Stat. 823. That act bolsters the FDA's authority to require a manufacturer to change a drug label if the agency becomes aware of information it believes should be included. 121 Stat. at 924 (to be codified at 21 U.S.C. §355(o)(4)). To ward off any claim that this expanded agency authority would lead to preemption, Congress included a “rule of construction” in Section 901 of FDAAA: “This paragraph shall not be construed to affect the responsibility of the responsible person or the holder of the approved application under section 505(j) to maintain its label in accordance with existing requirements, including subpart B of part 201 and sections 314.70 and 601.12 of Title 21, Code of Federal Regulations (or any successor regulations).” 121 Stat. at 925-26 (to be codified at 21 U.S.C. §355(o)(4)(I)). The “holder of the approved application under section 505(j)” is the manufacturer of a generic drug. Thus, FDAAA's rule of construction affirms Congress' intention that generic manufacturers remain subject to labeling requirements, including in particular the requirement to promptly strengthen label warnings under 21 C.F.R. §201.80(e), as well as the CBE supplement process under 21 C.F.R. §314.70(c).

For all of these reasons, this Court should hold that the generic appellees could have strengthened their metoclopramide warnings through the CBE supplement process. Because they were free to do so-but did not-Ms. Mensing's claims against the generic manufacturers are not preempted.
3. A generic manufacturer can employ other means to warn of its product's risks.

Even if this Court were to conclude that the generic appellees could not have invoked the CBE process to strengthen their metoclopramide warnings, preemption would still not be appropriate, because the companies had other means to warn of their products' risks. First, there is no dispute that generic drug companies could have sought to strengthen their warnings about the risks of EPS and tardive dyskinesia caused by prolonged exposure to metoclopramide through the prior approval supplement process, 21 C.F.R. §314.70(b), but none of them chose to do so. The generic appellees cannot show, nor is there any reason to believe, that the FDA would not have approved a stronger warning, for both generic metoclopramide and for Reglan, before Gladys Mensing's prescription was written. The generic appellees' failure even to seek such approval was both negligent and actionable. As the U.S. District Court for the Eastern District of Pennsylvania explained in rejecting a similar preemption motion: “state law may require a manufacturer to at least seek FDA approval for the addition of a new warning where there has been no determination by the agency whether there is a link between the adverse health effect to be warned against and the use of the drug.” Perry v. Novartis Pharm. Corp., 456 F. Supp. 2d 678, 685 (E.D. Pa. 2006) (footnote omitted); see also Kelly, 2007 WL 1302589, at *5 (“Even if the Court were to assume that Teva could not unilaterally make changes to its label through the moderate changes procedure, Teva still had the option and the obligation to apply for a labeling change through the major changes procedure”).

Even before FDA approval for a labeling change was obtained, the generic companies were free to employ other means to warn health care professionals and consumers of the increased risk of EPS and tardive dyskinesia from prolonged exposure to metoclopramide. When the agency originally promulgated its labeling regulations it made clear that:

These labeling requirements do not prohibit a manufacturer, packer, relabeler, or distributor from warning health care professionals whenever possibly harmful adverse effects associated with the use of the drug are discovered. The addition to labeling and advertising of additional warnings, as well as contraindications, adverse reactions, and precautions regarding the drugs, or the issuance of letters directed to health care professionals ( e.g., “Dear Doctor” letters containing such information) is not prohibited by these regulations.

44 Fed. Reg. 37434, 37447 (Jun. 26, 1979).[FN18] Based on this regulatory language, the Perry court concluded: “a modification of the label is not the only form that a warning could take…. [E]ven if we were to find that [the defendant drug company] could not have modified the FDA-approved labeling of [its product] to include a warning about [a serious hazard associated with the drug], we would still be obliged to deny defendants' [preemption] motion if a warning of some other type would have been permissible under the regulations.” 456 F. Supp. 2d at 686 (footnote omitted).

    FN18. In this same regulatory preamble, the FDA disclaimed any intent to preempt state tort law: “It is not the intent of the FDA to influence the civil tort liability of the manufacturer.” 44 Fed. Reg. at 37437.

FDA regulations would not have prevented any of the generic drug companies from sending a warning letter to health care professionals and patients without prior approval. See, e.g., Center for Drug Evaluation and Research, Manual of Policies and Procedures, 6020.10 (NDAs: “Dear Healthcare Professional” Letters) (July 2, 2003), available at http://www.fda.gov/cder/mapp/6020.10.pdf (“Occasionally, drug manufacturers and distributors mail important information about their drugs to health care professionals, including physicians, pharmacists, physician's assistants, and nurses. The FDA may or may not be involved in reviewing these DHCP letters before they are mailed.”).

