Handbook of Federal Drug Law [1 ed.] 081210997X, 9780812109979

Citation preview

James Robert Nielsen

Handbook

of

FEDERAL DRUG LAW

Digitized by the Internet Archive in

2012

http://archive.org/details/handbookoffederaOOniel

Handbook

of

FEDERAL DRUG LAW JAMES ROBERT NIELSEN,

J.D.

Lecturer in Law, School of Pharmacy,

University of California, San Francisco. Clinical Professor of Law, Hastings College of the Law, University of California,

San Francisco, California

Lea

&

Febiger

Philadelphia

1986

Lea

&

Febiger

600 Washington Square

PA

Philadelphia,

19106-4198

U.S.A. (215) 922-1330

Library of Congress Cataloging-in-Publication Data Nielsen, James Robert.

Handbook

of federal

drug

law.

Includes bibliographies and index. Title.

States.

—

—

Law and legislation United [DNLM: 1. Legislation, Pharmacy

Drugs

1. I.

QV

33

States.

—United

AA1 N6h]

KF3885.N54 1986 ISBN 0-8121-0997-X

344.73'04233

85-18164

347.3044233

Copyright © 1986 by Lea & Febiger. Copyright under the International Copyright Union. All rights reserved. This book is protected by copyright. No part of it may be reproduced in any manner or by any means without written permission from the publishers.

PRINTED IN THE UNITED STATES OF AMERICA Print

No.

4

3

2

1

PREFACE is traditionally a private matter. A contract or agreement between and the health care provider usually determines the nature and the extent of the care provided. Intrusion by the government into this private relationship is resented by both parties who deem it both unseemly and unwise. By and large, government authorities have acquiesced to this assertion of privacy in therapeutic matters and legislators have been remarkably reluctant to enter the operating theater and substitute their legislative wisdom for the surgeon's

Health care

the patient

judgment. When the therapy involves prescribing, administering, or dispensing drugs, however, this reluctance is abandoned. Always quick to sense a noncontroversial, topically popular bill like a resolution commemorating Mother's Day, legislators compete with each other to be first to announce the introduction of a bill to "impose stringent new drug controls." Unlike other professional activities performed for a patient's care, the act of providing drugs to a patient

and regulation of all professional acts. and dispensing drugs in a lawful manner for a therapeutic purpose takes place in a thicket of laws and regulations. Federal laws and administrative regulations, state laws and their administrative regulations, and even local hospital rules affect the manner in which the health

is

subject to the severest scrutiny

The

practice of prescribing

professional practices his or her licensed profession.

This handbook is designed to assist the student as well as the practitioner in understanding the basic federal drug laws that affect the daily practice of health care professionals in every state. What drugs may be prescribed? Who can manufacture, package, and dispense them? What may be said about them? What must be said about them? To whom? Who may prescribe which drugs for which patient for which indications? What records must be kept to validate a therapeutic act? What formalities are necessary to prescribe a drug? Federal law provides answers to these questions. To determine if a particular practice is prescribed or proscribed by law, one usually begins by examining the federal law and regulations, then the state law and regulations, then any local rules. Federal law, of course, governs all practitioners in every state. Article VI of the Constitution of the United States provides that federal law "shall be the supreme Law of the Land," prevailing over conflicting laws of any state. Sometimes there appears to be a conflict between federal and state law. For instance, federal law requires that, except in an emergency, a prescription for a schedule II controlled substance must originate as a written instrument as distinct from an oral communication to the pharmacist. Many states, however, have adopted laws that require the "written instrument" to be handwritten by the prescriber. Do these laws conflict? Certainly, they are different. The answer is no, they do not conflict. The stricter state law merely augments or supplements the federal law. The practitioner must comply with both. The practitioner does so by complying with the stricter state law.

vi

Preface

Federal law, then,

is

the primary source for laws governing the manufacture

and cosmetics in interstate commerce (the Food, Drug, and Cosmetic Act), all phases of manufacturing, distributing, prescribing, dispensing and administering of controlled substances (the Controlled Substance Act), as well as professional standards for handling drugs in institutions participating in Medicare funding. These federal laws may be and often are augmented by state and local laws. Indeed, the federal government itself is inclined to supplement these laws from time to time; the Poison Prevention Packaging Act and the Controlled Substance Registrant Protection Act of 1984 are recent examples. While every attempt has been made to assure an accurate statement of the law at the date of writing, laws and regulations change. Attorneys, you will be shocked to learn, often hold differing views as to the meaning of a statute. Accordingly, in all cases in which the practitioner is in doubt or where there is an apparent conflict with state or local law or practice, local counsel should be

and

distribution of drugs, devices,

consulted.

The reader will notice that from time to time certain material is repeated, sometimes more than once. Such repetition should not be diagnosed as galloping senility but rather as a deliberate effort to demonstrate yet another application of familiar material in a new environment without all the usual footnotes, see alsos, infras, swpras and the like, although there are still some of those. Because this handbook is designed to be used as an adjunctive text for a course in drug law at the School of Pharmacy, University of California, San Francisco, it is

intended to

fulfill

part of the course objectives: after reading the

handbook

should be able to examine any drug distribution system or professional practice and determine if the system or practice is lawful within the terms of the federal drug law. If it is not, the student or practitioner should be able to suggest changes that will make the system or practice lawful. If this handbook does that, it's a success. To test the mental acuity of my students as distinct from the lucidity of the text, I have included some random examination questions (Appendix D) and what I believe to be the correct answers (Appendix E). I wish to acknowledge the assistance of Frederick Minardi, Pharm. D., Dennis Kitayama, Pharm. D., Joseph Sorbello, Chief Inspector of the California Department of Business and Professions assigned to the California State Board of Pharmacy, and Del Konnor of the Drug Enforcement Administration. Each provided technical and professional advice as well as sharing their practical expea student or practitioner

The advice and assistance was theirs. The inaccuracies that have crept into the text are my sole responsibility. Elma P. Belenson typed seemingly endless revisions of the material in this handbook. rience in the field.

San Francisco, 1985

James Robert Nielsen,

J.D.

CONTENTS PART

I.

Chapter

1

FOOD, DRUG,

AND COSMETIC ACT

Introduction and History

3

Legislative Purpose

3

Sulfanilamide Disaster of 1937

3

Food, Drug, and Cosmetic Act of 1938

3

Durham-Humphrey Amendment

4

of 1951

Thalidomide Disaster of 1962

5

Kefauver-Harris Amendments of 1962 Medical Device Amendment of 1976

6

5

Orphan Drug Act of 1983 The Drug Price Competition and Patent Term Restoration Act of 1984

Chapter 2

6

Drug, Devices, and Cosmetics Drug Defined Adulteration of Drugs and Devices Misbranded Drugs and Devices

7 8

9

Policy of Full Disclosure

9

Acts Constituting Misbranding

9

The Prescription Drug Exemption New Drugs

11

13

Definitions

13

New Drug Procedures Notice of Claimed Investigational Exemption for a Drug (IND) Confidential Data Prescribing and Dispensing an Investigational Drug New Drug Application Continuing Reports on Approved NDAs Prescribing the Legend Drug

6

14

New 14 14 14

14 16

17

Authority to Prescribe Scope of Authorized Practice New Classes of Prescribers

17

Out-of-State Prescribers

17

Authority to Transmit Prescriptions

18

Formalities of a Prescription

and Dispensing for an Unapproved Use Directing an Unapproved Use as Negligence Dispensing the Legend Drug Diagnosis by Mail, Mail Order Prescriptions

Prescribing

Dispensing Prescribers Labeling Requirements

17

17

18

18 19

20 20 21 21 vii

viii

Contents

—

Patient Information Directions for Use Cautionary Statements Foreign Languages Prescription Drug Advertising Packaging the Drug Poison Prevention Packaging Act Exceptions Household Substances Subject to the Act Mailing the Prescription Drug Labeling the Container for Mailing Packaging for Mailing Mailing Drugs between Dealers The Pharmacy as Drug Manufacturer Devices

22

—

22

24 24

24 25 26 26 26 26

27

Definition Classification of Devices

Safety

and Effectiveness

of Devices

Classification Procedures

Restricted Devices

Cosmetics Definitions Registration of Cosmetic Manufacturers

Cosmetic Labeling Adulteration and Misbranding of Cosmetics Tamper-resistant Packaging for Certain Cosmetics Enforcement and Recall Procedures Federal Alcohol Tax Medicare Control of Drug Use Conditions for Participation Hospitals

—

—

31 31

32 32 32 32 32 32 33

33

—Skilled Nursing

Conditions for Participation

Chapter 3

31

Physical Facilities

Pharmacy Committee Drug Standards

II.

30

Hospital Pharmacy

Personnel Requirements Records and Labeling Requirements Control of Toxic or Dangerous Drugs

PART

27 27 27 28 28 28 29 29 29 29 29

33 Facilities ...

33

FEDERAL CONTROLLED SUBSTANCE ACT Registration

by Activity

37

Activities Requiring Registration

37

Separate Registration

38

Exemption from Registration

for

Employees and Agents of

Registrants Activities

and Coincident

Activities

Manufacture Pharmacist Exemption

38 39 39 39 39

Distribute

Dispense

40

Practitioner Defined

Research

40 43 45

Instructional Activities

45

Narcotic Treatment Programs

45

Practitioners

Exempt from

Registration

Contents

IX

Research with Schedule I Substances Chemical Analysis Importing Controlled Substances Exporting Controlled Substances

45 46 46 46 46

Compounder

Chapter 4

Exempt from

Separate Registration for Separate Sites Exceptions

46 46 47

Applications for Registration

49

Forms Annual Registration

49 49 49

Activities

Registration

Application for Registration as a Practitioner Applicant Investigation

49

Certificate of Registration

51

Security Requirements

51

Exceptions for Pharmacies and Institutional Practitioners Security of Personnel Miscellaneous Security Requirements

.

51 51 51

Application for Registration as a Manufacturer or Distributor

52

Applicant Investigation

52

Security

52

Physical Plant

—Nonpractitioners

52 52 54

Other Security Controls Security of Personnel Application for Registration as a Drug Treatment Program Security

Transfer of Business Transfer of Registration Transfer of Registration Chapter 5

— Practitioners —Nonpractitioners

Number Number

Schedules of Controlled Substances Establishment of Schedules Schedule I Schedule II Schedule III Schedule IV Schedule V Submission of Information Manufacturer Scheduling a Drug or Other Substance Symbols Required

—

Chapter 6

Obtaining Controlled Substances

.

55 55 57 57 57 59 59 59 59 60 60

60 60 61 61

—Transfer among

Registrants

63

Quotas

63

Acquisition of C-I and C-II Substances

63

Order Forms

63

Execution of the Order Form Who May Execute an Order Form? Power of Attorney

66

Completion of the Order Form by the Purchaser Avoiding Errors on the Order Form Additional Uses of Order Forms Returning CT or C-II Substances to the Supplier

66

66 66 68 68 68

x

Contents Distribution to Another Dispenser

68

Discontinuing Business or Transfer of Business Compounder of Narcotic Substances for Use at Off-Site Locations Research Other Regulations Order Forms

68

—

Chapter 7

69

Time Frame Endorsement Executed Order Forms Lost or Stolen Order Forms Etorphine Hydrochloride and Diprenorphine Acquisition of C-III, C-IV, and C-V Substances

69

Records

71

Definitions

71

Dispense

71

Individual Practitioner

71

69

69 69 69 70

Institutional Practitioner

71

Pharmacy

72

Records Maintained by a Pharmacy Central Record Keeping Inventory Biennial Inventory Date Inventory of Newly Scheduled Drugs Inventory Requirements for Different Schedules

72

72 72 73 73

73

Separate Activities

73

Continuing Records of Acquisition Continuing Records of Dispersals of Controlled Substances by Pharmacists

73

Prescriptions

74

Approved Filing Methods Order Forms or Invoices

74

74 for Coincident Distribution to

Other Registrants Record Book of Sales of Nonprescription Schedule V Substances Records of Coincident Manufacture for Distribution to An-

74 75 75

other Registrant

Records of Returns to Suppliers Records Maintained by an Institutional Practitioner Inventory Records of Acquisition Records of Dispersals Security Requirements Records Maintained by an Individual Practitioner Exemptions and Requirements Security Requirements Records Maintained by Narcotic Treatment Programs Records Maintained by Compounders, Manufacturers, and

75 76 76 76

76

77 77 77 78 78

78

Distributors

Chapter 8

69 69

Prescriptions

81

Who May

81

Issue a Prescription?

