Petition for Writ of Certiorari — Wyeth v. Levine

Supreme Court brief2009

Ask Donna

What actually matters in this document.

Text

’

Supreme Court. J

i FLED

No. 06- 061249 Map 12 9007

hemp OFFICE OF THE CLERK

Supreme Court of the United States

WYETH,

Petitioner,

DIANA LEVINE,

Respondent.

On PeviTion FOR A WRIT OF CERTIOKARI

TO THE SUPREME COURT OF THE STATE OF VERMONT

PETITION FOR A WRIT OF CERTIORARI

ALLAN R. KEYES Bert W. REIN

R. Josep O'Rourke Counsel of Record

RYAN, SmirxH, Carine, LTD. KARYN K. ABLIN

98 Merchants Row Wiittam S. Consovoy

P.O. Box 310 Witey Rein LLP

Rutland, VT 05702-0310 1776 K Street NW

(802) 786-1000 Washington, D.C. 20006

(202) 719-7000

Attorneys for Petitioner

A mal ce

P t pet

(Remap P74 TAIT © (ROOD 189-6854

QUESTION PRESENTED

Whether the prescription drug labeling judgments

imposed on manufacturers by the Food and Drug

Administration (“FDA”) pursuant to FDA’s comprehensive

safety and efficacy authority under the Federal Food, Drug,

and Cosmetic Act, 21 U.S.C. § 301 ef seg., preempt state

law product liability claims premised on the theory that

different labeling judgments were necessary to make drugs

reasonably safe for use.

LIST OF PARTIES

Pursuant to Rule 14.1(b), the following list identifies all

of the parties to the appellate proceeding in the Supreme

Court of Vermont, whose judgment is sought to be reviewed:

A. Petitioner

Wyeth

B. Respondent

Diana Levine

CORPORATE DISCLOSURE STATEMENT

Petitioner Wyeth has no parent corporation, and no

publicly held company owns 10% or more of its stock.

ill

TABLE OF CONTENTS

Page

QUESTION PRESENTED ..... cece ccscscces 1

Sg ere ore re Tree il

CORPORATE DISCLOSURE STATEMENT ..... il

pg ss en ee il

TABLE OF CITED AUTHORITIES ............ v

peo ee Xil

oe ok eek eek ee SRO ee l

+ tcc shed du eee Fone oe os me one |

PERTINENT CONSTITUTIONAL, STATUTORY,

AND REGULATORY PROVISIONS ......... I

EE Wes sis wh dpc uken ¥e bees 9070 l

STATEMENT OF THE CARE ...... ccc eeeeeess 3

a og ee ie we axees 3

1. FDA Regulatory Regime ............ 3

2. FDA’s Regulation of Phenergan ...... 6

3. The Operative Phenergan Label when

Respondent Was Treated ............ 8

Contents

Page

4. The Administration of Phenergan to

ES cat aay wh at an CoS Ke 9

I re 10

1. The Trial Court Proceedings ......... 10

2. The Appeal to the Vermont Supreme

re ene a eres yee eee 10

REASONS FOR GRANTING THE PETITION ... 13

I. The Court Should Grant Review To Correct

Vermont’s Rejection of Impossibility Conflict

Preemption Stemming from its Mischaracterization

of FDA’s Comprehensive Regulatory Regime.

Pe ee eee See eo Ce Eee 15

II. The Court Should Grant Review To Clarify the

Effect, If Any, of the Presumption Against

Preemption and Section 202 of the 1962 FDCA

Amendments on the Application of “Obstacle”

Conflict Preemption to Prescription Drug

ee rare re eee ae ee 2)

Ill. The Court Should Grant Review To Resolve

the Conflict Concerning the Degree of

Deference that Courts Should Accord FDA’s

Formal Position on the Extent to Which State

Tort Law Labeling Judgments Interfere with

PDAS Labetmeg Remene. ........ccsceees 27

SEE so0 6S Cee heehee We et eweee wae 30

TABLE OF CITED AUTHORITIES

Page(s)

FEDERAL CASES

Auer v. Robbins,

oo ree ry Teer ce 29

Bates v. Dow Agrosciences LLC,

SG Us Ge BN 5 co kets seceseveaveseta 26, 30

In re Bextra & Celebrex Marketing Sales Practices

& Product Liability Litigation,

No. 05-1699, 2006 WL 2374742

CPOE SA FO FE vet kee tcesccecss 29

Buckman Co. v. Plaintiffs’ Legal Committee,

Pe CH POPE 8:05-6:00 A cds Showa CRTs 26

Caraker v. Sandoz Pharmaceuticals Corp.,

172 F. Supp. 2d 1018 (S.D. Hl. 2001) .......-. 16,18

Cartwright v. Pfizer, Inc.,

369 F. Supp. 2d 876 (E.D. Tex. 2005) ......... 16

Cipollone v. Liggett Group, Inc.,

MS Perey ee 14, 24

City of Camden v. Beretta U.S.A. Corp.,

81 F. Supp. 2d 541 {D.N.J. 2000) ............ 23

Colacicco v. Apotex, Inc.,

432 F. Supp. 2d 514 (E.D. Pa. 2006) .......... 29

Cited Authorities

Page(s)

Ehlis v. Shire Richwood, Inc.,

233 F. Supp. 2d 1189 (D.N.D. 2002), aff'd,

367 F.3d 1013 (8th Cir. 2004) ............... 17

Fidelity Federal Savings & Loan Ass'n v. de la Cuesta,

cca bavenenseanences 14, 28

Florida Lime & Avocado Growers, Inc. v. Paul,

EE 14

Freightliner Corp. v. Myrick,

cer k kets ese ee dena 17

Geier v. American Honda Motor Co.,

deve eke cede ese seeeees passim

Heckler v. Chaney,

ee Ce wea eeheeuaenea 4 20

Hillsborough County v. Automated Medical

Laboratories, Inc., 471 U.S. 707 (1985) ....... 28

Hines v. Davidowitz,

ee Wed cab dude one enee 14

Horn v. Thoratec Corp.,

376 F.36 163 (36 Cir. 2004) ..... 2... ccc eens: 21, 29

International Paper Co. v. Ouellette,

Ee 24, 26

Jackson v. Pfizer, Inc.,

432 F. Supp. 2d 964 (D. Neb. 2006) .......... 29

vil

Cited Authorities

Mazur v. Merck & Co..,

742 F. Supp. 239 (E.D. Pa. 1990) .........

McDermott v. Wisconsin,

ot So oe Wid va 6 b'0.00 06 be

McNellis v. Pfizer, Inc.,

No. Civ. 05-1286, 2005 WL 3752269

(D.N.J. Dec. 29, 2005), stay granted and

motion to certify appeal granted,

No. Civ. 05-1286 (JBS),

2006 WL 2819046 (D.N.J. Sept. 29, 2006)

See eeeseeeeeegee@eedtceeePgcete@tee@eec@e~esgeeoe@@ete@esses8 @

Medtronic Inc. v. Lohr,

i ics; on cnc cck eee ewek

Needleman v. Pfizer, Inc.,

No. 3:03-C V-3073-N, 2004 WL 1773697

Ge Hs CE GR ED nic seve cccccce:

Nutraceutical Corp. v. Von Eschenbach,

459 F.3d 1033 (10th Cir. 2006) ..........

Perry v. Novartis Pharma. Corp.,

456 F. Supp. 2d 678 (E.D. Pa. 2006) ......

Rice v. Santa Fe Elevator Corp.,

Ec ccccncsceeestsevns

Schering Corp. v. FDA,

Fe Cede SOP EPO Ge SOUOD 6 cccccccccnses

Foss 22

Cans 16

wake 21

jeen 17

er 20

inne 28

dm 24

doles 20

vill

Cited Authorities

Schneidewind v. ANR Pipeline Co.,

SP EE wake Scevcdeccends

Sinnot v. Davenport,

63 U.S. (22 How.) 227 (1859) .........

Smith v. United States,

Fe rer rs

Thomas Jefferson University v. Shalala,

FE Ws SPE SOOED 0 0c chr ccccedeces

Udall v. Tallman,

Ps DE wawcnsceccncecesses

United States v. Locke,

ED bc vcccwonccceusae

United States v. Rutherford,

Se TED cecscbecececeseds

Weinberger v. Bentex Pharmaceuticals, Inc.,

Ge ee UD 0 0606s dedweceeees

Weiss v. Fujisawa Pharmaceutical Co.,

464 F. Supp. 2d 666 (E.D. Ky. 2006)

TTT Tr 23

padden 19

sep ae 30

-enee 28

reser 24

rodwus 25

paesséi 20

reer 19

Cited Authorities

Page(s)

FEDERAL STATUTES

re 6 EO bo ower eas eee eeews i

NS EES rrr reer re or re. 3

ie we id a ee ada ee eels 3

CE I eS ee se 18

is 4. 2s ete ile hes Ga noeee nee 18

scbs ts vee tiveadegee weakens 18

ee itis kuckistehevens <obeueaes 3

re ee ne 3, 4, 5, 6

De cise eteshicduesdskenesenene 3

i +s 'o ou dbey ees éUShehiedenkes l

Drug Amendments of 1962, Pub. L. No. 87-781,

CO 3

Federal Food, Drug and Cosmetic Act, Pub. L. No.

po Re 3

FEDERAL REGULATIONS

IUD oi vc divcvncccvscsiucccees 5

ee eS uluameaan 5

rr eee passim

Pn écevubecsiverstoneuseeipus 6

wna

Cited Authorities

Page(s)

Content and Format for Labeling for Human

Prescription Drugs, 44 Fed. Reg. 37,434 (June 26,

FOS ET TT Tee eT Te TT OTT Teer

New Drug and Antibiotic Regulations, 47 Fed. Reg.

SED sn home uses d60 teeta

New Drug and Antibiotic Regulations, 50 Fed. Reg.

Ps El CUED. Cb. ocvccdcenaentndcneees

Requirements on Content and Format of Labeling for

Human Prescription Drug and Biological Products,

71 Fed. Reg. 3922 (Jan. 24, 2006) ............

LEGISLATIVE MATERIALS

108 Cong. Rec. 21,083 (1962) (statement of Rep.

DT i cas cvenke a dareuek dibs ehe ws ken

Hearing on H.R. 6245 Before the Subcommittee On

Antitrust of the House Committee On the Judiciary,

87th Cong. 135 (1902) (statement of George P.

Larrick, Commissioner, FDA) ...............

S. Rep. No. 87-1744 (1962), as reprinted in 1962

no ote sc bstinisecdecenns

Cited Authorities

Page(s)

MISCELLANEOUS

FDA, Draft Guidance for Industry: Development and

Use of Risk Management Action Plans (Mar. 2005)

FDA, Guidance: Drug Safety Information — FDA's

Communication to the Public (Mar. 2007) ...... 5

Letter from Edward Cox, Acting Director, Center for

Drug Evaluation and Research, to David Hallinan,

VP Regulatory Affairs, Idenix Pharms., Inc. (Oct.

PE DKN 0000 08 0 00¥ de Vewosebits 0ed40 00 18

xil

TABLE OF APPENDICES

Page

Appendix A — Opinion of the Vermont Supreme

Court Filed October 27, 2006 ................ la

Appendix B — Decision of the Superior Court of

Washington County Filed August 2, 2004 ...... 49a

Appendix C — Decision of the Vermont Supreme

Court Filed December I1, 2006, Denying

EE Webb aed he kG een a Vees Obs) 600 75a

Appendix D — Constitutional Provision Involved,

United States Constitution, Article VI, Clause 2... 77a

Appendix E — 21 U.S.C. § 393 ................ 78a

Appendix F — 21 U.S.C. § 35S(a)-(e) ........... 84a

Appendix G — 21 U.S.C. § 352(f) .............. llla

Appendix H — Pub. L. No. 87-781, § 202 ....... L12a

Appendix | — 21 C.F.R. § 314.70 .............. 113a

Appendix J —- Requirements on Content and Format

of Labeling for Human Prescription Drug and

Biological Products, 71 Fed. Reg. 3922, 3933-36

(Jan. 24, 2006) (Preamble Part D) ............ 126a

Appendix K — FDA Regulatory History of Phenergan

nt ea ccs dee RO eee Ue ONE Loe es bn 139a

Appendix L — Phenergan’s Label as of 2000 ..... 167a

OPINIONS BELOW

The decision of the Supreme Court of Vermont is reported

at -- A.2d -- (Vt. 2006) and reprinted in the Appendix (“App.”)

at |a-48a. The trial court’s decision denying Petitioner's Motion

for Judgment as a Matter of Law is reprinted at App. 49a-74a.

JURISDICTION

The Supreme Court of Vermont rendered its decision on

October 27, 2006, App. la, and denied a timely motion for

reargument on December 11, 2006, App. 75a. This Court has

jurisdiction under 28 U.S.C. § 1257(a).

PERTINENT CONSTITUTIONAL, STATUTORY,

AND REGULATORY PROVISIONS

The pertinent constitutional, statutory, and regulatory

provisions are set forth in the Appendix, App. 77a-138a.

INTRODUCTION

Granting this petition would enable the Court to resolve

the pervasive aiid recurring conflict between state claims of

power to regulate prescription drug labeling and the integrity of

the congressionally mandated federal prescription drug labeling

regime that lies at the heart of the Food and Drug

Administration’s (“FDA's”) regulatory authority. This conflict

is currently at issue in tens of thousands of cases in our nation’s

courts, in which plaintiffs claim that manufacturers should have

modified FDA-approved prescription drug labeling. The lower

courts have resolved this conflict inconsistently and have given

varying weight to FDA’s formal statements on the extent to

which such claims obstruct its regulatory objectives. A ruling

by this Court on the preemption issues presented would provide

invaluable guidance to the hundreds of federal and state judges

now grappling with these claims.

In this case, Wyeth’s federally approved labeling of its anti-

nausea drug Phenergan reflected FDA’s expert judgment that

the option to administer the drug intravenously by direct, or

“push,” (“IV push’) injection' — which provides faster and more

potent relief than other methods of administration — should be

preserved. Respondent was injured when Phenergan was

administered to her by IV push injection and somehow came in

contact with arterial blood, causing gangrene and the loss of

her forearm. App. 2a. The approved labeling repeatedly and

prominently warmed of the hazard of arterial exposure, expressly

stating that, should a health care provider determine that IV

push injection was warranted, he or she must use “extreme care”

not to introduce the medicine into the patient’s arteries to avoid

serious injuries, including “gangrene requiring amputation,”

which was “likely under such circumstances.” App. 167a.

Respondent claimed that Phenergan’s labeling should have gone

further and foreclosed IV push injection altogether in light of

the risk of injury. Wyeth countered that Respondent's claim was

preempted under federal law.

Over the strong dissent of Chief Justice Reiber, a Vermont

Supreme Court majority held that Respondent’s claim was not

preempted by FDA’s decisions to preserve the IV push injection

option because Wyeth was not absolutely barred from implementing

labeling changes without FDA’s prior approval. The majority

reasoned that Wyeth could have — and, as the jury found, should

have — foreclosed IV push injection. It also declined to consider

Wyeth’s contention that the duty to bar IV push injection imposed

by Vermont law would obstruct the purposes and objectives of

FDA's supervision of Phenergan’s labeling, concluding that this

line of traditional preemption analysis was precluded by a savings

clause in the Federal Food, Drug and Cosmetic Act (“FDCA”).

App. 21a-24a. In reaching its decision, the majority rejected FDA’s

unequivocal position that claims precisely like Respondent's

disrupted the agency's ability to ensure that prescribers

receive the best information on how to balance the risks and

benefits of methods of drug administration. App. 24a-28a.

' IV push injections are administered by applying pressure to inject a

drug into a patient’s veins and differ from “IV dnp” administration, where

a drug is slowly “dripped” into a patient's veins from a hanging IV bay.

The Vermont Supreme Court’s decision is in error.

If allowed to stand, it would empower courts to review and overnde

FDA’s careful and comprehensive balancing of safety and

effectiveness concerns in prescription drug labeling and to

undermine the integrity of FDA’s statutorily mandated labeling

regime — as the expert agency has recognized. This Court should

grant review to restore the proper balance between federal and state

authority in this critical area affecting the nation’s public health.

STATEMENT OF THE CASE

A. Factual Background

1. FDA Regulatory Regime

Congress has established FDA as the sole federal agency

commissioned both to “protect the public health” by ensuring

that drugs are safe and effective and to “promote the public

health” by ensuring prompt public access to drugs it has found

to be safe and effective. 21 U.S.C. § 393(b). FDA’s power to

ensure the safety of drugs and their labeling dates back to the

1938 Federal Food, Dru, and Cosmetic Act (“FDCA”), in which

Congress first charged FDA to: (a) serve as the sole gatekeeper

for deciding whether a drug is safe for its labeled uses and

includes “adequate directions for [such] use”; and (b) seize drugs

it finds are inadequately labeled or dangerous when used as

intended. See Pub. L. No. 75-717, §§ 201(p), 301(a), 502(f),

505(d)(1), 52 Stat. 1040, 1041-42, 1051-52 (1938) (codified as

amended at 21 U.S.C. §§ 321(p), 33 1(a), 352(f), 355(d)). Marketing

a prescription drug with a label that is not FDA-

approved is a federal cnme. See 21 U.S.C. §§ 332(a), 333(a), 334.

Since 1962, Congress also has entrusted FDA with ensuring

that safe drugs are effective for their labeled uses. See Drug

Amendments of 1962, Pub. L. No. 87-781, § 102(b), 76 Stat.

780, 781 (1962) (codified as amended at 21 U.S.C. § 355(b)).