The district court erroneously reached the contrary conclusion by relying on certain statutory provisions regarding “risk evaluation and mitigation strategies” (REMS) for certain drugs. App. 299a. But such REMS have no bearing whatsoever on the generic appellees' actions in this case. First, the provisions requiring the promulgation of REMS were not even enacted until 2007 as part of the FDAAA, Pub. L. No. 110-85, 121 Stat. at 926 (to be codified at 21 U.S.C. §355-1), long after the conduct at issue in this case. Moreover, these REMS requirements apply only to certain particularly dangerous drugs, and metoclopramide has not been designated as a covered drug. See Identification of Drug and Biological Products Deemed to Have Risk Evaluation and Mitigation Strategies for Purposes of the Food and Drug Administration Amendments Act of 2007, 73 Fed. Reg. 16313 (Mar. 27, 2008) (identifying 16 drugs approved before the enactment of FDAAA that are deemed to require REMS; metoclopramide is not included). Finally, as noted earlier, supra p. 29-30, the FDAAA's rule of construction reveals Congress's clear intent that generic drug companies remain subject to the requirements to strengthen product warnings under 21 C.F.R. §§201.80(e) and 314.70(c).

Because the generic appellees could have warned health care professionals, such as Ms. Mensing's physician, of metoclopramide's risks through a Dear Health Care Professional letter, their failure to do so is, again, both negligent and actionable.
4. Appellant's failure-to-warn claims complement and advance the purposes and objectives of congress.

Finally, there are sound public policy reasons for rejecting the argument that failure-to-warn claims against generic manufacturers are preempted. First, it would unfairly favor generic manufacturers over manufacturers of innovator drugs, which have devoted considerable time and resources to the development and testing of their products. And it would create a perverse incentive for generic manufacturers not to strengthen their label warnings.[FN19] Second, it would create an arbitrary and irrational distinction between classes of patients, based on the vagaries of pharmacy practice: those whose prescriptions were filled with name brand products would retain their right to sue, while those whose pharmacies substituted generic products would lose that right. Most importantly, it would leave many injured persons, such as Ms. Mensing, remediless.

    FN19. As one court has observed:

    To argue that, once the FDA approves a package insert, the defendant has no further duty to give an adequate warning creates an incentive for pharmaceutical companies to oppose all efforts by the FDA to secure clearer package inserts. If that were the case, drug manufacturers could avoid liability simply by resting on the formerly approved package insert (regardless of how long ago the approval occurred and how much information about the drug had changed) and resist all efforts to change it.

    Globetti v. Sandoz Pharms. Corp., No. CV 98-TMP-2649-S, 2001 WL 419160, at *2 n. 1 (N.D. Ala. Mar. 5, 2001).

Congress passed the FDCA to protect consumers from dangerous products.[FN20] State tort suits are wholly consistent with this legislative purpose. They protect consumers directly, by providing a remedy to persons injured by unsafe drugs, and also indirectly, by creating financial incentives for pharmaceutical companies to make their products safer and to provide reasonable warnings about the dangers those products pose. See Witczak v. Pfizer, Inc., 377 F. Supp. 2d at 731 (“[S]tate failure-to-warn laws do not pressure manufacturers to include false or invalid warnings. Instead, they give drug manufacturers every incentive to warn of real, known risks as soon as they are discovered-even before any FDA action.”). As the former Chief Counsel of the FDA, Margaret Jane Porter, has written, “FDA product approval and state tort liability usually operate independently, each providing a significant, yet distinct, layer of consumer protection.” Porter, The Lohr Decision: FDA Perspective and Position, 52 FOOD & DRUG. L.J. 7, 11 (1997); Kellogg, 2008 WL 5272715, at *8 (“the FDA's regulatory scheme has consistently relied on a role for state tort law”); see also [former FDA Commissioner] Kessler & Vladeck, A Critical Examination of the FDA's Efforts to Preempt Failure-to-Warn Claims, 96 GEO. L.J. 461, 484 (2008) ( “failure-to-war litigation … provides the FDA, doctors, and patients with information about new risks that is otherwise unavailable to the agency”) (footnote omitted); cf. Bates, 544 U.S. at 451 (“Private remedies … would seem to aid, rather than hinder, the [statute's] functioning”).[FN21]

    FN20. See United States v. Dotterweich, 320 U.S. 277, 280 (1943) (“The purposes of this legislation … touch phases of the lives and health of people which, in the circumstances of modem industrialism, are largely beyond self-protection”); 62 Cases, More or Less, Each Containing Six Jars of Jam v. United States, 340 U.S. 593, 596 (1951) (stating that Congress intended the FDCA to protect consumers who are unable to protect themselves); United States v. Sullivan, 332 U.S. 689, 696 (1948).

    FN21. See also 63 Fed. Reg. 66378, 66383-84 (Dec. 1, 1998), the preamble to FDA regulations governing point-of-sale medication guides. The FDA rejected a suggestion by drug manufacturers that it preempt “State regulation with respect to civil tort liability claims and other labeling requirements,” and instead expressly acknowledged that state tort law is not in conflict with the FDCA: “FDA does not believe that the evolution of state tort law will cause the development of standards that would be at odds with the agency's regulations. FDA's regulations establish the minimal standards necessary, but were not intended to preclude the states from imposing additional labeling requirements. States may authorize additional labeling but they cannot reduce, alter, or eliminate FDA-required labeling.”

For all of these reasons, Appellant's claims against the generic appellees are not preempted.
5. This Court should not defer to pronouncements by the FDA under the Bush Administration regarding preemption.

