Amicus Curiae Brief — Buckman Co. v. Plaintiffs' Legal Comm.

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No. 98-1768 SEP 13 2000

IN THE CLERK

Supreme Court of the United States

THE BUCKMAN COMPANY,

Petitioner,

V.

PLAINTIFFS’ LEGAL COMMITTEE,

Respondent.

On WrRiT OF CERTIORARI TO THE

UNITED STATES COURT OF APPEALS FOR THE THIRD CIRCUIT

BRIEF OF AMICUS CURIAE PHARMACEUTICAL

RESEARCH AND MANUFACTURERS OF AMERICA IN

SUPPORT OF PETITIONER THE BUCKMAN COMPANY

MARJORIE E. POWELL Bert W. REIN

ASSISTANT GENERAL COUNSEL Counsel of Record

PHARMACEUTICAL RESEARCH DANIEL E. Troy

AND MANUFACTURERS OF AMERICA JENNIFER A. SHAH

1100 Fifteenth Street, N.W. Wirey, REIN & FIELDING

Washington, D.C. 20005 1776 K Street, N.W.

(202) 835-3400 Washington, D.C. 20006

(202) 719-7000

Attorneys for Amicus Curiae

Pharmaceutical Research and Manufacturers of America

Rr Oe pe ee a

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TABLE OF CONTENTS

Page

Table of Cited Authorities .................... iil

Interest of Amicus Curiae .................045. l

Statement of the Case .........ccccccccccccves 3

Summary of Argument ....................45. 3

PE 6a cee ihecbbunbeonseseesaetéees'es 6

I. The Lower Court Wrongly Opened

The Door To Second-Guessing Of FDA

Approval Determinations By State Courts,

Juries, And Agencies. .........ccecceeee 6

A. Medtronic Does Not Control This

SE GG eatin dev cians sb4s000 0-0 7

B. State-Law Causes Of Action Or

Standards Permitting Collateral Review

Of FDA Approval Decisions Must Be

TE Sctckevedsesdsnceceases 9

II. Respondents’ “Intended Use” Position

Conflicts With The Use Of That Term In The

FFDCA And State-Law Claims Based On

That Position Are Necessarily Preempted By

The Medical Device Amendments Of

RK Kndbeduaeses ppneweeaeedeoeneceses 15

il

Contents

Page

A. Respondents’ Claims Are Expressly

Preempted Because They Would Impose

A State-Law Requirement For “Intended

Use” Disclosure That Is Different From,

And In Addition To, The Requirement

Under Federal Law. ..3...ccccccsees 16

B. Sustaining Respondents’ Claims Would

Severely Limit “Substantial

Equivalency” Approvals For Medical

Devices And Hinder Research And

Development Of New Devices And

DOUG. oo cccccncecensee heen 20

C. Sustaining Respondents’ Claims Would

Impede The Dissemination Of

Information Regarding Off-Label Uses

Of Devices And Drugs. ............. 24

CORGROIGR 20 cccccccccccesseseensne 28

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TABLE OF CITED AUTHORITIES

Page

Cases:

Chaney v. Heckler, 718 F.2d 1174 (D.C. Cir. 1983),

rev'd on other grounds, Heckler v. Chaney,

iD ccc cccecetsccecceccccce 26

Food & Drug Administration, et al. v. Brown &

Williamson Tobacco Corp., etal., U.S.__, 120

S. Ct. 1291, 146 L. Ed. 2d 121 (2000) ........ 20

Heckler v. Chaney, 470 U.S. 821 (1985) ......... 14, 26

Hines v. Davidowitz, 312 U.S. 52 (1941) ........ 9

In re Orthopedic Bone Screw Prods. Liab. Litig., 159

TD occccccccccccccces 7, 16, 26

Johnson v. Maryland, 254 U.S. 51 (1920)........ 12

Kuiper v. American Cyanamid Co., 131 F.3d 656

(7th Cir. 1997), cert. denied, 523 U.S. 1137

ELSES SOPOT TEST TTT ETT 13

Leslie Miller, Inc. v. Arkansas, 352 U.S. 187

EE EEE OEP S OTT TTT TTT TEE Te 12

Lewis v. Brunswick Corp., 107 F.3d 1494 (11th Cir.

1997), cert. dismissed, 523 U.S. 1113 (1998)

iv

Cited Authorities

Page

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

péneedneeéunuhseeaneundtiuwe> an 3, 7, 8, 9, 21, 23

Michael v. Shiley, Inc., 46 F.3d 1316 (3d Cir. 1995)

sneouneesenceésenssncebbesdseseasnesunen 7, 13

Mitchell v. Collagen Corp., 67 F.3d 1268 (7th Cir.

1995), judgment vacated, 518 U.S. 1030 (1996),

on remand, 126 F.3d 902 (7th Cir. 1997) ...... 12-13

Reeves v. Acromed, 44 F.3d 300 (Sth Cir. 1995) .. 13

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

SPEED coucosencncesenteeshesesekeesdunaet 9

Talbott v. Bard, Inc., 63 F.3d 25 (ist Cir. 1995) .. 13

United States v. Algon Chem., Inc., 879 F.2d 1154

PP MED co hvcusccnecacenseckseeneene 26

Washington Legal Found. v. Friedman, 13 F. Supp.

2d 51 (D.D.C. 1998), order amended, 36 F . Supp.

2d 16 (D.D.C. 1999), appeal dismissed, judgment

vacated in part on other grounds by Washington

Legal Found. v. Henney, 202 F.3d 331 (D.C. Cir.

BEES scncesesqcveswdadeosekanteuciiieuas 25, 26

Vv

Cited Authorities

Page

United States Constitution:

ULS. Comet, 60. VEG 2 ccccccccccccccccccce 6, 9, 12

Statutes:

BB WBE. GR FRY ccccccsccccccccececccess 3

Be Ce ED hich acccdccdedccececcsceses 10, 11

BB ULB. GB BEGRIED cccccccccevcccccccccense 17

BO DBA. BTR cccvccvecccccccccteccsconce 24

21 U.S.C. § 355GjK2MAMV) «2.6... ee ee ee eee 18

21 U.S.C. § 360c(a)(1M(CY3MA) ......---- eee 18

21 U.S.C. § SEBSGEIMA) .... 2c cccccccccccccess 21

21 U.S.C. § 360c(i)(1 (EM) .. 2. ee ee eee eee 18, 19

21 U.S.C. § 360c(i)(1 (EMiv) .. 2... 6 eee ee ee eee 19

21 U.S.C. § 360e(b)(1)(B) ..........20 2 ee eee 6, 20

BE ULB. 8 BEBIEE ..o ccccccccccccccccccescucs 10, 11

21 U.S.C. § SGC a)... cece ccccccccccccece 3, 7, 13

vi

Cited Authorities

Page

Be Das SOR oh ccecccccnsecess peqeeseuese 9

Se UE Ksccdcvenesecesnscecossees 9

Se Se OED véhercudivcscecoesccuwecieses 9

Be Gs ED 6 obbecdeicneséveseddoedssencs 25

Fe ee PE ccecesdeddcsenscdsssandoveewes 10

Pub. L. No. 75-717, 52 Stat. 1040 (1938) ........ 17

Pub. L. No. 87-781, 76 Stat. 780(1962) .......... 17

Pub. L. No. 98-417, 98 Stat. 1585 (1984) ........ 17

Pub. L. No. 105-115, 111 Stat. 2296 (1997) ...... 18, 19

Other Authorities:

Be Ges ED vc cvcccsecccccecevcecs 23

Be Gees ED o cnccceesevcoesvosiees 21

Se Gy SOUND coccescccsensdesaseeneces 21

Be Cle SURV OUEEEED cccccccccccceccccess 21

SP Oe EE SEED ccovesccccsoesonctes 25, 27

vil

Cited Authorities

H.R. Conf. Rep. No. 105-399 (1997) ............