This significant expansion of FDA’s regulatory oversight

authority recognized that the use of any drug entails some risk

and that marketing approval should rest on FDA’s scientific

determination that a drug’s overall health care benefit outweighs

its nsks. See S. Rep. No. 87-1744, at 15 (1962), as reprinted in

1962 U.S.C.C.A.N. 2884, 2891-92 (observing that, for very risky

drugs, “the determination of safety is, in the light of the purposes

of the new drug provisions, considered by [FDA] to be

inseparable from consideration of the drug’s effectiveness’’);

Requirements on Content and Format of Labeling for Human

Prescription Drug and Biological Products, 71 Fed. Reg. 3922,

3934 (Jan. 24, 2006), App. 128a (“Under the Act and FDA

regulations, the agency makes approval decisions based .. . on a

comprehensive scientific evaluation of the product’s risks and

benefits under the conditions of use prescribed, recommended, or

suggested in the labeling.” (citation omitted)). Balancing risks

against benefits for particular prescription drugs, dosages, and

methods of administration thus has been the central task of FDA

for nearly a half-century.

As FDA has repeatedly made clear, the agency conducts

this risk-benefit assessment from a forward-looking perspective,

with the overall public health in mind, rather than through the prism

of individual cases. As a former Commissioner has testified:

Every time the scientists on our staff allow a new drug to

come to market, they have to take the sum total of

scientific knowledge that they can muster about the drug,

and reach a conclusion as to whether or not the good that

the drug will do, the lives it will save or the suffering that

it will prevent, outweighs the known side-effects.

See Hearing on H.R. 6245 Before the Subcomm. On Antitrust

of the H. Comm. On the Judiciary, 87th Cong. 135 (1962)

(statement of George P. Larrick, Commissioner, FDA); see a/so

FDA, Draft Guidance for Industry: Development and Use of

Risk Management Action Plans 4 (Mar. 2005), available at hitp./

/wwwfda.gov/cder /guidance/6358fnl.pdf (describing FDA's

risk-benefit assessment as measuring whether, under labeled

conditions of use, “the clinical significance and probability of

{a drug’s] beneficial effects outweigh the likelihood and medical

importance of its harmful or undesirable effects”).

To obtain FDA approval of a new prescription drug, the

manufacturer must submit a New Drug Application (“NDA”).

See 21 U.S.C. § 355(b). As part of the NDA, the manufacturer

must submit comprehensive information concerning the new

drug, “full reports of investigations” concerning safety and

effectiveness, and “specimens of the labeling proposed to be used

for such drug.” /d. § 355(b)(1); 21 C.E.R. § 314.50. The information

submitted must establish that the new drug is safe and effective

“for use under the conditions prescribed, recommended, or

suggested in the proposed labeling thereof” before FDA will

approve it for distribution and marketing. 21 U.S.C. § 355(d)(1).

The review and approval of a drug’s labeling therefore is a

critical means through which FDA carries out its risk-benefit

assessment. See New Drug and Antibiotic Regulations, 50 Fed.

Reg. 7452, 7470 (Feb. 22, 1985) (“Drug labeling serves as the

standard under which FDA determines whether a product is safe

and effective.”); see also FDA, Guidance: Drug Safety

Information — FDA's Communication to the Public 7 (Mar.

2007), available at http://www.fda.gov/cder/guidance/

7477 fnl.pdf (“FDA-approved drug product labeling 1s the

primary source of information about a drug’s safety and

effectiveness ... .”’). For this reason, FDA has issued a series

of regulations that comprehensively dictate the form and

substance of all prescription drug labels. Those drug labels must

include, among a host of other requirements, “a summary of

the essential scientific information needed for safe and effective

use of the drug,” 21 C.F.R. § 201.56(1), including a description

of “clinically significant adverse reactions,” “other potential

safety hazards,” “limitations in use imposed by them, . . . and

steps that should be taken if they occur,” id. § 201.57(c)(6)(1).

Accordingly, FDA’s approval of an NDA 1s inseparable from

the agency’s approval of the precise language contained on the

new drug’s label. See id. § 314.50(e)(2)(11), (D(1)().

FDA’s regulatory authority over prescription drug labeling

continues after a drug is initially approved for marketing and

distribution. Manufacturers have an ongoing obligation to

submit reports “of data relating to clinical experience” —

including adverse drug events. 21 U.S.C. § 355(k)(1); see also

21 C.F.R. § 314.80. FDA has the authority to withdraw a drug

from the market if it concludes the drug is unsafe or ineffective

for its labeled uses. See 21 U.S.C. § 355(e). Although

manufacturers may initiate labeling changes, they must submit

to FDA full descriptions of all proposed changes and ordinarily

await FDA approval before implementing a proposed change.

See id. § 355(b)(1)(F); 21 C.F.R. § 314.70. FDA has, however,

adopted a regulation — known as the “change being effected,”

or “CBE,” provision — that extraordinarily allows manufacturers

to initiate interim post-approval labeling changes pending FDA

approval. The CBE provision is designed to operate only when

scientifically significant, newly discovered information demands

changes to: (a) add or strengthen a contraindication, warning,

precaution, or adverse reaction; or (b) add or strengthen an

instruction about dosage and administration intended tc increase

safe use of a drug. /d. § 314.70(c)(6)(i1)(A), (C). CBE changes

are interim; “the determination whether labeling revisions are

necessary is, in the end, squarely and solely FDA’s under the

act.” 71 Fed. Reg. at 3934, App. 132a.

2. FDA’s Regulation of Phenergan

Wyeth sold injectable Phenergan for treatment of nausea.

FDA found injectable Phenergan safe for labeled conditions of

use and approved it for sale with no limitation on any method

of IV injection in 1955. In 1967, Wyeth first received a report

of gangrene and subsequent amputation resulting from arterial

blood exposure to Phenergan, which it reported to FDA. App.

139a. At that time, Phenergan’s labeling already warned against

such arterial blood exposure through perivascular extravasation

or intra-arterial injection.” App. 139a-140a.

Between 1967 and 1981, FDA worked closely with Wyeth

> Perivascular extravasation occurs when a drug administered

intravenously leaks out of the vein into the surrounding tissue, where it

may come into contact with arterial blood. App. 4a, 42a. Perivascular

extravasation occurs through no fault of the physician or the drug

manufacturer. App. 42a.

through a series of communications and at least one in-person

meeting to refine Phenergan’s warnings with respect to [V push

administration. As of at least 1974, Phenergan’s label made clear

that intramuscular (““IM”’) injection was the “preferred parenteral

route of administration” and advised that IV administration was

“well-tolerated” but “not without some hazard” because

gangrene could result from exposure of Phenergan to arterial

blood. App. 53a.

As of 1981, the Phenergan label included the following

language: ““When administering any irritant drug intravenously,

it is usually preferable to inject it through the tubing of an

intravenous infusion set that is known to

be functioning satisfactorily” — i.e., through IV drip

administration. App. 54a (emphasis added). While FDA noted

its preference for the IV drip method, it never suggested that

the [V push method of injection should be contraindicated or

foreclosed.

In 1987, after Wyeth complied with a general FDA mandate

to reformat Phenergan’s labeling and submit it by a supplementa:

New Drug Application (“sNDA”) for approval, FDA

recommended revisions concerning the “recognition and

management of unintended intra-arterial injection.” App. 150a-

157a. These changes included an enhanced instruction

concerning IV drip administration: “Injection through a properly

running intravenous infusion [set] may enhance the possibility

of detecting arterial placement. In addition, this results in

delivery of a lower concentration of any arteriolar irritant.”

App. 152a. Again, however, FDA never suggested that the IV

push method should be contraindicated or foreclosed.

On May 3, 1988, Wyeth submitted new draft labeling for

FDA approval that essentially incorporated FDA’s recommended

changes relating to IV drip administration: “Injection into an

intravenous infusion set that is known to be running properly

should decrease the possibility of inadvertently injecting

promethazine intra-arterially. In addition, this results in delivery

of a lower concentration of any arteriolar irritant.” App. 54a.

In 1997 — explaining that it had taken extra time to review

Phenergan’s proposed labeling changes to ensure that it had

“dotted every ‘i’ and crossed every ‘t’” — FDA specifically

ordered Wyeth to “[rJetain [the] verbiage in [the] current label”

concerning inadvertent intra-arterial injection and to make other

labeling changes. App. 158a-159a, 162a. Wyeth submitted a

revised draft package insert on May 8, 1998 in compliance with

FDA’s orders. FDA then approved that labeling and expressly

commanded Wycth that “(tthe final printed labeling (FPL) for

the package insert must be identical to the draft package insert

submitted May 8, 1998.” App. 165a (emphasis added).

FDA’s consistent decision not to foreclose IV push

administration of | aenergan reflected a classic balancing of risks

and benefits. The beneficial effects of IV injection generally

begin within five minutes; IV drips (when equipment is

available) are slower to administer, and IM injection can require

twenty minutes or more to take effect. App. 165a. This is no

small difference: extreme nausea can cause a patient to lose

fluids quickly, which leads to dehydration, a serious medical

condition. A doctor, confronted with a patient in dire need of

relief from nausea, could reasonably decide that the benefits of

IV push administration would warrant taking its increased nsk.’

3. The Operative Phenergan Label when

Respondent Was Treated

In 2000, as a result of the foregoing FDA oversight over a

45-year period and a series of revisions, Phenergan’s two-page

label included repeated, prominent notice of the risk of gangrene

arising from inadvertent arterial exposure in no fewer than four

‘ Moreover, under certain circumstauces, IM injection is unreliable

or ineffective, such as in the treatment of overweight patients and patients

with poor blood flow to the various muscle groups due to dehydration or

cardiac disease. In such a situation, a doctor could determine that TV push

injection is the only way to provide the patient with the needed relief.

separate sections — i.e., “Contraindications,” “Warnings,”

“Adverse Reactions,” and “Dosage and Administration.” Two

such sections provided the following notice in upper-case type:

INADVERTENT INTRA-ARTERIAL INJEC-

TION CAN RESULT IN GANGRENE OF THE

AFFECTED EXTREMITY.

App. 4a, 167a. The label further warned that:

Due to the close proximity of arteries and veins in the

areas most commonly used for intravenous injection,

extreme care should be exercised to avoid perivascular

extravasation cr inadvertent intra-arterial injection.

Reports compatible with inadvertent intra-arterial

injection of Phenergan Injection, usually in conjunction

with other drugs intended for intravenous use, suggest

that pain, severe chemical imitation, severe spasm of

distal vessels, and resultant gangrene requiring

amputation are likely under such circumstances.

App. 4a, 167a. The label also included lengthy instructions

concerning the means of minimizing this risk in both the “Dosage

and Administration” and “Warnings” sections. App. 167a.

4. The Administration of Phenergan to Respondent

On April 7, 2000, Respondent sought treatment from

Northeast Washington County Community Health, Inc. (the

“Health Center”) for a severe migraine headache and associated

nausea and dehydration. App. 2a. Respondent was initially

treated with Phenergan via IM injection, the preferred method

of administration. App. 2a.

Respondent returned to the Health Center later that day

because she had not obtained effective relief. App. 2a. A second

dose of Phenergan was then administered directly into

Respondent's vein via IV push injection. App. 2a. Phenergan’s

FDA-approved label specifically instructed practitioners to

proceed with extreme caution in any administration; the

administering physician assistant was aware of these instructions

and of the risk of arterial exposure through misinjection.

2 es

Respondent thereafter developed the symptoms of arterial

exposure and had to have her forearm amputated. App. 2a.

Before the commencement of this case, Respondent sued the

health care providers for malpractice and settled for $700,000.

B. Proceedings Below

1. The Trial Court Proceedings

Respondent brought state-law-based liability claims against

Wyeth on the theory that Wyeth should have revised Phenergan’s

FDA-approved label to bar [V push administration. App. 38a,

4a. The jury returned a verdict in favor of Respondent, who

was ultimately awarded $ 6,774,000. App. 3a.

Wyeth sought judgment as a matter of law on the ground

that federal law preempted Respondent’s claims. The trial court

denied Wyeth’s motion, issuing an opinion independently

addressing preemption as a matter of law. App. 4a, 74a. In its

view, FDA’s CBE regulation, 21 C.F.R. § 314.70, “permit[s]}

strengthened warnings without approval on an interim basis,”

App. 64a, such that Wyeth could be required to conform its

labeling to common law tort duties. The court acknowledged

the inevitable differences between FDA’s comprehensive

balancing of public safety and efficacy interests and the tort

precess, which views “the matter in hindsight through the lens of a

single catastrophic case,” App. 62a, but still found that the jury’s

state-law-based judgment presented no obstacle to FDA’s regulatory

objectives, App. 63a.

2. The Appeal to the Vermont Supreme Court

Wyeth timely appealed to the Vermont Supreme Court.

Wyeth contended that the tral court erred, inter alia, by failing

to hold that Respondent’s common law claims were preempted

because: (1) Wyeth would have been unable to comply with

both Vermont’s common law duty to foreclose IV push injection

and FDA’s directive, as evidenced by the drug’s approved label,

to retain it; and (2) the claims would obstruct the full

accomplishment of FDA's risk-benefit objective to optimize use

of Phenergan by imposition of a duty to foreclose [V push

injection. App. Sa-6a. The Vermont Supreme Court rejected both

arguments and affirmed the trial court’s decision. App. | 9a, 28a.

The court first rejected Wyeth’s claim that it would be

impossible for Wyeth to comply with both a Vermont common

law duty to foreclose IV push injection and a federal duty to use

an FDA-approved label that allowed the drug to be administered

in this fashion. Like the trial court, the Supreme Court relied on

the CBE regulation, 21 C.F.R. § 314.70(c). In the court’s view,

“FDA approval of a particular label does not preempt a jury

finding that the label provided insufficient warning, as defendant

was free under § 314.70(c) to strengthen the warning without

prior FDA approval.” App. | 7a. The court also declined to accord

any significance to FDA’s directive to Wyeth to “[r]etain

verbiage in current label.” App. 17a.

The court next refused to consider Wyeth’s claim that

Vermont's decision to impose a state tort law duty on Wyeth

created an obstacle to the objectives of the FDA regulatory

regime. The court held that all such “obstacle” preemption

claims were foreclosed by language in the 1962 amendments to

the FDCA that premised preemption on a “direct and positive

conflict between such amendments and [a] provision of State

law.” App. 21a (quoting Drug Amendments of 1962, § 202, 76

Stat. at 793, App. 1 12a). The court reasoned that section 202

restated the standard for “impossibility” preemption and thus

“remove[d] from ... consideration the question of whether

common-law tort claims present an obstacle to the purposes

and objectives of Congress.” App. 21a.

Last, the court refused to give any weight to FDA’s formal

preemption analysis. Specifically, in a regulatory preamble to

recent amendments to its labeling rule, FDA rejected the

positions adopted by many federal courts and the Vermont

Supreme Court that (1) section 314.70 broadly permits

manufacturers to make unilateral labeling changes and (2)

“[s}]tate law serves as an appropriate source of supplementary

safety regulation for drugs by encouraging or requiring

manufacturers to disseminate risk information beyond that

required by FDA under the act.” App. 24a (quoting 71 Fed.

Reg. at 3934, App. 126a). To the court, FDA’s analysis was

“neither an authoritative interpretation of an ambiguous statutory

provision entitled to deference, nor a persuasive policy statement

entitled to respect.” App. 28a (internal citation omitted).

Chief Justice Reiber dissented. The Chief Justice first

concluded that an “actual conflict” existed between the jury

verdict and federal law because “the FDA clearly addressed the

risks attending IV administration of the drug[,] .. . approved

IV administration generally, and specifically warned of the

dangers of direct IV administration, including inadvertent arterial

injection possibly resulting in amputation.” App. 38a. “These

assessments are, in fact, the very essence of the FDA’s approval

and are in furtherance of the federal objective of advancing

public health by balancing the risks and benefits of new drugs

and facilitating their optimal use.” App. 38a.

The Chief Justice also found that Wyeth was not “‘free’ to

change drug labels under [section] 314.70” because the purpose

of this regulatory provision “ts to allow manufacturers to address

newly discovered risks.” App. 39a-40a. Here, not only was there

a complete absence of new evidence concerning IV push

administration of Phenergan, but “FDA had already evaluated

the risk of inadvertent arterial injection .. . and had mandated

warming language for the label to reflect that risk assessment”

in its 1997 directive to Wyeth. App. 40a. Wyeth thus “could not

both list all forms of IV administration as an approved use, as

required by the FDA, and exclude all or some forms of IV

administration as unsafe, as required by the jury’s verdict in

this case.” App. 43a.

The Chief Justice next rejected the majority’s view that the

section 202 “direct and positive conflict” language forbade the

court from assessing whether state tort law obstructed the federal

purposes and objectives served by FDA’s regulatory regime.

App. 44a-45a. On the merits of Wyeth’s argument, the Chief

Justice concluded that “obstacle preemption” applied in this

case under the reasoning of Geier v. American Honda Motor

Co., 529 U.S. 861 (2000). App. 45a. The Chief Justice

analogized the federal safety standard at issue in Geier — which

“allow[ed] a choice of passive restraint systems while not

mandating any particular system” and “was a deliberate decision

that reflected a balance of diverse policy concerns” — with FDA’s

risk-benefit balancing judgment, which “considers various

policy factors that are sometimes in tension with one another”

to “maximize the availability of beneficial treatments.” App.

48a. According to the Chief Justice, FDA’s conclusion that

“Phenergan is safe and effective when delivered through IV

administration” preempts any tort duty that would require Wyeth

to bar that particular use. App. 48a.

REASONS FOR GRANTING THE PETITION

The Vermont Supreme Court held that a manufacturer may

be liable under state law for failing to bar a particular method

of administration of a prescription drug. The federal agency

expert in evaluating the safety and efficacy of drugs had

concluded that this highly potent method of administration

should remain available and directed the manufacturer to retain

a label that, while urging prescribers to use extreme care in

administering the drug, nonetheless retained it as a medical

option. This case thus presents a direct conflict between the

considered labeling decision of a federal agency exercising its

ex ante responsibility to make comprehensive public health

judgments and an ex post case-specific determination of one

state jury that the federally approved labeling was inadequate.