Thus, Ms. Mensing's failure-to-warn claims against the generic appellees neither directly conflict with FDA regulation of generic drugs, nor do they pose an obstacle to congressional purposes. The district court reached its erroneous conclusion on this issue, in substantial part, because it granted excessive deference to statements regarding preemption by the FDA under the Bush administration, App. 292a n.7. (granting Chevron deference to “FDA's position on the ability of a generic manufacturer to unilaterally alter its label”), in particular statements made in an amicus brief and in a footnote in the “Supplementary Information” section of a notice of proposed rule-making. App. 295a (quoting Colacicco amicus); App. 297a (quoting 73 Fed. Reg. at 2849 n.1).[FN22] But such deference was unwarranted; this Court need not, and should not, defer to these agency pronouncements.[FN23]

    FN22. See Demahy, 586 F. Supp. 2d at 655 (“The FDA essentially took the opportunity to make a significant statement on preemption of generic drug labeling claims in the relative obscurity of a footnote in the introductory statement of a document that has nothing at all to do with rules pertaining to generic drugs or to the ANDA process.”).

    FN23. The discussion that follows presupposes that the position of the FDA set forth in the Colacicco amicus and the January 2008 notice of proposed rulemaking remains the position of the agency. As noted earlier, supra n. 11, the Obama administration has not yet expressed its views on the issue of FDA preemption. An agency's former position is “deprived of all claim to deference, by the fact that it is no longer the agency's position.” Riegel v. Medtronic, Inc., 128 S.Ct. 999, 1009 (2008).

To begin with, these FDA statements are not entitled to heightened deference from the courts under Chevron, U.S.A., Inc. v. Natural Resources Defense Council, Inc., 467 U.S. 837 (1984); such deference “is warranted only ‘when it appears that Congress delegated authority to the agency generally to make rules carrying the force of law, and that the agency interpretation claiming deference was promulgated in the exercise of that authority.’ ” Gonzales v. Oregon, 546 U.S. 243, 255-56 (2006) (quoting United States v. Mead Corp., 533 U.S. 218, 226-27 (2001)) (emphasis added). As FDA regulations make clear, a statement in the Supplementary Information section of a notice of proposed rulemaking is not an “exercise of [the FDA's rulemaking] authority.” See 21 C.F.R. §10.85(d) ( “A statement of policy or interpretation made in … [any portion of a Federal Register notice other than the text of a proposed or final regulation] will constitute an advisory opinion.”).

For the same reason, agency views set forth in amicus curiae briefs are not entitled to heightened deference. Fed. Labor Relations Auth. v. U.S. Dep't of Navy, 966 F.2d 747, 762 & n.14 (3d Cir. 1992) (declining to defer to agency position expressed in amicus curiae brief because such a statement lacks the force and effect of law); see also Bowen v. Georgetown Univ. Hosp., 488 U.S. 204, 212-13 (1988) (declining to afford deference to agency interpretation advanced for the first time in a litigation brief).

Nor are these FDA statements entitled to heightened deference under Auer v. Robbins, 519 U.S. 452 (1997), as an agency interpretation of its own regulations. Such deference “is warranted only when the language of the regulation is ambiguous.” Christensen v. Harris County, 529 U.S. 576, 588 (2000). Here, the FDA's labeling regulations, in particular 21 C.F.R. §§201.57(e) and 314.97 (2005), are not ambiguous and the FDA's position is flatly inconsistent with the language of the regulations. See Kellogg, 2008 WL 5272715, at*12-13; Demahy, 586 F. Supp. 2d at 655 (FDA's statement in proposed rule “contradicts the FDA's own regulations”) (emphasis in original). Under these circumstances, “[t]o defer to the agency's position would be to permit the agency, under the guise of interpreting a regulation, to create de facto a new regulation.” Christensen, 529 U.S. at 588.

At most, these FDA assertions are entitled to the lesser form of deference under United States v. Mead Corp., 533 U.S. 218 (2001), and Skidmore v. Swift & Co., 323 U.S. 134 (1994). Where an agency interpretation is not entitled to Chevron or Auer deference, it is “ ‘entitled to respect’ only to the extent it has the ‘power to persuade.’ ” Gonzales v. Oregon, 546 U.S. at 256 (quoting Skidmore, 323 U.S. at 140); see also Good Samaritan Hosp. v. Shalala, 508 U.S. 402, 418 (1993). As the Supreme Court has explained,

[t]he weight [accorded to an administrative] judgment in a particular case will depend upon the thoroughness evident in its consideration, the validity of its reasoning, its consistency with earlier and later pronouncements, and all those factors which give the power to persuade, if lacking power to control.

Mead, 533 U.S. at 228 (internal quotations omitted) (quoting Skidmore, 323 U.S. at 140). See also Riegel v. Medtronic, 128 S.Ct. at 1009 (FDA's views on preemption entitled to “mere Skidmore deference”); id. at 1016 n.8 (Ginsburg, J., dissenting) (FDA position “entitled, at most, to deference under Skidmore”). Here, where the agency's position is in conflict with the statutory scheme, cannot be squared with applicable regulations, and represents a complete reversal of the FDA's longstanding views on preemption, it has no “power to persuade” and is not entitled to any judicial respect whatsoever.