H.R. Rep. No. 94-853 (1976) .........2-02.005-

H.R. Rep. No. 98-857 (1984) ............-5005.

S. Rep. No. 73-493 (1934) .........05 cece eeeee

S. Rep. No. 105-43 (1997) ......... ccc eee eeee

Kenneth P. Berkowitz, et al., Congress Tries to

Bridge the ‘Label Gap’ But Nobody Is Cheering,

Med. Mktg. & Media, Jan. 1998 .............

William L. Christopher, Off-Label Drug Prescription:

Filling the Regulatory Vacuum, 48 Food & Drug

Rel ETE cc ccccccesscocscoesescoeses

Deirdre Davidson, Reform Eyed For Landmark Drug

Law, Legal Times, Sept. 11, 2000 ............

Food and Drug Admin., Center for Devices and

Radiological Health, Off. of Device Evaluation,

Annual Report: Fiscal Year 1998 ............

More Information for Better Patient Care: Hearings

on S. 1477 Before the Senate Comm. on Labor

and Human Resources, 104th Cong. 81 (1996)

“eeeveeeneeeeeeeeeeeeeeeeeeeeeeeeneeeeee eee *

Page

25

23

24

17

19

26

26

10

22-23

vili

Cited Authorities

Page

Robert L. Rabin, Reassessing Regulatory

Compliance, 88 Geo. L.J. 2049 (2000) ..... 10, 24, 25

Robert Samuelson, Beware of a Regulatory

Overdose, Wash. Post, Sept. 5, 2000

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INTEREST OF AMICUS CURIAE'

The Pharmaceutical Research and Manufacturers of

America (PhRMA) is a voluntary, nonprofit association

representing the country’s leading research-based

pharmaceutical and biotechnology companies, which are

devoted to inventing medicines that allow patients to lead

longer, healthier, and more productive lives.? These

companies produce the majority of new medicines that are

developed and marketed throughout the world. A number of

PhRMA’s members also are engaged in the development and

sale of medical devices.

1. This brief was authored by the amicus and counsel listed on

its cover, and was not authored in whole or in part by counsel for a

party. No one other than the amicus or its counsel made any monetary

contributions to the preparation or submission of this brief. This

brief is being filed in accordance with a consent agreement entered

into by both parties, which has been filed with the Clerk.

2. PhRMA's brief is submitted on behalf of PARMA members

Abbott Laboratories, Allergan, Inc., ALZA Corporation, American

Home Products Corporation (and subsidiaries), Amgen, Ares-Serono

International, AstraZeneca LP, Aventis Pharma AG, Bayer

Corporation Pharmaceutical Division, Biogen, Inc., Bio-Technology

General Corp., Boehringer Ingelheim Corporation (and subsidiaries),

Bristol-Myers Squibb Company (and subsidiaries), E.1. duPont de

Nemours and Company, Elan Pharmaceuticals (and subsidiaries),

Fujisawa Healthcare, Inc., Genentech, Inc., Genzyme Corporation,

Gilead Sciences, Inc., Glaxo Wellcome Inc., Hoffman-La Roche Inc.,

Immunex Corporation, Johnson & Johnson (and subsidiaries), Knoll

Pharmaceutical Company, Eli Lilly and Company, Merck & Co.,

Inc. (and subsidiaries), Novartis Pharmaceuticals Corporation,

Nycomed Amersham Imaging, Organon Inc., Otsuka America

Pharmaceutical; Inc., Pfizer Inc., Pharmacia Corporation, The Procter

& Gamble Company, Purdue Pharma L.P., Sanofi-Synthelabo Inc.,

Schering-Plough Corporation, SCHWARZ PHARMA, Inc.,

SmithKline Beecham (and subsidiaries), Solvay Pharmaceuticals,

Inc. and 3M Pharmaceuticals.

2

PhRMA’s member companies will invest almost $26

billion this year in discovering and developing new

medicines, leading the way in the search for cures. PhRMA

estimates that the current average cost of developing a single

new drug is approximately $500 million, and that the

development process requires about fifteen years.’ This

lengthy development period already cuts significantly into

the patent protection period that affords manufacturers their

best opportunity to recover these enormous development

costs. Opening the door to additional pre-approval burdens

arising under state law, and casting doubt on the finality of

federal device and drug approvals, would diminish the

economic incentive for new device and drug development.

PhRMA’s members are concerned that the lower court’s

decision, unless reversed, would improperly permit the states,

through common-law fraud actions, to add a second, state-

administered Food and Drug Administration (FDA) approval

process. Allowing state courts and juries to second-guess

FDA approval decisions would undermine the certainty and

uniformity of the federal approval scheme, upon which

manufacturers rely in developing and marketing their

products. Moreover, the specific distortion of the federal

regulatory regime upon which respondents’ claims are based

would, in practice, delay, or even eliminate, the availability

of many new and competitive devices and drugs, to the

detriment of PhRMA’s members and the public health.

For these reasons, PhRMA joins petitioner The Buckman

Company in urging this Court to reverse the lower court’s

holding on the question presented for review.

3. This total includes time spent on (1) “pre-clinical” testing;

(2) clinical testing of the drug on human populations; and

(3) applying for and awaiting final FDA approval.

3

STATEMENT OF THE CASE

In the interest of judicial economy, PhRMA adopts the

statement of the case as set forth in petitioner’s brief.

SUMMARY OF ARGUMENT

The Medical Device Amendments of 1976, 21 U.S.C.

§ 360k(a) (MDA), to the Federal Food, Drug and Cosmetic

Act of 1938, 21 U.S.C. §§ 301-397 (FFDCA), expressly and

impliedly preempt respondents’ claims. The lower court’s

holding to the contrary should be reversed.

The lower court erred in holding that the present case is

controlled by Medtronic, Inc. v. Lohr, 518 U.S. 470 (1996).