Pharmacist's Responsibilities Verification of Registration

and

81

DEA Number

82

Contents

Nurse

Practitioners, Physician Assistants,

XI

and Pharmacists

as Individual Practitioners

Authority of Office Nurses, Secretaries, and Receptionists

Purpose of Issue

82 84 85

Pharmacist's Responsibilities

85

DEA Guidelines

85

Restrictions

on Treating Addiction

86 86 88

Formalities of a Prescription

Dispensing a Schedule

Emergency Oral

II

Substance

88

C-II Prescriptions

89

Partial Filling of a C-II Prescription

Dispensing a Schedule

III

or IV Substance

89 90

Refills

—

Record of Authorized Refills Computer Records Partial Filling of Schedule III and IV Prescriptions Dispensing a Schedule V Substance Labeling the Container of Prescription Medication Cautionary Statements Schedules II, III, and IV Exemptions from Labeling Requirements Schedule II Labeling the Medication Container for Schedule III and IV Substances Transferring Prescriptions Between Pharmacies Purpose of Transfer

—

—

.

90 90

90 91 91 .

Pharmacists' Responsibilities

.

92

92 92 92 92

Chapter 9

Disposal of Controlled Substances

95

Chapter 10

Native American Church

99

Chapter 11

Violations of the

Chapter 12

CSA

101

Penalties

101

Controlled Substance Registrant Protection Act of 1984

102

Administrative Inspections

103

103 103

riistory

What May Be

Inspected and

When

Inspection by Consent

104

Inspection by Administrative Warrant

104

Chapter 13

Theft of Controlled Substances and Order Forms

107

Chapter 14

Packaging and Mailing a Controlled Substance Prescription Packaging a Controlled Substance Mailing a Controlled Substance

111

Between Registrants Between a Registered

Ill Ill Ill

Practitioner

and

a Patient

Ill

Appendix A Appendix B Appendix C Appendix D Appendix E

141

Index

157

113 131

145

155

Part

I

FOOD, DRUG, AND COSMETIC ACT 21 U.S.C. 301-695 Public

Law

75-717, effective date June 25, 1938

—

Chapter

1

INTRODUCTION AND HISTORY

LEGISLATIVE PURPOSE The purpose of the Federal Food, Drug and Cosmetic Act is commerce in drugs to those that are safe and effective. Originally enacted as the Federal Food and Drugs Act of hibited adulterated or

1906 Act 1.

misbranded food or drugs from

to limit interstate

1906, the act pro-

interstate

commerce. The

was considered inadequate because:

False statements

made about

a

drug by a manufacturer were held by the

courts not to be misbranding. 2. 3.

The The

act did not

extend to cosmetics.

act did not grant the authority to

ban

In 1912, Congress cured the false statement definition of misbranding

unsafe drugs.

problem and included within the powers of

false or fraudulent claims for the curative

drugs.

SULFANILAMIDE DISASTER OF

1937

was widely hailed as the first of the "miracle drugs." Every was trained to sprinkle a wound with "sulfa powder" to prevent infection. The antiinfective properties of the drug appeared limitless. A manufacturer decided to market the drug in a liquid form for sore throats and mixed the sulfanilamide with diethylene glycol the same stuff one uses today as antifreeze Sulfanilamide

soldier

—

in car radiators. Diethylene glycol had,

seems, a pleasant color

—

pink deadly poison. No clinical tests were made prior to marketing. Actually, that statement may not be completely accurate. Presumably, some chemist somewhere must

and

a not

unpleasant taste

have stuck

—

It

was

new

FOOD, DRUG

legislation

were 107

and approved the taste from this product.

reported deaths

was passed the following

AND COSMETIC ACT OF

light

also, of course, a

his finger in a batch, licked off the result,

prior to a marketing effort. There

Predictably,

it

slightly sweet.

year.

1938

The public furor over the sulfanilamide disaster finally resulted in a legislative for safety. The new act required that drugs be adequately tested for safety. Because all drugs are to some degree harmful if used contrary to common sense or the manufacturer's intent, "safe" meant nontoxic when used in accordance with the conditions set forth on the label. The term label is a term of art. It means "a display of written, printed, or graphic matter upon the immediate container of any article." The law requires that

demand

Food, Drug, and Cosmetic Act

4 Notes if

is required to be on the label of a drug, the information on the outer container or wrapper of the retail package, or the

certain information

must

also be

inner label clearly visible through such outer wrapper. 21 U.S.C. 321(k)

Comment: This requirement

prohibits marketing of products

tainer does not inform the purchaser of the contents.

It is

whose outer con-

the reason one often

sees a box containing an aspirin bottle with the front panel cut the label

on the

The term

labeling also is a

term of

printed or graphic matters either: upon

and means all labels and other written any container or any of its wrappers or

art

accompanying such article. Comment: In the obvious case, a package drug,

is

away displaying

aspirin bottle.

part of the drug's "labeling."

insert, while not part of the "label" of a

The law

can, for instance, require that certain

information accompany a drug as part of its labeling while not requiring the information to appear on the drug's label. This new law, in addition to requiring proof of safety, expanded the meaning of adulteration

and misbranding

the courts. Labels were

consumer. In addition, arations, the label

that previously

had been

strictly

construed by

now if

required to provide adequate directions for use to the the drug contained certain narcotic or hypnotic prep-

was required

to bear the legend,

"Warning:

May

be habit

forming."

The

act also

extended the operation of the law to include cosmetics. Separate drug advertising under the control of the Federal Trade Com-

legislation placed

mission.

During and immediately following World War II, the pharmaceutical industry experienced unprecedented growth. The discovery of penicillin led to the requirement in 1949 for batch certification procedures for all antibiotics prior to marketing. During those years, drugs increased in potency as well as efficacy. It was widely believed that one could insulate one's body from the grossest abuse simply by taking the right pill. One had only to discover the right medicament and new ones were discovered virtually every day to achieve health, happiness, wealth, slimness, and a lasting tan. Anxiety, a prescription for Miltown, and a credit card were the combat badges of the "with-it" executive in the postwar zone. With so many new drugs on the market, drug manufacturers and the Food and Drug Administration realized they had a problem. Manufacturers were required to provide labeling for their products that included adequate directions for use so that a person of ordinary intelligence could understand them. It was virtually impossible, owing to space limitations, to write such directions includ-

—

—

ing indications, contraindications, and what-have-you for these

new

drugs. To

understand such directions, the consumer might require a short course in differential diagnosis. The result was yet another amendment, the Durham-Humphrey Amendment of 1951.

DURHAM-HUMPHREY AMENDMENT OF The Durham-Humphrey Amendment

1951

of 1951

exempted

certain drugs from

the requirement that their labeling contain adequate directions for use. These

drugs, which could be taken safely only under medical supervision, were exempted provided they were sold pursuant to order of a licensed prescriber or administered under a prescriber's supervision. This amendment provided that

such an exempt drug, instead of adequate directions for use, must have on

its

Introduction and History

5 Notes

label prior to

dispensing the

words

or legend "Caution: Federal law prohibits dispensing

without a prescription." 21 U.S.C. 353

These words or legend became an eponym

for a

major drug

classification.

Legend drugs are drugs that bear the federal legend and are restricted to sale and use under medical supervision.

THALIDOMIDE DISASTER OF

1962

In 1962, thalidomide, a sleeping pill developed and widely used abroad, was being studied for use in the United States. William S. Merrell Company of Cincinnati was using the drug investigationally when it was discovered that the drug could harm a fetus when taken by a pregnant woman during the first trimester of pregnancy. Children born to such mothers often were born without arms or with other severe deformities. Fortunately, the number of infants injured by the drug in the United States remained very low. The press capitalized on the public's growing concern about a drug-dependent population. A woman who had taken the drug, which she had purchased during a trip abroad, during the first trimester of pregnancy sought a legal abortion. Upon being denied an abortion in one state, she left the country to obtain abortion rather than "give birth to a deformed child." The matter put the press at full cry, pulpits rocked, physicians dithered, lawyers became drug litigation experts overnight, and manufacturers consulted their insurance carriers. (See Taussig: A study of the outbreak of phocomelia. J. Am. Med. Assoc, 280:1106, 1962 and Lear: The unfinished story of thalidomide. SR/September 1, 1962:35. Whatever else may be said about the thalidomide disaster, drugs, all drugs, were publicly unfrocked. It was clear that people were taking drugs and neither the prescriber nor the manufacturer had a clear knowledge of their effects. Despite a massive publicity campaign designed to bolster public confidence, drugs never again received the universal public acceptance they had previously enjoyed. The Durham-Humphrey 1951 Amendment was simply inadequate to protect the public. A series of lawsuits demonstrated that by and large prescribers had been relying on manufacturers for their information about drugs, and that information in some instances had been based on inadequate testing and, in

one or two celebrated

was

cases,

on deliberate

the 1962 Kefauver-Harris

fectiveness

and

falsification

and deception. The

Amendments, which addressed

result

the issues of ef-

safety.

KEFAUVER-HARRIS AMENDMENTS OF

1962

These amendments, generally referred to as the drug efficacy amendments, were much broader in scope. They provided for registration of manufacturers and inspection of manufacturing sites, and they required an unprecedented program of accountability from manufacturers. in reality

1.

2.

Before marketing any new drug, manufacturers were required to supply: a) proof of effectiveness, and b) proof of safety.

Good Manufacturing

3.

Practices, the so-called

GMP, were

established,

and

manufacturer produced a drug without adhering to such practices, that drug was considered adulterated. Prescription drug advertising was placed under the supervision of the FDA, while the FTC continued to supervise the advertising of over-the-counter if

a

(OTC) items.

Food, Drug, and Cosmetic Act Notes a procedure for new drug applications and drug procedures which required assurances of the in-

The amendments established for investigational

formed consent of the research subjects and required reporting of adverse drug reactions. Qualifications of drug investigators were subjected to review.

MEDICAL DEVICE AMENDMENT OF

1976

had been subject to control only under misbranding sections of the Food, Drug, and Costhe general adulteration and subjected to extensive new requirements. In (FDCA), were Act of 1938 metic order to keep pace with a rapidly expanding medical and scientific technology, devices were classified, and subjected to varying degrees of control depending upon an evaluation of their function. For the first time, the safety and effectiveness of life-sustaining and life-supporting devices are now required to have pre-market approval of the FDA. In 1976, medical devices that previously

ORPHAN DRUG ACT OF

1983

New Drug Application procedures that were imposed upon manufacby the 1962 amendments require substantial evidence of both safety and effectiveness before a new drug can be marketed. The procedure is arduous, lengthy, and extremely expensive. The cost of the procedure deterred research and development of valuable new drugs whose efficacy was directed toward a disease that affected only a relatively small number of persons. Drug companies, it was argued, could hardly be expected to invest the millions of dollars and the years of research necessary to secure approval of the drug when the potential market doomed the financial future of the project. In order to provide incentives for manufacturers to meet this need, the Orphan Drug Act provides tax incentives and a limited exclusive license to manufacturers of drugs for rare diseases or conditions. A rare disease or condition is one that affects less than 200,000 persons in the United States or one that affects more than 200,000 persons in the United States and for which there is no reasonable expectation of recovering the development costs from the drug's sales in the United States. The

turers

21 U.S.C. 360(bb)

THE DRUG PRICE COMPETITION AND PATENT TERM RESTORATION ACT OF 1984 amendment is largely consumer oriented and designed to lower drug by providing a mechanism to increase competition in the drug industry. In general, the legislation provides for abbreviated New Drug Applications and an accelerated procedure for approval of generic versions of approved drugs whose patent protection is about to expire. The Act includes a provision that This

prices

restricts the

abbreviated application procedure to bioequivalent drugs

route of administration, dosage form or strength

drug.