Once the question is examined free from the distorting lens of the Bush FDA's statements, it is clear that there is no conflict between Ms. Mensing's failure-to-warn claims and the federal regulatory scheme for generic drugs. Therefore, Ms. Mensing's claims are not preempted and the district court's decision to dismiss her claims against the generic appellees must be reversed.
II. Name-Brand Manufacturers Schwarz and Wyeth Are Liable for Their False and Misleading Statements.
A. Standard of Review.

This Court “review[s] a district court's decision to grant summary judgment de novo, viewing the record favorably to the nonmoving party.” Wuebker v. Wilbur-Ellis Co., 418 F.3d 883, 886 (8th Cir. 2005). In a diversity case, this Court reviews de novo the district court's interpretation of state law, and “attempt [s] to predict how the highest court in [Minnesota] would resolve the issues before” the Court. Ehlis v. Shire Richwood, Inc., 367 F.3d 1013, 1016 (8th Cir. 2004).
B. Introduction.

The district court also erred in granting summary judgment to name-brand manufacturers Wyeth and Schwarz on Ms. Mensing's claims for intentional fraud and negligent misrepresentation.

Ms. Mensing alleges that Schwarz and Wyeth made material misrepresentations about the risks of metoclopramide, that her physician reasonably relied on these name-brand manufacturers' statements, and that, as a result, she now suffers permanently from the Parkinson's-like symptoms of tardive dyskinesia.[FN24] Cf McNeil v. Wyeth, 462 F.3d 364, 369-72 (5th Cir. 2006) (allowing similar claims against Wyeth to proceed). In moving for summary judgment, neither Schwarz nor Wyeth disputed Ms. Mensing's ability to prove her factual allegations at trial. Instead, the name-brand manufacturers argued that they are immune from liability because Ms. Mensing's pharmacy, in compliance with Minnesota's generic-drug substitution statute, Minnesota Statutes §151.21, dispensed a generic version of metoclopramide, rather than name-brand Reglan. The district court accepted this argument, holding that the name-brand manufacturers did not owe a duty of care and can never be held for their own fraud and negligence when a pharmacy dispenses a bioequivalent, generic version of the drug at issue.

    FN24. See, e.g., App. 35a-36a, 45a-48a, 52a-54a; App. 260a-262a.

As explained below, the district court's decision cannot be reconciled with well-settled Minnesota precedent, which makes clear that a defendant is liable for false or misleading statements that lead a plaintiff to purchase another's product, and that an allegedly negligent defendant owes a duty of care whenever it is foreseeable, as here, that harm may result from its negligent conduct.
C. The District Court Erred in Granting Summary Judgment on Ms. Mensing's Intentional Fraud Claims.
1. Schwarz and Wyeth are liable for fraud regardless of whether they produced the product that caused Ms. Mensing's injuries.

The elements of Ms. Mensing's fraud claims are “intent, inducement, reliance, and damages.” Iverson v. Johnson Gas Appliance Co., 172 F.3d 524, 529 (8th Cir. 1999) (citation omitted). Thus, Schwarz and Wyeth are liable if (as Ms. Mensing alleged) their intentional misrepresentations and material omissions induced reliance that resulted in damage. See id. Specifically, a fraud defendant is liable whenever it makes an intentional misrepresentation to someone who is “justified in acting” on the misrepresentation and who does, in fact, rely on it. E.g., Gaetke v. Ebarr Co., 263 N.W. 448, 452 (Minn. 1935). The defendant's liability is not limited “to those persons whose conduct the misrepresentation is intended to influence, or to harm received in the particular transaction which the misrepresentation was intended to induce.” RESTATEMENT (SECOND) OF TORTS §310 cmt. d (1965); see also Larson v. Wasemiller, 738 N.W.2d 300, 306 (Minn. 2007) (Minnesota often looks to the Restatement for guidance).

Contrary to the conclusions of the court below, Wyeth and Schwarz are not immune from these ordinary principles of liability because Ms. Mensing's pharmacy dispensed a bioequivalent, generic version of their name-brand drug.

First, a defendant may be held responsible for fraud even if its misrepresentation pertains to another's conduct or product. See, e.g., Richfield Bank & Trust Co. v. Sjogren, 244 N.W.2d 648 (1976) (bank committed fraud by failing to disclose the insolvency of its depositor, furthering the depositor's own fraud against the plaintiff); Busterud v. Farrington, 31 N.W. 360, 361-62 (Minn. 1887) (person who is not the vendor of a product may be held liable for misrepresentations about that product); RESTATEMENT (SECOND) OF TORTS §549 cmt. g (1977)) (rules for measuring fraud damage apply “[w]hen the plaintiff has not entered into any transaction with the defendant but has suffered his pecuniary loss through reliance upon the misrepresentation in dealing with a third person”).