In so doing, the lower court wrongly opened the door to

disruptive second-guessing of FDA approval determinations

by state courts, juries, and administrative agencies. At most,

Medtronic holds that, where the federal regulatory regime

governing medical devices has accorded broad discretion to

manufacturers (such as in the design and manufacture of

products), the MDA does not preempt the states from “filling

in the gaps” in federal regulation by enforcing traditional

common-law standards of behavior.

Here, however, respondents’ state-law claims do not arise

from traditional areas of state authority. Rather, they are

premised on the peculiar theory that liability under state law

arises from fraud on a federal agency. Nor do the state-law

claims concern matters on which the federal regime has failed

to speak or has given discretion to manufacturers. To the

contrary, respondents’ claims rest on a challenge to the

validity of an FDA approval determination — a specific,

adjudicative ruling by the FDA with respect to the device at

issue. Thus, Medtronic does not control in this case.

Respondents’ claims must be preempted. These claims

challenge the legality of marketing an FDA-approved

product. If state law could support such claims, plaintiffs

4

who believe that their injuries are associated with the use of

any FDA-approved product could assert that the product was

approved only because of “fraud,” other alleged manufacturer

misconduct, or because the FDA “got it wrong.” Although

federal law gives iinality to FDA premarketing approvals

claims such as respondents’ effectively add state approval

requirements to this federal review. By imposing a state-law

requirement different from, and in addition to, the federal

requirement, recognition of respondents’ claims would

directly contravene § 360k(a).

State-based collateral review of FDA approval decisions

also interferes with the legislative purposes of the FFDCA

and MDA. The federal regulatory regime governing approval

of devices and drugs accords uniformity and finality to the

FDA approval process. In the premarket approval context

the FDA grants market access to a device or drug only after

careful consideration of the product’s possible benefits versus

its potential risks for the labeled uses. Once the approval

determination has been made, the product’s manufacturer’

enjoys the certainty that it may lawfully market its product

in interstate commerce, so long as it does so in accordance

with the approved labeling. This certainty is essential to

facilitating the research, development, and marketing of new,

innovative medical products, all of which carry possible risks,

and none of which can be proven safe and effective in all

circumstances.

Permitting state review of the FDA approval process

would turn this system on its head. Even where, as here, the

States purport to follow federal approval standards: in

assessing the validity of an FDA approval decision, the states

may interpret those approval criteria inconsistently with

4. In this brief, “manufacturer” is intended to encompass

manufactufers of medical devices and pharmaceuticals, as well as

the regulatory agents of those manufacturers (such as petitioner).

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5

Congressional intent or FDA practice. Manufacturers then

would be faced with enormous and unfair potential liability

for failing to comply with the ex post facto interpretation of

the approval standards adopted by each state (or each state

court or jury). As a result, a dual regime could radically delay,

or even preclude, the introduction of beneficial new products.

This case aptly illustrates the adverse consequences of

permitting state review of FDA approval decisions.

Respondents’ state-law claims are premised on the theory

that the availability of petitioner’s bone screws itself caused

them harm, and that the FDA “got it wrong” in approving

the screws as labeled due to petitioner’s alleged fraud. If

allowed to proceed, these claims would require state courts

and juries to inquire into whether, in fact, the FDA “erred”

in allowing the screws to be marketed.

In order for respondents to prevail, moreover, the

reviewing state courts and juries would necessarily have to

adopt an interpretation of federal standards different from

that which has been adopted by Congress. Specifically,

- sespendents assert that federal law requires an applicant for

FDA approval to “truthfully” disclose to the FDA its

subjective intent or expectation regarding the product’s use.

Since the early federal food and drug laws, however,

Congress has made clear that the “intended use” statement

in a premarket notification application is an objective

description of the claims made in the labeling. Congress's

objective construction of “intended use” reflects its long-

standing effort to regulate the promotional claims made by

manufacturers, rather than to interfere with the freedom of

physicians to practice medicine in accordance with their

professional judgment.

By necessitating, under state law, a broader construction

of “intended use” than that intended by Congress,

respondents’ claims would inevitably expand the scope of

6

testing and review required for the approval of new drugs and

devices. In addition; where off-label uses develop for such drugs

and devices, as is commonly the case, respondents’ broader

construction of “intended use” would foreclose use of the

“§ 510(k)” and Abbreviated New Drug Application processes

established by Congress to accelerate new entry. Respondents’

construction also would interfere with the delicate federal

regulatory balance governing the dissemination of information

regarding off-label uses.

The Supremacy Clause, U.S. Const., art. VI, cl. 2, and the

Medical Device Amendments require preemption of state-law

standards that permit the states to scrutinize the FDA approval

process and second-guess the validity of FDA approval

determinations. These standards, whether imposed through

common-law causes of action or statutory schemes, would

impermissibly disrupt the intended uniformity and certainty of

the federal approval regime, and could lead to reduced

availability of important medical products.

ARGUMENT

I. THE LOWER COURT WRONGLY OPENED

THE DOOR TO SECOND-GUESSING OF FDA

APPROVAL DETERMINATIONS BY STATE

COURTS, JURIES, AND AGENCIES.

Respondents’ state-law claims against petitioner are

premised on the very availability of petitioner’s bone screws.

Without such availability, respondents claim, the surgical

procedures that allegedly caused their injuries would never have

been performed. Put another way, respondents assert that the

FDA “got it wrong” in approving petitioner’s bone screws,

because the screws never would have been approved absent

petitioner’s alleged “fraud” during the approval process.

Respondents thus seek to use their “fraud on the FDA”

claims to set aside the FDA’s determination that the screws

at issue were entitled to a § 510(k) approval, see 21 U.S.C.

§ 360e(b)(1)(B), and could lawfully be marketed.

7

The court below, reversing its earlier position in Michael

v. Shiley, 46 F.3d 1316 (3d Cir. 1995), permitted respondents’

claims to go forward over preemption challenges.

In re Orthopedic Bone Screw Prods. Liab. Litig., 159 F.3d

817, 819, 823 (3d Cir. 1998). The majority believed that this

Court’s decision in Medtronic, Inc. v. Lohr, 518 U.S. 470

(1996), required this result because (a) respondents were not

challenging a specific federal requirement with respect to a

device; and (b) respondents’ challenge was premised on a

federal standard of candor and thus supported, rather than

contradicted, federal goals. 159 F.3d at 823. The lower court

was wrong in both respects.

A. Medtronic Does Not Control This Case.

Medtronic is inapplicable in this case. At most,

Medtronic stands for the proposition that, where the federal

regulatory regime governing medical devices provides

manufacturers with broad discretion in designing and

manufacturing their products, the states are not precluded

from “filling in the regulatory gaps” by imposing traditional

common-law duties and statutory standards. 518 U.S. at 500-

01 (plurality opinion); id. at 508 (Breyer, J., concurring in

part and concurring in the judgment).* A majority of this

Court in Medtronic concluded that the plaintiff’s state-law

negligence and product liability claims were not preempted

by the MDA, 21 U.S.C. § 360k(a), because there were no

specific federal regulations governing the manufacture or

design of the device in question. 518 U.S. at 501 (plurality

opinion); id. at 508 (opinion of Breyer, J.). The plurality

opinion noted that the case at bar was

quite unlike a case in which the Federal

Government has weighed the competing interests

5. PhRMA recognizes that petitioner’s brief asks this Court to

reconsider its holding in Medtronic. Such reconsideration may in

fact be appropriate in this case.