Unfortunately, this conflict is far from uncommon. There

are tens of thousands of individual claims, and potentially

millions of class action claims, currently pending in the lower

federal and state courts, in which plaintiffs contend that a

manufacturer’s use of FDA-approved labeling for its

prescription drug is inadequate to satisfy state-law duties to

warn.* Divided lines of authority already have emerged and are

* See, e.g., In re Bextra & Celebrex Marketing, Sales Practices &

Prods. Liab. Lit., No. 05-cv-01699-CRB (N.D. Cal.) (litigation consists

of over 1,800 lawsuits); Jn re Prempro Prods. Liab. Litig., No.

4:03C V01507 (F.D. Ark.); In re Vioxx Marketing, Sales Practices &

(Cont'd)

highly unlikely to be reconciled by further lower court decisions.

By deciding key preemption issues here on a record that squarely

and cleanly presents them,’ this Court can forestall erroneous

decisions in numerous cases and the huge expenditure of

resources required to correct those errors and reprocess the

underlying cases.

The Vermont Supreme Court made basic and fundamental

doctrinal errors in its preemption analysis. Wyeth has

consistently argued that a jury verdict premised on the alleged

inadequacy under state law of an FDA-approved prescription

drug label is preempted when it “actually conflicts” with the

federal drug labeling regime. State law “actually conflicts” with

federal law when “compliance with both federal and state

regulations is a physical impossibility,” Florida Lime & Avocado

Growers, Inc. v. Paul, 373 U.S. 132, 142-43 (1963), or when

state law “stands as an obstacle to the accomplishment and

execution of the full purposes and objectives of Congress,”

Hines v. Davidowitz, 312 U.S. 52, 67 (1941). These bedrock

principles apply with equal force to federal regulations, see

Fidelity Federal Savings & Loan Ass'n v. de la Cuesta, 458

U.S. 141, 153 (1982), and do not differentiate between common

law rules arising from state jury verdicts and positive legislative

enactments, see Cipollone v. Liggett Group, Inc., 505 U.S. 504,

522 (1992). Prescription drug labeling cases implicate both

species of conflict preemption. |

Determining whether state tort claims “actually conflict”

(Cont'd)

Prods. Liab. Litig., No. 05-MDL-1657 (E.D. La.) (approximately 27,400

lawsuits, including over 46,100 plaintiff groups, and approximately 264

putative class actions as of December 2006). Individual suits like that

presented here are almost too numerous to count.

* This case presents an ideal vehicle for resolving these legal issues

because the facts underlying the preemption question are not in dispute.

There is no allegation that Wyeth had failed to react to safety information

not considered by FDA or that Wyeth breached any other state law duty

that might make the Vermont Supreme Court’s mistaken preemption

analysis insufficient to reverse the judgment.

with FDA prescription drug labeling rules requires resolution

of three key legal questions. First, does FDA’s labeling

regime developed under congressional mandate provide

only a minimum safety standard open to unlimited state

supplementation or a fully calibrated risk-benefit balance of

national applicability that state law should not disrupt? Second,

are principles of “obstacle” conflict preemption trumped in

prescription drug cases either by a presumption against

preemption or by a statutory requirement that preemption arise

from a “direct and positive” conflict? Third, should weight be

given in the preempti- = analysis to FDA’s recent formal

assessment of the adverse impact of tort actions on the integrity

of its labeling regime?

The Vermont Supreme Court answered al! of these questions

incorrectly. First, it concluded — contrary to the agency’s view

of its own regulations — that FDA’s labeling requirements merely

provided a “floor” and that a manufacturer was free unilaterally

to change its labeling without prior FDA approval. Second, the

court erroneously declined even to consider whether the state

tort law duty would “stand as an obstacle” to the effectiveness

of federal drug regulation, mistakenly reading a provision in

the FDCA as precluding this entire line of traditional preemption

analysis. Finally, the court dismissed FDA's carefully considered

judgment that tort suits like the instant one disrupt the agency's

ability to ensure that the optimal information about the risks

and benefits of using prescription drugs is provided to

prescribers. Each of these conclusions was erroneous, and each

independently warrants reversal.

I. The Court Should Grant Review To Correct Vermont’s

Rejection of Impossibility Conflict Preemption

Stemming from its Mischaracterization of FDA’s

Comprehensive Regulatory Regime.

The Vermont Supreme Court's opinions in this case

exemplify an ongoing dispute in the lower courts as to whether

FDA's labeling approvals establish only a minimum requirement

(“floor”) for safety-related disclosures or, alternatively, a

calibrated approach (‘floor and ceiling”) that neither underwarns

nor overdeters effective use. This base disagreement is very often

outcome determinative and has been characterized by FDA as a

threat to the integrity of its comprehensive regulatory regime.

See 71 Fed. Reg. at 3934, App. 130a (“FDA has learned of

several instances in which product liability lawsuits have directly

threatened the agency’s ability to regulate manufacturer

dissemination of risk information for prescription drugs in

accordance with the act.”’).

A majority of the Vermont Supreme Court adopted the

former view in this case, following a line of cases holding that

“FDA’s drug labeling decisions impose only ‘minimum’

standards that are open to supplementation by state law through

a jury’s verdict enforcing a manufacturer’s common law duty

to warn.” Caraker v. Sandoz Pharm. Corp, 172 F. Supp. 2d

1018, 1033 (S.D. Ill. 2001); Mazur v. Merck & Co., 742 F. Supp.

239, 247 (E.D. Pa. 1990) (“Manufacturers must meet state safety

requirements, whether codified or embodied in the common

law, in addition to satisfying initial FDA requirements.”);

Cartwright v. Pfizer, Inc., 369 F. Supp. 2d 876, 883 (E.D. Tex.

2005) (“FDA only sets forth minimum standards for labeling

and safety of drugs.”); McNellis v. Pfizer, Inc., No. Civ. 05-

1286, 2005 WL 3752269, at *7 (D.N.J. Dec. 29, 2005) (“FDA's

regulations do not conflict with New Jersey’s failure to warn

law because those federal regulations merely set minimum

standards with which manufacturers must comply.”’), stay

granted and motion to certify appeal granted, No. Civ. 05-1286

(JBS), 2006 WL 2819046 (D.N.J. Sept. 29, 2006). Under this

approach, state labeling requirements — whether imposed through

positive legislative enactments or judicial decree — can almost never

be incompatible with FDA’s labeling regime. App. |5Sa

(“When further warnings become necessary, the manufacturer is

at least partially responsible for taking additional action,

and if it fails to do so, it cannot rely on the FDA’s continued

approval of its labels as a shield against state tort liability.”).

Chief Justice Reiber’s dissent looked to different authority

holding that “inadequate warning claim[s] would . . . conflict

with the federal requirements imposed during the regulation

of” the prescription drug by, “in effect, allowing a state regulation

to impose labeling requirements contrary to those required by

federal law.” Needleman v. Pfizer, Inc., No. 3:03-CV-3073-N,

2004 WL 1773697, at *2 (N.D. Tex. Aug. 6, 2004); /n re Bextra

& Celebrex Marketing Sales Practices & Prod. Liab. Litig.,

No. 05-1699, 2006 WL 2374742, at *10 (N.D. Cal. Aug. 16,

2006) (“Plaintiffs’ state law failure-to-warn-claims conflict with

the FDA’s determination of the proper warning and pose an obstacle

to the full accomplishment of the objectives of the FDCA.”);

Ehlis v. Shire Richwood, Inc., 233 F. Supp. 2d 1189, 1198 (D.N.D.

2002) (finding that prescription drug warning claim was preempted

where “FDA dictates the contents of the label” and where

“defendants were prohibited from changing it without prior

approval from the FDA, except in limited circumstances for a

limited period of time”’), aff ‘d, 367 F.3d 1013 (8th Cir. 2004).

As Chief Justice Reiber explained, it would have been

literally impossible for Wyeth to have complied with both the

duty newly imposed under Vermont common law and FDA’s

command that Phenergan be marketed under labeling identical

to that submitted by Wyeth on May 8, 1998. Respondent’s cause

of action onginated from — and inis case ultimately turned on —

the premise that Phenergan’s labeling should have foreclosed

IV push administration of Phenergan. App. 37a (“[W]hat

plaintiff sought was an elimination of a use of Phenergan that

had been approved by the FDA.”) (Reiber, C.J., dissenting).

Thus, Wyeth could have complied with the legal duty it allegedly

breached under Vermont law only if it had modified its FDA-

approved label without prior FDA authorization before April 7,

2000, when Respondent was injected. Unless federal law

permitted such modification, well-established conflict

preemption principles would preclude holding Wycth liable for

failing to follow a state mandate that would have forced it to

violate federal law. See Freightliner Corp. v. Myrick, 514 US.

280, 287 (1995).

No FDCA provision authorizes manufacturers to modify

FDA-approved labeling without prior FDA consent. Indeed, as

the Vermont Supreme Court acknowledged, the FDCA

conditions the right to ship prescription drugs in interstate

commerce on the use of FDA-approved labeling. As FDA

routinely advises manufacturers receiving New Drug approvals,

“[mJarketing the product with [labeling] that is not identical to

the approved labeling text may render the product misbranded

and an unapproved new drug.” Letter from Edward Cox, Acting

Director, Center for Drug Evaluation and Research, to David

Hallinan, VP Regulatory Affairs, Idenix Pharms., Inc. (Oct. 25,

2006), available at http://www.fda.gov/cder/foi/appletter/2006/

02201 15000ltr.pdf (approving NDA 22-011 (Tyzeka)); see also

App. 165a (commanding that Phenergan’s “final printed labeling

. must be identical to the [FDA-approved] draft package

insert”). Marketing a misbranded or unapproved prescription

drug would subject the manufacturer to substantial criminal and

civil penalties. 21 U.S.C. §§ 332(a), 333(a), 334.

To meet the need to disseminate newly discovered safety

information without delay, FDA adopted its “change being

effected,” or “CBE,” regulation, 21 C.F.R. § 314.70(c)(6)(iii),

in 1982. Rather than properly interpreting that regulation as a

limited exception to FDCA’s pre-approval labeling regime,

however, courts adopting the “minimum” standards approach

have seized on it to open the door to far-reaching state safety

regulation. The CBE regulation descnbes certain categories of

interim labeling changes that manufacturers may make without

prior FDA approval, including “[t]o add or strengthen

an instruction about dosage or administration that is intended

to increase the safe use of the drug product.” /d.

§ 314.70(c)6)(ii(C). Under the Vermont court’s construction,

this regulation allows “unilateral changes to drug labels

whenever the manufacturer believes it will make the product

safer, and places no limit on the duration of pre-approval

warnings unless the FDA disapproves of the change.” App. 13a

(citation omitted); see also Caraker, 172 F. Supp. 2d at 1034

(“Even after approval, additional or more forceful warnings may,

in the drug manufacturer’s judgment, be added to labeling

without prior FDA approval and on the drug manufacturers’

own initiative.”). Thus, “[w]hile specific federal labeling

requirements and state common-law duties might otherwise

leave drug manufacturers with conflicting obligations, § 314.70(c)

allows manufacturers to avoid state failure-to-warn claims

without violating federal law.” App. | 1a (citation omitted).

This expansive and result-oriented reading of the CBE

regulation is clearly incompatible with FDA’s overall regulatory

labeling regime. As FDA explained in adopting the CBE

provision in 1982, that regulation creates a limited exception to

the general pre-approval regime to permit newly discovered

information to be timely disseminated. See New Drug and

Antibiotic Regulations, 47 Fed. Reg. 46,622, 46,623, 46,635

(Oct. 19, 1982) (codified at 21 C.F.R. pts. 310, 312, 314, 430,

431, 433); see also Perry v. Novartis Pharma. Corp., 456 F.

Supp. 2d 678, 682 (E.D. Pa. 2006) (“This particular regulation

was promulgated precisely to allow drug-makers to quickly

strengthen label warnings when evidence of new side effects

are discovered.” (emphasis added) (internal quotation marks

and citation omitted)); Weiss v. Fujisawa Pharm. Co., 464 F.

Supp. 2d. 666, 675 (E.D. Ky. 2006) (explaining that a “drug

manufacturer may warm patients and healthcare providers should

they discover new evidence of a particular risk following the

approval of the original label” (emphasis added)). While a “new

information” trigger for using the CBE provision is not express

in its text, it is necessarily implicit in FDA’s larger regulatory

scheme. See Labeling and Prescription Drug Advertising;

Content and Format for Labeling for Human Prescription Drugs,

44 Fed. Reg. 37,434, 37,447 (June 26, 1979) (codified at 21

C.F.R. pts. 201-202); 71 Fed. Reg. at 3934, App. 128a-132a.

FDA’s comprehensive, particularized regulation of label formats

and wording at the time of NDA approval cannot be reconciled

with according manufacturers thereafter an unlimited ability to

modify critical label language without prior FDA approval. See

Smith v. United States, 508 U.S. 223, 234 (1993) (“A provision

. . . lS often clanfied by the remainder of the statutory scheme . . .

because only one of the permissible meanings produces a

substantive effect that is compatible with the rest of the law.”

(internal quotation marks and citation omitted)). In the words of

Chief Justice Reiber, “the regulation does not allow manufacturers

to simply reassess and draw different conclusions regarding the

same risks and benefits already balanced by the FDA.” App. 40a.

The facts of this case clearly show how the FDA regime can

be disrupted by the CBE minimum standards approach. Here, the

record unequivocally established that all information relating to

the risks of IV injection of Phenergan put before the jury was

available to FDA when it.acted on Wyeth’s supplemental NDA in

1997. The Vermont judicial process simply differed with FDA on

the risk-benefit assessment appropriate to these facts, thus turning

the CBE regulation into a recipe for balkanized and unbounded

state second-guessing of federal regulatory actions. See App. 65a

(calling FDA’s regulatory process “slow and imperfect” and

suggesting that FDA did not review “intravenous administration

of Phenergan with scientific ngor or any sense of urgency”).

This Court and the federal courts of appeal consistently have

made clear that Congress has safeguarded FDA's science-based

discretionary decisions from second-guessing in the federal courts,

let alone fifty state courts. See, e.g., Heckler v. Chaney, 470 U.S.

821, 835 (1985); see also Weinberger v. Bentex Pharms., Inc.,412

U.S. 645, 653-54 (1973) (“The determination whether a drug is

generally recognized as safe and effective . . . necessarily implicates

complex chemical and pharmacological considerations” and is

“peculiarly suited to initial determination by the FDA.”):

Nutraceutical Corp. v. Von Eschenbach, 459 F.3d 1033, 1043 (10th

Cir. 2006) (“The review of scientific literature is properly m the

province of the FDA, to which this Court grants deference based

on its expertise.”); Schering Corp. v. FDA, 51 F.3d 390, 399 (3d

Cir. 1995) (“[FDA’s] judgments as to what is required to ascertain

the safety and efficacy of drugs fall squarely within the ambit of

the FDA’s expertise and merit deference from us.”’).

Distorting the CBE regulation to permit second-guessing by

judges and junes in prescription drug injury cases, as occurred here,

is particularly pernicious. While FDA makes risk-benefit

labeling decisions from a systemic, forward-looking perspective

to optimize use of beneficial treatments, supra at 4, state judicial

decisions make the same determinations “in hindsight through

the lens of a single catastrophic case,” App. 62a, and with an

inevitable bias toward finding fault as a basis for compensation.

Were manufacturers to labei in response to, or in anticipation

of, state determinations, they would be subject to myriad

conflicting mandates, and numerous FDA judgments concerning

optimal labeling and administrations of prescription drugs could

be overridden, to the detriment of overall public health. See

Horn v. Thoratec Corp., 376 F.3d 163, 178 (3d Cir. 2004)

(observing that excessive risk-oriented regulation “can harm

the public health ... by encouraging ‘defensive labeling’ by

manufacturers to avoid state liability, resulting in scientifically

unsubstantiated warnings and underutilization of beneficial

treatments”).

This Court should grant review to restore the integrity of

FDA’s regulatory regime in a “case in which the Federal

Government has weighed the competing interests relevant to

the particular requirement in question, reached an unambiguous

conclusion about how those competing considerations should

be resolved in a particular case or set of cases, and implemented

that conclusion via a specific mandate on manufacturers or

producers.” Medtronic Inc. v. Lohr, 518 U.S. 470, 501 (1996).

At least absent newly discovered scientific information

permitting action under section 314.70(a), manufacturers like

Wyeth should not be held liable for adhering to an FDA-

approved label.

Il. The Court Should Grant Review To Clarify the Effect,

If Any, of the Presumption Against Preemption and

Section 202 of the 1962 FDCA Amendments on the

Application of “Obstacle” Conflict Preemption to

Prescription Drug Cases.

Review also would allow the Court to articulate the

analytical framework for applying conflict preemption principles

to the prescription drug regime when FDA's labeling regime

permits manufacturers to initiate some modifications. Even if

states have some authority to regulate such discretion as FDA

affords to manufacturers, well-establis»ed principles of

preemption forbid states from exercising that authority in a

manner that would obstruct the objectives of federal law.

See McDermott v. Wisconsin, 228 U.S. 115, 132 (1913) (“[T]o

the extent that state law interferes with or frustrates the operation

of the acts of Congress, its provisions must yield to the superior

Federal power. . . .”). This Court has consistently made clear

that conflict preemption analysis requires consideration both

of whether it would be impossible to comply with federal and

state law and of whether the state law would stand as an obstacle

to the objectives of federal law:

The Court has not previously driven a legal wedge -

only a terminological one — between “conflicts” that

prevent or frustrate the accomplishment of a federal

objective and “conflicts” that make it “impossible” for

private parties to comply with both state and federal

law. Rather, it has said that both forms of conflicting

state law are “nullified” by the Supremacy Clause, and

it has assumed that Congress would not want either

kind of conflict.

Geier, 529 U.S. at 873 (citations omitted).

The Vermont Supreme Court majority, however, simply

declined to analyze obstacle preemption. The court determined

that this line of inquiry was foreclosed by sect‘on 202 of the

1962 amendments to the FDCA, which it read as limiting the

operation of preemption to cases in which it ts impossible for a

manufacturer to comply with both state and federal law. App.