Some

limited protection

plemental approved use.

is

is

whose

identical to the

approved

owner

for a sup-

afforded the original patent

Chapter

Z

DRUG, DEVICES,

AND COSMETICS

DRUG DEFINED The terms drug and counterfeit drug are defined by the Food, Drug, and Cosmetic Act as follows: (1) The term "drug" means (A) articles recognized in the official United States Pharmacopoeia, official Homoeopathic Pharmacopoeia of the United States, or official National Formulary, or any supplement to any of them; and (B) articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and (C) articles (other than food) intended to affect the structure or any function of the body of man or other animals; and (D) articles intended for use as a component of any article specified in clause (A), (B), or (C); but does not include devices or their components, parts, or accessories. (2) The term "counterfeit drug" means a drug which, or the container or labeling of which, without authorization, bears the trademark, trade name, or other identifying mark, imprint, or device, or any likeness thereof, of a drug manufacturer, processor, packer, or distributor other than the person or persons who in fact manufactured, processed, packed, or distributed such drug and which thereby falsely purports or is represented to be the product of, or to have been packed or distributed by, such other drug manufacturer, processor, packer, or distributor.

21 U.S.C. 321

Comment: The practice,

definition appears to be straightforward and unambiguous. In however, whether a substance falls within this definition is not always

readily apparent.

—

Take water, for instance plain old faucet water or backyard hose water. Is it drug? Technically, it appears to come within the scope of the literal definition of a drug it certainly affects the functions of the body and plays an important role in the "cure, mitigation, treatment, or prevention of disease in man." But is it a drug? The answer is maybe. Water, which is sold as "water," clearly is not a drug. The same water, however, sold as water but accompanied by a therapeutic claim is a drug. Suppose, for instance, pure water were bottled and labeled "Dr. Gibson's Crystal Remedy a

—

for Colds, Flu, as a drug,

and Ague." The

would bring

terms of the statute. The rule is that if it

an

be used as a drug,

therapeutic claim, the intent to market the substance

the substance within the definition

article is

it is

and

marketed as a drug, that

the product within the

is,

with the intent that

a drug. 21 C.F.R. 201.128

So pure honey for which the manufacturer claims therapeutic benefits, "starch because they are intended to affect digestion, and laetrile (ground up apricot kernels) sold to prevent cancer are obvious drugs. Some articles not

blockers"

Food, Drug, and Cosmetic Act

8 Notes

generally thought of as drugs have been held to be drugs because they are "used in the

treatment of disease in man," for example, antibiotic sensitivity disks.

ADULTERATION OF DRUGS AND DEVICES Appendix A presents selected sections of the FDCA.

Included in these selec-

amended, which should be consulted for precise language on adulterated drugs and devices. The following information relates to prescribing and dispensing drugs and is not intended to tions

is

a

copy of the exact

text of 21 U.S.C. 351, as

be a comprehensive review of the statute. Adulteration as distinct from misbranding is a relatively simple concept. The act prohibits from interstate commerce drugs and devices with impurities, poisons, and decomposed ingredients. The statute also recognizes that while the drug itself may be pure, it may still be adulterated within the meaning of the statute

if:

1.

It is

2.

It is

prepared, packed, or held under unsanitary conditions, or manufactured in a way that does not conform to good manufacturing

practices,

the so-called

GMP

standards fixed by the FDA. 21 C.F.R. 211.1-211.208

Comment: Why should this be? If the product is "pure," why should the FDA be able to prevent its movement in commerce? The answer lies in expediency rather than legal philosophy. Experience tells us that articles produced in a sloppy manner or contaminated environment will be adulterated more often than those produced in a sanitary facility adhering to GMP. It is unrealistic to require the FDA to check each article produced in a substandard facility until an impure product is produced before remedial sanctions can be imposed. The risk to public health from impure articles is greater than the financial hardship and the inconvenience suffered by a manufacturer who desires to produce a product under such conditions. The opposing argument is that GMP is nothing more than governmental connivance with large drug manufacturers who can afford the expense of compliance with such requirements to stifle competition by the little guys. After all, the argument goes, just because a teenager has a cut down, souped-up Chevy capable of doing 130 mph, it doesn't mean he's going to break the law. Does it?

A 3.

drug

is

also considered to be adulterated

The container

may

is

composed

if:

of a poisonous or deleterious substance that

leech into the contents.

6.

is an unsafe color additive. from an official compendial standard, that is, the United States Pharmacopeia, National Formulary, or Homeopathic Pharmocopeia of the United States, unless its variations are plainly stated on the label. It is either a new unsafe animal drug or an animal feed containing such a drug.

7.

It is

4.

It

contains or

5.

It

varies

a class

III

device without premarket approval or a banned device. 21 U.S.C. 351

OTC

drug and not packaged in tamper-resistant packaging. of OTC drugs that are accessible to the public while being held for retail sale are required to package such drugs (certain dermatologic preparations and dentifrices are excepted) in tamper-resistant packages. Such a package is described as one that has a barrier which, if broken, will give reasonable visual evidence of tampering. The barrier should be a distinctive seal that would be difficult to duplicate or counterfeit. The drug's labeling must carry 8.

It is

an

Comment: Manufacturers

Drug, Devices, and Cosmetics

9 Notes

prominent warning directing the purchaser's attention to evidence of possible tampering. The regulation provides that packages that do not conform to this standard are subject to seizure as adulterated or misbranded or both.

a

21 C.F.R. 211.132

MISBRANDED DRUGS AND DEVICES Included in Appendix A is an exact copy of the text of 21 U.S.C. 352, as amended, which should be consulted for the precise statutorv language on misbranded drugs and devices. Only selected portions of the statute are relevant to prescribing or dispensing practice, and the following is not intended to reflect the entire scope of the statute.

we have seen, is concerned with drugs and devices that enter form other than that intended by the manufacturer or distributor, that is, drugs and devices that are "impure." Misbranding, on the other hand, is concerned w'th the representations made by the manufacturer about the drug or device. Most of the adulteration and misbranding sections of the FDCA are directed primarily toward the manufacturer. It is not uncommon, however, for a pharmacy to manufacture drugs. The most common example is the sale of repackaged or compounded medications to other pharmacies. Under such circumstances, the pharmacist is acting as a manufacturer, and the misbranding and adulteration statutes apply equally to the pharmacist. Adulteration, as

commerce

in a

Policy of Full Disclosure

The

policy of the law

Of

disclosure.

about the qualities of an car,

one of full and complete and complete disclosure commerce, whether a drug, a horse, or a used

with respect

to misbranding is

course, a policy of requiring such

seems contrary

article in

full

to the principles of a mercantile society,

i.e.,

caveat emptor.

The imperative to recover acquisition or development costs and make a profit is the same whether one is selling a race horse, a used car, or a miracle drug. The seller is likely to depreciate or ignore a product's faults and emphasize its virtues. With respect to drugs and devices, the misbranding statute is designed to control these tendencies and curb the unbridled enthusiasm of the sellers and their advertising agencies.

Acts Constituting Misbranding

A

drug or device

is

misbranded

or labeling

1.

Its label

2.

Its label fails to state

is

if:

false or

misleading in any particular.

the name and place of business of the manufacturer, packer, or distributor and an accurate statement of quantity. 21 C.F.R. 201.1

3.

The

information required to be

on the

label

is

not prominently placed with

respect to other information. 21 C.F.R. 201.15

In other words, you can not put warnings in type that can be read only with a magnifying glass.

Comment:

4.

In the case of habit-forming substances the label does not bear the legend:

"Warning:

May

be habit forming." 21 U.S.C. 352(d)

10

Food, Drug, and Cosmetic Act

Notes 5.

In the case of prescription (or legend) drugs, the label

does not bear

the

generic "established name," or that of ingredients, in type not less than one-

brand name.

half the size of the trade or

21 U.S.C. 352(e) 21 C.F.R. 201.50 21 C.F.R. 299.3,

6.

The drug

is listed

an

in

official

compendium unless

it

is labeled

.4, .5

and packed by

compendial standards. 21 U.S.C. 352(g)

7.

The

package or the drug

imitative of

is

misleading in the

way

it is

filled

or formed or

is

another drug. 21 U.S.C. 352(i)

8.

The drug

is

subject to deterioration, unless

its

label bears appropriate pre-

cautionary statements. 21 U.S.C. 352(h)

9.

The drug or device by the labeling.

is health

endangering

if

used

in the

manner suggested 21 U.S.C. 352(j)

10.

The drug is composed of either insulin unless batch

or an antibiotic drug such as penicillin,

certified.

21 U.S.C. 352(1)

11.

The drug contains

and

a color additive

is

not labeled in accordance with

color additive requirements. 21 U.S.C. 352(m)

12.

The manufacturer was not registered with the FDA, and the drug was not

listed

as manufactured by the manufacturer. 21 U.S.C. 352(o)

Comment: Pharmacists who propose

FDA and

with the

file

a

list

of drugs

to engage in manufacturing must manufactured every six months.

register

21 U.S.C. 360(a)(g)(l) 21 C.F.R. 207.20

13.

The drug

is

subject to the Poison Prevention Packaging Act of 1970

and

is

not

packaged accordingly. 21 U.S.C. 352(p)

15 U.S.C. 1472, 1473

14.

In the case of a prescription drug or a restricted device, advertisements include the generic or established in

summary form

tiveness,

name

of the

drug and a

fail to

brief statement

of the side effects, warnings, contraindications, effec-

and quantitative formula.

Comment: The FTC and the FDA share responsibility for regulating drug advertising. The FTC regulates the advertising of OTC drugs, and the FDA controls advertising of prescription drugs and devices. The requirement for prescription drugs

is

that the advertisement

must contain

a fair balance of information;

i.e.,

Drug, Devices, and Cosmetics

11 Notes

its effectiveness must be fairly balanced with warnings. Use of selected articles from professional journals to substantiate a claim must be fair and based on substantial clinical evidence. The FTC in regulating ad-

information concerning

vertisements for OTC drugs is concerned with false advertisements or claims that mislead a person into buying the article. Deceptive trade practices, pricing, etc.,

are

15.

more common complaints before the FTC than

false therapeutic claims.

There are not adequate directions for use on its label and adequate warnings against use by children or in those conditions in which its use may be dangerous to health, or adequate warnings against unsafe dosage and

methods or duration of use. Comment: It is this requirement

that is the basis for the distinction between and prescription drugs and devices. The fundamental question is: Can adequate directions for use and warnings against use be written? As we have said earlier, some drugs simply are not safe to be taken without supervision. As a theoretical proposition, adequate directions and warnings probably could be written for all drugs. However, because the indications for use often depend on differential diagnosis, the directions would be so complex as to take up a whole volume. The alternative to providing such adequate directions and warnings is to provide an exemption for drugs which are sold and administered under medical supervision. There are two assumptions under the exemption. First,

OTC

the prescriber

company

is

familiar with the detailed information that

is

required to ac-

the drug, including indications, contraindications, warnings,

ommended

dosages and

is

satisfied the

drug

is

and

rec-

appropriate for the patient.