8

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.

Id. at 501.

In this case, the federal government (i.e., the FDA) has

made a specific determination that petitioner’s device is

entitled to be sold as labeled. Thus, the FDA has “reached

an unambiguous conclusion” in a “particular case,” and

“implemented that conclusion via a specific mandate on

[petitioner]” — by granting § 510(k) approval. See id.

Indeed, FDA device approval determinations necessarily

involve federal actions specific to a device, as they are

decided on a case-by-case basis on the strength of a

manufacturer’s § 510(k) application or premarket test data.

Further, the federal regulatory regime governing device

approvals does not confer discretion on manufacturers with

respect to initiating marketing, or leave “gaps” for states to

fill with common-law causes of action: an FDA approval

determination is the final word regarding whether a product

may or may not be marketed in interstate commerce as

labeled.

Moreover, respondents’ claims are of a different

character from those in Medtronic. Medtronic involved state-

law claims in areas of traditional state concern; i.e., product

liability and negligence. 518 U.S. at 481. Here, by contrast,

respondents’ claims are based on the odd premise that

liability under state law may arise when an actor commits

“fraud” on a federal agency. Certainly, the relationship

between federal agencies and those they regulate is not a

field of historic state concern or legislation. See Brief of

United States, at 15. Thus, the “assumption that the historic

9

police powers of the States were not to be superseded by the

Federal Act unless that was the clear and manifest purpose

of Congress” does not apply here. Medtronic, 518 U.S. at

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

230 (1947)).

Because this case involves an attempt to overturn a

specific federal approval determination, using a non-

traditional theory of state-law liability based solely on alleged

violations of federal duties, Medtronic cannot control its

outcome.

B. State-Law Causes Of Action Or Standards Permitting

Collateral Review Of FDA Approval Decisions Must

Be Preempted.

In sustaining respondents’ claims, the court below

wrongly opened the door to second-guessing of federal

approval determinations by state courts, juries, and

administrative agencies.

These claims, resting on the alleged invalidity of FDA

approval decisions, add a layer of state-based review to the

FDA approval process. They permit the states to examine

and determine whether the FDA was caused to err in granting

market access. This would, in turn, allow states, through the

imposition of massive civil liability, to effectively override

the FDA’s approval decision.

This type of claim inherently runs afoul of the

Constitution’s Supremacy Clause. U.S. Const., art. VI, cl. 2;

see also Hines v. Davidowitz, 312 U.S. 52, 67 (1941)

(the Supremacy Clause requires preemption where state law

conflicts with federal law or “stands as an obstacle to the

accomplishment and execution of the full purposes and

objectives of Congress”). The federal regime confers primary

enforcement jurisdiction on the FDA, the purpose of which

is to accord finality to the agency's approval determinations.

See 21 U.S.C. §§ 371(a), (h), 393 (charging the FDA with

10

enforcement jurisdiction over the FFDCA and MDA, and

particularly with ensuring that drugs and medical devices

are safe and effective). This finality provides manufacturers

with certainty that they may lawfully place their products in

interstate commerce. Finality is critical to the approval

process, which, as it stands, involves tremendous cost and

risk to applicants.

Applicants for FDA approval frequently spend many

years and millions of dollars researching, developing, and

testing new products before the FDA approval process even

begins. Obtaining approval often means spending millions

more in testing or running clinical trials. See Robert

Samuelson, Beware of a Regulatory Overdose, Wash. Post,

Sept. 5, 2000, at A25 (citing studies reporting that, on

average, developing a new drug costs from $200 to $500

million and takes about 15 years). Further, the time spent in

seeking FDA approval cuts into the statutory patent

protection period afforded to new, innovative products.

See 35 U.S.C. § 154; see also Deirdre Davidson, Reform Eyed

For Landmark Drug Law, Legal Times, Sept. 11, 2000, at |

(citing study reporting that pharmaceuticals enjoy an average

of 11.5 years of patent protection, while other types of

products are protected for an average of 18 years). The longer

the process takes, the less time a manufacturer has to market

its product on an exclusive basis and recoup its development

costs.

In reviewing a premarket approval application for a

medical device or drug, the FDA carefully balances the

potential benefits and possible risks of the product in question

for its labeled uses. See 21 U.S.C. §§ 355(d), 360e(d);

see also Robert L. Rabin, Reassessing Regulatory

Compliance, 88 Geo. L.J. 2049, 2075 (2000). Both the FDA

and the applicant know that no product for which approval

is sought can be proven entirely safe or effective; the FDA’s

role is to decide whether the product’s potential health

11

benefits for the proposed uses outweigh its possible dangers.

If the FDA so determines, it will approve the product to be

marketed for the uses specified in proposed labeling.

21 U.S.C. §§ 355(d); 360e(d).

Allowing state courts and juries to “look behind the

labeling” and second-guess FDA approval determinations

would turn this system on its head. The very existence of

state-based re-evaluations of the FDA approval process

subverts the finality of the FDA’s decisions. Any time the

use of an FDA-approved product allegedly causes harm, .

plaintiffs could assert, as here, that the federal approval

decision was erroneous, whether due to “fraud,” FDA

mistake, or for other reasons. The FDA approval

determination would then be subject to intrusive scrutiny by

state courts and juries. Even assuming that the states

purported to follow federal standards in examining the

approval process, the states might interpret such standards

differently from Congress and the FDA. Permitting such an

inquiry would raise the significant possibility that FDA

approval determinations would be judged “invalid” by state

decision-makers. The question of whether any given federal

approval decision was valid also could be answered

differently from court to court and from jury to jury, leaving

the approval status of a medical device or drug entirely up in

the air.

Additionally, allowing common-law challenges to FDA

approvals could open the door to state administrative schemes

designed to provide collateral review of FDA approvals.

If common-law, de facto challenges to FDA approval

decisions are permissible, it might be difficult to prevent a

state from establishing an administrative scheme to review

FDA approvals before permitting in-state marketing.

As a result, manufacturers could find themselves forced to

apply for approval in each state before being able to market

a product in interstate commerce.

12

Permitting state collateral review of federal approval

decisions would impermissibly disrupt the federal approval

system. Manufacturers could no longer rely on FDA approval

determinations in marketing their products. Rather, because

they could face ex post facto state-based challenges to FDA

approval decisions (leading to potentially enormous liability

under state law), manufacturers would be left with massive

uncertainty regarding the legality of marketing any given

product. This uncertainty could have severe and adverse

effects on the research and development of medical devices

and drugs: because the risks associated with new products

would be exponentially higher, many potentially beneficial

devices and drugs might never be developed.