22a (“[U]nder any circumstances where it is possible to comply

with both state law and the FDCA the state law in question is

consistent with the purposes and objectives of Congress.”). The

majority attempted to bolster its conclusion by relying on a

“presumption against preemption” of state regulatory powers

in the area of public health. App. 23a-24a.

The majority’s construction of section 202’s “direct and

positive” language is mistaken. This Court has made clear that

the existence of such savings clauses specifically designed to

protect the operation of state law does not preclude application

of conflict preemption — including obstacle preemption. See

Geier, 529 U.S. at 373-74 (“The Court has thus refused to read

general “saving” provisions to tolerate actual conflict both in

cases involving impossibility and in frustration-of-purpose

cases. ...” (internal quotation marks and citations omitted)).

Instead of foreclosing conflict preemption, such provisions —

within an otherwise comprehensive regulatory scheme — ave

best read to indicate Congress’s intent merely to preclude field

preemption — on which Wyeth does not rely. See Schneidewind

v. ANR Pipeline Co., 485 U.S. 293, 299-300 (1988).

That is precisely the effect of section 202. Because the 1962

FDCA amendments greatly expanded FDA’s regulatory

authority, there was legitimate concern that Congress might have

been deemed to occupy the field of drug safety. The use of the

phrase “direct and positive” was intended to preclude field

preemption while fully preserving conflict preemption, nothing

more. As the House sponsor of section 202 explained, this

provision “would merely say that this Food and Drug Act shall

not be construed as the intent of Congress to abolish a// State

laws on the same subject where they are not in conflict with the

Federal law.” See 108 Cong. Rec. 21,083 (1962) (statement of

Rep. Smith) (emphasis added). Indeed, courts determining

whether a “direct and positive” conflict exists routinely conduct

both an impossibility conflict and an obstacle conflict

preemption analysis and make clear that this language operates

only to bar field preemption. See, e.g., Sinnot v. Davenport, 63

U.S. (22 How.) 227, 242-43 (1859) (finding “direct and positive”

conflict between federal and state law coasting trade provisions

despite vessel owner’s ability to comply with both and holding

that “if this State law can be upheld, the full enjoyment of the

right to carry on the coasting trade . . . is denied to the vessel in

question”); City of Camden vy. Beretta U.S.A. Corp., 8\ F. Supp.

2d 541, 549 (D.N.J. 2000) (finding that Gun Control Act's

“direct and positive conflict” phrase “compels a finding that

the Gun Control Act only may be raised as an ordinary

preemption defense to a conflicting state Jaw, and not as a

jurisdictional bar to all state claims relating to firearms” (internal

quotation marks omitted)).°

The general presumption against preemption does not alter

this result. The presumption is designed to ensure that “the

historic police powers of the States were not to be superseded

by the Federal Act unless that was the clear and manifest purnose

of Congress.” Rice v. Santa Fe Elevator Corp., 33\ U.S. 218,

230 (1947). Importantly, however, this presumption “is not

triggered when the State regulates in an area where there has

been a history of significant federal presence.” United States v.

Locke, 529 U.S. 89, 108 (2000); see also Int'l Paper Co. v.

Ouellette, 479 U.S. 481, 491 (1987) (“[I]t is not necessary for a

federal statute to provide explicitly that particular state laws

are pre-emptec.”). In this regard, FDA has observed that “[i}n

determining the proper role for state law in this context, . . . it is

significant that the federal government has been regulating the

meaufacture and sale of drugs since 1906” — i.e., for more than

a century. Br. of the United States as Amicus Curiae in Support

of Defendants-Appellees (filed Dec. 4, 2006), Colacicco v.

Apotex, Inc., No. 06-3107 (3d Cir.), at 17-18 n.7 (“Colacicco

Br.”). Granting review would enable this Court to make clear

that state courts are not free simply to ignore this Court's settled

“obstacle” conflict preemption doctrine through the overzealous

application either of “direct and posiiive conflict” provisions

or of the presumption against preemption.

The Vermont court should have examined whether the

common law duty imposed on Wyeth posed an obstacle to FDA's

* This Court also has made clear that a federal statute's use of the

term “provision” refers to positive enactments - not tort suit judgments.

See Cippollone v. Liggett Group. Inc., SOS U.S. 504, 518 (1992); see

also Black's Law Dictionary 1262 (8th ed. 2004) (defining “provision”

as “[a] clause im a statute, contract, or other legal instrument”). By its

express terms, section 202 thus would not bar obstacle preemption even

under the Vermont majority's misconstruction.

accomplishment of its congressionally mandated regulatory

objectives. Under that analysis, the jury’s verdict is preempted.

As explained supra at 3, Congress specifically charged FDA

with optimizing the use of prescription drugs by balancing their

risks against their benefits to the overall public health. Permitting

state tribunals to impose differing risk-benefit judgments on

manufacturers, and to coerce labeling changes that FDA would

not accept, would defeat congressional intent and lead to

conflicting safety and warning standards imposed through the

backward-looking lens of individual claims instead of the forward-

looking public health determination that Congress mandated.

The facts of this case demonstrate why a state court’s

backward-looking, case-specific focus is inconsistent with

FDA’s broader regulatory perspective. FDA evaluated the risks

associated with IV injection of Phenergan over a period of

decades. Based on its scientific expertise, FDA determined that

the efficacy benefits outweighed the nsks and that physicians

should retain the option to administer Phenergan via IV push,

taking account of the extensive precautions and warnings in the

approved label. App. 167a. FDA’s determinations reflect its

considered judgment that Phenergan’s label reflected the correct

risk-benefit balance and thus would render the drug of greatest

benefit to the greatest number of people. See United States v.

Rutherford, 442 U.S. 544, 555 (1979) (“[FDA] generally

considers a drug safe when the expected therapeutic gain justifies

the risk entailed by its use.”). The Vermont Supreme Court would

allow a jury to disagree with FDA’s risk-benefit assessment and

to override the federal regime by imposing a different labeling

regime on Wyeth.

This 1s a paradigmatic case of state law frustrating the

objectives and purposes of a federal regulatory regime by

foreclosing a treatment option that the federal government has

decided to hold open. As this Court made clear in Geier, such

interference cannot survive constitutional scrutiny. In Geier. this

Court held that a state common law duty to install airbags in all

cars was preempted where federal regulation “deliberateiy

provided the manufacturer with a range of choices among

different passive restraint devices.” 529 U.S. at 875. Geier held

that the state duty “would have presented an obstacle to the

variety and mix of devices that the federal regulation sought”

and “‘stood as an obstacle to the general passive restraint phase-

in that the federal regulation deliberately imposed.” /d. at 881;

see also Int'l Paper Co., 479 U.S. at 494 (striking down state

law under conflict preemption that “upset{] the balance of public

and private interests so carefully addressed by the [federal] Act”);

Buckman Co. v. Pls.’ Legal Comm., 531 U.S. 341, 348 (2001)

(observing that FDA uses its authority “to achieve a somewhat

delicate balance of statutory objectives” and that this balance

“can be skewed by allowing” state tort law claims that second-

guess FDA’s enforcement decisions).

Just as the petitioner in Geier could not use tort law to

foreclose choices that the Department of Transportation deemed

appropriate, Vermont here cannot be permitted to disturb the

hierarchy of options for Phenergan administration that FDA

repeatedly chose to preserve in Phenergan’s labeling. This Court

should grant certiorari and reverse the decision below so that

lower courts will undertake the careful review necessary to

determine whether compliance with a state-enforced duty, even

if not expressly foreclosed by federal command, would, as here,

obstruct rather than complement the objectives and purposcs of

FDA regulation.’

’ Bates v. Dow Agrosciences LLC, 544 U.S. 431 (2005), is fully

consistent with this understanding. In Bates, this Court held that federal

law did not expressly preempt “parallel” state law remedies for violation

of federal misbranding law. See 544 U.S. at 449-51. Here, unlike Bates,

Vermont common law secks to provide litigants a cause of action scparate

and distinct from federal law; indeed, the Vermont courts made clear that

Wyeth would be held liable irrespective of its fidelity to the federal labeling

mandate. App. 28a. Accordingly, the reasoning that saved state “parallel

requirements ' from preemption is wholly inapposite here. The Vermont

common law rule and FDA’s labeling regime are not parallel.

I1l. The Court Should Grant Review To Resolve the Conflict

Concerning the Degree of Deference that Courts Should

Accord FDA’s Formal Position on the Extent to Which

State Tort Law Labeling Judgments Interfere with

FDA’s Labeling Regime.

Finally, this Court should grant review to resolve a lower

court split on whether FDA’s recently expressed judgments with

respect to the adverse impact of state tort suits on its

comprehensive prescription drug labeling regime are entitled

to deference. In its preamble to an amended labeling regulation,

FDA recently reiterated its longstanding view that suits such as

this one obstruct its ability to ensure that prescribers receive

accurate and helpful information about the proper uses of

prescription drugs. See 71 Fed. Reg. at 3935, App. 132a-133a.

The agency has explained why, in its expert judgment, additional

labeling requirements imposed by state law may interfere with

its ability to carry out its congressionally mandated function:

State law actions ... threaten FDA's statutorily

prescribed role as the expert Federal agency responsible

for evaluating and regulating drugs. State actions are

not characterized by centralized expert evaluation of

drug regulatory issues. Instead, they encourage, and in

fact require, lay judges and juries to second-guess the

assessment of benefits versus risks of a specific drug

to the general public — the central role of FDA -

sometimes on behalf of a single individual or group of

individuals. That individualized reevaluation of the

benefits and risks of a product can result in relief --

including the threat of significant damage awards or

penalties - that creates pressure on manufacturers to

attempt to add warnings that FDA has neither approved

nor found to be scientifically required. This could

encourage manufacturers to propose ‘‘defensive

labeling’’ to avoid State liability, which, if implemented,

could result in scientifically unsubstantiated warnings

and underutilization of beneficial treatments.

Id. at 3935.

This observation, based on FDA’s expertise and experience,

fully supports FDA’s view that “[s]tate law conflicts with and

stands as an obstacle to achievement of the full objectives and

purposes of Federal law if it purports to preclude a firm from

including in labeling . . . a statement that is included in [FDA-

approved] prescription drug labeling.” /d.; see also id. at 3934

(“FDA approval of labeling under the act, whether it be in the

old or new format, preempts conflicting or contrary State law.”).

For all these reasons, FDA reiterated that it “interprets the act

to establish both a ‘floor’ and a ‘ceiling,’ such that additional

disclosures of risk information can expose a manufacturer to

liability under the act if the additional statement is

unsubstantiated or otherwise false or misleading.” /d. at 3935."

FDA expressed this same view in a number of recent amicus

briefs. See, e.g., Colacicco Br., supra; Letter Br. for FDA (filed

Sept. 21, 2006), Perry v. Novartis Pharms., No. 05-5350 (E.D.

Pa.) (“Perry Br.”). FDA explained therein that, “[i]n that context

of drug labeling, Congress has authorized FDA to use scientific

expertise to determine, in the first instance, what warnings are

appropriate and necessary for a particular drug.” Colacicco Br.,

supra, at 20. Moreover, “[i]f the agency had made a

determination at a relevant time that a particular warning was

unsubstantiated or would otherwise render the drug misbranded,

then federal preemption bars liability for the failure to provide

that warning.” /d. at 23 n.10. Accordingly, “[e}ven if compliance

with both state and federal law in these circumstances would

not be impossible, state tort liability would pose a sufficient

* See Hillsborough County v. Automated Med. Labs., Inc., 47\

U.S. 707, 718 (1985) (confirming that agencies “can speak through a

variety of means, including regulations, preambles, interpretive

statements, and responses to comments”); Fid. Fed Sav. & Loan Ass'n v.

de la Cuesta, 458 U.S. 141, 158 (1982) (looking to regulatory preamble

“for the administrative construction of the regulation, to which ‘deference

is... clearly in order’” (quoting Udall v. Tallman, 380 U.S 1, 16 (1965)).

threat to federal regulatory objectives to be preempted under

the Supremacy Clause.” Perry Br., supra, at 10.°

According to the Vermont Supreme Court, “FDA’s

statement is neither an authoritative interpretation of an

ambiguous statutory provision entitled to deference, nor a

persuasive policy statement entitled to respect.” App. 28a

(internal citations omitted); see also Jackson v. Pfizer, Inc. , 432

F. Supp. 2d 964, 968 (D. Neb. 2006) (“The recent notice issued

by the FDA claiming preemption is not persuasive.”). In

particular, the majority refused to credit FDA’s conclusion that

the “direct and positive” language of section 202 did not

foreclose an analysis of state law interference with FDA's

regulatory objectives. App. 135a, 21a.

Other courts have taken a different view of the importance

of FDA’s views on how °tate tort suits conflict with its regulatory

regime and hamper its ability to do its job. See /n re Bextra,

2006 WL 2374742, *6 (“The FDA’s interpretation of the

preemptive effect of its regulations is entitled to deference.”’);

Colacicco v. Apotex, Inc., 432 F. Supp. 2d 514, 525 (E.D. Pa.

2006) (“The FDA’s view is critical to this Court’s analysis

because Supreme Court precedent dictates that an agency’s

interpretation of the statute and regulations it administers is

entitled to deference.”); see also Horn, 376 F.3d at 171 (“[T]he

Supreme Court has instructed us that the FDA’s preemption

determinations are significant and should inform our

interpretation. .. .”).

This latter view is correct - FDA’s substantive interpretation

of its own regulations should be entitled to considerable

deference — not the dismissive treatment given by the Vermont

Supreme Court. See Auer v. Robbins, 519 U.S. 452, 461 (1997)

* See Geier v. Am. Honda Motor Co., 529 U.S. 861, 883 (2000)

(granting deference to the views expressed in an amicus brief submitted

by the Solicitor General); Auer v. Robbins, 519 U.S. 452, 453 (1997)

(“The Secretary’s interpretation is not rendered unworthy of deference

by the fact that it is set forth in an amicus brief; it is not a position

adopted in response to litigation, and there is no reason to suspect that

it does not reflect the Secretary's fair and considered judgment.”).

(holding that an agency’s interpretation of its regulations is

“controlling unless plainly erroneous or inconsistent with the

regulation” (internal quotation marks and citation omitted)).

Similarly, FDA is best able to determine what interferes with

its ability to fulfill its statutory mandate, and its views on that

issue also merit substantial deference:

Congress has delegated to [the agency] authority to

implement the statute; the subject matter is technical;

and the relevant history and background are complex

and extensive. The agency is likely to have a thorough

understanding of its own regulation and its objectives

and is “uniquely qualified” to comprehend the likely

impact of state requirements.

Geier, 529 U.S. at 883; see also Thomas Jefferson Univ. v.

Shalala, 512 U.S. 504, 512 (1994) (finding that deference is

especially warranted where agency decisions “require significant

expertise and entail the exercise of judgment grounded in policy

concerns” (internal quotation marks and citation omitted)).

Prescription drug labeling is precisely the type of complex

and technical regulatory regime that warrants deference to the

expertise of the agency that Congress charged with administering

it. See Bates v. Dow Agrosciences LLC, 544 U.S. 431, 455 (2005)

(“As suggested by Medtronic, the federal agency charged with

administering the statute is often better able than are courts to

determine the extent to which state liability rules mirror or distort

federal requirements.”) (Breyer, J., concurring). By disrecarding

FDA's interpretation of its own regulations and its views on the

impact of state tort suits on the agency's regulatory objectives,

the Vermont court committed a crucial error that infected its

entire preemption analysis. The Court should grant review to

correct this error and resolve this split in authority.

CONCLUSION

For the foregoing reasons, this Court should grant the

petition for a writ of certiorari

Respectfully submitted,

ALLAN R. Keyes Bert W. Rein

R. JosepH O’ RourKE Counsel of Record

Ryan, SmitH, Carsine, LTD. Karyn K. ABLIN

98 Merchants Row WILLIAM S. Consovoy

P.O. Box 310 Wiey Rem LLP

Rutland, VT 05702-0310 1776 K Street NW

(802) 786-1000 Washington, D.C. 20006

(202) 719-7000

Attorneys for Petitioner

APPENDIX A — OPINION OF THE VERMONT

SUPREME COURT FILED OCTOBER 27, 2006

SUPREME COURT

No. 2004-384

Diana Levine

Wyeth

On Appeal from

Washington Superior Court

October Term, 2005

Geoffrey W. Crawford, J.

Richard I. Rubin and Kerry B. DeWolfe of Rubin, Kidney,

Myer & DeWolfe, Barre, for Plaintiff-Appellee.

Allan R. Keyes and R. Joseph O’Rourke of Ryan, Smith &

Carbine, Ltd., Rutland, and Bert W. Rein, Karyn K. Ablin

and Sarzh E. Botha of Wiley Rein & Fielding LLP, and Daniel

S. Pariser of Arnold & Porter LLP, Washington, D.C., for

Defendant-Appellant.

Present: REIBER, C.J.,. DOOLEY and JOHNSON, JJ., and

MORRIS, D.J., and ALLEN, C.J. (Ret.), Specially Assigned.

Appendix A

JOHNSON, J.

Defendant Wyeth, a drug manufacturer, appeals from a

jury verdict in favor of plaintiff Diana Levine, who suffered

severe injury and the amputation of her arm as a result of

being injected with defendant’s drug Phenergan. Plaintiff

claimed at trial that defendant was negligent and failed to

provide adequate warnings of the known dangers of injecting

Phenergan directly into a patient’s vein. Defendant argues

that the trial court should not have allowed the jury to

consider plaintiff's claims because the claims conflict with

defendant’s obligations under federal law regulating

prescription drug labels. We hold that there is no conflict

between state and federal law that requires preemption of

plaintiff's claim. Defendant also raises two claims of error

relating to the jury instructions on damages. We hold that

the court’s rulings on these jury instructions were correct,

and we affirm.

In April 2000, plaintiff was injected with defendant’s

drug Phenergan at Northeast Washington County Community

Health, Inc. (“the Health Center”). The drug was administered

to treat plaintiff's nausea resulting from a migraine headache.