Second, a fraud defendant may be held liable regardless of whether it benefitted from its fraud or had any interest in the transaction that resulted:

The gravamen of the charge is to be found in the deception practiced upon the plaintiff, … not that the defendant has gained an advantage. Whether the person making the representation received any benefit from the deceit is unimportant[;] nor is it necessary that he should collude with the party who has benefited.

Lehman v. Hansord Pontiac Co., 74 N.W.2d 305, 311 (Minn. 1955); cf. S.E.C. v. Capital Gains Research Bureau, Inc., 375 U.S. 180, 193 n.39 (1963) (“it is not necessary that the person making the misrepresentations intend to … gain a profit for himself”).
2. Flynn is not to the contrary.

The district court erred in relying on Flynn v. American Home Products Corp., 627 N.W.2d 342 (Minn. Ct. App. 2001), to reach a contrary conclusion. As an initial matter, Flynn did not involve a claim based on affirmative misrepresentations, and its holding cannot be applied to those allegations in Ms. Mensing's complaint. See Flynn, 627 N.W.2d at 349-50; App. 35a-36a, 45a-46a, 48a, 52a-53a.

The Flynn plaintiff's fraudulent concealment claim also depended on a legal theory of “fraud-on-the-FDA” that is entirely different from what Ms. Mensing claims in this case. The plaintiff in Flynn sought to hold name-brand defendants liable for fraud, but she did not allege that her physician relied on any misrepresentations made by those defendants. Id. at 349-50. Instead, she sought to hold the name-brand defendants liable for facts they omitted from communications with the FDA-communications to which neither she nor her physician was a party. Id. at 349.

The Minnesota Court of Appeals held only (in dicta, see id.) that the plaintiff could not stand in the shoes of the FDA and recover for “fraud on the FDA” as a “third part[y]” when she did not allege any “direct communication” between the defendants and her physician and on which her physician relied. Id. at 349, 350. In this case, by contrast, Ms. Mensing does not rely on any theory of fraud on the FDA, and her claim for recovery depends on the very facts missing in Flynn- direct communication between these defendants and her physician on which her physician relied. See App. 30a, 47a-48a, 53a.[FN25]

    FN25. Flynn also relied on the lack of a fiduciary relationship between the defendants and the plaintiff. Flynn, 627 N.W.2d at 350; see also In re Minn. Breast Implant Litig., 36 F. Supp. 2d 863, 879-80 (D. Minn. 1998). A fiduciary relationship is one circumstance that gives rise to a duty to disclose, but such a duty also arises when one has spoken and must give more information to present the entire truth, or when one has special knowledge of material facts. Richfield Bank, 244 N.W.2d at 650. The plaintiff in Flynn could not establish either of the latter circumstances because of the lack of any direct communication with her physician. In this case, the direct communication via defendants' labeling-and Ms. Mensing's allegations that defendants' half-truths were misleading-makes the existence of a fiduciary relationship irrelevant.

D. The District Court Erred in Granting Summary Judgment on Ms. Mensing's Negligent Misrepresentation Claim.

The district court also erred in granting summary judgment on Ms. Mensing's negligent misrepresentation claim on the ground that Schwarz and Wyeth did not owe a duty of care. As explained below, it is clear that Minnesota's test for determining duty is met.[FN26]

    FN26. In granting summary judgment, the district court noted that the Minnesota Supreme Court has not yet decided whether to adopt the specific negligent-misrepresentation tort articulated in Restatement §311: negligent misrepresentation involving a risk of physical injury. The district court assumed that such a tort exists and held that Ms. Mensing could not prove duty as a matter of law. App. 322a. This section of Appellant's brief explains why Minnesota's standard test for determining duty is met, and because that same test applies to all theories of negligence, this Court need not decide whether a specific §311-based tort will be adopted in order to decide the narrow question of duty under Minnesota negligence law. Nevertheless, in Part II.D.3, infra, Appellant explains why the Minnesota Supreme Court will likely recognize a claim for negligent misrepresentation involving a risk of physical injury when squarely presented with the question.

1. Schwarz and Wyeth owed a duty of care.

The settled test for determining whether a duty exists under Minnesota law is the foreseeability of resulting injury. E.g., Molloy v. Meier, 679 N.W.2d 711, 719 (Minn. 2004) (“the risk reasonably to be perceived defines the duty to be obeyed”) (quotation marks and citation omitted); see also Holthusen v. United States, 498 F. Supp. 2d 1236, 1244 (D. Minn. 2007) (Minnesota “imposes a duty of care to avoid foreseeable harm.”) (citation omitted); Mulroy v. Wright, 240 N.W. 116, 117 (Minn. 1931) (“[W]hen one assumes to act and knows that others will act in reliance upon such conduct the law imposes a duty.”). The specific manner or nature of a plaintiff's injury need not have been expected in order for liability to be imposed; what matters is that some injury was foreseeable. See, e.g., Fjellman v. Weller, 7 N.W.2d 521, 529 (Minn. 1943). Further, once the foreseeability test is met, the defendants' liability extends to anyone they could reasonably have expected to rely on their representations. RESTATEMENT (SECOND) OF TORTS §552 cmt. i (1977) (liability extends to “any person to whom [the defendant] should expect physical harm to result through action taken in reliance”); Molloy, 679 N.W.2d at 719 (“risk imports relation; it is risk to another or to others within the range of apprehension”) (internal quotations omitted).