The Supremacy Clause, U.S. Const., art. VI, cl. 2, does

not permit state law to undermine the finality of FDA

approval determinations in this manner.-The Supremacy

Clause mandates preemption of state common-law or

legislative standards that permit scrutiny of the federal

regulatory process andschallenges to the approval

determinations that result therefrom. See Leslie Miller, Inc.

v. Arkansas, 352 U.S. 187, 190 (1956) (per curiam)

(invalidating the application of a state licensing requirement

to federal contractors whose bids had been approved under

federal criteria; such a requirement gives the state “a virtual

power of review over the federal determination,” and “does

not merely touch the Government servants remotely by a

general rule of conduct; it lays hold of them in their specific

attempt to Obey orders and requires qualifications in addition

to those that the Government has pronounced sufficient’’§

(quoting Johnson v. Maryland, 254 U.S. 51, 57 (1920)).®

6. Several lower courts have recognized this principle.

See, e.g., Lewis v. Brunswick Corp., 107 F.3d 1494, 1505 (11th Cir.

1997), cert. dismissed, 523 U.S. 1113 (1998); Mitchell v. Collagen

Corp., 67 F.3d 1268, 1283 (7th Cir. 1995) (the MDA preempted

plaintiffs’ “fraud on the FDA” claims because such claims “require[]

(Cont'd)

Pie” ee «

13

In addition, the express preemption provision of the

MDA, 21 U.S.C. § 360k(a), requires preemption of this

category of claims in the context of medical devices. A state-

law claim that requires the collateral review of the FDA's

approval decision with respect to a device necessarily

imposes a requirement (i.e., another stage of review) that is

“different from, or in addition to,” the requirements for

federal approval. In other words, once a device has, in the

FDA’s view, met the federal criteria for approval, section

360k(a) precludes a state from adding the effective

requirement that the device satisfy state-administered

premarket criteria.

Preempting state actions that permit re-evaluation of

FDA approval decisions would not mean that “fraud on the

FDA” or other unlawful conduct occurring during the

approval process would go uncorrected or unpunished.

(Cont'd)

"a court, applying state law, to perform the same functions initially

entrusted to the FDA”) (quoting Michael v. Shiley, Inc., 46 F.3d 1316,

1329 (3d Cir. 1995)), judgment vacated, 518 U.S. 1030 (1996),

on remand, 126 F.3d 902 (7th Cir. 1997); Talbott v. Bard, Inc., 63

F.3d 25, 29 (ist Cir. 1995) (noting the disruptive effect that state

“fraud on the FDA” claims would have on the uniformity of FDA

decisions, and observing that the FDA has “broad” authority to

withdraw approval decisions and initiate criminal prosecutions

against manufacturers who commit fraud); Reeves v. Acromed, 44

F.3d 300, 307 (Sth Cir. 1995) (“Allowing a jury or court to second-

guess the FDA’s enforcement of its own regulations contravenes

Congress’ expressly stated intent in § 360k(a) to eliminate attempts

by states to impose conflicting requirements on medical device

manufacturers”); Kuiper v. American Cyanamid Co., 131 F.3d 656,

666 (7th Cir. 1997) (finding state “misbranding” claims against

herbicide manufacturer preempted where manufacturer's label

conformed with EPA-approved label; “FIFRA does not allow states

to second-guess EPA’s labeling decisions under the guise of enforcing

the requirements of FIFRA itself”), cert. denied, 523 U.S. 1137

(1998).

14

The FDA has primary responsibility for policing violations

of its regulations. It also has ample authority to withdraw

approval and/or seek criminal penalties where it finds that

violations have been committed. See Heckler v. Chaney, 470

U.S. 821, 835 (1985).’ Given its central role in reviewing

and approving devices and drugs, the FDA is in the best

position to decide whether a “fraud” or other wrong has

occurred, and, if so, how the culpable party should be

penalized.*

The integrity of the FDA approval regime requires

preemption of state-law standards — including respondents’

“fraud on the FDA” claims — that permit ad hoc

(or systematic) challenges to the validity of FDA approval

decisions. Allowing such standards to exist would undermine

the finality and uniformity of federal approval decisions, and,

as a result, distort manufacturer behavior in a manner that

undercuts the purposes of the statutory scheme.

The consequence of permitting state courts, juries, and

agencies to second-guess FDA approval decisions could be

to slow the approval process and expose manufacturers to

potentially massive liability simply for marketing FDA-

approved products. This result #s not permitted under the

Supremacy Clause or section 360k(a) of the MDA.

7. Manufacturers frequently are “repeat players” before the

FDA, and want to maintain credibility before the agency to ensure

the continued approvals of their products. As a result, they have a

strong incentive not to defraud the agency or engage in other

wrongful conduct during the approval process.

8. Congress's decision not to create a federal private right of

action to enforce the FFDCA and MDA does not suggest that injured

parties should be permitted to seek compensation under state law.

To the extent that there are policy reasons for permitting injured

parties to recover when FDA approval is wrongfully secured,

preservation of the finality and uniformity of the federal regime

mandates that such a remedy be granted by Congress, not

haphazardly by the states.

15

II. RESPONDENTS’ “INTENDED USE” POSITION

CONFLICTS WITH THE USE OF THAT TERM

IN THE FFDCA AND STATE-LAW CLAIMS

BASED ON THAT POSITION ARE NECESSARILY

PREEMPTED BY THE MEDICAL DEVICE

AMENDMENTS OF 1976.

This case brings into sharp focus the problems with

permitting state review of the federal approval process even

where a federal standard is purportedly applied. At a

minimum, respondents’ claims would require state courts and

juries to “look behind” the FDA decision-making process to

determine what information was conveyed to the FDA;

whether the FDA relied upon alleged misstatements; and

whether, but for the alleged fraud, petitioner’s bone screws

would have been FDA-approved. As the Solicitor General

has advised this Court, this examination itself would unduly

impair the FDA review process. United States Br., at 16-18.

Respondents’ claims also are preempted because their

“intended use” theory would severely disrupt the federal

regime. If respondents’ subjective intent construction were

to be adopted in even one jurisdiction, manufacturers would

be forced to change their behavior during the approval stage

in a manner that would severely undermine the “substantial

equivalency” approval process and hinder the development

of both breakthrough and follow-on devices and drugs.

16

A. Respondents’ Claims Are Expressly Preempted Because

They Would Impose A State-Law Requirement For

“Intended Use” Disclosure That Is Different From, And

In Addition To, The Requirement Under Federal Law.

As noted, respondents here assert that the FDA, as a

result of petitioner’s “fraud,” “got it wrong” in approving

petitioner’s bone screws. In particular, respondents allege

that petitioner misled the FDA regarding the screws’ intended

use, and that the FDA relied upon this misrepresentation in

clearing the screws for markei access. Orthopedic Bone

Screw Prods. Liab. Litig., 159 F.3d at 820. Because the screws

were FDA-approved and available to physicians, physicians

were able to use the screws off-label to perform pedicle

surgeries, Causing respondents’ alleged physical injuries.