Plaintiff received two injections. The drug was first

administered by intramuscular injection. Later the same day,

when plaintiff's nausea continued, she received a second dose

by a direct intravenous injection into her arm, using a

procedure known as “IV push.” The second injection resulted

in an inadvertent injection of Phenergan into an artery. As a

result, the artery was severely damaged, causing gangrene.

After several weeks of deterioration, plaintiff's hand and

forearm were amputated.

Appendix A

Plaintiff brought a superior court action for negligence

and failure-to-warn product liability, alleging that defendant’s

inadequate warning of the known dangers of direct

intravenous injection of Phenergan caused her injuries.

During a five-day jury trial, both parties presented expert

testimony regarding the adequacy of the warnings defendant

placed on Phenergan’s label. Plaintiff’s experts testified that

the label should not have allowed IV push as a means of

administration, as it was safer to use other available options,

such as intramuscular injection or administration through the

tubing of a hanging IV bag. Defendant’s expert testified that

allowing IV push with instructions cautioning against

inadvertent arterial injection was sufficient. The court

instructed the jurors that they could consider the FDA’s

approval of the label in use at the time of plaintiff's injury,

but that the label’s compliance with FDA requirements did

not establish the adequacy of the warning or prevent

defendant from adding to or strengthening the warning on

the label. At the conclusion of the trial, the jury found in

favor of plaintiff on both the negligence and product-liability

claims and awarded her $2.4 million in economic damages

and $5 million in non-economic damages. Pursuant to the

parties’ stipulation, this award was reduced to a total of

$6,774,000 to account for pre-judgment interest and

plaintiff's recovery in a settlement of a separate action she

had filed against the Health Center.

In a summary judgment motion prior to trial, as well as

in its timely motion for judgment as a matter of law following

trial, both of which the superior court denied, defendant

argued that federal law preempted plaintiff's claim. These

arguments rested in part on defendant’s contention that it

Appendix A

had submitted an adequate warning to the FDA, but that the

FDA rejectedthe change because it did not favor

strengthening the warning.' Plaintiff contended that neither

warning would have been adequate. The trial court stated, in

1. The warning on the label that was in use in 2000 read in

relevant part:

INADVERTENT INTRA-ARTERIAL INJECTION: Due to the

close proximity of arteries and veins in the areas most commonly

used for intravenous injection, extreme care should be exercised to

avoid perivascular extravasation or inadvertent intra-arterial

injection. Reports compatible with inadvertent intra-arterial injection

of [Phenergan], usually in conjunction with other drugs intended for

intravenous use, suggest that pain, severe chemical irritation, severe

spasm of distal vessels, and resultant gangrene requiring amputation

are likely under such circumstances. Intravenous injection was

intended in all the cases reported but perivascular extravasation or

arterial placement of the needle is now suspect. There is no proven

successful managemert of this condition after it occurs. . . .

When used inti enously [Phenergan] should be given in a

concentration no greater than 25 mg per ml and at a rate not to exceed

25 mg per minute. WHEN ADMINISTERING ANY IRRITANT

DRUG INTRAVENOUSLY IT IS USUALLY PREFERABLE TO

INJECT IT THROUGH THE TUBING OF AN INTRAVENOUS

INFUSION SET THAT IS KNOWN TO BE FUNCTIONING

SATISFACTORILY.

(Emphasis added.) The revised warning the FDA failed to adopt

read in relevant part:

INADVERTENT INTRA-ARTERIAL INJECTION: There are

reports of necrosis leading to gangrene, requiring amputation,

(Cont'd)

Appendix A

its decision on defendant’s motion for judgment as a matter

of law, that although the FDA had rejected a new warning,

the agency’s “brief comment” failed to explain its reasoning

or demonstrate that it “gave more than passing attention to

the issue of whether to use an IV infusion to administer the

drug. The proposed labeling change did not address the use

of a free-flowing IV bag.” The court concluded that there

was “no basis for federal preemption” and upheld the jury’s

verdict.

Defendant claims the superior court erred by: (1) failing

to dismiss plaintiff's claim on the basis that the Food and

Drug Administration’s approval of the Phenergan label

(Cont'd)

following injection of [Phenergan], usually in conjunction with other

drugs; the intravenous route was intended in these cases, but arterial

or partial arterial placement of the needle is now suspect. . . .

There is no established treatment other than prevention:

1. Beware of the close proximity of arteries and veins at

commonly used injection sites and consider the possibility of aberrant

arteries.

2. When used intravenously, |[Phenergan] should be given in a

concentration no greater than 25 mg/ml and a rate not to exceed 25

mg/minute. INJECTION THROUGH A PROPERLY RUNNING

INTRAVENOUS INFUSION MAY ENHANCE THE POSSIBILITY

OF DETECTING ARTERIAL PLACEMENT. IN ADDITION, THIS

RESULTS IN DELIVERY OF A LOWER CONCENTRATION OF

ANY ARTERIOLAR IRRITANT.

(Emphasis added.)

Appendix A

preempted state common law claims that the label was

inadequate; (2) failing to instruct the jury to reduce plaintiff's

damages by the amount of fault attributable to the Health

Center; and (3) failing to instruct the jury to calculate the

present value of plaintiff's damages for future non-economic

losses. We reject these claims of error, and we affirm.

I. Federal Preemption

Defendant’s principal argument on appeal is that the

court should have dismissed plaintiff's claim because it was

preempted by federal law. Defendant asserts that any state

common law duty to provide a stronger warning about the

dangers of administering Phenergan by IV push conflicts with

the FDA’s approval of the drug’s label. As preemption is a

question of law, we review the trial court’s decision de novo.

Office of Child Support v. Sholan, 172 Vt. 619, 620, 782

A.2d 1199, 1202 (2001) (mem.). We hold that the jury’s

verdict against defendant did not conflict with the FDA’s

labeling requirements for Phenergan because defendant could

have warned against IV-push administration without prior

FDA approval, and because federal labeling requirements

create a floor, not a ceiling, for state regulation.

The United States Constitution provides that federal law

is the supreme law of the land. U.S. Const. art. V1, cl. 2. The

Supremacy Clause is the basis for the doctrine of preemption,

according to which “state law that conflicts with federal law

is ‘without effect.”” Cipollone v. Liggett Group, Inc., 505

U.S. 504, 516, 112 S.Ct. 2608, 120 L.Ed.2d 407 (1992)

(quoting Maryland v. Louisiana, 451 U.S. 725, 746, 101 S.Ct.

2114, 68 L.Ed.2d 576 (1981)). In Cipollone, the Court

Appendix A

described the relevant analysis for determining whether

Congress intended a federal statute to preempt state law:

Congress’ intent may be explicitly stated in the

statute’s language or implicitly contained in its

structure and purpose. In the absence of an express

congressional command, state law is pre-empted

if that law actually conflicts with federal law, or

if federal law so thoroughly occupies a legislative

field as to make reasonable the inference that

Congress left no room for the States to supplement

it.

Id. (quotations and citations omitted). Absent clear

congressional intent to supersede state law, including state

common law duties, there is a presumption against

preemption. Medtronic, Inc. v. Lohr, 518 U.S. 470, 485, 116

S.Ct. 2240, 135 L.Ed.2d 700 (1996) (“[B]ecause the States

are independent sovereigns in our federal system, we have

long presumed that Congress does not cavalierly pre-empt

state-law causes of action.”’); Cipollone, 505 U.S. at 516

(“Consideration of issues arising under the Supremacy Clause

‘start|s] with the assumption that the historic police powers

of the States [are] not to be superseded by ... Federal Act

unless that [is] the clear and manifest purpose of Congress.’”

(quoting Rice v. Santa Fe Elevator Corp., 331 U.S. 218, 230,

67 S.Ct. 1146, 91 L.Ed. 1447 (1947))). This presumption

has “add[{ed] force” when there has been a “long history of

tort litigation” in the area of state common law at issue. Bates

v. Dow Agrosciences LLC, 544 U.S. 431, 449, 125 S.Ct. 1788,

161 L.Ed.2d 687 (2005).

Appendix A

Defendant concedes that Congress has not expressly

preempted state tort actions through the Food, Drug and

Cosmetics Act (FDCA), 21 U.S.C. 4 4 301-399, and that

Congress did not intend ‘he FDCA to occupy the entire field

of prescription drug regulation. Rather, it asserts that

plaintiff's action “actually conflicts with federal law.”

Cipollone, 505 U.S. at 516. This requires defendant to show

either that “it is impossible for a private party to comply

with both state and federal requirements,” or that Vermont’s

common law “stands as an obstacle to the accomplishment

and execution of the full purposes and objectives of

Congress.” Freightliner Corp. v. Myrick, 514 U.S. 280, 287,

115 S.Ct. 1483, 131 L.Ed.2d 385 (1995) (quotations and

citations omitted).

Defendant presents two alternative bases for its assertion

of conflict preemption: (1) in the specific context of the

Phenergan label, the FDA was aware of the dangers of IV-

push administration and specifically ordered defendant to

use the warning it used, making it impossible for defendant

to comply with both its state common-law duty and the

requirements of federal law; and (2) by penalizing drug

companies for using FDA-approved wording on drug labels,

state tort claims like plaintiffs present an obstacle to the

purpose of the FDA’s labeling regulations. Before reaching

these issues, we briefly examine the FDA’s role in regulating

prescription drug labels and the general approach courts have

taken to the preemptive effect of federal labeling

requirements.

Appendix A

A. Regulatevy Background

Prior to distributing a prescription drug such as

Phenergan, the manufacturer must submit a New Drug

Application (NDA) for FDA approval. 21 U.S.C, 4 355(a).

The FDA must approve the application unless it fails to meet

certain criteria, including whether test results and other

information establish that the drug is “safe for use under the

conditions prescribed, recommended, or suggested in the

proposed labeling thereof,” whether there is “substantial

evidence that the drug will have the effect it purports or is

represented to have under the conditions of use prescribed,

recommended, or suggested in the proposed labeling thereof,”

and whether, “based on a fair evaluation of al] material

facts, such labeling is false or misleading in any particular.”

Id. 4 355(d).

“FDA regulations mandate the general format and

content of all sections of labels for all prescription drugs as

well as the risk information each section must contain,” and

“{f]inal approval of the NDA is ‘conditioned upon the

applicant incorporating the specified labeling changes exactly

as directed, and upon the applicant submitting to FDA a copy

of the final printed label prior to marketing.”” McNellis v.

Pfizer, Inc., 2005 WL 3752269, at *4 (D.N.J.) (citing 21

C.F.R. 4 201.56, 201.57, and quoting 21 C.F.R. 314.105(b)).

Once a drug and its label have been approved, any changes

to the label ordinarily require submission and FDA approval

of a “Supplemental NDA.” /d.; 21 C.F.R. 314.70(b)(2)(v)(A).

19a

Appendix A

If the NDA process and the submission of changes for

FDA approval were the exclusive means of creating and

altering prescription drug labels, this might be a very different

case. A key FDA regulation, however, allows a drug’s

manufacturer to alter the drug’s label without prior FDA

approval when necessary. The regulation provides in relevant

part:

(6) The agency may designate a category of changes

for the purpose of providing that, in the case of a change

in such category, the holder of an approved application

may commence distribution of the drug product

involved upon receipt by the agency of a supplement

for the change. These changes include, but are not

limited to:

(111) Changes in the labeling ... to accomplish any

of the following:

(A) To add or strengthen a contraindication,

warning, precaution, or adverse reaction;

(B) To add or strengthen an instruction about

dosage and administration that is intended to

increase the safe use of the drug product{.]

21 C.F.R. § 314.70(c).

lla

Appendix A

Section 314.70(c) creates a specific procedure allowing

drug manufacturers to change labels that are insufficient to

protect consumers, despite their approval by the FDA. “The

FDA’s approved label ... can therefore be said to set the

minimum labeling requirement, and not necessarily the

ultimate label where a manufacturer improves the label to

promote greater safety.” McNellis, 2005 WL 3752269, at *5.°

While specific federal labeling requirements and state

common-law duties might otherwise leave drug

manufacturers with conflicting obligations, 4 314.70(c)

allows manufacturers to avoid state failure-to-warn claims

without violating federal law. /d. (“[I]t is apparent that prior

FDA approval need not be obtained, nor will a product be

deemed mislabeled, if the manufacturer voluntarily or even

unilaterally strengthens the approved warnings, precautions

or potential adverse reactions upon the label pursuant to 21

C.F.R. § 314.70(c)(6)(ii1)(A).”). There is thus no conflict

between federal labeling requirements and state failure-to-

warn claims. Section 314.70(c) allows, and arguably

encourages, manufacturers to add and strengthen warnings

that, despite FDA approval, are insufficient to protect

consumers. State tort claims simply give these manufacturers

a concrete inceritive to take this action as quickly as possible.

B. Conflict Preemption in Other Jurisdictions

In light of the leeway created by 4 314.70(c) for drug

manufacturers to add warnings, courts have been nearly

unanimous in holding that state failure-to-warn tort claims

do not conflict with federal law. See, e g., McNellis, 2005

WL 3752269, at *7 (“[T]he FDCA and the FDA’s regulations

do not conflict with New Jersey's failure to warn law because

12a

Appendix A

those federal regulations merely set minimum standards with

which manufacturers must comply.”). McNellis is the latest

in a series of recent cases addressing this issue as it relates

to the anti-depressant Zo/oft, which allegedly increases the

risk of suicide in some patients. See id., at *7-8 (denying

summary judgment and rejecting conflict preemption in

Zoloft case); accord Zikis v. Pfizer, Inc., 2005 WL 1126909,

at *2-3 (N.D.III.); Witczak v. Pfizer, Inc., 377 F.Supp.2d 726,

729-30 (D.Minn.2005); Motus v. Pfizer, Inc., 127 F.Supp.2d

1085, 1096-1100 (C.D.Cal.2000); see also Cartwright v.

Pfizer, Inc., 369 F.Supp.2d 876, 882 (E.D. Tex. 2005) (“With

little exception, courts that have considered this exact issue

have concluded that state failure to warn claims are not

preempted by the FDCA and its attendant regulations.”).

Contra Needleman vy. Pfizer, Inc., 2004 WL 1773697, at *1

(N.D. Tex.) (granting summary judgment to the defendant

on basis of conflict preemption).

The Zoloft cases are representative of a general rule that

FDA approval of a drug’s label does not preempt state failure-

to-warn claims. See, e.g., Eve v. Sandoz Pharm. Corp., 2002

WL 181972, at *1-3 (S.D.Ind.) (rejecting conflict preemption

of failure-to-warn claim regarding the drug Parlodel);

Caraker v. Sandoz Pharm. Corp., 172 F.Supp.2d 1018, 1032

(S.D.111.2001) (same); Bryant v. Hoffman-La Roche, Inc. , 262

Ga.App. 401, 585 S.E.2d 723, 725 (Ga.Ct.App.2003) (heart

medication); Bell v. Lollar, 791 N.E.2d 849, 854-55

(Ind.Ct.App.2003) (prescription pain medication); Kurer v.

Parke, Davis & Co., 2004 WI App 74, 21, 272 Wis.2d 390,

679 N.W.2d 867 (oral contraceptive). But see Eh/is v. Shire

Richwood, Inc., 233 F.Supp.2d 1189, 1198 (D.N.D.2002)

(granting summary judgment to defendant on basis of conflict

preemption of claim regarding the drug Adderall).

l3a

Appendix A

Defendant cites two cases, Needleman and Ehlis, that

support the preemptive effect of the FDCA in failure-to-warn

cases regarding prescription drug labels. Needleman, 2004

WL 1773697, at *1; Ehlis, 233 F.Supp.2d at 1198. Needleman

is not perticularly helpful under the circumstances here. Its

holding relied on the facts of the Zo/oft litigation, particularly

an FDA statement that the warning advocated by the plaintiff

would have been misleading. 2004 WL 1773697, at *1. The

courts in the other Zoloft cases took a different approach to

the FDA’s statement, in part because the FDA’s statement

was not “an official agency position,” and in part because

the FDA later retracted its position regarding the link between

Zoloft and suicide. See, e.g., Witczak, 377 F.Supp.2d at 730.

Here, the FDA has not indicated that a stronger warning

would be misleading, so the reasoning of Needleman appears

inapplicable to this case. Ehlis interpreted 4 314.70(c) as

allowing unapproved changes to a label only temporarily,

and only under “limited circumstances.” 233 F.Supp.2d at

1197-98. We can find no support for this interpretation in

the language of the regulation, which appears to allow

unilateral changes to drug labels whenever the manufacturer

believes it will make the product safer, and places no limit

on the duration of pre-approval warnings unless the FDA

disapproves of the change. 21 C.F.R. 4 314.70(c).

Defendant next attempts to draw a comparison to the

regulation of medical devices under the FDCA, citing medical

device cases in which state tort law has been preempted. See

Buckman Co. v. Plaintiffs’ Legal Comm., 531 U.S. 341, 348,

121 S.Ct. 1012, 148 L.Ed.2d 854 (2001) (holding that “fraud-

on-the-FDA” claim relating to device regulated by Medical

Device Amendments to FDCA was preempted); Horn v.

l4a

Appendix A

Thoratec Corp., 376 F.3d 163, 177 (3d Cir.2004) (holding

that failure-to-warn claim was preempted by Medical Device

Amendments). We find this analogy unpersuasive. Neither

Buckman nor Horn weakens the force of the drug-labeling

cases cited above. The claim that was preempted in Buckman

was for “fraud on the FDA,” not failure to warn; the Court

held that the presumption against preemption applies only

when a claim implicates “‘the historic primacy of state

regulation of health and safety,” which is not the case when

the claim arises from a federal statute. 531 U.S. at 347-48

(quoting Medtronic, 518 U.S. at 485). Plaintiff's negligence

and product-liability claims fall squarely withn the scope of

traditional state regulation, so it is appropriate to apply the

presumption against preemption here. In Horn, the Third

Circuit relied on an express preemption clause in the FDCA

that relates only to medical devices. 376 F.3d at 176. Because

no such clause exists for prescription drugs, Horn’s reasoning

does not apply to this case.