Second, the prescriber will communicate to the patient adequate directions for use as well as appropriate warnings if the medication is to be self-administered by the patient outside of the presence of the prescriber. These assumptions are based upon an ideal standard of practice. A review of recent drug injury litigation shows that these assumptions may be unrealistic in daily practice. 21 C.F.R. 201.50-.57

THE PRESCRIPTION DRUG EXEMPTION

A

drug intended for use by humans which is (a) habit-forming or (b) unsafe use except under the supervision of a practitioner licensed by law to administer such drug need not comply with those requirements of the misbranding statute that require all drug labels to contain adequate directions for use and warnings provided that at all times prior to dispensing its label bears the statefor

ment: "Caution: Federal law

prohibits dispensing without a prescription."

from access to the drug except upon order of the prescriber, the manufacturer is exempted from writing a label that would adequately and safely advise the general public in the use of the drug. This is not to suggest that the manufacturer is exempt from labeling the drug at all. The prescription drug exemption merely means that the manufacturer in labeling such a legend drug may assume a basic medical and scientific competency on

By

restricting the general public

The manufacturer's labeling of a prescription-only and alert a reasonably sophisticated and prudent inform to intended drug is and hazards of the drug. It is intended to enable the uses the as to prescriber prescriber to make a professional judgment with respect to the drug's use for a particular patient. To that end, the label on the manufacturer's container of a the part of the prescriber.

prescription-only drug

must

contain:

Food, Drug, and Cosmetic Act

12 Notes 1.

A

statement of the drug's identity in terms of quantity of each active ingredient.

its

established

name and

21 C.F.R. 201.50 21 C.F.R. 201.100(b)(4) 21 C.F.R. 201.10

2.

A

declaration of net quantity. 21 C.F.R. 201.51

3.

A

statement of the usual dosage. 21 C.F.R. 201.55

4.

The

federal caution legend. 21 C.F.R. 201.100(b)(1)

5.

The route

of administration

if it is

not for oral use. 21 C.F.R. 201.100(b)(3)

6.

If it is

a habit forming drug, the federal warning. 21 C.F.R. 201.100(b)(4)

7.

If

other than for oral use, the

are

made

for flavorings,

names

of

all

inactive ingredients

—exceptions

perfumes, and color additives. 21 C.F.R. 201.100(b)(5)

8.

An

identifying lot or control number. 21 C.F.R. 201.100(b)

9.

A statement directed to the pharmacist specifying the type of container be used in dispensing.

to

21 C.F.R. 201.100(7)

10.

The name and place

of business of the manufacturer, packer, or distributor. 21 U.S.C. 352(a)

11.

The expiration date unless exempted. 21 C.F.R. 201.17 21 C.F.R. 211.137

Some

exceptions are allowed with respect to the placement of the information; if the label is too small, some information may be included on the

for instance,

accompanies the drug. To repeat, the purpose of the labeling of a manufacturer's container is to inform and alert the prescriber and the dispensing pharmacist. It contains a summary of the essential information about the drug which is necessary for the prescriber and the dispenser to have in order to form a judgment about its safe and effective use (see Prescribing and Dispensing for an Unapproved Use, Chapter 2). labeling that

21 C.F.R. 201.56

Unless clearly inapplicable, 1.

Description.

2.

Clinical

3.

Indications

Pharmacology. and Usage.

the labeling

must contain the following information:

Drug, Devices, and Cosmetics

13 Notes

4.

Contraindications.

5.

Warnings.

6.

Precautions.

7.

Adverse Reactions. Drug Abuse and Dependence. Overdosage.

8.

9.

10.

How

11.

The date

supplied. of the

most recent revision

of the labeling. 21 C.F.R. 201.56

Who

determines what information shall be included on a drug's label or Who determines if adequate directions for use can be written or to

labeling?

restrict the

drug

to prescription-only sales?

proceedings through which it arrives New Drug Applications (NDAs).

The answer

is

the

FDA, and

at these regulatory decisions are

the

based on

Originally, as we have seen, the FDA exercised its regulatory authority over drugs by prohibiting commerce in adulterated and misbranded items. That power is still exercised and is not to be depreciated. It is now generally agreed that the power of the FDA to regulate which drugs can be commercially marketed in the United States by its control over the New Drug Applications is the most

formidable of

all its

regulatory authority.

NEW DRUGS Under the provisions of the FDCA, with very few exceptions, there are only two ways in which drugs can be sold lawfully in interstate commerce: 1) the drug must be one that was exempted from the operation of the act by the 1962 amendments, that is, the drug was generally recognized as safe and effective, or 2) the drug must be approved by the FDA under the New Drug Application procedures. Definitions

A

new drug

is

defined by the

FDCA

as:

(except a new animal drug or an animal feed bearing or containing animal drug) the composition of which is such that such drug is 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, except that such a drug not so recognized shall not be deemed to be a "new drug" if at any time prior to June 25, 1938, it was subject to the Food and Drugs Act of June 30, 1906, as amended, and if at such time its labelling contained the same representations concerning the "(1)

a

Any drug

new

use; or (except a new animal drug or an animal feed bearing or containing a new animal drug) the composition of which is such that such drug, as a result of investigations to determine its safety and effectiveness for use under such conditions, has become so recognized, but which has not, otherwise than in such investigations, been used to a material extent or for a material time under such conditions."

conditions of (2)

its

Any drug

21 U.S.C. 321

That a drug is new does not mean it is a heretofore unknown substance that has been discovered or that has been determined to possess heretofore unknown therapeutic qualities. A drug becomes a new drug and subject to the New Drug Application procedures when: 1.

A

substance that composes such a drug, whether an active substance,

carrier, or coating, is

new

for

drug use.

Food, Drug, and Cosmetic Act

14 Notes 2.

or more substances, neither of which is a new drug, are combined drug use. There is a change in the proportions of a combination of substances for drug use. A new use for a drug is claimed even though the drug is not new when used in the treatment of another disease, that is, an addition to the listed indications for drug use. A new dosage, method, or duration of application is recommended or

Two for

3.

4.

5.

suggested. 21 C.F.R. 310.3

the new drug procedures under a "grandamendments, provided the claims and representations made on its labeling remained the same. The above regulations are designed to subject to new drug procedures any drug, including previously exempted drugs unless they are exactly the same in chemistry, strength, route of administration, dosage and intended for the same patient population as their previously exempt status. In other words, "new versions" of exempt drugs must comply with new drug procedures.

Some drugs were exempted from

father clause" in the 1962

NEW DRUG PROCEDURES Notice of Claimed Investigational Exemption for a All

new drugs must

be approved by the

FDA as

New Drug

(IND)

being both safe and effective

before they can be imported, transported in interstate commerce, or cially

commer-

marketed.

Assume that a manufacturer has been conducting preclinical investigations and studies on laboratory animals from which he has concluded that drug X shows a high degree of promise in treating a specific disease. The studies indicate that it is reasonably safe to initiate clinical trials. The first step for the sponsor is to file a Notice of Claimed Investigational Exemption for a New Drug (IND) with the FDA. 21 C.F.R. 312

The following 21 C.F.R. 312.1, 1.

2. 3.

4.

5.

is

a

summary

of the contents of an

provides a detailed

list

IND. The regulation itself, and format of the notice.

of the contents

A description of the composition of the drug and methods of manufacture. A statement of methods of manufacture and quality control. A statement of all information derived from preclinical investigations including identification and qualifications of the investigators, and enough information to allow scientific review of the sponsor's conclusions. A statement about the drug's history, copies of information supplied to the investigator including all relevant hazards, the identities and experience of each clinical investigator.

An

outline of the proposed phases of the investigation

conducted

in three phases. In Phase

1

the drug

is

which

is

usually

just introduced in

man

amounts with the purpose of determining toxicity, safe dosage range, metabolism, absorption and elimination. Phase 2 covers initial trials on a limited number of persons for specific disease control or prophylaxis. Phase 3 covers the final testing of the drug for safety and effectiveness, and optimum dosage ranges on a large number of patients affected by the in small

disease or research subjects sought to be diagnosed or affected by the drug.

Drug, Devices, and Cosmetics

15 Notes

6.

7.

A statement identifying an institutional review board with continuing review authority over the investigation. An agreement by the sponsor to report any significant hazards, contraindications, side effects encountered, or adverse drug experiences during the investigation.

Clinical studies

on humans may not be commenced FDA.

until thirty

days

after the

date of the receipt of the notice by the

The purpose of the IND and procedure

a protocol

is

to alert the

FDA of the investigation, and to provide and protect The IND, it should be interpreted as an

to assure the quality of the investigation

the rights of the patients or other investigational subjects.

is a notice of investigation and is not to endorsement of the investigation by the FDA. The claimed exemption is an exemption from the labeling requirements of the FDCA. Shipments of drugs made pursuant to an IND carry the following legend:

be emphasized,

"Caution:

New

—Limited by

drug

federal law to investigational use." 21 C.F.R. 312.1(a)(1)

The sponsor agrees investigators to

to maintain

whom

adequate records reflecting the names of the

the drugs were shipped, the dates and quantities of

shipment. Confidential Data

The information contained in an IND could have enormous commercial value. Accordingly, the FDA agrees not to disclose it except that a person on whom such an investigational drug has been used, has the right to any adverse reaction report concerning such drug. 21 C.F.R. 312.5

Prescribing and Dispensing an Investigational

Drug

It is not uncommon for many independent investigators to be involved in the Phase 3 investigation. Obviously, only an investigator named in the protocol is

authorized to prescribe the investigational drug. Patients of clinical investigators involved in the research in addition to being required to sign an elaborate informed consent statement may be required to pay for the investigational drug. Investigational drugs are notoriously expensive. For that reason, many health plans, HMOs, and insurance carriers who otherwise cover prescription drugs as a plan benefit specifically exclude all investigational drugs. Prescribing practitioners

and dispensing pharmacists who

who

members

are participating in an investigation

would be wise to encourage each patient to review the schedule of benefits of their specific plan to determine if reimbursement will be made. involving patients

are

of such a plan

NEW DRUG APPLICATION Upon

IND

procedure, if the sponsor determines intended, the next step is to purpose that the drug is Application (NDA). It is this procedure that has New Drug FDA a file with the become the principal regulatory device for the control of drugs in the United successful completion of the safe

and

effective for the

States.

The

NDA

virtually

all

submitted by the drug's sponsor contains an exhaustive review of the information the sponsor possesses about the drug.

It

includes

16

Food, Drug, and Cosmetic Act

Notes

references to any

methods

INDs affecting the drug, evaluations of safety and effectiveness, lists of investigators and their full reports,

of manufacture, chemistry,

proposed labeling of the drug and proposed instructions such as limiting the drug to prescription sales only. The regulations specifying the requirements for an NDA cover several pages and should be consulted for specifics. 21 C.F.R. 314.1

Prior to

December, 1984, most drug studies that were part of

carried out in the United States.

One

of the effects of this policy

NDAs

was

were

to require

duplicate studies in this country of studies that had previously been conducted elsewhere. In 1985, the FDA adopted guidelines that will allow the incorporation of approved studies of international research to be included in IND/NDA pro-

cedures. This action should not be interpreted as a relaxation of investigative

standards, but rather as a refreshing relief from an excessively parochial tradition. 21 C.F.R. 312.20

When

the

NDA is complete,

supplemental information as

it

the

FDA

feels

reviews the application, requests such necessary, and if the application is drug will have the effect it purports or is

may be

supported by substantial evidence that the

represented to have under the conditions of use prescribed or suggested in the labeling,

approves the

NDA. 21 U.S.C. 355

Comment: Both

the prescribing practitioner and the dispensing pharmacist should be acutely aware of the emphasized language. The problem faced by the prescriber and the pharmacist is: May a prescriber prescribe an approved drug for a condition not listed in the labeling's indications, or in a dosage other than that recommended in the labeling? May a pharmacist dispense such a prescription? (see Prescribing and Dispensing for an Unapproved Use, Chapter 2).