Ibid.

Respondents’ claims of fraud are based on the premise

that federal law requires an FDA applicant to “truthfully”

disclose any bona fide, subjectively intended or expected use

for the device in question. Under federal law as defined by

Congress, however, an FDA applicant’s statement of

“intended use” in its § 510(k) application is solely an

objective description of the scope of marketing authority

requested in the proposed labeling.

Federal law does not require a manufacturer to reveal

its subjectively intended or expected uses for a device or

drug in seeking FDA approval. Rather, the statement of

“intended use,” as defined by Congress, is a term of art

objectively describing a manufacturer’s requested authority

for FDA-approved labeling and promotional claims.

Congress’s objective interpretation of intended use reflects

its attempt to accommodate both the FDA’s premarket review

authority and the freedom of physicians to practice in

accordance with their professional judgment.

17

Throughout the administration of the federal food and

drug laws, “intended use” has been understood to refer only

to the use set forth for a product in the product’s labeling.

The Food, Drug and Cosmetic Act of 1938 (FFDCA),

Pub. L. No. 75-717, 52 Stat. 1040 (1938), established the

requirement that, before the marketing of a new drug, a

manufacturer must affirmatively demonstrate that the drug

is safe “for use under the conditions prescribed,

recommended, or suggested in the proposed labeling

thereof.” Id. § 505(d)(1), 52 Stat. at 1052 (codified as

amended at 21 U.S.C. § 355(d)(1)) (emphasis added).

This explicit limitation of premarket review to review of the

uses claimed in the labeling illustrates Congress’s clear

intention to limit “intended uses” to uses labeled or promoted

by the manufacturer, as opposed to all uses that the medical

community may find attractive.

The FFDCA’s legislative history recognized the essential

tie between manufacturer claims and FDA authority to

conduct premarket review:

The use to which a product is to be put will

determine the category into which it will fall. . ..

The manufacturer of the article, through its

representations in connection with its sale, can

determine the use to which the article is to be put.

S. Rep. No. 73-493, at 2-3 (1934) (emphasis added).’

9. Congress's subsequent amendments to the food and drug laws

consistently adhered to the objective interpretation of “intended use.”

See, e.g., Pub. L. No. 87-781, § 102(c), 76 Stat. 780, 781-82 (1962)

(requiring manufacturers to make a premarket showing of effectiveness,

as well as safety, for each “use ... prescribed, recommended, or

suggested in the labeling”) (codified at 21 U.S.C. § 355(d)(1)); Drug

Price Competition and Patent Term Restoration Act of 1984, Pub. L.

No. 98-417, 98 Stat. 1585 (1984) (creating an “Abbreviated New Drug

Application” (ANDA) procedure under which generic versions of

(Cont'd)

18

As with drugs, in regulating medical devices,

Congress consistently has limited the definition of “intended

use” to uses claimed in labeling or promotional materials.

See 21 U.S.C. § 360c(a)(1)(C)(3)(A) (a Class III device’s

“effectiveness” is based on whether it is demonstrated that

“the device will have the effect it purports or is represented

to have under the conditions of use prescribed, recommended,

or suggested in the labeling of the device”).

In fact, recently, Congress has explicitly declared that

the statement of “intended use” in a premarket notification

provision for a medical device is purely objective, and does

not incorporate an applicant’s subjective intent or

expectations. In 1997, after the initiation of the present

lawsuits against petitioner, Congress amended the FFDCA

to include an instruction to the FDA that “[a]ny determination

by [the FDA] of the intended use of a device [submitted for

§ 510(k) approval] shall be based upon the proposed

labeling[.]” Food and Drug Administration Modernization

Act, Pub. L. No. 105-115, 111 Stat. 2296 (1997) (FDAMA)

(codified at 21 U.S.C. § 360c(i)(1)(E)(i)). Thus, under

FDAMA, the FDA may not consider a § 510(k) applicant’s

subjectively intended uses for a device.

The legislative history of FDAMA makes Congress’s

intent unmistakable. The Senate Report provided:

With the “Medical Device Amendments of 1976,”

Congress intended that device classification and

approval decisions be made based on the intended

use of devices as described in labeling... .

(Cont'd)

pioneer drugs could receive expedited approval; limiting the FDA’s

authority to approve ANDAs to those where “the labeling proposed

for the new drug is the same as the labeling proposed for the [pioneer]

drug”) (codified at 21 U.S.C. § 355(j)(2)(A)(v)).

19

For premarket notification submissions, the

labeling proposed in the submission will be

controlling of a device’s intended use. If the

intended use is the same or sufficiently similar to

the intended use of a predicate device, then the

device may be found to be substantially equivalent

to the predicate. No considerations outside of the

proposed labeling for the § 510( k) device should

bear on the question of whether or not the

proposed labeling of the newer device is

compatible with the labeling of the predicate

device.

S. Rep. No. 105-43, at 27 (1997) (emphasis added).'°

In sum, Congress has repeatedly and expressly restricted

the definition of “intended use” to claims made in proposed

10. Although it refused to alter the objective understanding of

“intended use,” Congress enacted a provision directed at remedying

the problem of potentially harmful uses that were not “intended

uses.” Specifically, Congress temporarily authorized the FDA, in

reviewing a premarket notification submission, to require a

manufacturer to include in the proposed labeling of its device a

statement of “appropriate information” about an unclaimed use,

where such a use is foreseeable and could pose a potential for harm.

FDAMA, § 205, 111 Stat. at 2337 (codified at 21 U.S.C.

§ 360c(i)(1)(E)(i)); see also 21 U.S.C. § 360c(i)(1 (E)(iv) (five-year

sunset on FDA authority).

An unclaimed use for which the FDA may require “appropriate

information,” however, still is not an “intended use” as that term of

art has been defined by Congress. Rather, in enacting this provision,

Congress explicitly segregated the “intended use” determination —

which establishes the “substantial equivalency” necessary for

§ 510(k) approval — from the consideration of what, if any, further

information should appear on the label regarding potentially

dangerous off-label uses.

20

labeling.'' To sustain respondents’ theory of the case,

however, state courts would have to reject this established

construction and adopt a subjective interpretation of

“intended use,” thereby imposing disclosure obligations

different from, and in addition to, those imposed under

federal law. Any state action of this kind would clearly run

afoul of section 360k(a) of the MDA. |

B. Sustaining Respondents’ Claims Would Severely

Limit “Substantial Equivalency” Approvals For

Medical Devices And Hinder Research And

Development Of New Devices And Drugs.

By creating uncertainty regarding the meaning of

“intended use,” respondents’ claims ultimately would hamper

the research and development of new and follow-on medical

devices and drugs.