Applying these principles here, Schwarz and Wyeth owed a duty of care because of the regulatory landscape in which their representations were made.[FN27] First, Schwarz and Wyeth must have foreseen that physicians would rely on their representations in deciding whether to write prescriptions for Reglan/ metoclopramide. FDA regulations make clear that one of the principal purposes of required labeling is to inform doctors of risks associated with approved medications and, because federal law requires name-brand drugs and generics to be bioequivalent, it makes sense for a physician to rely on a name-brand label regardless of which drug will actually be dispensed (particularly when, as here, the name-brand label is more readily available to physicians in both product samples and the Physician's Desk Reference (PDR)). See 21 U.S.C. §355(j)(2)(A)(iv) (requiring bioequivalence); 71 Fed. Reg. 3922, 3922 (Jan. 24, 2006) (labeling contains “information necessary for safe and effective use” and is “intended for the health care practitioner audience”); App. 260a-262a.[FN28]

    FN27. Because this case involves statements made to a physician, who is a learned intermediary between drug manufacturers and patients, the relevant question is whether the name-brand defendants owed a duty of care to Ms. Mensing's doctor. See Mulder v. Parke Davis & Co., 181 N.W.2d 882, 885 & n. (Minn. 1970); Conte, 85 Cal. Rptr. 3d at 308 n.5 (“Wyeth's duty to warn of risks associated with [metoclopramide's] usage runs to the physician”).

    FN28. In this case, the evidence in the record indicates that Ms. Mensing's physician prescribed name-brand Reglan. See App. 263a-281a (medical records showing that Ms. Mensing's physician prescribed “Reglan”). It would be absurd to suggest that a name-brand manufacturer could not foresee a physician's reliance on its own warnings to prescribe its own drug.

Second, Schwarz and Wyeth must also have foreseen that pharmacies would fill a prescription for name-brand Reglan by dispensing a generic version of the drug. It is the law in many states, including Minnesota, that pharmacies must fill a name-brand prescription with the generic bioequivalent absent a specific physician's instruction. See Minn. Stat. §151.21; Inwood Labs., Inc. v. Ives Labs., 456 U.S. 844, 847 n.4 (1982).

Given these facts, “[Schwarz and] Wyeth should reasonably [have] perceive[d] that there could be injurious reliance on [their] product information by a patient taking generic metoclopramide.” Conte v. Wyeth, 85 Cal. Rptr. 3d 299, 313 (Cal. Ct. App. 2008), review denied (Jan. 21, 2009). Under the controlling Minnesota rule that foreseeability determines duty, this settles the question of whether Schwarz and Wyeth owed a duty of care. Cf. Clark v. Pfizer, Inc., 2008 Phila. Ct. Comm. P1. LEXIS 74, at *22 (Phila. Ct. Com. P1. Mar. 14, 2008) (name-brand manufacturer could be liable when it was foreseeable that its drug would be “copied and sold by competitors as a generic” and generics “are often required by law … to be prescribed as a substitute”).[FN29]

    FN29. Flynn did not address the merits of Ms. Mensing's claim for negligent misrepresentation, 627 N.W.2d at 351, and thus its holding cannot apply to this claim.

2. The name-brand Appellees failed to establish any basis for immunity.

In moving for summary judgment, the name-brand appellees did not dispute the foreseeability of events alleged in Ms. Mensing's complaint. Instead, Schwarz and Wyeth argued that they are immune from liability because their representations only concerned name brand Reglan, and because Ms. Mensing's pharmacy dispensed generic metoclopramide. App. 301a. The first of these arguments fails as a matter of fact; the second as a matter of law.

As a matter of fact, the labeling approved for prescription Reglan does not limit itself to a discussion of the name-brand drug. To the contrary, the “[w]amrings” section of the label refers to the drug using its generic chemical name, “metoclopramide.” See, e.g., App. 261a; cf Clark, 2008 Phila. Ct. Com. P1. LEXIS 74, at *22 (relying on similar facts). It is simply inaccurate for the name-brand appellees to suggest that their misrepresentations were limited to “Reglan.”

As a matter of law, Schwarz and Wyeth are also incorrect to argue that they are immune from liability because Ms. Mensing's pharmacy dispensed generic metoclopramide. Liability in a misrepresentation case is based on “reliance on the manufacturer's misleading written information”, not on “defects in the formulation or manufacture of the competitor's drug.” Conte, 85 Cal. Rptr. 3d at 317 n. 16. In this situation, “the fact that the name-brand manufacturer has no control over the production of the generic competitor's products is not relevant to [the] narrow” question of whether Wyeth and Schwarz may be held liable for their own false and misleading statements about the drug at issue. Id. (emphasis in original).