Finally, defendant cites a third group of cases relating

generally to the United States Supreme Court’s recent use of

conflict preemption in other fields. This argument relies

primarily on Geier v. American Honda Motor Co., 529 U.S.

861, 120 S.Ct. 1913, 146 L.Ed.2d 914 (2000). In Geier, the

Court held that state tort claims based on the production of

automobiles without airbags conflicted with federal

regulations making airbags one of several permissible safety

equipment options. 529 U.S. at 881. Geier, however, rested

on the conclusion that the Department of Transportation’s

intent in drafting the regulation at issue was to provide a

range of different safety options, thus precluding any state

determination that a specific type of equipment should be

1Sa

Appendix A

required. /d. The history of the regulation at issue indicated

that the agency intended to phase in automobiie safety

requirements gradually, allowing the public to choose

between mandatory seatbelt laws at the state level and a

federal passive-restraint requirement. /d. at 880-81. Allowing

state tort claims based on the lack of a particular safety

mechanism would have conflicted with both the agency’s

phase-in plan and its intent to provide consumers with a range

of safety options. /d. at 881. The Court explicitly stated that

in a different context, an agency could promulgate regulations

that provided a floor, but not a ceiling, for state regulation.

Id. at 870.

The FDA’s labeling requirements are exactly that type

of regulation. Section 314.70(c) does not allow us to interpret

FDA approval of a drug label as anything but a first step in

the process of warning consumers. When further warnings

become necessary, the manufacturer is at least partially

responsible for taking additional action, and if it fails to do

so, it cannot rely on the FDA’s continued approval of its labels

as a shield against state tort liability. While a state common-

law duty may encourage departure from a label that the FDA

has approved in great detail, such a duty does not create a

conflict with federal requirements because the FDA and the

state share the purpose of encouraging pharmaceutical

companies to alter their drug labels when they are inadequate

to protect consumers. We agree with the significant majority

of courts that state failure-to-warn claims are generally not

preempted by federal labeling requiremenis.

l6a

Appendix A

We must now apply this reasoning to defendant’s two

original contentions: (1) notwithstanding the fact that it is

generally possible for manufacturers to comply with both

federal and state law through the procedures created by

314.70(c), the FDA’s specific actions with respect to

Phenergan made it impossible for defendant to comply with

both federal and state law; and (2) even if plaintiff's claim

and the cases cited above do not make it impossible for

manufacturers to comply with both state and federal law, they

present an obstacle to federal objectives.

C. Impossibility of Compliance

Defendant contends that in this case, it was impossible

to comply with both state and federal law because the FDA

prohibited the use of a stronger warning with respect to IV-

push administration of Phenergan. This claim is not supported

by the evidence defendant presented to the trial court. The

record lacks any evidence that the FDA was concerned that

a stronger warning was not supported by the facts, that such

a stronger warning would distract doctors from other

provisions in the drug’s label, or that the warning might lead

to less effective administration of the drug. Instead, defendant

essentially relies on two factual assertions: 1) the FDA

approved the label that was in use in 2000; and 2) the FDA,

in reviewing the label for use in a different version of

Phenergan, expressed its opinion of the adequacy of the

warning in the original label by stating, “Retain verbiage in

current label.” AB 5, 5 n. 7

17a

Appendix A

With respect to defendant’s first assertion, our analysis

above demonstrates that FDA approval of a particular label

does not preempt a jury finding that the label provided

insufficient warning, as defendant was free under 4 314.70(c)

to strengthen the warning without prior FDA approval.

Defendant’s second assertion depends on the meaning of the

instruction, “[rjetain verbiage in current label.” Tort liability

for defendant’s failure to strengthen its warningcould have

created a direct conflict requiring federal preemption only if

the FDA intended the instruction to prohibit any language

strengthening the original warning. In other words, unless

we interpret the FDA’s statement as evidence that it would

have rejected any attempt by defendant to strengthen its label

through 4 314.70(c), we cannot conclude that it was

impossible for defendant to comply with its state common-

law duty without violating federal law.

Defendant argues that the instruction reflected the FDA’s

opinion not only that a stronger warning was unnecessary,

but also that it would have harmed patients by eliminating

IV push as an option for administering Phenergan. The record

does not support this interpretation. Defendant has provided

a number of letters exchanged by the FDA and defendant

regarding Phenergan’s label, but these letters do not indicate

the FDA’s opinion of the value of I[V-push administration.

Neither the letters nor any other evidence presented to the

jury indicated that the FDA wished to preserve the use of IV

push as a method of administering Phenergan. Nor can we

infer such concern from the agency’s instruction to “[r]etain

current verbiage” instead of adopting the proposed warning.

The specific warning the agency rejected in favor of the

original label did not indicate any more clearly than the

Appendix A

original label that IV-push administration was unsafe, which

is what plaintiff argued made the original label inadequate.

The FDA could have rejected the new warning for any number

of reasons, including clarity or technical accuracy, without

implicitly prohibiting a stronger warning. Defendant’s

unsupported hypothesis that the FDA saw the new warning

as harmful seems among the least likely explanations, as the

rejected proposal would not have eliminated IV push as an

option for administering Phenergan.’ With respect to IV

administration, the original label read, “When administering

any irritant drug intravenously it is usually preferable to inject

it through the tubing of an intravenous infusion set that is

known to be functioning satisfactorily,” while the proposed

label stated, “[i]njection through a properly running

intravenous infusion may enhance the possibility of detecting

arterial placement. In addition, this results in delivery of a

lower concentration of any arteriolar irritant.” See supra 4 n.

| (comparing proposed and original warnings). Simply stated,

the proposed warning was different, but not stronger. It was

2. The dissent appears to interpret any warning that would

eliminate IV-push administration as inherently inconsistent with the

FDA's approval of Phenergan for |V administration in general. We

see no such inconsistency, as an approval of a drug for IV

administration is not the same as a conclusion that all methods of IV

administration are safe. In any case, a jury verdict in a failure-to-

warn case simply establishes that the relevant warning was

insufficient; it does not mandate a particular replacment warning.

There may have been any number of ways for defendant to strengthen

the Phenergan warning without completcly eliminating I1V-push

adininistration. Our purpose in pointing out that the proposed warning

the FDA rejected did not eliminate IV push is simply that rejecting

this warning could not be seen as an affirmative effort by the FDA

to preserve IV push as an option.

19a

Appendix A

also no longer or more prominent than the original warning,

so it could not have raised a concern that it might overshadow

other warnings on the label or drive doctors away from

prescribing the drug. There is no evidence that the FDA

intended to prohibit defendant from strengthening the

Phenergan \abel pursuant to 4 314.70(c).’ Thus, we cannot

conclude that it was impossible for defendant to comply with

its obligations under both state and federal law.

D. Obstacle to Congressional Purposes and Objectives

Defendant next contends that state common-law liability

for its use of an FDA-approved label presents an obstacle to

federal objectives. We hold that plaintiff's claim does not

interfere with any objective that can legitimately be ascribed

to Congress. We agree with the reasoning in the cases cited

above, supra 14-15, that federal labeling requirements

pursuant to the FDCA create a floor, not a ceiling, for state

regulation. Defendant presents a new FDA rule containing

language disputing this reasoning, but this statement does

not alter our conclusion that there is no conflict between

federal objectives and Vermont common law.

3. We also reject defendant's argument that it would have been

prosecuted for “misbranding” if it had strengthened the label without

prior approval. See Witczak, 377 F.Supp.2d at 731, 729 (“[T]he

validity and authority of state law ... does not depend on speculative

hypotheticals” regarding “assumptions of what the FDA would have

done™ in response to a stronger warning. ).

20a

Appendix A

1. The Purposes and Objectives of Congress

In the absence of a conflict that makes it impossible for

a regulated entity to comply with both state and federal law,

federal law will preempt state law only if it “stands as an

obstacle to the accomplishment and execution of the full

purposes and objectives of Congress.” Freightliner, 514 U.S.

at 287 (quotations omitted). We must therefore examine what

“the full purposes and objectives of Congress” were with

respect to federal labeling requirements for prescription

drugs. We agree with the McNellis court that a system under

which “federal regulations merely set minimum standards

with which manufacturers must comply” is

fully consistent with Congress’ primary goal in

enacting the FDCA, which is “to protect

consumers from dangerous products,” United

States v. Sullivan, 332 U.S. 089, 696, 68 S.Ct. 331,

92 L.Ed. 297 (1948), as well as Congress’ stated

intent that the FDCA “‘must not weaken the

existing laws,’ but on the contrary ‘it must

strengthen and extend that law’s protection of the

consumer.’” United States v. Dotterweich, 320

U.S. 277[, 282] (1943) [quoting S.Rep. No. 152,

75th Cong., Ist Sess., p. |].

2005 WL 3752269, at *7; see also Witczak, 377 F.Supp.2d

at 731 (“Congress certainly did not intend to bar drug

companies from protecting the public when enacting the

FDCA; its goal was to protect the public.... Any contrary

interpretation of Congress's intent is perverse.”).

2la

Appendix A

In fact, Congress has expressed its purposes clearly, not

only in the general sense that the statute was intended to

“protect the public,” but also more specifically, with respect

to the FDCA’s preemptive effect. In the 1962 amendments

to the FDCA, Congress included a clause expressly limiting

the preemptive effect of the statute: “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 ... unless there 1s a direct and positive

conflict between such amendments and such provision of

State law.” Drug Amendments of 1962 (Harris Kefauver Act),

Pub.L. No. 87 781, 4 202, 76 Stat. 780, 793 (1962).

This amendment essentially removes from our

consideration the question of whether common-law tort

claims present aa obstacle to the purposes and objectives of

Congress. Congress intended that the FDCA would leave

state law in piace except where it created a “direct and

positive conflict” between state and federal law. Drug

Amendments 4 202. This language “simply restates the

principle that state law is superseded in cases of an actual

conflict with federal law such that ‘compliance with both

federal and state regulations is a physical impossibility.””

See S. Blasting Servs., Inc. v. Wilkes County, 288 F.3d 584,

591 (4th Cir.2002) (interpreting “direct and positive conflict”

language in the preemption clause of a federal statute

governing explosive materials to allow states to “impose

more stringent requirements than those contained in the

federal regulations”) (quoting Hillshorough County v.

Automated Med. Labs., Inc., 471 U.S. 707, 713, 105 S.Ct.

22a

Appendix A

2371, 85 L.Ed.2d 714 (1985)).* In other words, under any

circumstances where it is possible to comply with both state

law and the FDCA, the state law in question is consistent

with the purposes and objectives of Congress. Thus, our

4. The debate surrounding the amendment helps confirm that

it was intended to preserve the right of states to regulate beyond the

federal requirements of the FDCA. During the floor debate in the

House, the subject of preemption arose several times. First,

Congressman Smith of California expressed concern that the bill, as

reported, contained “no language ... which says anything to the effect

that this particular measure will not preempt all State food and drug

laws,” and thus, might risk interfering with the efforts of some states

to make their own, stricter regulations. 108 Cong. Rec. 21046 (1962)

(“[I]t seems to me that if we are going to pass this law, someone

ought to offer an amendment to make certain that the passage of this

bill, which gives all of this power to the Department of Health,

Education, and Welfare and the Food and Drug Administration, will

not preempt any State laws”). Shortly thereafter, Congressman Harris

of Arkansas, the primary House sponsor of the bill, offered his

opinion that “there is nothing in this bill that in any way preempts

the authority and prerogatives of the States.” /d. at 21047.

Congressman Schenck of Ohio agreed, stating, “[m]Jany very helpful

State laws are in effect; many such laws in some instances are even

stronger than Federal laws for the protection of human health in the

public interest.” /d. at 21056.

Congressmen Schenck and Harris, despite insisting that the bill

as written would not preempt stronger state laws, eventually

supported the “direct and positive conflict” amendment, and Schenck

reiterated that preemption should not apply in the “many instances

where State laws in the area of food and drugs and health are even

stronger than some of the Federal laws.” /d. at 21083. Neither the

desirability of allowing states to regulate beyond the FDCA nor the

intent of the amendment to protect such regulation from preemption

was called into question during the debate.

23a

Appendix A

discussion above regarding defendant’s impossibility

argument, supra 21-23, provides a complete answer to the

question of preemption.

We recognize that our dissenting colleague has reached

the opposite conclusion. There is little to say, beyond what

we have already said, except that we respectfully disagree

with his analysis of the FDCA, the FDA’s regulations, and

the specific context of this lawsuit. Numerous courts have

concluded, over the course of decades, that the FDCA

provides a floor, not a ceiling, for state regulation. See supra,

14-15. While the dissent cites favorably the minority view,

we agree with the majority view. There is much to be said

for the policy arguments employed by courts adopting this

minority view, including the argument that permitting too

much state activity in this area will make beneficial dmgs

less available to consumers. Similarly, there is merit to the

majority perspective that eliminating lawsuits like the one

at issue here would leave consumers without recourse in the

event the FDA cannot move quickly enough to require

strengthened warnings when they are appropriate. Our view

is that neither policy argument is relevant here. The plain

language of the statute indicates that Congress did not intend

to interfere with state prerogatives except where doing so is

absolutely necessary, see supra, 25-27, and the plain language

of the regulation makes such interference unnece *ary here,

see supra, 12-13. This analysis is consistent with the

constitutionally rooted presumption against preemption. To

look more broadly at arguments relying on assumptions about

safety and economic efficiency is to apply the opposite

presumption-the presumption that Congress could not

possibly have intendec' to allow states to intrude on what

24a

Appendix A

seers, intuitively, to be an area of federal expertise. It is

weither our responsibility, nor that of the FDA, to question

the policy judgments of Congress. The litigation at issue here

does not pose a direct and positive conflict with federal law,

and thus, there is no basis for federal preemption.

2. The FDA’s New Statement on Preemption

Defendant, after oral argument in this case, cited a new

FDA regulation that contains a statement relating to the

preemptive cffect of the FDCA. The substance of the

regulation changes certain aspects of labeling requirements

for prescription drugs, but these changes are irrelevant to

this appeal because the new rule did not take effect until

June 2006. Food and Drug Administation, Requirements on

Content and Format of Labeling for Human Prescription

Drug and Biological Products, Supplementary Information,

71 F d.Reg. 3922, 3922 (Jan. 24, 2006). The rule’s

“Supplementary Information” section, however, contains a

broad statement regarding the preemption of state common-

law failure-to-warn claims. /d. at 3933-36. In this statement,

the FDA asserts that recent cases rejecting preemption of

these claims, including those cited above, pose an obstacle

to the agency’s enforcement of the labeling requirements.

Id. Among the interpretations the agency claims are incorrect

are: (1) those rejecting preemption on the basis of 4 314.70(c);

and (2) those stating that federal labeling requirements are

minimum standards and that “[s]tate law serves as an

appropriate source of supplementary safety regulation for

drugs by encouraging or requiring manufacturers to

disseminate risk information beyond that required by FDA

under the act.” /d. at 3934.

25a

Appendix A

We are ordinarily required to defer to an agency’s

interpretation of a statute it administers. Chevron, U.S.A.,

Inc. v. Natural Res. Def. Council, 467 U.S. 837, 844, 104

S.Ct. 2778, 81 L.Ed.2d 694 (1984) (“We have long

recognized that considerable weight should be accorded to

an executive department’s construction of a statutory scheme

it is entrusted to admuinister....”). Plaintiff, however, urges

us noi to defer to the FDA's statement because it “was adopted

without the requisite comment period” and “lack[s] the force

of law.” Presumably, if we were to credit plaintiff's argument,

we would owe the statement only the limited deference due

to agency statements made outside the agency's rulemaking

authority. See United States v. Mead Corp., 533 U.S. 218,

226-27, 121 S.Ct. 2164, 150 L.Ed.2d 292 (2001) (stating

that Chevron deference applies 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”). We need not decide this difficult

question of administrative law, however, because we

conclude that irrespective of the level of deference we might

apply, the statement woul? not affect the outcome of this

appeal.

Under Chevron, deference to an agency’s interpretation

is appropriate only when a statute is “silent or ambiguous

with respect to the specific issue” the agency has considered;

otherwise, “the court, as well as the agency, must give effect

to the unambiguously expressed intent of Congress.” $67

U.S. at 842-43. Moreover, “[t}he judiciary is the final

authority on issues of statutory construction and must reject

administrative constructions which are contrary to clear

26a

Appendix A

congressional intent.” /d. at 843 n. 9. “If a court, employing

traditional tools of statutory construction, ascertains that

Congress had an intention on the precise question at issue,

that intention is the law and must be given effect.” Jd. When

an agency's interpretation is not the type of interpretation

entitled to Chevron deference, we must still grant it some

respect, but only “a respect proportional to its ‘power to

persuade.’” Mead, 533 U.S. at 235 (quoting Skidmore v. Swift

& Co., 323 U.S. 134, 140, 65 S.Ct. 161, 89 L.Ed. 124 (1944)).

Under either standard, the FDA’s statement deserves no

defereuce. We have already concluded, supra 26-27, that

Congress intended the FDCA to preempt only those state

laws that would make it impossible for manufacturers to

comply with both federal and state requirements. Nothing in

the FDA’s new statement alters our conclusion that it would

be possible for defendant to comply with both its federal

obligations and the obligations of state common law. The

regulatory framework for prescription drug labeling allows

drug manzfacturers to add or strengthen a warning “to

increase the safe use of the drug product” without prior

FDA approval. See supra 10-13 (citing 21 C.F.R.

{ 314.70(c)(6)(iti)(C)). Even if the new rule eliminated or

altered this provision, the change in the regulation did not

take effect until June 2006.° Without such a change, it is

possible for manufacturers to comply with beth FDA

regulations and duties imposed by state common law, and

there is no “direct and positive conflict” between state and

federal law.

is that changes to the new “Highlights” section of a drug labe! may

not be made without prior approval. 71 Fed.Reg. at 3934.

