Regulatory and Enforcement Framework

• Pages: 69-155

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CHAPTER II

REGULATORY AND ENFORCEMENT

FRAMEWORK

Pharmaceutical products in the United States are regulated by the U.S.

Food and Drug Administration (FDA). No new drug or biologic can be

marketed lawfully in the United States without authorization from the

FDA. Authorization signifies that the new drug or biologic is safe and

effective for its intended uses.

A. FDA Drug Approval Requirements

1. Innovative Drugs

a. Drugs (Small Molecules)

The Federal Food, Drug, and Cosmetic Act (FDCA),1 as amended,

regulates drug manufacturing, marketing, and distribution.2 The FDCA

grants the FDA, as the designee of the Secretary of the Department of

Health and Human Services (HHS), the authority to regulate, among other

items, drugs and devices.3 The Act defines the term drug to include

“articles intended for use in the diagnosis, cure, mitigation, treatment, or

prevention of disease in man or other animals” and “articles (other than

food) intended to affect the structure or any function of the body.”4

Whether an article is a drug for purposes of the act, therefore, often turns

on the intended uses of the article.5

How a product is advertised and sold may make it a drug. Drugs

include more than just medicines: fluoride toothpastes, antiperspirants,

dandruff shampoos, and sunscreens are all considered drugs. In fact, the

1. 21 U.S.C. §§ 301-397.

2. Thompson v. W. States Med. Ctr., 535 U.S. 357, 361 (2002).

3. 21 U.S.C. §§ 321(g)-(h), 393; FDA v. Brown & Willi amson Tobacco, 529

U.S. 120, 126 (2000).

4. 21 U.S.C. § 321(g)(1)(C); Brown & Williamson, 529 U.S. at 126.

5. United States v. Vitek Supply, 144 F.3d 476, 484 (7th Cir. 1998) (stating

that 21 U.S.C. § 321(g)(1)(C) is “concerned wit h intended, not actua l

effect”); United States v. Livdahl, 459 F.Supp. 2d 1255, 1259 (S.D. Fla.

2005).

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definition of drug is “broader than any strict medical definition might

otherwise allow.”6

The FDCA further grants the FDA the authority to regulate so-called

combination products, which “constitute a combination of a drug, device,

or biological product.”7 The FDA has construed this provision to give it

the discretion to regulate combination products as drugs, as devices, as

biological products, or as any combination of the three.8

Section 505(a) of the FDCA provides that “[n]o person shall introduce

or deliver for introduction into interstate commerce any new drug, unless

an approval of an application filed [with the FDA] . . . is effective with

respect to such drug.”9 The FDCA defines a new drug as “[a]ny drug . . .

not generally recognized, among experts qualified by scientific training

and experience to evaluate the safety and effectiveness of drugs, as safe

and effective for use under the conditions prescribed, recommended, or

suggested in the labeling thereof.”10 Generally, all newly developed drugs,

with the exception of certain OTC drugs, meet the definition of “new

drugs” and require pre-approval by the FDA before they may be marketed.

The FDCA grants the FDA the exclusive power to enforce its

requirements.11 The burden of establishing safety and efficacy of a new

drug under the conditions prescribed, recommended, or suggested in the

6. United States v. Article of Drug Bacto-Unidisk, 394 U.S. 784, 798 (1969);

see also Brown & Williamson, 529 U.S. at 165 (quoting Bacto-Unidisk).

7. 21 U.S.C. § 353(g)(1).

8. 21 C.F.R. §§ 3.2(e)(1) & 4.3 (stating that each constituent part is regulated

as its constituent part); Miller v. Mylan Inc. (In re Estate of Kelly), 741

F.3d 674 (6th Cir. 2014).

9. 21 U.S.C. §355(a).

10. Id. § 321(p). The new drug definition was expanded to include “efficacy”

by the 1962 drug amendments, Pub. L. No. 87-781, 76 Stat. 780 (1962).

Except for three references to “effectiveness,” today’s 21 U.S.C.A.

§ 321(p) is the same text as originally enacted in 1938. Certain exceptions

apply, particularly the pharmacy compounding of drugs. 21 U.S.C.

§ 353a(a); Thompson v. W. States Med. Ctr., 535 U.S. 357, 364 (2002).

11. 21 U.S.C. §§371(a) & 337(a). Accordingly, no private cause of action

exists to enforce the FDCA. See Buckman Co. v. Plaintiffs ’ Legal Comm.,

531 U.S. 341, 349 n.4 (2001) (“The FDCA leaves no doubt that it is the

Federal Government rather than private litigants who are authorized to file

suit for noncomplianc e.”); Carmine v. Po ffenburger, 154 F. Supp. 3d 309,

313 (E.D. Va. 2015) (“Congress explicitly chose not to provide a private

cause of action to consumers harmed by violations of the FDCA.”

(quotation omitted)).

Regulatory and Enforcement Framework 71

proposed labeling of the drug remains at all times on the manufacturer.12

The FDCA “is to be given a liberal construction consistent with [its]

overriding purpose to protect the public health.”13 The FDA’s Center for

Drug Evaluation and Research (CDER) is delegated the authority to

regulate drug product approvals.14

The FDA’s new drug approval process is intended to ensure that drugs

meet certain statutory standards for safety and effectiveness,

manufacturing and controls, and labeling15 to ensure that manufacturers

market their drugs only for those indications for which the drug sponsor

has demonstrated substantial evidence of effectiveness.16 FDA estimates

that, on average, it takes seven to eight years to study and test a new drug

before the agency can approve it for public marketing, including early

laboratory and animal testing, as well as later clinical trials using human

subjects.17

Even before the FDA approval process is implicated, the drug

discovery process begins by identifying a target that plays a role in a

disease. Researchers then screen thousands of compounds for the ability

to fight the disease. Hundreds of possible drugs may emerge from the

screening, and some will be subject to laboratory testing and examined in

animals as a possible pharmacological “new chemical entity” that might

be medically useful without toxicity.

During preclinical research, drug sponsors study a product’s chemical

properties, develop steps for synthesis and purification, and begin short-

12. See Wyeth v. Levine, 555 U.S. 555, 565-67 (2009).

13. FDA v. Brown & Williamson Tobacco, 529 U.S. 120, 162 (2000) (Breyer,

J., dissenting); United States v. Article of Drug B acto-Unidisk, 394 U.S.

784, 798 (1969); United States v. Genendo Pharm., 485 F.3d 958, 963-64

(7th Cir. 2007); United States v. Baxter Healthcare, 901 F.2d 1401, 1408

(7th Cir. 1990).

14. See U.S. FOOD & DRUG ADMIN., FDA STAFF MANUAL GUIDE 1410.104

(2007), available at http://www.fda.gov/smg/vol2/1410/1410_104.html.

15. 21 C.F.R. §314.105(c).

16. Id. § 314.126(a); Weaver v. Reagen, 886 F.2d 194, 198 (8th Cir. 1989).

Drug research is complicated, time-consuming, expensive, and ultimate

success as a commercial drug product is always uncertain. See, e.g., Merck

KGaA v. Integra Lifesc iences I, Ltd., 545 U.S. 193, 20 6 (2005). Thousands

of chemical compounds can be tested to find a single product that is safe,

effective, and marketable.

17. U.S. FOOD & DRUG ADMIN., FROM TEST TUBE TO PATIEN T: PROTECTING

AMERICA ’S HEALTH THROUGH HUMAN DRUGS: A SPECIAL REPORT FROM

THE FDA CONSUMER MAGAZINE AND THE FDA CENTER FOR DRUG

EVALUATION AND RESEARCH (4th ed. 2006).