Consistent with this view, both the Restatement and Minnesota case law make clear that a defendant may be held liable for negligent misrepresentations made about its own product or about someone else's-regardless of whether the defendant benefits from the misrepresentation. See RESTATEMENT (SECOND) OF TORTS §311 cmt. c (1965) (defendant may be liable even if he “derives no benefit from giving” incorrect information); id. cmt. d, illus. 8 (company that negligently certifies the safety of another's boiler is liable to anyone subsequently injured); Florenzano v. Olson, 387 N.W.2d 168, 170-72, 175 (Minn. 1986) (private insurance agent liable for misleading statements about Social Security; citing no evidence that defendant had a financial stake in the result of his misstatements); Bonhiver v. Graff, 248 N.W.2d 291, 297-99 (Minn. 1976) (independent accountant liable for misrepresentations about insurance company's financial condition; citing no evidence that accountant had a stake in an agent's resulting decision to do business with the company); Mulroy, 240 N.W. at 116-18 (clerk liable for misrepresentation about another's real estate, with no stake in its sale).[FN30]

    FN30. See also, e.g., Hanberry v. Hearst Corp., 81 Cal. Rptr. 519, 522-23 (Cal. Ct. App. 1969) (magazine could be liable for seal of approval on another's product); Rottinghaus v. Howell, 666 P.2d 899, 902, 907 (Wash. Ct. App. 1983) (non-profit liable for its certification of others' products); cf. Mattingly v. Sportsstuff, Inc., No. 07-cv-0403-MJR, 2007 WL 2410105, at *1-*2 (S.D. Ill. Aug. 23, 2007) (trade association not fraudulently joined as defendant in personal-injury action when association had named product its “product of the year”).

3. The Minnesota Supreme Court would likely recognize a negligent misrepresentation tort based on Restatement §311 if squarely presented with the question.

The district court noted in its opinion that the Minnesota Supreme Court has not yet decided whether to adopt the specific tort described in Restatement §311: negligent misrepresentation involving a risk of physical injury. App. 315a. The district court did not predict whether Minnesota will approve such a claim, and this Court need not reach the issue in order to determine that the district court erred. As explained above, the district court incorrectly concluded as a matter of law that Schwarz and Wyeth could not owe a duty of care. The question of duty must be decided according to Minnesota's well-established test of foreseeability, see supra Part II.D.1., and this Court can apply that test to decide the threshold issue of duty and remand for consideration of whether Minnesota would recognize a claim for negligent misrepresentation involving physical injury.

It is also unnecessary to reach the question of a §311-based tort because, regardless of whether the Minnesota Supreme Court approves that specific claim, Schwarz and Wyeth are subject to liability under general principles of negligence. See Albertson v. Chicago, M., St. P. & P. R. Co., 64 N.W.2d 175, 180 (Minn. 1954) (“Where an act is negligent, the person committing it is liable for any injury proximately resulting from it[.]”); Mulroy, 240 N.W. at 117 (“[W]hen one assumes to act and knows that others will act in reliance upon such conduct the law imposes a duty.”). The name-brand appellees may also be held liable under Restatement §323, which provides that a defendant who acts voluntarily ( e.g., by providing information about metoclopramide) is liable if harm results from reliance on its undertaking. See Isler v. Burman, 232 N.W.2d 818, 822 (Minn. 1975) (applying §323).

Nevertheless, if this Court does reach the issue of whether Minnesota would adopt a §311-based claim, all available evidence suggests that the Minnesota Supreme Court would likely approve such a claim if squarely presented with the question. Minnesota courts have often held that defendants may be liable for misrepresentations made without an intent to deceive, and they have made this point using broad language that does not distinguish among different types of negligent misrepresentation. See, e.g., Gen. Ins. Co. of Am. v. Lebowsky, 252 N.W.2d 252, 255 (Minn. 1977); Hollerman v. F.H. Peavey & Co., 130 N.W.2d 534, 539-40 (Minn. 1964). Minnesota courts have also already adopted the tort of negligent misrepresentation leading to pecuniary harm, see, e.g., Smith v. Brutger Cos., 569 N.W.2d 408, 413-14, and have approved similar claims for nondisclosure and negligent failure to warn in cases involving physical harm. See, e.g., Plutshack v. Univ. of Minn. Hosps., 316 N.W.2d 1, 9 (Minn. 1982); Clark v. Rental Equipment Co., 220 N.W.2d 507, 511 (1974). In addition, many other jurisdictions have approved the tort or have cited Restatement §311 as persuasive authority. See, e.g., Conte, 85 Cal. Rptr. 3d at 311-12; Richey v. Philipp, 259 S.W.3d 1, 7-8, 15 (Mo. Ct. App. 2008); Davis v. Bd. of County Comm'rs of Dona Ana County, 987 P.2d 1172, 1179 (N.M. Ct. App. 1999); cf. Cozza v. Culinary Foods, Inc., 723 N.E.2d 1199, 1205 (Ill. App. Ct. 2000) (citing RESTATEMENT (FIRST) OF TORTS §311 (1934)).[FN31]

    FN31. In deciding whether to recognize a tort, Minnesota courts look to whether it would be a natural extension of already-recognized common law rights, whether other states have recognized it, and whether any tension it would create with existing law is outweighed by the benefit to injured victims. Larson, 738 N.W.2d at 304. The first two factors weigh in favor of approving the tort, and there is no tension with existing law.