27a

Appendix A

The FDA does not attempt to establish such a conflict or

explain the inconsistency between its position and the

language of the preemption amendment. The statement cites

the amendment, but then proceeds as if Congress had not

spoken on the issue of preemption. The agency relies on Geter

to support its disregard of Congress’s “direct and positive

conflict” language, asserting that “[t]he existence of a

legislative provision addressing pre-emption does not bar the

operation ofordinary principles of implied preemption.” 71

Fed.Reg. at 3935 (citing Geier, 529 U.S. at 869). Geier does

state that implied preemption applies even when a statute

addresses preemption expressly, 521 U.S. at 869, but it does

not allow courts or agencies to preempt state laws that have

been expressly preserved by Congress. Instead, it simply

stands for the proposition that Congress’s intent not to

preempt a provision of state law cannot be inferred from

either (1) an express preemption clause that does not include

the state law in question in its scope, or (2) a clause that

prevents regulated entities from using compliance with

federal law as a defense in state common-law suits. /d. at

869-70. According to Geier, the former clause does not

support a negative inference that Congress must have

intended to preserve laws it did not expressly preempt; the

latter indicates only that Congress intended to preserve some

common-law claims, not that it intended to allow even claims

that conflict with federal requirements. /d. But see id. at 870

(stating that even the latter clause would “preserve [ ] those

actions that seek to establish greater safety than the minimum

safety achieved by a federal regulation intended to provide a

floor’).

28a

Appendix A

Here, we are not attempting to infer the effect of statutory

language that only indirectly addresses the specific state law

at issue. Instead, we are interpreting an unambiguous express

preemption clause that specifically preserves the type of state

law at issue. Under these circumstances, ordinary preemption

principles must give way to Congress’s intent to preserve

state laws that do not create a “direct and positive conflict”

with federal law. Drug Amendments §| 202. There is no such

conflict here. Accordingly, the FDA’s statement is neither an

authoritative interpretation of an ambiguous statutory

provision entitled to deference, Chevron, 467 U.S. at 842-

43, nor * persuasive policy statement entitled to respect.

Mead, 533 U.S. at 235. Plaintiff's claim does not impose

conflicting obligations on defendant or present an obstacle

to the objectives of Congress. We therefore agree with the

trial court that the claim is not preempted by federal law.

Il. Apportionment of Damages

Defendant next contends the court erred by ‘ailing to

instruct the jury to reduce plaintiff's damages by che’amount

of fault attributable to the Health Center. “Reversing a jury

verdict based on allegedly faulty jury instructions is

warranted where the party claiming error establishes that the

instructions were erroneous and prejudicial.” Simpson v.

Rood, 2005 VT 21, 5, 178 Vt. 474, 872 A.2d 306 (mem.).

We hold that there was no error in the court's failure to require

apportionment of damages between defendant and the Health

Center.

Defendant argues that pursuant to Vermont's comparative

negligence statute, a defendant is liable for only the portion

of the plaintiffs damages attributable directly to that

_—

29a

Appendix A

defendant’s negligence. 12 V.S.A. | 1036. Our traditional

rule is that multiple tortfeasors are jointly and severally liable.

See Zaleskie v. Joyce, 133 Vt. 150, 158, 333 A.2d 110, 115

(1975) (“[T]he law of this state ... permits a plaintiff to pursue

all, or any part, of his recovery from either joint tortfeasor’).

According to defendant, § 1036 applies not only under

circumstances where comparative negligence is alleged on

the part of the plaintiff, and not only when multiple

defendants are sued in the same action, but also any time the

plaintiff recovers from someone besides the defendant. Thus,

because plaintiff and the Health Center reached a settlement

in a separate lawsuit related to the same injury, defendant

claims the jury should have been required to calculate the

Health Center’s proportion of causal negligence and subtract

that percentage from the verdict.

Section 1036 states, under the heading of “Comparative

negligence,”

Contributory negligence shall not bar recovery in

an action by any plaintiff, or his legal

representative, to recover damages for negligence

resulting in death, personal injury or property

damage, if the negligence was not greater than the

causal total negligence of the defendant or

defendants, but the damage shall be diminished

by general verdict in proportion to the amount of

negligence attributed to the plaintiff. Where

recovery is allowed against more than one

defendant, each defendant shall be liable for that

proportion of the total dollar amount awarded as

damages in the ratio of the amount of his causal

30a

Appendix A

negligence to the amount of causal negligence

attributed to all defendants against whom recovery

is allowed.

12 V.S.A. 4 1036. We interpreted this statute under slightly

different circumstances in Plante v. Johnson, 152 Vt. 270,

565 A.2d 1346 (1989). In Plante, the defendant resisted

joinder of the plaintiffs’ claims against her and a third party,

resulting in a joint trial with two separate verdicts. The jury

first returned a verdict against the third party for the entire

amount of the plaintiff's damages, then found against the

defendant for the same amount, and the court consolidated

the judgments. The defendant appealed, arguing that the first

verdict made the third party’s share of the fault 100%. She

concluded that under 4 1036, she was entitled to a ruling

apportioning 100% of the liability for the plaintiff's damages

to the third party. The defendant failed to argue this point at

trial, making a holding regarding 4 1036 unnecessary. We

nevertheless examined the statute in depth to demonstrate

that our determination that the defendant was not entitled to

apportionment was “more than a technical omission.” /d. at

272, 565 A.2d at 1347. We concluded that the statute did not

apply to the defendant in Plante because “the statute provides

for apportionment among defendants, suggesting that only

those joined in the same action should be considered in

apportioning damages,” and “there is no allegation that the

plaintiff was negligent in this case.” /d. at 273, 565 A.2d at

1347-48.

6. We also listed as an additional reason, not applicable here,

that the third party whose liability was at issue in Plante was held

liable under a different theory of liability that was not clearly within

the scope of 1036. Id. at 273, 565 A.2d at 1348.

3la

Appendix A

In reaching this conclusion, we relied in part on the fact

that “the New Hampshire Supreme Court has held that its

nearly identical statute does not apply to create several

liability in the absence of an allegation of negligence on the

part of the plaintiff.” /d., 565 A.2d at 1348 (citing Lavoie v.

Hollinracke, 127 N.H. 764, 513 A.2d 316, 319-20

(N.H.1986)). Defendant points out that Lavoie has since been

overruled, but the decision overruling it, Nilsson v. Bierman,

150 N.H. 393, 839 A.2d 25 (N.H.2003), relied on a legislative

revision of New Hampshire’s statute that placed the concepts

of comparative negligence and apportionment under separate

headings. /d. at 29. In the absence of action by the Legislature

to amend Vermont's comparative negligence statute, we see

no reason to depart from the interpretation of 4 1036

contained in Plante. The Health Center was not a party to

plaintiff's action against defendant, and defendant does not

allege that plaintiff was comparatively negligent, so 4 1036

‘does not apply in this case.

Defendant argues that whether or not 4 1036 applies, we

can depart from our common law and determine that joint

and several liability should no longer prevent apportionment

among joint tortfeasors when one tortfeasor has settled in a

previous action. We decline to do so. In Howard v. Spafford,

132 Vt. 434, 321 A.2d 74 (1974), which also involved an

interpretation of 4 1036, we expressed our hesitation to depart

from the rule precluding contribution among joint tortfeasors,

preferring not to “substitute judicial fiat for legislative

action.” /d. at 435, 321 A.2d at 75. Among the many reasons

cited in Howard for adhering to the common law was the

sheer number of alternative schemes adopted by other states.

Id. at 436-37, 321 A.2d at 75-76. This reasoning applies here

32a

Appendix A

as well. Our choice is not between the traditional rule and a

uniform new rule, but rather between a traditional rule and a

number of potential new rules or combinations of rules. The

Nilsson court pointed out the divide among states requiring

jury verdicts to be reduced by the dollar amount of the

plaintiff's settlement with a third party (pro tanto), those

requiring verdicts to be reduced by the percentage of the

settling party's fault (proportional share), and those requiring

verdicts to be divided among all joint tortfeasors equally (pro

rata). 839 A.2d 30-31. That court pointed out that while “[t}he

American Law Instituie favors the proportional share

approach ..., the overwhelming majority of States reject the

proportional share approach in favor of some version of the

pro tanto approach,” and New Hampshire’s legislature chose

a combination of the two. Id. at 31 (citations and quotations

omitted). It is important to note that if we were to adopt the

majority rule, our decision would have no effect on this case,

as plaintiff and defendant have stipulated to a pro tanto

reduction. Like the New Hampshire court, we will allow the

Legislature to determine which approach is best, if it has not

done so already by leaving 4 1036 in place after our

interpretation in Plante.

Ill. Present Value of Damages

Finally, defendant contends the court erred by failing to

instruct the jury to calculate the present vale of plaintiff's

damages for future non-economic losses, such as pain and

suffering. Defendant claims that the jury’s verdict, which

granted plaintiff $5 million in non-economic damages,

exceeded the present value of plaintiff's requested amount

by $856,073. In rejecting defendant's proposed instruction,

33a

Appendix A

the court pointed out that defendant failed to provide the

jury with expert guidance as to how present value should be

calculated, and that “[j]udges and lawyers are universally

incapable of performing the discount calculations with or

without a calculator and the tables of historic interest rates

and inflationary factors.” We agree that it would have been

inappropriate to instruct the jury to make such a calculation

under these circumstances.

Even if defendant had presented testimony allowing the

jury to make an informed calculation, we would have upheld

the jury’s verdict for several reasons. First, defendant’s

assertion that the jury did not take account of the present

value of plaintiff's non-economic damages is pure

speculation, as plaintiff's calculation of her economic

damages was presented in terms of its present value, and

“the jury was not required to demonstrate its calculations”

with respect to plaintiff's non-economic damages. Debus v.

Grand Union Stores of Vt., 159 Vt. 537, 543, 621 A.2d 1288,

1292 (1993). Second, we limit pre-judgment interest to

economic damages because non-economic damages are

“inchoate and rarely ascertainable at the time of injury.”

Turcotte v. Estate of LaRose, 153 Vt. 196, 200 n. 2, 569 A.2d

1086, 1088 n. 2 (1989). These damages become no less

inchoate following a judgment, and we will not require juries

to apply a precise economic calculation to a figure we have

identified as inherently imprecise.

Finally, most jurisdictions and the Restatement (Second)

of Torts reject the concept of requiring juries to make present-

value calculations with respect to non-economic damages.

See, e.g., Tavior v. Denver & Rio Grande W. R.R., 438 F.2d

34a

Appendix A

351, 353 (10th Cir. 1971) (holding that instruction requiring

present-value reduction for pain and suffering was crror and

stating that most courts that have considered the issue have

decided “that the better reasoned authority supports the rule

that future pain and suffering should not be reduced to current

worth”); Restatement (Second) of Torts 4 913A cmt. a(1979)

(stating that while future pecuniary losses should be reduced

to present value, “an award for future pain and suffering or

for emotional distress is not discounted in this fashion’’).

But see Olivieri v. Delta S.S. Lines, Inc., 849 F.2d 742, 750-

51 (2d Cir.1988) (stating that “[i]f we were writing on a clean

slate, we might be inclined to accept the view of the other

circuits and reject any discounting of future non pecuniary

losses,” but previous Second Circuit holdings required such

discounting in some form). Defendant's reliance on our

decision in Parker v. Roberts, 99 Vt. 219, 131 A.2d21 (1925),

is misplaced, as Parker, while it required a jury instruction

on the present value of future losses, did not address the

distinction between pecuniary and non-pecuniary losses. /d.

at 224-25, 131 A. 21, 131 A.2d at 23. The trial court did not

err in refusing to instruct the jury to reduce plaintiffs non-

economic damages to present value.

Affirmed.

Associate Justice

35a

Appendix A

Dissenting

REIBER, C.J., dissenting. The overarching issue in this

appeal is whether plaintiff's common-law claim for failure

to warn conflicts with the FDA’s regulation of Phenergan,

the drug responsible for plaintiff's injuries. I would conclude

that the jury’s verdict in this case conflicts with federal law

for two reasons.

First, it would be impossible for defendant Wyeth to

comply with the requirements of both state and federal law.

Specifically, the FDA approved IV administration of

Phenergan and required that IV administration be listed on

the Phenergan label. By contrast, plaintiff's theory of the case

required Wyeth either to remove this approved use from the

Phenergan label, add a warning that would directly contradict

the label’s indication that [V administration was a safe and

effective use, or, at a minimum, add a warning that only

certain types of IV administration should be used. Thus,

compliance with state law in this case would require Wyeth

to eliminate uses of Phenergan approved by the FDA and

required to be included in the Phenergan labeling.

Second, plaintiff's state-law claim conflicts with federal

law in that it poses an obstacle to federal purposes and

objectives. In short, by approving Phenergan for marketing

and distribution, the FDA concluded that the drug-with its

approved methods of administration and as labelea-was both

safe and effective. See 21 U.S.C.;9 355(d) (listing criteria

for drug approval). In finding defendant liable for failure to

warn, a Vermont jury concluded that the same drig-with its

approved methods of administration and as labeled-was

“unreasonably dangerous.” See Town of Bridport v. Sterling

36a

Appendix A

Clark Lurton Corp., 166 Vt. 304, 308, 693 A.2d 701, 704

(1997) (to succeed on failure-to-warn claim, plaintiff must

show that “failure to warn made the product unreasonably

dangerous and therefore defective”). These two conclusions

are in direct conflict.

For both of these reasons I would conclude that the state-

law cause of action is preempted. I respectfully dissent.

1. Impossibility of Compliance

As explained by the majority, because there is no clause

in the FDCA expressly preempting state law, Wyeth must

demonstrate that preemption is implied by showing either

that federal law thoroughly occupies the regulatory field (a

claim that Wyeth does not advance) or that there is an actual

conflict between state and federal law. Actual conflict, in

turn, can be demonstrated in one of two ways: by showing

that it 1s impossible for the regulated party to comply with

both state and federal law or that state law “stands as an

obstacle to the accomplishment and execution of the full

purposes and objectives of Congress.” Freightliner Corp. v.

Myrick, 514 U.S. 280, 287, 115 S.Ct. 1483, 131 L.Ed.2d 385

(1995) (quotations omitted).

The majority in essence concludes that it is not

impossible for Wyeth to comply with both federal and state

standards because Wyeth never sought FDA approvai of a

“stronger warning” ofthe type advocated by plaintiff.

According to the majority, because the FDA was not

presented with, and therefore did not explicitly reject, such

strengthened language, there 1s no reason to presume that

37a

Appendix A

the FDA would disapprove. Therefore, the majority reasons,

there 1s no actual conflict between state and federal law. See

ante § 21-22. It is inaccurate, however, to characterize the

requirements imposed by the jury verdict in this case as

merely requiring a “stronger warning.” Rather, what plaintiff

sought was an elimination of a use of Phenergan that had

been approved by the FDA. Furthermore, the FDA’s rejection

of Wyeth’s efforts to alter the language of the warning in

2000 supports Wyeth’s claim that the FDA had an affirmative

preference for the language of the original warning.

The crux of plaintiff's claim was not based on the label

warnings per se, but on the approved uses listed there. See,

e.g., ante ¥ 3 (“Plaintiff's experts testified that the label

should not have allowed IV push as a means of

administration....”"). A review of plaintiff's complaint and the

evidence presented at trial makes clear that the standard

plaintiff seught to establish (i.e., the change to the label that

would be required in light of the jury’s finding of liability)

was to remove IV administration-or at least certain types-as

an approved use. For example, plaintiit’s complaint asserted

that the warnings on the label were inadequate and that:

[t]he Phenergan sold by defendant is ... NOT

REASONABLY SAFE FOR INTRAVENOUS

ADMINISTRATION because the foreseeab!c

risks of harm posed by intravenous administration

of the drug are sufficiently great in relation to its

foreseeable theraputic benefits that reasonable

health care providers, knowing of such foreseeable

38a

Appendix A

risks and benefits, WOULD NOT PRESCRIBE

THE DRUG INTRAVENOUSLY FOR ANY

CLASS OF PATIENTS.”

(Emphasis added.) !n her appellate brief, plaintiff

characterizes the evidence as revealing “that Wyeth was

aware of research indicating that DIRECT IV

ADMINISTRATION OF PHENERGAN WAS UNSAFE.”

(Emphasis added.) Plaintiff further refers to expert testimony

“that the LABEL SHOULD HAVE RESTRICTED

PHENERGAN TO INTRAMUSCULAR INJECTION as this

method of administration presents no risk of inadvertent

arterial injection; or, alternatively, that if |1V administration

is used, it must be by injecting the Phenergan into a hanging

|V bag, not through a direct IV.” (Emphasis added.)

Here, the FDA clearly addressed the risks attending IV

administration of the drug. The label approved IV

administration generally, and specifically warned.of the

dangers of direct [V administration, including inadvertent

arterial injection possibly resulting in amputation. In light

of this, it cannot be argued that the FDA déd not (1) assess

the risk of 1V administration, including direct IV

administrationand the associated risk of amputation due to

inadvertent arterial injection; (2) conclude that the benefits

of allowing IV administration with appropriate warnings

outweighed the risk; and (3) reach a decision regarding

precisely what warning language should be used. These

assessments are, in fact, the very essence of the FDA's

approval and are in furtherance of the federal objective of

advancing public health by balancing the risks and benefits

of new drugs and facilitating their optimal use. See 2! U.S.C.

39a

Appendix A

{| 355(d) (listing factors to be considered in approving or

refusing new drug application); 21 U.S.C. 4 392{b)(1),

(b)(2)(B) (FDA is charged with promoting public health by

acting promptly on new drug applications and protecting

public health by ensuring that new drugs are both safe and

effective).