Sustaining respondents’ claims could severely hinder the

ability of medical device manufacturers to seek expedited

§ 510(k) approval based on a device’s “substantial

equivalency” to a preexisting device. See 21 U.S.C.

§ 360e(b)(1)(B). Under § 510(k), a manufacturer seeking to

market a new device may avoid the extended premarket

11. Four members of this Court, dissenting in Food & Drug

Administration, et al. v. Brown & Williamson Tobacco Corp., et al.,

__U.S.__, 120 S. Ct. 1291, 146 L. Ed. 2d 121 (2000), took the

position that “intended use” can, for purposes of determining the

FDA's jurisdiction over drugs, incorporate uses that are fostered or

expected by manufacturers. 120 S. Ct. at 1320-22, 146 L. Ed. 2d at

157-59 (Breyer, J., dissenting). The dissent’s discussion, however,

concerned the FDA’s alleged authority to regulate products whose

objectively “intended uses” are discernible from the circumstances

surrounding the products’ marketing. 120 S. Ct. at 1320, 146 L. Ed.

2d at 157. Brown & Williamson did not involve the disclosure

requirements for FDA approval. None of the regulations cited by

the dissent in that case suggests that the “intended use” statement in

an application for § 510(k) approval incorporates a manufacturer’s

future expectations or desires regarding the product's use.

21

approval process by demonstrating that the device

is “substantially equivalent” to a predicate device. /d.;

see also Medtronic, 518 U.S. at 477-79. The manufacturer

must submit a premarket notification to the FDA describing,

among other things, the “intended uses” of the device.

21 C.F.R. § 807.92(a)(5). If the FDA determines that the

proposed device is “substantially equivalent” to its predicate

for the specified “intended uses,” it will grant approval.

Id. § 807.100.

Importantly, a manufacturer may not secure

§ 510(k) approval for a device with materially different or

additional “intended uses” from those of its predecessor.

21 U.S.C. § 360c(i)(1)(A) (“substantial equivalence” of

devices requires that the devices have the same intended

uses); 21 C.F.R. § 807.100(b)(1). Thus, where a new device

has uses in addition to those of its predicate, the manufacturer

is precluded from seeking expedited approval.

In the § 510(k) context, situations frequently arise where

uses have developed for a predicate device beyond those

approved by the FDA. Once a predicate device has been

placed on the market, medical practitioners are free

to adopt such off-label uses. By the time “substantial

equivalency” approval is sought, these off-label uses are often

documented in scientific literature, making them clearly

foreseeable to § 510(k) applicants.

If respondents’ claims are not preempted, a § 510(k)

applicant could face potentially massive state fraud liability

if it failed to list as “intended uses” all foreseeable uses of

the device it wished to market. Plaintiffs claiming to be

harmed in connection with a foreseeable off-label use could

(and likely would) allege, as here, that the manufacturer

subjectively intended the device to be put to that use —

either in lieu of, or in addition to, the listed “intended

22

use” — and defrauded the FDA by failing to disclose such

intent. '?

If, to protect themselves from claims such as

respondents’, manufacturers disclosed all potential uses as

“intended,” they would be ousted from the § 510(k) process

and forced to submit their devices instead to the premarket

approval process.'’ This would radically change the current

trend in device approval applications, see Food and Drug

12. The fact that respondents in this case assert that petitioner

committed “fraud on the FDA” by providing an allegedly pretextual

“intended use” statement would not alter this result. As a practical

matter, a manufacturer could face “fraud on the FDA” claims any

time an off-label use allegedly caused harm, regardless of whether

such claims were based on an allegedly pretextual “intended use”

Statement or on an alleged failure to disclose an additional

subjectively intended use. The manufacturer also would face

potentially enormous litigation costs associated with either type of

“fraud on the FDA” claim. Here, for example, the issue of whether

petitioner falsely asserted a pretextual “intended use” for its bone

screws is inherently factual in nature. Its resolution would require a

determination of, among other things, (1) whether petitioner had a

bona fide intent to market the screws in accordance with their listed

“intended use”; (2) whether petitioner in fact intended for the screws

to be marketed for pedicle surgeries; (3) precisely what was disclosed

or not disclosed to the FDA; and (4) whether the FDA was misled

by petitioner's alleged misrepresentation.

13. A manufacturer could not defend itself from claims such

as these merely by disclosing to the FDA all foreseeable uses, without

seeking either approval or “contraindication” labeling therefor. This

is because, with respect to any off-label use for which labeling is

not sought, plaintiffs could assert, as here, that the manufacturer

subjectively intended the use to be adopted, yet failed to reveal such

intent to the FDA. As a result, a manufacturer’s only affirmative

defenses to such a claim would be either: (1) that it did subjectively

intend for the off-label use in question to be adopted, and disclosed

such intent to the FDA by seeking approval for that use; or (2) that

it did not intend the use, and foreclosed it by seeking contraindication

labeling.

23

Admin., Center for Devices and Radiological Health, Off.

of Device Evaluation, Annual Report: Fiscal Year 1998 21

(reporting that, during fiscal year 1998, 4,623 original

§ 510(k) applications were filed, as compared with

55 original premarket approval applications); Medtronic, 518

U.S. at 479-80 (reporting that, in 1990, 80% of new Class

III devices were approved through the § 510(k) mechanism),

and would thwart the salutary legislative purposes for which

the expedited approval scheme was enacted. 518 U.S. at 478

(noting that the scheme was intended to “prevent

manufacturers of grandfathered devices from monopolizing

the market while new devices clear the PMA hurdle, and to

ensure that improvements to existing devices can be rapidly

introduced into the market”).

In addition to directly undermining the § 510(k) process,

sustaining respondents’ claims would impede the approval

of new medical devices. Because the threat of state fraud

liability would force manufacturers to disclose and rigorously

test for all potential uses and seek labeling therefor, these

claims would work to significantly slow the already laborious

premarketing approval process. This adverse consequence

conflicts with the MDA’s goal of ensuring the

ready availability of safe and effective medical devices.

See H.R. Rep. No. 94-853, at 12 (1976). |

The adverse effects of allowing respondents’ claims also

could spill over into the drug approval context. Applicants

for FDA approval of a drug must list the drug’s intended

indications. See 21 C.F.R. § 314.50(c)(2). Claims such as

respondents’ therefore could be asserted any time a

foreseeable off-label use caused harm. To avoid exposure to

such claims, drug approval applicants presumably would be

forced to shoulder the same pre-approval burden as medical

device applicants — namely, testing and seeking labeling

for all known or foreseeable uses of proposed drugs. Thus,

24

as with medical devices, the existence of respondents’ claims

likely would raise costs for and slow all drug approvals.