For these reasons, the Minnesota Supreme Court will likely adopt the specific tort based on Restatement §311.
E. The Minnesota Supreme Court Would Follow Conte, not Foster. The district court cited Foster v. American Home Products Corp., 29 F.3d 165 (4th Cir. 1994), as support for its order granting summary judgment. But Foster was based on Maryland law, not Minnesota law, and, in considering it, the district court did not have the benefit of the recent appellate decision in Conte, 85 Cal. Rptr. 3d at 315-18, which explains the flaws in Foster's analysis and approves claims nearly identical to Ms. Mensing's.

Foster's first flaw is that the Fourth Circuit assumed that the plaintiff could not state a misrepresentation claim independent of her products liability claim. See Foster, 29 F.3d at 168, 171; Conte, 85 Cal. Rptr. 3d at 316. However, under Minnesota law (as under California law), intentional deceit and negligent misrepresentation are both species of fraud, not products liability, see Florenzano, 387 N.W.2d at 173, and the rights, duties, and alleged wrongdoing at issue are different for the two types of claims. See Smith v. Brutger Cos., 569 N.W.2d 408, 413 (Minn. 1997) (duty at issue on negligent misrepresentation claim is duty to exercise reasonable care in conveying information); Conte, 85 Cal. Rptr. 3d at 317 n. 16 (misrepresentation claim seeks to recover for the defendants' false statements; products liability claim seeks to recover for injuries caused by product defects). Because Ms. Mensing only seeks to recover against the name-brand appellees for their misrepresentations, not for any product defects, the products-liability cases cited in Foster are inapposite.

Foster's holding also rests on the Fourth Circuit's mistaken view that it would be “unfair” to hold name-brand defendants liable. Foster, 29 F.3d at 170. As Conte explains, however, this policy rationale provides an insufficient basis for departing from the accepted rule-applicable in Minnesota as in California-that foreseeability determines a defendant's duty. See Conte, 85 Cal. Rptr. 3d at 316; supra Part II.D.1.

There is nothing unfair about holding joint tortfeasors liable for their own wrongdoing. Conte, 85 Cal. Rptr.3d at 317. This is hornbook tort law, and Minnesota provides for shared liability among negligent tortfeasors, including in cases of misrepresentation. See, e.g., Bursch v. Beardsley & Piper, a Div. of Pettibone Corp., 971 F.2d 108, 111 (8th Cir. 1992); Ellis v. Lindmark, 225 N.W. 395 (Minn. 1929) (manufacturer and pharmacist who misrepresented nature of product both held liable); Minn. Stat. §604.01 (providing for apportionment of damages).[FN32]

    FN32. Minnesota does recognize a defense to such shared liability where one tortfeasor's conduct is a superseding cause of the plaintiff's injury. Canada by and through Landy v. McCarthy, 567 N.W.2d 496, 507 (Minn. 1997); see also RESTATEMENT (SECOND) OF TORTS §440 (1965). That defense, however, is not available to Wyeth and Schwarz here. First, the defense is only available for unintentional tort claims; it cannot be used against Ms. Mensing's claims for intentional fraud. 4 Minn. Dist. Judges Ass'n, MINN. PRAC.: JURY INSTRUCTION GUIDES-CIVIL, CIVJIG 27.20 (5th ed. 2006) (use note). Second, a third party's conduct does not relieve a negligent tortfeasor of liability unless, among other things, the subsequent conduct was unforeseeable. Bursch, 971 F.2d at 112; Canada by and through Landy, 567 N.W.2d at 507. The entire chain of events alleged in Ms. Mensing's complaint was easily foreseeable to these defendants. See supra Part II.D.1.

Further, name-brand manufacturers are granted significant advantages in exchange for the burden they bear in producing the original drug and its label. They are entitled to an initial period of patent protection, see 35 U.S.C. §§154, 156, and they enjoy “the fiscal rewards of name-brand recognition and the commensurate ability to charge a higher price …, even after [their] exclusive marketing period expires.” Conte, 85 Cal. Rptr. 3d at 317. Balancing these benefits against name-brand manufacturers' risks is precisely the policy analysis that Congress undertook in passing the Hatch-Waxman amendments to the FDCA. See Drug Price Competition and Patent Term Restoration Act of 1984, Pub. L. No. 98-417, 98 Stat. 1585 (1984) (pairing provisions for generic approval with patent-term extension). If name-brand manufacturers believe that balance needs adjustment, it is to Congress or the Minnesota legislature that they should turn. See M.H. v. Caritas Family Servs., 488 N.W.2d 282, 288 n.6 (Minn. 1992) (“If there are policy considerations that should override the [defendant's] common law liability for misrepresentation, the legislature is the appropriate body to extend such immunity.”).

CONCLUSION

For the foregoing reasons, Appellant urges this Court to reverse the judgment of the district court, reinstate Appellant's claims against all appellees, and remand for further proceedings.