The majority reconciles this manifest conflict by relying

on 21 C.E.R. 4 314.70(c), which allows a drug manufacturer

to alter a label “[t]o add or strengthen a contraindication,

warning, precaution, or adverse reaction” or “add or

sirengthen an instruction about dosage and administration”

prior to FDA approval.’ On this basis, the majority concludes

that Wyeth “was free under 4] 314.70(c) to strengthen the

warning without prior FDA approval.” Ante 4 22. But, it is

an overstatement to claim that manufacturers are “free” to

change drug labels under {| 314.70(c). To the contrary, a

manufacturer may change a label only to add or strengthen a

warning, not to eliminate an approved use, as plaintiff would

require here. In other words, what plaintiff advocates is not

a stronger warning but language that would directly contradict

language approved and mandated by the FDA.

7. This is also the approach employed by the numerous federal

district court decisions cited by the majority. Ante 4 14, 565 A.2d

1346. Because | disagree with this analysis of the import of 4

314.70(c), | do not find these decisions to be persuasive. Instead, |

side with the minority view expressed in Needleman, which

concludes that 4 314.70(c) gives manufacturers very little latitude

in unilaterally revising drug labels. Needleman v. Pfizer, Inc., 2004

WL 1773697, at *3 (N.D.Tex.).

40a

Appendix A

Further, the apparent purpose of 4 314.70(c) is to allow

manufacturers to address newly-discovered risks. See 44

Fed.Reg. 37434, 37447 (June 26, 1979) (allowing supplement

to label “whenever possibly harmful adverse effects

associated with the use of the drug are discovered”). Even

courts that conclude that 4 314.70(c) provides manufacturers

broad latitude to add warnings to labels acknowledge that

such supplements are aimed at previously unknown and

unanalyzed risks. See McNellis v. Pfizer, Inc., 2005 WL

3752269, at *6 (D.N.J.) (concluding that {| 314.70(c) “was

promulgated precisely to allow drug manufacturers to quickly

strengthen label warnings when evidence of new side effects

[is] discovered”’) (citing 30 Fed.Reg. 993 (Jan. 20, 1965));

Kurer v. Parke, Davis & Co., 2004 WI App 74, 18, 272 Wis.2d

390, 679 N.W.2d 867 (noting that, under 4 314.79(c), “[d]rug

manufacturers can strengthen warnings or petition for

additional warnings when new risk information arises”).

Another section of the regulation makes clear that any

changes to a label that exceed the scope of 4 314.70(c) are

considered “major changes” that require prior approval before

the drug may be distributed. 4 314.70(b), (b)(2)(v). In short,

the regulation does not allow manufacturers to simply

reassess and draw different conclusions regarding the same

risks and benefits already balanced by the FDA. Here, the

FDA had already evaluated the risk of inadvertent arterial

injection from direct 1V administration of Phenergan, and

had mandated warning language for the label to reflect that

risk assessment.

Y ;

In addition, any change accomplished under 4] 314.70(c)

is subject to ultimate FDA review and approval. See 4

314.70(c)(7) (providing that FDA may order manufacturer

4la

Apperdix A

to cease distribution of drug if it disapproves supplemental

application); see also Needleman v. Pfizer, Inc., 2004 WL

1773697, at *3 (N.D.Tex.2004) (noting that changes to label

under 4] 314.70(c) are temporary and “must later be approved

by the FDA”). Thus, any additional or different warnings

must ultimately be supported by scientific research that meets

the FDA’s standards. Neither a manufacturer, a state court,

nor a state legislature can permanently substitute its judgment

of the risk-benefit analysis for that of the FDA.

At its core, plaintiff's argument in this case was not that

the warnings on the label were inadequate, but that an

approved use (direct 1V administration) was in fact

unreasonably unsafe. Plaintiff did not seek to “add or

strengthen” a warning or a dosage/administration instruction,

but rather to eliminate an approved use of the drug. This is a

disagreement that cannot be overcome by operation of

314.70(c). Plaintiff's claim in this case-that a method of

administration of the drug should be partially if not entirely

eliminated from the labeling-represents a substantive

disagreement with FDA policy that goes beyond labeling/

warning issues alone. This disagreement creates opposing

requirements and a manufacturer could not satisfy both at

once.

Wyeth argues that even if 4 314.70(c) theoretically allows

a manufacturer to make unilateral changes to a drug label, in

this case, the FDA actually rejected Wyeth’s attempts in 2000

to change the warning regarding intra-arterial injection and

amputation. The trial court concluded that the FDA gave only

42a

Appendix A

“passing attention” to the risks of IV administration in 2000.

Ante 4 4. The majority similarly concludes that the record

does not indicate “that the FDA wished to preserve the use

of IV push as a method of administering Phenergan.” Ante

{| 23. | cannot agree with this assessment of the record.

Both the original label and Wyeth’s proposed alternative

were titled “INADVERTENT INTRA-ARTERIAL

INJECTION.” On the original label, the first two sentences

of the warning read:

Due to the close proximity of arteries and veins

in the areas most commonly used for intravenous

injection, extreme care should be exercised to

avoid perivascular extravasation or inadvertent

intra-arterial injection. Reports compatible with

inadvertent intra-arterial injection of [Phenergan],

usually in conjunction with other drugs intended

for intravenous use, suggest that pain, severe

chemical irritation, severe spasm of distal vessels,

and resultant gangrene requiring amputation are

likely under such circumstances.

On the proposed label, the first sentence of the warning read:

“There are reports of necrosis leading to gangrene, requiring

amputation, following injection of [Phenergan], usually in

conjunction with other drugs; the intravenous route was

intended in these cases, but arterial or partial arterial

placement of the needle is now suspect.” While the proposed

change to the warning language may not reflect what plaintiff

would require in a warning, it cannot be disputed that Wyeth’s

proposed alternative warning (1) placed greater emphasis on

43a

Appendix A

the risk of necrosis and amputation by referencing it in the

first sentence, and (2) gave the FDA the opportunity to

consider the specific, alternative warning advanced by Wyeth,

as well as the adequacy of the warning in general. Despite

this opportunity, the FDA mandated that Wyeth retain the

language of the existing warning. The alleged extent of the

FDA’s consideration of the issue is not relevant, in my view.

In 2000, the FDA confirmed its assessment that health

care professionals should be permitted to choose IV

administration in its various forms as a means of delivering

the drug, where appropriate. Wyeth could not both list all

forms of IV administration as an approved use, as required

by the FDA, and exclude all or some forms of IV

administration as unsafe, as required by the jury’s verdict in

this case. It would be impossible to comply with both

requirements.

Il. Obstacle to Federal Purposes and Objectives

| would further conclude that Wyeth has demonstrated

actual conflict preemption by showing that plaintiff's state-

law failure-to-warn claim poses an obstacle to federal

purposes and objectives. The majority does not address this

issue, concluding that Wyeth does not have the option of

proving this form of actual conflict preemption. The majority

reaches this conclusion by relying on the following clause in

the 1962 amendments to the FDCA:

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 ... unless there is a direct and positive conflict

between such amendments and such provision of

state law.

44a

Appendix A

Ante 4 26 (quoting Drug Amendments of 1962 (Harris

Kefauver Act), Pub.L. No. 87 781, 4 202, 76 Stat. 780, 793

(1962)). Citing Southern Blasting Services, Inc. v. Wilkes

County, 288 F.3d 584, 591 (4th Cir.2002), the majority

concludes that the provision “essentially removes from our

consideration the question of whether common-law tort

claims present an obstacle to the purposes and objectives of

Congress,” because the 1962 provision “simply restates the

principle that state law is superseded in cases of actual

conflict with federal law such that compliance with both

federal and state regulations is a physical impossibility.” Ante

§| 27 (internal quotations omitted). “In other words,” the

majority explains, “under any circumstances where it is

possible to comply with both state law and the FDCA, the

state law in question is consistent with the purposes and

objectives of Congress.” Id. Thus, the majority eliminates

the possibility of proving actual conflict preemption

independently through the “obstacle” prong of that standard.

But neither the passage in Southern Blasting on whichthe

majority relies nor the United States Supreme Court decision*®

cited as authority in that passage provide an explanation or

8. See Hillsborough v. Automated Med. Labs., 471 U.S. 707,

713, 105 S.Ct. 2371, 85 L.Ed.2d 714 (1985). The cited passage in

Hillsborough does not interpret the phrase “direct and positive

conflict.” It merely cites the different forms of preemption, including

the “obstacle” prong. It is worth noting that the federal statute at

issue in Geier v. American Honda Motor Co., 529 U.S. 861, 120

S.Ct. 1913, 146 L.Ed.2d 914 (2000) (discussed below), contained

an even broader savings clause than the 1962 amendment to the

FDCA. The provision in Geier stated simply that the federal safety

standard at issue did “not exempt any person from any liability under

common law.” /d. at 868.

45a

Appendix A

even an affirmative statement that the phrase “direct and

positive conflict” in the 1962 amendment eliminates the

“obstacle” prong of the actual conflict preemption standard.

Thus, the majority eliminates one of the two means by which

Wyeth may show actual conflict based on a single, unclearly-

reasoned Fourth Circuit decision that is itself lacking in case

law support. There is no basis for eliminating this prong of

the actual conflict standard, and I disagree with the majority's

conclusion to the contrary.”

Assuming, then, that Wyeth may demonstrate actual

conflict preemption by showing that state law is an obstacle

to federal regulatory purposes and objectives, I believe the

facts here support the conclusion that the state tort-law verdict

in this case is preempted. The United States Supreme Court's

decision in Geier v. American Honda Motor Co., 529 U.S.

861, 120 S.Ct. 1913, 146 L.Ed.2d 914 (2000), is controlling

on the question of when state law poses an obstacle to federal

purposes and objectives. In that case, the Department of

Transportation had issued a safety standard that required

automobile manufacturers “to equip some but not all of their

1987 vehicles with passive restraints.” /d. at 864-65. Among

the optional passive restraints were air bags. Honda was in

9. Nonetheless, the Court concluded that all ordinary

preemption principles-including actual conflict preemption and the

obstacle prong of the standard-applied. The Court rejected the notion

that Congress would so limit the effect of preemption as to allow an

actual conflict with a federal objective: “Insofar as petitioners’

argument would permit common-law actions that ‘actually conflict’

with federal regulations, it would take from those who would enforce

a federal law the very ability to achieve the law’s congressioally

mandated objectives that the Constitution, through the operation of

ordinary pre-emption principles, seeks to protect.” /d. at 872.

46a

Appendix A

compliance with this standard. Nonetheless, the plaintiff was

seriously injured in a car accident while driving a 1987 Honda

that was not equipped with an air bag, but with another form

of passive restraint. The plaintiff brought suit, alleging Honda

was negligent in failing to install a driver’s-side air bag in

the car. Honda argued that the federal safety standard

preempted the plaintiff's state-law negligence claim. The

Supreme Court held that a lawsuit premising negligence on

the failure to install an air bag conflicted with the objectives

of the federal safety standard and was therefore preempted.

Id. at 866.

In reaching this conclusion, the Court noted that the

plaintiff and the dissenting opinion-like the majority in the

instant case-viewed the federal regulation as setting a

minimum safety standard that states were free to supplement

or strengthen. /d. at 874. However, by examining the

comments accompanying the regulation, the Court concluded

that a safety standard allowing a choice of passive restraint

systems while not mandating any particular system was a

deliberate decision that reflected a balance of diverse policy

concerns. See id. at 875 (noting that allowing mix of available

safety devices available over time would “lower costs,

overcome technical safety problems, encourage technological

development, and win widespread consumer acceptance”).

“In sum, ... the 1984 version of [the safety standard] embodies

the Secretary's judgment that safety would best be promoted

if manufacturers installed alternative protection systems in

their fleets rather than one particular system in every car.”

Id. at 881 (quotations omitted). Accordingly, the Court

concluded that the tort action sought to impose a duty on

manufacturers to impose air bags, rather than other types of

47a

Appendix A

passive restraint systems, and that this state-law requirement

was an obstacle to the federal objective of allowing a mix of

safety devices.

Application of the Supreme Court precedent in Geier

dictates the same result in this case. As with the DOT in

Geier, the FDA is primarily concerned with public safety.

The conclusion of what is best for public safety is arrived at

by considering various policy factors that are sometimes in

tension with one another. For example, in developing the

safety regulation at issue in Geier, the DOT considered not

only which passive-restraint systems were safest on an

absolute scale, but which were most cost-effective and which

would gain consumer acceptance. Similarly, here the FDA

balances its assessment of a drug's safety against concerns

for the drug’s efficacy, taking into account that a safer but

less effective drug is not necessarily best for the public health

overall. See 21 U.S.C. 4 355(d) (FDA must consider safety

and efficacy); 21 U.S.C. 4 393(b)\(1), (b)(2)(B) (FDA’s

mission is to protect public from unsafe drugs and to promote

public health by approving regulated products in timely

manner). In the specific context oarnings on drug labels, the

FDA considers not only what information to include, but also

what to exclude. As the Eighth Circuit has noted in the

medical device context, “[t]here are ... a number of sound

reasons why the FDA may prefer to limit warnings on product

labels.” See Brooks v. Howmedica, Inc., 273 F.3d 785, 796

(8th Cir.2001). For example, “warning about dangers with

less basis in science or fewer hazards could take attention

away from those that present confirmed, higher risks.” /d.

48a

Appendix A

No drug is without risks. The FDA balances the risks of

a drug against its benefits to maximize the availability of

beneficial treatments. The FDA’s decision in approving a

drug, its uses and labeling reflect consideration of these and

other policy factors. While a state-court jury presumably

shares the FDA’s concern that drugs on the market be

reasonably safe, the jury does not assess reasonableness in

the context of public health and the associated risk-benefit

analysis. A jury does not engage in a measured and multi-

faceted policy analysis. Rather, a jury views the safety of the

drug through the lens of a single patient who has already

been catastrophically injured. Such an approach is virtually

guaranteed to provide different conclusions in different courts

about what is “reasonably safe” than the balancing approach

taken by the FDA. In act, different conclusions were reached

in this case.

The jury in this case was instructed that “[a] prescription

drug is unreasonably dangerous due to inadequate warnings

or instructions if reasonable instructions regarding

foreseeable risks of harm are not provided to the physician

and other medical professionals who are in a position to

reduce the risks of harm.” Faced with plaintiff's tragic

injuries, the jury concluded that allowing Phenergan to be

delivered through IV administration was “unreasonably

dangerous.” The jury’s verdict conflicts squarely with the

FDA's assessment of precisely the same issue: whether

Phenergan is safe and effective when delivered through IV

administration. The claim is preempted.

For the above reasons, | dissent.

& hief ‘Justice

49a

APPENDIX B — DECISION OF THE SUPERIOR

COURT OF WASHINGTON COUNTY

FILED AUGUST 2, 2004

STATE OF VERMONT

COUNTY OF WASHINGTON, SS.

Washington Superior Court

Docket No.: 670-12-01

DIANE LEVINE,

Plaintiff,

AMERICAN HOME PRODUCTS, INC.

(now WYETH),

Defendant.

DECISION ON MOTION FOR JUDGMENT

UNDER V.R.C.P. 50

This is a motion for judgment under Rule 50 following entry

of judgment in a product liability case. The motion was timely

filed and follows an earlier motion for judgment on the same

grounds submitted at the close of the evidence.

Factual Background

This case arises out of an incident on April 7, 2000, when

plaintiff received an injection of the drug Phenergan from

physician's assistant Jessica Fisch at the Health Center in

Plainfield, Vermont. Phenergan is an anti-nausea medication

50a

Appendix B

manufactured and sold by defendant. As a result of the

injection, plaintiff developed gangrene in her nght hand. She

underwent an amputation of her right arm at the elbow.

Plaintiff settled a separate claim against the Health Center

and her physician prior to suit.

The parties tried this case from March 8—March 11, 2004.

The jury verdict was for $7,400,000. The parties stipulated

to adjustments for the prior settkement and pre-judgment

interest. The Court entered judgment on March 17, 2004,

for $6,774,000.

Standard of Review

The standard of review for a Rule 50 motion is whether

“during a trial by jury a party has been fully heard on an

issue and there is no legally sufficient evidentiary basis for a

reasonable jury to find for that party on that issue.” V.R.C.P.

50(a). If the basis for the jury’s verdict is insufficient, “the

court may determine the issue against that party.” /d. The

trial court may grant the motion against a party “with respect

to a claim or defense that cannot under the controlling law

be maintained or defeated without a favorable finding on

that issue.” /d.; see also Brueckner v. Norwich University,

169 Vt. 118, 122 (1999) (“[A] trial court considers the

evidence in the light most favorable to the nonmoving party,

excluding the effect of any modifying evidence.) (citation

omitted).)

~~ —

Sla

Appendix B

1. Federal Preemption by FDA approval of

Phenergan labeling

Plaintiff's claim against defendant is based on allegations

that defendant failed to warn of the hazards of intravenous

injection of Phenergan. At trial plaintiff introduced evidence

that Phenergan should be administered by intra-muscular

injection or through a free-flowing IV bag. Plaintiff's

witnesses testified that injection into the patient's vein

through a “butterfly” infusion set was too dangerous and

should have been strongly discouraged in the instructions

for use — the “package insert” or label which accompanies

the product when it is provided to a physician.

Defendant argues that the approval of the Phenergan label

by the Food and Drug Administration preempts Vermont

product liability law on the issue of labeling and provides a

defense as a matter of law to a claim based on failure-to-

warn.

Factual Record at Trial

At trial defendant received wide latitude to introduce

evidence about its interaction with the FDA concerning the

Phenergan label. The factual record relevant to the Rule 50

motion is as follows:

1. The corrosive nature of Phenergan can lead to catastrophic

tissue damage if it enters a patient's arterial blood flow. As

the arteries become smaller and more diffuse, the tiny vessels

can be damaged by exposure to Phenergan. The patient suffers

spasm of the arteries, inflammation, loss of blood flow due

52a

Appendix B

to clotting, gangrene, and, in some cases, the loss of a limb

or other serious injury. Green. Tr. 212, 216. Once Phenergan

enters

This text is long and has been trimmed here. Open the source document for the complete record.

This is a copy of a public record, reproduced as it was published. It is not legal advice, and it may not be the version a court would rely on. Check the official source before you cite it.