Generic drug applications, which require manufacturers to

use labeling identical to the pioneer predecessor’s, would

be particularly affected, as off-label uses of pioneer

drugs are widespread. See Rabin, 88 Geo. L.J. at 2078

(off-label uses of drugs are “critical to adequate health

care” and are widespread in the pediatric and cancer

fields). The required disclosure of such uses would

foreclose access to the Abbreviated New Drug Application

process under the FFDCA. See 21 U.S.C. § 355(j). The end

result — diminished availability of both pioneer and generic

medicines — would be directly at odds with Congressional

intent. See, e.g., H.R. Rep. No. 98-857, pt. 1, at 14 (1984)

(Abbreviated New Drug Application process was intended

“to make available more low cost generic drugs by

establishing a generic drug approval procedure for pioneer

drugs first approved after 1962”).

C. Sustaining Respondents’ Claims Would Impede The

Dissemination Of Information Regarding Off-Label

Uses Of Devices And Drugs.

Respondents’ intent theory also would disrupt the

delicate federal regulatory balance that has been struck with

respect to the proper role of manufacturers in the

dissemination of information regarding off-label uses.

Congress recognizes the importance of limiting federal

regulatory interference with the practice of medicine by

health care professionals, and specifically with physicians’

freedom to use medical devices and drugs off-label. With

respect to medical devices, Congress has declared:

Nothing in [the FFDCA] shall be construed to

limit or interfere with the authority of a health

care practitioner to prescribe or administer any

legally marketed device to a patient for any

25

condition or disease within a legitimate health

care practitioner-patient relationship.

21 U.S.C. § 396. As its legislative history explains, this

section was intended to restrict regulatory interference with

off-label uses of devices. See H.R. Conf. Rep. No. 105-399,

at 219 (1997) (“The conference agreement includes a

provision intended by the conferees to emphasize that the

FDA should not interfere in the practice of medicine.

Specifically, the conferees note that the off-label use of a

medical device by a physician using his or her best medical

judgment in determining how and when to use the medical

product for the care of a particular patient is not the province

of the FDA”).

Off-label uses have long been viewed by Congress and

the FDA as a rational and beneficial part of the practice of

medicine. See, e.g., 59 Fed. Reg. 59820, 59821 (1994)

(the FDA has long held that “‘unlabeled’ uses may be

appropriate and rational in certain circumstances, and may,

in fact[,] reflect approaches to drug therapy that have been

extensively reported in medical literature”); More

Information for Better Patient Care: Hearings on S. 1477

Before the Senate Comm. on Labor and Human Resources,

104th Cong. 81 (1996) (Statement of William B. Schultz,

FDA Deputy Comm’r for Policy) (“[OJ}ff label uses of

approved products are appropriate, rational, and accepted in

medical practice. FDA knows that there are important off

label uses of approved drugs”). Such uses are prevalent, and

even predominant, in important fields such as oncology and

pediatrics. See Rabin, 88 Geo. L.J. at 2078; see also

Washington Legal Found. v. Friedman, 13 F. Supp. 2d 51, 56

(D.D.C. 1998), order amended, 36 F. Supp. 2d 16 (D.D.C.

1999), appeal dismissed, judgment vacated in part on other

grounds by Washington Legal Found. v. Henney, 202

F.3d 331 (D.C. Cir. 2000). In the case of AIDS, experts

report that between ninety and one hundred percent of

pharmaceutical treatments, including the antiretroviral

26

“cocktail” therapies, are off-label. See Kenneth P. Berkowitz,

et al., Congress Tries to Bridge the ‘Label Gap’ But Nobody

Is Cheering, Med. Mktg. & Media, Jan. 1998, at 39-40.

Off-label uses frequently constitute the standard of good

medical care. See Washington Legal Found., 13 F. Supp. 2d

at 56.

Congress had a compelling practical reason for

structuring the FFDCA to allow off-label uses — medicine

simply moves faster than the FDA possibly can:

New uses for drugs are often discovered after FDA

approves the package inserts that explain a drug’s

approved uses. Congress would have created

havoc in the practice of medicine had it required

physicians to follow the expensive and time-

consuming procedure of obtaining FDA approval

before putting drugs to new uses.

United States v. Algon Chem., Inc., 879 F.2d 1154, 1163

(3d Cir. 1989) (quoting Chaney v. Heckler, 718 F.2d 1174,

1180 (D.C. Cir. 1983), rev'd on other grounds, Heckler vy.

Chaney, 470 U.S. 821 (1985)). See William L. Christopher,

Off-Label Drug Prescription: Filling the Regulatory Vacuum,

48 Food & Drug L.J. 247, 261 (1993) (the FDA “could not

review drugs . . . at a pace equal to that at which physicians

discover off-label uses”).

The FDA has recognized the need for disseminating

adequate information regarding off-label uses and has

attempted to regulate the manner and extent to which

manufacturers can participate in the development and

dissemination of such information. See Washington Legal

Found., 13 F. Supp. 2d at 56-58. As Judge Cowen stated in

his dissent below, given the FDA’s acceptance of off-label

uses, “difficult and subtle balancing is called for in evaluating

manufacturers’ roles in the creation and distribution

of information about [such] uses[.]” 159 F.3d at 831;

27

see also 59 Fed. Reg. 59820, 59823 (1994) (the FDA has

recognized “the delicate balance required to accommodate

the need for industry-supported scientific and educational

activities and the statutory mandate that products be safe

and effective for their intended uses”).

Sustaining respondents’ claims would wreak havoc on

this balancing by permitting state courts and juries to force

manufacturers, to the extent they are able, to eliminate off-

label uses entirely. As discussed above, to avoid massive state

“fraud” liability, manufacturers would be forced to include

as many uses as possible “on-label.” Further, the threat of

state liability would discourage manufacturers from

providing information regarding and contributing to efforts

to study alternative uses of their products, since such efforts

might be viewed as evidence of manufacturers’ subjective

intent to market their products for such uses. Thus, sustaining

respondents’ claims could curtail the information flow

relating to off-label uses in a sweeping and misdirected

manner that is discordant with the federal regulatory scheme,

and further compels reversal of the decision below.

28

CONCLUSION

Claims such as respondents’ — which are premised on

the alleged invalidity of an FDA approval determination —

are preempted by federal law. Allowing such claims would

improperly impose an additional layer of state review of FDA

approval decisions, undermining the finality and certainty

of the federal approval scheme. Sustaining respondents’

claims also would introduce a new theory of “intended use,”

which would distort manufacturer behavior and reduce the

availability of beneficial medical devices and drugs to the

public.

For all of the foregoing reasons, this Court should reverse

the lower court’s decision.

Respectfully submitted,

Marorie E. Poweie Bert W. REIN

ASSISTANT GENERAL COUNSEL Counsel of Record

PHARMACEUTICAL RESEARCH DanieL E. Troy

AND MANUFACTURERS OF JENNIFER A. SHAH

AMERICA WILEY, Rew & Fie_piInGc

1100 Fifteenth Street, N.W. 1776 K Street, N.W.

Washington, D.C. 20005 Washington, D.C. 20006

(202) 835-3400 (202) 719-7000

September 13, 2000

Attorneys for Amicus Curiae

Pharmaceutical Research and Manufacturers of America