Continuing Reports on Approved

NDAs

The approval of an NDA does not terminate the applicant's responsibility to maintain a system of records and to make periodic reports to the FDA respecting the drug. Because some drugs require use over a lifetime, the FDA has authority to require reports over a span of many years as a condition of an NDA approval. 21 C.F.R. 310.300 21 C.F.R. 310.303

More stringent regulations require reporting to the FDA within 15 days of information relating to an adverse drug experience such as any unexpected side effects, injury, toxicity, or any information that may be grounds to revoke or withdraw approval of the NDA. 21 C.F.R. 310.300

drug experiences was similarly exempt from reporting adverse drug experiences. Many of these exempt pre-1938 drugs are still commonly used in medical treatment such as epinephrine, morphine, and vitamins. In 1983, an exempt form of vitamin E was the suspected cause of the deaths of 30 premature infants. The FDA believes that had adverse drug reaction reporting been required of this product, it might have taken steps to warn the physicians treating these infants. In March, 1985, the FDA sought to Until very recently, this obligation to report adverse

tied to

NDAs. Exempt drugs under

the 1962

amendments were

Drug, Devices, and Cosmetics

17 Notes

remedy

by adopting a regulation subjecting all prescription-only adverse drug experience reporting requirements even though be otherwise exempt from regulation.

this situation

manufacturers the drug

may

to

PRESCRIBING THE LEGEND DRUG Authority to Prescribe Habit-forming drugs and drugs bearing the federal caution legend may be prescribed only by a practitioner licensed to administer such drug.

Comment: The

federal

government does not

license practitioners to administer

or prescribe legend drugs. State law fixes the terms

and

fixes the

and conditions

for licensure

scope of the authorized practice.

Scope of Authorized Practice "Scope of authorized practice" is a relatively simple concept. For instance, a is authorized by the state to treat oral disease and perform dental surgery and in connection therewith to administer anesthetics. So it is within the scope of authorized practice for a dentist to diagnose and treat an aching

licensed dentist

beyond the

tooth but, obviously,

dentist's scope of authorized practice to di-

agnose and treat a stomachache. Included within the authority

to diagnose and treat usually is the authority administer and prescribe drugs. Just as it would be beyond the scope of authorized practice for a dentist to, say, diagnose stomach pains as acute appendicitis and perform an appendectomy, so it is beyond the dentist's scope of authorized practice to prescribe drugs for a stomachache. to

is less clearly defined when it comes to extremely unlikely that a hospital would permit a dentist to perform an appendectomy in its operating theater. Because there are virtually no limitations on the types of drugs a dentist may prescribe, and because the act of prescribing is performed in private, and because diagnosis is rarely if ever included on a prescription, whether a prescriber is acting within the scope of authorized practice in writing a prescription may be impossible for a dispensing pharmacist to determine (see Purpose of Issue, Chapter 8).

The scope

of authorized practice

prescribing drugs.

New

It is

Classes of Prescribers

The problem has

recently

become magnified

as

more and more

states

extend

prescribing authority to health professionals in disciplines that traditionally have not exercised prescribing privileges. Traditionally, prescribing practitioners have

been: physicians and surgeons, doctors of osteopathy, doctors of doctors of podiatry, and doctors of veterinary medicine. Some tended the authority to practitioners of chiropractic, who are scribing only certain restricted devices. More recently, eighteen

dental surgery, states

have ex-

limited to pre-

states have extended drug-prescribing authority to physician assistants and registered nurse practitioners, while two states allow pharmacists limited prescribing authority. Three states allow unrestricted prescribing by qualified nurse practitioners. Others restrict the prescribing authority to specific drugs or to a protocol or require

a physician's supervision.

Out-of-State Prescribers

The confusion that arises from this delegation of prescribing authority is compounded in those states that allow a pharmacist to fill a prescription written by an out-of-state

prescriber. The

FDCA

does not require the prescriber to be licensed in

Food, Drug, and Cosmetic Act

18 Notes

where the prescription is filled, provided the prescription was valid where written (see Diagnosis by Mail, Mail Order Prescriptions, in this chapter). Many states, however, prohibit filling prescriptions written by out-of-state prescribers, arthe state

to be "legal" must be written by a licensed prescriber is one licensed by the state where the licensed only prescriber, the prescription is filled. Other states allow pharmacists to fill prescriptions written by out-of-state prescribers only on an emergency basis, or they restrict the type of drugs that may be dispensed pursuant to such a prescription. In each instance, state law must be reviewed to determine the validity of such a prescription.

guing that because a prescription

Authority to Transmit Prescriptions

—

FDCA

does not deal directly with the problem of transmission whether a authorize an employee, say, a receptionist or office nurse, to communicate an oral prescription to a pharmacist. Based on the stricter rules relating to prescriptions for controlled substances which allow such a procedure (see Authority of Office Nurses, Secretaries, and Receptionists, Chapter 8), it would seem fair to say that while a receptionist or office nurse cannot initiate a prescription or authorize a refill, such an employee may transmit the prescriber's

The

practitioner

may

prescription or authorization.

Formalities of a Prescription

The FDCA does not deal with the format or the formalities of a prescription except to provide that when a prescription or authorization for a refill is transmitted orally to a dispenser, the pharmacist must promptly reduce the prescription or refill

authorization to writing and

file

it.

21 U.S.C. 353(b)

PRESCRIBING AND DISPENSING FOR AN UNAPPROVED USE It can now be taken as settled that a prescriber may prescribe an approved drug for an unapproved use or in a dosage not recommended by the labeling and a pharmacist may dispense such a prescription without violating federal law.

U.S.

FDA

v.

Evers, 643 F.2d 1043 (1981)

Policy Statement, 37 Fed. Reg. 16503

Why, then, all the fuss? Why are we so concerned about labels and labeling and whether the recommended dosages are safe and effective for the indicated use? If prescribers can prescribe and pharmacists dispense without regard to the drug's labeling, are not the NDA procedures an exercise in futility much like pounding sand down a gopher hole? The answer is an emphatic no. From its inception, the FDCA was never intended by the Congress to be a medical practice act. The legislative history is very clear that the act was not intended to limit a physician's

ability to treat his patient. S.

Rep. No. 361, 74th Cong. 1st Sess. (1935)

S.

Rep. No. 646, 74th Cong. 1st Sess. (1935) 79th Cong. Rec. 8351 (1935)

The FDCA regulates the manufacturing and distribution of drugs in interstate commerce which includes the labels and the labeling that accompany those drugs across state lines. It is generally agreed that the FDA's requirements that such drugs be free from contamination, adulteration, and misbranding as well as

19

Drug, Devices, and Cosmetics

Notes

being safe and effective for their intended use are in the public interest in such commerce. Those requirements, however, are entirely different from ones that would require a physician treating his patient with drugs to use only certain drugs in predetermined amounts. This is how a federal court explained the intent of Congress: "The better explanation for the practice of medicine exemption is that Congress did not want to interfere with physician's treatment of their patients. New uses for drugs are often discovered after the FDA approves the package insert that explains 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."

Chaney

The use

is

v.

Heckler, 718 F.

prescribing, administering, or dispensing of a

not

(Pitressin,

uncommon. Take

Vasopressin injection, U.S. P.)

is

an unapproved of the drug ampules for injection.

drug

vasopressin, for instance.

supplied in

2d 1174 (1983)

for

One form

The drug is indicated by its labeling "for prevention and treatment of postoperative abdominal distention, in abdominal roentgenography to dispel interfering gas shadows, and in diabetes insipidus." The FDA approved route of admin"subcutaneously or intramuscularly" nonetheless a common occurrence for a gastroenterologist to administer this drug intravenously to arrest gastric bleeding, an unapproved use through an unapproved route. It is a common occurrence for a hospital pharmacist to dispense this drug knowing it is to be used in an unapproved manner for an unapproved indication. Neither the gastroenterologist nor the dispensing pharmacist in the above situation have violated federal law. The FDA recognizes that there may be acceptable usage of a drug, other than that described in the official information contained in the labeling, such as articles in medical journals. However, this apparent ambivalence should not be interpreted as a retreat by the FDA. The agency has made it quite clear that it will not tolerate manufacturers sponsoring an informal whispering campaign sugistration is It is

gesting additional unapproved uses.

"Where a manufacturer or his representatives or any person in the chain of distribution does anything that directly or indirectly suggest to the physician or the patient that an approved drug may properly be used for unapproved uses for which it is neither labeled nor advertised, that action constitutes a direct violation of the Act and is punishable accordingly."

FDA

Policy Statement

37 Fed. Reg. 16504

Directing an Unapproved Use as Negligence a serious mistake for a prescriber or pharmacist to ignore the information contained on the drug's label or labeling. While prescribing and dispensing for an unapproved use does not violate federal law, the practice is a departure from the standards of safety and effectiveness fixed by the FDA. If a patient is injured as a result of the therapy, the departure from the official standards of safe and effective drug use has been held to be prima facie evidence It

would be

official

of negligence. {Mulder

v.

Parke-Davis

variation or insignificant departure sional

judgment poses

little

&

Co., 181

from the

N.W. 2nd 882

official

(1970)).

A

slight

standards based on profes-

therapeutic or legal threat.

As

the significance of

the departure increases so too does the therapeutic and legal risk. Conservative practice would dictate that a significant departure from the labeling, which may

involve serious risk to the patient, should be fully and fairly explained to the

Food, Drug, and Cosmetic Act

20 Notes

and documented with an informed consent form. Some law firms suggest that clients file an IND for any significant departures. Many major drug manufacturers have furnished prescribers and pharmacists alike with letters of indemnity undertaking to defend against and pay any claims patient

A careful reading of these letters limits approved use of the drug. Failure to the manufacturer to the liability of the departing from the recommended significantly labeling by the drug's adhere to prolonged therapy may serve to tests during recommended ignoring uses or liability. manufacturer from the insulate Community pharmacists as distinct from hospital pharmacists usually do not have access to diagnosis. In such a case, the community pharmacist would not be negligent in dispensing a drug for an unknown unapproved use. If, however, the prescribed dosage represented a substantial deviation from the recommended dosage, conservative practice would dictate that the pharmacist query

resulting from the use of their drugs.

the prescriber.

DISPENSING THE LEGEND DRUG Unless exempted by the following language, drugs dispensed pursuant to a must carry all of the information required for all drugs including adequate directions for use. prescription

"Any drug dispensed by

or refilling a written or oral prescription of a pracsuch drug shall be exempt from the requirements of section 502 (21 U.S.C. 352), except paragraphs (a), (i)(2) and (3), (k) and (1) and the packaging requirements of paragraphs (g), (h) and (p), if the drug bears a label containing the name and the address of the dispenser, serial number and date of the prescription or of its filling, the name of the prescriber, and if stated in the prescription, the name of the patient, and the directions for use and cautionary statements, if any, contained in such prescription. This exemption shall not apply to any drug dispensed in the course of the conduct of a business of dispensing drugs pursuant to diagnosis by mail, or to a drug dispensed in violation of paragraph (1) of this subsection." titioner licensed

by law

filling

to administer

21 U.S.C. 353(b)(2)

Comment: As

a practical matter, the above language exempts virtually all drugs dispensed by a pharmacy pursuant to a prescription. The exceptions to the exemption, those drugs which must comply with all the requirements of 21 U.S.C. 352, deserve some passing comment. First, neither the drug nor the consumer container dispensed by the pharmacist can itself be labeled in a false or misleading manner, nor may the drug be imitative of another drug. Second, if the dispensed drug is or contains insulin or an antibiotic it must come from a batch certified source. Third, the pharmacist must dispense the drug in accordance with compendial standards and the Poison Prevention Packaging Act (see Poison Prevention Packaging Act, in this chapter). These are all pretty straightforward requirements which are routinely followed by a pharmacist. If a pharmacist failed to comply with these requirements, the drug would have to be labeled as any nonprescription drug, that is, the manufacturer's name and address and all the labeling requirements of 21 U.S.C. 352, including adequate directions for use in terms designed to be understood by

the general public.

Diagnosis by Mail, Mail Order Prescriptions

Although the

FDCA

and the

FDA deny

the intention to regulate the practice

of medicine, the section specifically excepts drugs dispensed pursuant to a busi-

ness of dispensing drugs pursuant to diagnosis by mail. Although as a theoretical

Drug, Devices, and Cosmetics

21 Notes

made through an exchange of correspondence just as adequate directions for use could probably be written for any drug, the business of diagnosis mail is perceived as providing too fertile a field for quackery and charlatans to allow drugs dispensed pursuant to such a business an exemption from 21 U.S.C. 352. Notice, however, that the prescriber need not be licensed to administer the drug where the drug is dispensed or where the patient resides. All that the statute requires is that the prescriber be licensed to administer the drug. Accordingly, drugs dispensed pursuant to a mail-order prescription are entitled to this prescription drug exemption provided only the prescription was not issued in furtherance of a diagnosis by mail business. proposition a reasonably accurate diagnosis could probably be

Dispensing Prescribers Lastly, the terms of the statute

do not

specifically exclude prescribers

furnish their patients with drugs. This omission has been seized

who

who

upon by those

perceive great danger in the growing practice of prescribers to dispense

They argue that the drugs furnished by a prescriber should be subject to the same restrictions and formalities as those dispensed by a pharmacist pursuant to a prescription. The opposing argument is that the statute is addressed to filling an oral or written prescription, and a prescriber is not filling a prescription but furnishing his patient with drugs. The matter has been settled by the FDA who, while holding the section applicable to physicians, have exempted prescribers "from strict compliance with the labeling requirements of 21 U.S.C. 353(b)(2) ." directly to their patients.

Letter of A. Lavender, Chief

Drug Compliance Branch FDA, Bureau of Drugs, Nov. 15, 1979

Prescription

And,

of course,

an agency statement has the

legal effect of a rule.

5 U.S.C. 551(4)

Comment: As more and more individual practitioners supplement their services and income by dispensing their own drugs, organized pharmacists have become concerned and carried their concern to state legislatures. By and large state legislators have been sympathetic to the problem, and have demonstrated their concern by enacting state labeling laws that are not only more onerous but subject to more vigorous enforcement. The theory being, one supposes, that if labeling becomes administratively troublesome, practitioners will abandon it. That theory may have had some validity in precomputer days. Now, as each new labeling requirement requires only a slight program modification, one wonders if the web is not too complex, even for the spider. Labeling Requirements

Thus, according to the section just quoted, the label of a medication container dispensed pursuant to a prescription must contain: 1.

Name and

2.

Serial

address of dispenser (pharmacy)

number

3.

Date of prescription or

4.

Name

The 5.

label

Name

filling

of prescriber

must

also include the following

of patient

if

they are stated

in the prescription:

22

Food, Drug, and Cosmetic Act

Notes 6. 7.

Directions for use Cautionary statements

Comment: The relative paucity ment to comply with the statute

by the federal governmost pharmacists and prescribers. Although most states have supplemented these requirements, the answer to why the federal government has so few requirements probably lies in the hisstartling to

intrude into the physician-patient relationship.

torical reluctance to

Most

of information required

is

of the information required

on the

considerable confusion about dating the

label is self-explanatory,

label.

but there

is

In order not to be misbranded, the

must contain either the date of the prescription or the date of Presumably the date of filling means the date of refilling refilled pursuant to an authorization of the prescribes

label of the container

filling, i.e., dispensing. if

the prescription

A

is

prescription for a schedule

III

controlled substance can be refilled

if

au-

thorized by the prescriber within certain limitations. Such a refilled prescription

must bear on its label the date of original filling. Thus such a prescription label, unless it bore two dates the date of original filling and either the date the prescription was issued or the date the container was filled would violate either the Controlled Substance Act or the FDCA (see Labeling the Container of Prescription Medication, Chapter 8). The idea of a prescription bearing two dates is, of course, ludicrous. The purpose of such a rule simply is to ease the burden of the inspectors by transferring it to a phar-

—

—

macist.

Patient Information

—Directions for Use

Except for certain drugs, estrogens, progestational drug products, oral and do not require the prescription containers's label or labeling to contain either directions for use or cautionary injectable contraceptives, the federal regulations

The justification for this, as we said earlier, is the assumption that the patient receives adequate directions for use and relevant warnings and prestatements.

cautions from the prescriber. Experience has

may be

unrealistic.

If

the patient

is

shown

taking an

that such

OTC

an assumption

preparation, the patient

receives adequate directions for use as part of the drug's labeling. But,

if the taking a prescribed medication, a far more potent drug which by definition is unsafe, the patient may lawfully receive nothing at all. In the 1960s the introduction of oral contraceptives caused the FDA to seek

patient

to

is

remedy

this

anomaly. Faced with an estimated 11 million healthy American

women taking a potent drug for a purpose other than the treatment of an illness, injury, or disease, the FDA adopted regulations requiring manufacturers to furnish dispensers with patient labeling, a printed informational brochure about the drug. Dispensers in turn are required to furnish the material to the patient. The text of the regulation is set forth in Appendix C. 21 C.F.R. 310.510

In general, the brochure describes the uses

and

limitations of the drug,

potential for injury of the fetus in the event the recipient

adverse

effects, contraindications,

is

its

pregnant, possible

and precautions.

Patient labeling or a patient information procedure

is

required to be dispensed

with the following prescription drugs: 1.

Oral contraceptives 21 C.F.R. 310.501(a)

2.

Oral postcoital contraceptives (Diethystilbestrol) 21 C.F.R. 310.501(b)

Drug, Devices, and Cosmetics

23 Notes

3.

Injectable contraceptives (Medroxyprogesterone acetate) 21 C.F.R. 310.501a

4.

Estrogens 21 C.F.R. 310.515

5.

Progestational drug products 21 C.F.R. 310.516

who "express interest in IUDs," intrauterine devices for contraception be provided with an informational brochure.

Patients shall

21 C.F.R. 310.502(2)(b)(2)

In each case the required labeling

penser. Prescribers

is

furnished by the manufacturer to the dis-

who dispense these drugs and devices are required to provide

The patient labeling is required to be dispensed in each package dispensed. If the patient is in a hospital, then prior to the administration of the first dose and at least once every thirty days therafter. the patient with the printed information.

21 C.F.R. 310.501(a)

Appendix C

Comment: The program was enthusiastically accepted by consumers while ensomewhat more reserved response from manufacturers. The program's success encouraged those who wished to see more patient information available for all drugs. A move to include patient package inserts (PPIs) on a broad range of drugs was defeated in what may have been a patrol skirmish. Withholding

joying a

drug information from the patient manently defensible position. Cautionary Statements

for

whatever reason

is

unlikely to be a per-

— Foreign Languages

As we shall see (see Labeling the Medication Container, Chapter 8) when the drug dispensed is a schedule II, III or IV controlled substance, the prescription container dispensed to the patient must contain the following warning: "Caution: Federal law prohibits the transfer of this drug to any person other than the patient for

whom

it

was prescribed." 21 C.F.R. 290.5

Although the regulations provide that any words or statements that are required by the act to appear on a label or on a drug's labeling shall be in English, the regulations also provide for approved Spanish translations. 21 C.F.R. 201.15(3)(c)

21 C.F.R. 290.6

In addition, the regulations provide for official versions of Spanish translations for the federal caution

legend and the warning given for

all

habit-forming drugs. 21 C.F.R. 201.16

The use of the Spanish translation is approved for labels and labeling of drugs and cosmetics packed for distribution solely in Puerto Rico. If the label or labeling of a drug or cosmetic contains any representation in a foreign language then all the information required by law label

and

to

appear on the

label or labeling

must

also appear

on the

labeling in the foreign language. 21 C.F.R. 701.2(b)(l)(2)(3)

21 C.F.R. 201.15(c)

24

Food, Drug, and Cosmetic Act

Notes

Comment: By and

large, pharmacists and prescribers have paid scant attention language regulations. The present federal law provides that the labels and cautionary statements shall be in English if dispensed in the United States. If a pharmacist or a dispensing prescriber knows that the patient speaks and reads only Spanish (or any other language) and yet provides the patient with warnings and vital drug information only in English, the dispenser has to these foreign

not violated federal law.

It is

a repetition of the situation that arises

prescriber prescribes a drug for an

unapproved use

when

a

in treatment of a patient.

That the federal law has not been violated is not to suggest that the dispenser has not been negligent. Large segments of the population are non-English speaking. Providing these patients and consumers with vital information about the drugs and cosmetics they use is a challenge to the professions and industry that serve them. Relief for the injured provided by the law of negligence and professional malpractice is an expensive, unequal, and essentially unjust alternative to an articulated policy of self-regulation which, after all, distinguishes a profession from a trade. Prescription

Drug Advertising

FDA has promulgated a comprehensive regulatory scheme for prescripdrug advertising. In general, advertisements must contain in fairly balanced fashion all the material that is required to be included on the drug's label or labeling. Advertisements on radio or television must include major side effects The

tion

and contraindications or include proved package labeling

in

a provision for the dissemination of the apconnection with the broadcast. 21 C.F.R. 202.1

Comment: The

latter requirement can only be interpreted to be the regulatory equivalent of an ice cold shower to cool the ardor of an enthusiastic advertising

agency. is an exempt form of prescription drug advertiswas designed to accommodate consumer groups interested in price competition. Reminder advertisements are intended to provide consumers with the price charged for a prescription including all charges to the consumer except mailing and delivery fees which may be separately stated. Such advertisements may contain no representations of a drug's safety or recommended use. Reminder advertisements that comply with the regulation need not include the

So-called reminder advertising

ing that

drug's label or labeling information required of other drug advertisements. 21 C.F.R. 200.200

Packaging the Drug

The container and packaging of a drug dispensed pursuant to prescription must, of course, meet compendial standards. The type of container to be used for dispensing is described in the product's "labeling" (see Exemptions from Labeling Requirements Schedule II, Chapter 8).

—

21 C.F.R. 201.100(7)

Poison Prevention Packaging Act

The

Poison Prevention Packaging Act, 15 U.S.C. 1471 provides that

and

all

controlled

with the following exceptions are subject to special packaging requirements. "Special packaging" means a container designed or constructed to be significantly difficult for children under five years

substance drugs

all

prescription drugs

25

Drug, Devices, and Cosmetics

Notes of age to open. For the pharmacist,

it

means dispensing

the drug in a

child

proof container. 16C.F.R. 1700.14

Exceptions

Those drugs that are excepted and that packaging are: 1.

2.

may

be dispensed without special

Sublingual doses of nitroglycerin. Sublingual and chewable forms of isosorbidc dinitrate in dosage forms containing 10 or less. Erythromycin ethylsuccinate granules for oral suspension and oral sus-

mm

3.

7.

pensions in packages containing not more than 8 g of erythromycin. Anhydrous cholestyramine in powder form. All unit dose forms of potassium supplements. Sodium fluoride drug preparations containing less than 264 mg of sodium fluoride per package. Betamethasone tablets containing in the package less than 12.6 mg of the

8.

Pancrelipase preparations.

9.

Prednisone in tablet form

4. 5. 6.

drug.

10.

when dispensed

than 105 mg of the drug. Mebendazole in tablet form

in

in

packages containing not more

packages containing not more than 600

mg

of the drug. 11.

Methylprednisolone in tablet form in packages containing not

mg 12.

more than 84

of the drug.

Colestipol in

powder form

in

packages containing not more than 5 g of the

drug. 13.

Erythromycin ethylsuccinate in tablet form in packages containing no

more

than 16 g of erythromycin. 21 C.F.R. 1700.14

Drugs dispensed

to inpatients in hospitals

quirements. Manufacturers

may

are

exempt from

special packaging re-

distribute prescription drugs in "stock bottles" without

intended that the pharmacist repackage the drug the manufacturer distributes a prescription containers designed to be dispensed in that consumer pharmacies in drug to container with only the addition of a label, then the manufacturer's container must conform to the special packaging requirements. special packaging provided

prior to dispensing.

it is

When, however,

21 C.F.R. 1701.1

Prescription drugs that are subject to special packaging may be dispensed in a if (a) the prescriber authorizes such a con-

plain or non-child-resistant container

tainer, or (b) the patient requests that the

medication be dispensed in a nonchild-

resistant container. 15 U.S.C. 1473(b)

Comment: The purpose

of these exceptions

able to the elderly or handicapped.

and faced by the pharmacist

is

is

to

make medications

easily avail-

The problem created by these exceptions

establishing that the patient did indeed order

the medication in a conventional container. The issue arises only when a child has been poisoned. Did the grandmother really order the medication in such a

container? Accurate recollections of such technicalities are hard to establish.

A

26

Food, Drug, and Cosmetic Act

Notes careful pharmacist will preserve a written record of

such a request.

Many

phar-

macists require the patient to sign an authorization for dispensing in a noncon-

forming package. Drugs furnished to a patient directly by the prescriber are not exempt from the operation of the Poison Prevention Packaging Act. However, as a practical matter, since such a drug may be dispensed in a plain container if the prescriber "authorizes such a container," if the prescriber delivers the medication to the patient in a non-child-proof container, one can assume he has "authorized" such a container and thus is complying with the act. As a result, no prescriber has been charged with violating the act for failing to furnish such drugs in a childproof container. However, the story may not end there. While a prescriber may have a technical defense to an alleged violation of the act, the decision to deliver drugs to a patient in a plain container when the prescriber knows the patient resides with very young children may be negligent and may subject the prescriber to liability if a child is poisoned. Accordingly, conservative practice dictates that a prescriber use restraint and careful judgment in ordering medication dispensed in a non-child-proof container and take special care to determine that medication that the prescriber furnishes directly to the patient is appropriately packaged.

Household Substances Subject

Among

to the

Act

and acetaminophen, drug and unflavored aspirin or acetaminophen containing preparations in powder form providing not more than 13 g of the drug per unit dose. Manufacturers are allowed one household substances subject

to the act are aspirin

excluding effervescent tablets containing less than

exception.

Noncomplying packaging

is

10%

of the

allowed for one single size of packaging, e.g., the nonconforming package contains the fol-

100-tablet size container, provided the

PACKAGE FOR HOUSEHOLDS WITHOUT YOUNG CHILDREN," or, if space does not permit the above legend, "PACKAGE NOT CHILD-RESISTANT." lowing legend in bold characters: "THIS

Other products subject to the act are: furniture polish, sodium and/or potassium hydroxide, turpentine, kindling or illuminating preparations, methyl alcohol, sulfuric acid, ethylene glycol, paint solvents, iron-containing drugs, and dietary supplements.

Mailing the Prescription Drug

Most drugs dispensed pursuant to a prescription can be mailed to the patient. The U.S. Postal Service prohibits mailing of narcotic drugs to patients except to certain veterans

from V.A. hospitals.

Labeling the Container for Mailing

United States Postal Service regulations require the label of the medication list the name and address of the patient and the name and address of the prescriber, which, of course, is a significant addition to the labeling requirements of the FDA. Postal regulations govern only materials in U.S. mail. Private alternative delivery systems are not governed by such regulations. container to

39 C.F.R. 1245

Domestic Mail Manual, 124.364-5

Packaging for Mailing

When the prescription contains nonnarcotic controlled substances, the outer mailing wrapper must be plain and must not indicate contents. The medication container must be securely sealed.

Drug, Devices, and Cosmetics

27 Notes

Mailing Drugs between Dealers

The same regulations do not apply

to mailings between persons authorized legend drugs. Controlled substances (narcotic and nonnarcotic) may be mailed between persons holding Drug Enforcement Agency (DEA) registrations or persons exempt from registration. Postal regulations provide that when controlled substances are mailed between registrants generally, they must be sent by registered mail with a return receipt requested. The sender registrant's DEA number must be used as part of the address. to deal in

THE PHARMACY AS DRUG MANUFACTURER To the extent that a pharmacist compounds, prepares, and packages or repackages medications, he performs the same tasks as a manufacturer. The FDCA requires that every manufacturer register with the FDA upon commencing activity as a manufacturer and thereafter submit annually a list of drugs or devices manufactured, submit to a biennial inspection, and adhere to an elaborate set of regulations designed to insure compliance with current good manufacturing practices.

21 U.S.C. 360 21 C.F.R. 207.20

Pharmacies are exempt from compliance with the regulations affecting facturers provided their practice

upon

or devices

is

restricted to dispensing prescription

prescription of licensed prescribers

manudrugs

and provided they do not

manufacture, prepare propagate compound or process drugs or devices other than in the regular course of their business of dispensing or selling drugs or devices at

retail.

21 U.S.C. 360(g)

Bulk compounding apparently are dispensed at retail

falls within this exemption provided the drugs by the compounding pharmacy and not sold to other

pharmacies. 21 C.F.R. 207.10(a)

DEVICES Definition

The term

device

means:

an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is:

1.

2.

3.

Recognized in the official National Formulary, or the United States Pharmacopeia, or any supplement to them, Intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or Intended to affect the structure or any function of the body of man or other animals, and which does not achieve any of its principal intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its principal intended pur-

poses. 21 U.S.C. 321(h)

28

Food, Drug, and Cosmetic Act

Notes

Before 1976, the adulteration and misbranding sections of the FDCA were applicable to devices. The law was considered inadequate because it did not

provide for premarket testing or provide standards of performance. The Medical Device Amendments of 1976 broadened the definition of devices, including within their scope in vitro reagents, and clarified the distinction between drugs and devices. Classification of Devices

to

The 1976 amendments established a panel determine which devices should be subject

of experts to review devices to

more

and

stringent controls. There

are three classifications of devices: 1.

Class

I

covers those devices that have relatively low potential for causing for which specific performance standards and premarket testing

harm and

are not considered necessary. These devices are subject only to general

Examples of

controls.

class

I

devices are scissors, forceps, hemostats, and

needles. 21 C.F.R. 860.3(c)(1)

2.

Class

II

covers those devices for which, in order to assure their safety and

effectiveness, specific performance standards are fixed by the panel of experts. Examples of class II devices are hearing aids, sun lamps, tampons, ther-

mometers, and catheters. 21 C.F.R. 860.3(c)(2)

3.

covers devices that are usually life-supporting systems and whose might cause death or serious injury. These devices are subject to premarket testing and to review for safety and effectiveness of construction, testing, labeling, or directions for safe use. Examples of Class III devices are: contact lenses, indwelling neuromuscular stimulators.

Class

III

failure

21 C.F.R. 860.3(c)(3) 21 U.S.C. 360(c)

Safety and Effectiveness of Devices

To determine whether a device

is

"safe

and

effective," qualified experts

must

consider: 1.

2. 3.

The persons for whom the device is intended. The conditions of use described in the label. The probable benefit to health balanced against any

potential risk. 21 C.F.R. 860.7

The device must also have the effect it is represented to have under the conditions of use described in

its label.

21 U.S.C. 360(c)

Classification Procedures

The FDCA provides an elaborate procedure for the classification of devices intended for human use. Basically, all devices are classified as class III devices, and then, through a procedure that is initiated by the manufacturer or importer of the device, they may be reclassified as class I or II. For instance, if a new device is substantially equivalent to a device already in class II, and complies

29

Drug, Devices, and Cosmetics

Notes

with the specific performance standards of that class, it may be exempt from the premarket testing required for class III devices. Applications for premarket approval of class III devices require detailed reports from the manufacturer concerning:

3.

and effectiveness. on components and the principle of operation Description of manufacturing process and controls.

4.

Identification of

1.

Investigations for safety

2.

Full reports

5. 6.

performance standards Samples of the device. Samples of the proposed labeling.

of the device.

for the device.

21 U.S.C. 360(e)(c) 21 C.F.R. 860.l-860.13b

Restricted Devices

Like prescription drugs, devices because of their potentially harmful effects be restricted to sale only upon the written or oral order of a practitioner licensed to

may

administer such a device. 21 U.S.C. 360(j)(e)

Comments: The pharmacist should be

may authorize

especially

a chiropractor to prescribe devices

aware of any

although he

is

state

laws that

prohibited from

prescribing drugs.

COSMETICS Definitions (i) The term "cosmetic" means (1) articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance, and (2) articles intended for use as a component of any such articles; except that such term shall not include soap. There are no classes of cosmetics and, a cosmetic manufacturer may market a product as a cosmetic without FDA approval. However, if a cosmetic manufacturer makes a

therapeutic claim for his product (prevent skin cancer and sunburn) or the product is intended to treat or prevent disease (prevent cavities with fluoride dentifrice) or otherwise affect the structure of the body (deter aging with hormone cream) the product is also a drug and subject to the rules respecting safety and efficacy that apply to all

drug manufacturers. Registration of Cosmetic Manufacturers

Cosmetic manufacturers are requested by the of voluntary registration

and voluntary

filing of

FDA

to participate in a

system

product ingredients. 21 C.F.R. 710.1, 720.1

Pharmacies that compound cosmetics, well as physicians, hospitals

retailing them from a single site, as and clinics, are excluded from the request to register. 21 C.F.R. 710.9

Cosmetic Labeling Cosmetics,

like

drugs, are subject to specific labeling requirements. The

fol-

lowing mandatory information must appear on the principal display panel of each cosmetic package:

30

Food, Drug, and Cosmetic Act

Notes 1.

A

statement of the identity or usual name of the cosmetic. of business of the manufacturer, distributor, or packer.

3.

The name and place The net quantity of

4.

An

2.

contents.

ingredient declaration in descending order of predominance. 21 C.F.R. 701.3, 11, 12

and 13

Some cosmetics require specific warnings. For instance, cosmetics in selfpressurized containers must warn against spraying in eyes, and bubble bath preparations must carry warnings of the hazards of excessive use. 21 C.F.R. 740.11, 17

There are elaborate regulations directing the placement of the mandatory label. The purpose of such regulations is to ensure that the information is most likely to be seen by the consumer under ordinary information on the conditions of

retail sale. 21 C.F.R. 701.10

Adulteration and Misbranding of Cosmetics

Cosmetics are treated separately from drugs and devices cosmetic

is

adulterated

in the

FDCA. A

if:

contains a poisonous or deleterious substance that may injure users. Hair dye that contains coal tar even though it can cause irritation to the skin of the user or be otherwise harmful is an exception. Such dye is not adulterated provided it carries the warning: Caution: This product contains ingredients which may cause skin irritation on certain individuals and a preliminary test according to accompanying directions should first be made. This product must not be used for dyeing eyelashes or eyebrows; to do so may cause blindness. The label of such hair dye must include directions for patch testing. If, in addition, such a coal tar hair dye contains 2,4-diaminoanisole and a 2,4-

1.

It

2.

diaminoanisole sulfate, then the principal display panel must contain the following: Warning: Contains an ingredient that can penetrate your skin and has been determined to cause cancer in laboratory animals. It contains any filthy, putrid, or decomposed substance, or has been prepared

under unsanitary 3.

Its

conditions.

container contains any substance that

Comment: The FDA from time

may

render the contents unsafe.

to time issues opinions as

safety of substances used in cosmetics. In

some

with respect to the FDA has deter-

instances, the

mined

that certain injurious substances should not be used in cosmetics, and has declared that cosmetics containing these substances are adulterated, for instance, chloroform, bithionol, and sprays using vinyl chloride as an ingredient or propellant. The complete list is set forth in the regulations. 21 C.F.R. 700.11, 14, 18

4.

A

If it

contains an uncertified color additive (hair dyes are excepted).

cosmetic

is

misbranded

if:

1.

Its labeling is false or misleading.

2.

It is

in

package form, and

its label

does not state the

mandatory labeling

requirements. 3.

Any

statement required to be

displayed.

made about

the product

is

not conspicuously

Drug, Devices, and Cosmetics

31 Notes

4.

The container

5.

A color additive is contained in the to

conform

is

made, formed, or

to the

filled

so as to be misleading.

product, and the product

not labeled

is

law respecting such color additive. 21 U.S.C. 362

Tamper-resistant Packaging for Certain Cosmetics

Cosmetic liquid oral hygiene products and vaginal products that are not packaged in a tamper-resistant package (see Adulteration of Drugs and Devices in this chapter) are adulterated or misbranded or both. 21 C.F.R. 700.25

ENFORCEMENT AND RECALL PROCEDURES to the FDCA are criminal in nature. For example, first be punished by a fine of $1,000 and up to a year's imprisonment or, if there was intent to defraud or mislead, up to three years' imprisonment and a fine of $10,000. The FDA, however, has until very recently proceeded informally except in the most aggravated cases. The law additionally provides remedies in the form of seizures and injunctions. When possible, the FDA has attempted to secure the cooperation of the manufacturer. In some instances, instead of initiating a seizure, the FDA has suggested that the manufacturer recall a product. Recall procedures have been classified with respect to the degree of hazard presented by the product.

The sanctions attached

offenses

1.

2.

may

A class recall is for products that will cause serious or fatal consequences. A class II recall is for drugs or devices that may cause serious but reversible I

health effects. 3.

A

class

III

recall is for

products that are not likely to cause adverse health

consequences.

The

recall strategy

depends on the depth

of distribution, the gravity of

the anticipated harm, and a determination of the most effective instituting a recall. Recalls for violative drugs

may

method

of

take the form of public

warnings or professional communications including personal telephone calls.

21 C.F.R. 200.5

FEDERAL ALCOHOL TAX One way to make sense of the present federal law respecting alcohol is to remember that prior to 1906, liquor labeled as a medicine for example, "Dr. Goyan's Golden Elixir" was part of many family medicine cabinets. During Prohibition, the "back room" of many pharmacies dispensed 80-proof "tonic." As late as the 1960s, a physician who was trying to demonstrate the absurdity

—

of a public assistance

patients

"any item

program

—

that allowed prescribers to prescribe for their

in the U.S. P." prescribed "a case of I.W.

Harper bourbon,

take as directed."

The alcohol tax is levied on all persons who sell alcoholic liquor. The use of alcohol for medicinal purposes is considered an industrial use provided the alcohol it is furnished to patients in treatment in hospitals. Hospitals may purchase such alcohol free of alcohol tax. Of course, tax-free alcohol may not be furnished to patients as a beverage or used in foods. And hospitals may not sell their

Food, Drug, and Cosmetic Act

32 Notes

medicines compounded of tax-free alcohol to outpatients or the general public. An exception is made for charitable or eleemosynary clinics, which may furnish their patients with medications composed of tax-free alchol provided no charge is

made The

to the patient.

hospital

pharmacy wishing

to take

advantage of the tax-free alcohol pro-

vision of the federal law should apply directly to the Regional Office, Internal

Revenue Service, Alcohol, Tobacco, and Firearms emption forms.

Division, for the proper exI.R.C. 5214

MEDICARE— CONTROL OF DRUG USE Since the enactment of the various Medicare programs,

(42 U.S.C. 1302)

the

payor-consumer status enforced certain conditions upon pharmacies and pharmacists in hospitals and skilled nursing facilities. The federal government disclaims any intent to regulate the profession. The regulations are, they say, merely conditions for participation. One may elect not to participate, just as one may elect not to eat. The conditions are not onerous. In general, they raise the quality of care provided, and that is good. federal

government has by

virtue of

Conditions for Participation

its

—Hospitals

Hospital Pharmacy 1.

The

hospital must have a pharmacy directed by a registered pharmacist or competently supervised drug room. The pharmacist must have some training in hospital pharmacy procedures and must be responsible for drafting and supervising the hospital's drug a

2.

procedures. 3.

employ a pharmacist, then prescription medications by a pharmacist elsewhere and only stored and distributed by the hospital. Such a hospital must have a consulting pharmacist

If

the hospital does not

are to be dispensed

who

schedules regular

visits to the hospital.

Physical Facilities 1.

2.

There must be an approved floor stock policy with proper controls and security, and the pharmacist must visit the facilities regularly. There must be appropriate pharmacy facilities that meet the security requirements of federal law (see Chapter 4).

Personnel Requirements 1.

vision

and

distribution.

of beds) of the 2.

number of persons required for drug superThe number of persons is tied to the size (number

Regulations provide for the facility.

the hospital does not have a staff pharmacist, there must be a consulting pharmacist and a staff person who is responsible for the execution of the consultant's orders. If

Records and Labeling Requirements

must maintain adequate records. must be kept of stock on hand and of the dispensing of all narcotic drugs. This record must be maintained in such a manner that the disposition of any

1.

The

2.

A

hospital

record

particular item can be readily traced.

.

Drug, Devices, and Cosmetics

33 Notes

3.

Records for precription drugs dispensed to each patient (inpatients and outpatients) must be maintained in the pharmacy or drug room and must include the following:

c.

name name Prescription number

d.

Name and

e.

Date of issue

f

Expiration date of

g.

Lot and control

h.

Name

i.

Unless the physician orders otherwise,

Patient's full

a.

Prescriber's

b.

strength of drug all

time-dated medications

number

of the

of manufacturer or,

if

drug

name name of the drug

generic, trade

dispensed.

42 C.F.R. 405.1027(d)(3)

Comment:

would be surprising

any hospital pharmacy complied with the records in the pharmacy of the expiration date of dispensed medications or the lot and control number of dispensed medications? The regulation appears to have confused labeling requirements with record-keeping requirements.

The 1.

2. 3.

It

terms of

literal

label

this regulation.

if

What pharmacy maintains

of each outpatient's prescription

must

bear:

Lot and control number of the drug of the manufacturer (or trade name) Unless the physician directs otherwise, name of the medication

Name

Control of Toxic or Dangerous Drugs

The cation,

institution

such as

must adopt

a written policy that

all

toxic or

dangerous medi-

narcotics, sedatives, anticoagulants, antibiotics, oxytocics,

and cortisone

products are automatically stopped after a reasonable time, unless specifically pre-

scribed by dose or time.

Comment: The automatic

stop order

from receiving medications long

was found necessary

after the

to

prevent patients

need ceased.

Pharmacy Committee There must be a pharmacy and functions and meets at

therapeutics committee that

performs the traditional

least quarterly.

Drug Standards Drugs stocked in the pharmacy must be compendial drugs, and a drug mulary or list of drugs stocked by the pharmacy must be maintained.

— Skilled Nursing

Conditions for Participation

for-

Facilities

As one might expect, the conditions for participation in skilled nursing facilities more relaxed than those for a hospital.

are

1.

2.

services must be under the general supervision of a licensed pharmacist. If the pharmacist is not a full-time employee (and the pharmacist rarely is), the pharmacist must: a. Schedule regular visits to the facility to supervise the drug handling

The pharmaceutical

and administration procedures.

34

Food, Drug, and Cosmetic Act

Notes b.

Review

at least

monthly the drug regimen of each patient and report any to the administrator and the medical director.

discrepancies or irregularities

Comment: This is

requirement in terms of patient safety and profeshis duty to report irregularities, the pharmacist has veto power over irresponsible drug utilization. Accompanying this power sional integrity.

is

a significant

By exercising

the obligation to exercise c.

it

responsibly.

Submit a written report quarterly to the pharmacy services committee on the status of the service provided. Serve on the pharmacy services committee, which meets quarterly and preserves written records of

its

meetings. 42 C.F.R. 405.1127

Part

II

FEDERAL

CONTROLLED SUBSTANCE ACT 21 U.S.C. 801-904

Public

Law

91-513, effective date October 27, 1970

The Controlled Substance Act establishes a "closed system" for the distribution of drugs and other substances of abuse. The system is called "closed" because, in general, it provides that controlled substances may be distributed only between persons who are registered with the Drug Enforcement Administration

The

(DEA).

DEA is an agency of the United States Department of Justice and is jointly

responsible with the Food and

Drug Administration (FDA)

for administering

two agencies cooperate in supervising treatment of narcotic addicts. Medical guidelines for a narcotic treatment program are fixed by the FDA, whereas the DEA supervises the dispensing and record-keeping activities of the program. the provisions of the Controlled Substance Act. For example, the

21 C.F.R. 291.501-5

DEA to prevent the unlawful distribution and use of performs this function in two ways: 1) normal law enforcement activities, i.e., investigation and arrest of persons engaged in the unlawful distribution and abuse of controlled substances and, more important for our purpose, (2) the regulation, registration, and control of persons who are legitimately engaged in handling and distributing controlled substances. The control of these persons those legally handling control substances is deemed necessary to prevent or discourage the diversion of controlled substances into the illicit market. It is

the function of the

controlled substances.

It

—

—

D

Chapter

REGISTRATION BY ACTIVITY

The Controlled Substance Act provides for registration with the DEA by persons handling controlled substances. This registration, while primarily designed to reveal the identities of parties lawfully handling controlled substances, classifies such parties by the type of activity engaged in, i.e., manufacturer or pharmacy, and the type of controlled substance handled by the registrant.

ACTIVITIES REQUIRING REGISTRATION "Every person who manufactures or distributes any controlled substance or who proposes to engage in the manufacture or distribution of any controlled sub." stance, shall obtain annually a registration issued by the Attorney General. "Every person who dispenses, or proposes to dispense, any controlled substance, shall obtain from the Attorney General a registration. The Attorney General shall determine the period of such registrations. In no event, however, shall such registrations be issued for less than one year nor for more than three years." .

.

.

.

.

21 U.S.C. 824(a)

Accordingly, with the noted exception, the following

activities

are each subject

to registration: 1.

2.

3. 4.

Manufacturing controlled substances. Distributing controlled substances. Dispensing controlled substances which are listed in Schedules II through V. Conducting research with controlled substances listed in Schedules II through V. Separate registration for practitioners

capacity

is

who

are already registered in another

not required to conduct research. 21 U.S.C. 823(f)

5.

Conducting instructional ules

6.

II

through

activities

with controlled substances

listed in

Sched-

V.

Conducting a narcotic treatment program using any narcotic drug listed in Schedules II through V. If such a program is conducted at more than one location, each location or site must secure a separate registration and secure its

drugs by means of an

and

official

7.

Conducting research

8.

Conducting chemical analysis with

order form.

with Schedule any controlled substances.

instructional activities

I

substances.

Importing controlled substances. 10. Exporting controlled substances. 9.

11.

A

"compounder"

—a person who

cation treatment

program who

is

engaged

in a

maintenance or

detoxifi-

mixes, prepares, packages, or changes the dosage

37

Federal Controlled Substance Act

38 Notes

form of a narcotic drug listed in Schedules treatment program.

II

through

V

for

use by another 21C.F.R. 1301.22

SEPARATE REGISTRATION In general, each activity listed

is deemed independent and requires a pharmacy may be registered to dispense

above

separate registration. For instance, a

may

controlled substances to the ultimate user and, in addition,

sell

certain

controlled substances to other registrants, for example, to physicians for their office use.

Must such a pharmacy also

register as a distributor?

5%

If

the total

amount

and any 12-month period, the pharmacy must register as a distributor as well (see Activities and Coincident Activities section in this chapter). The Controlled Substance Act was amended on October 12, 1984, to provide

of such sales to practitioners exceeds

of the total dosages distributed

dispensed during

that practitioners

who

are already registered in

some other

capacity, for example,

need not obtain separate registration to conduct research on schedule II through V controlled substances. Research on schedule I substances does require separate registration, and specific approval by the Attorney General not a dispenser,

only of the research protocol but research investigators. 21 U.S.C. 823(f)

Certain allied activities are so associated with the registrant's activity as to be

an integral part of the registered

activity.

For instance, a registered manufacturer

may distribute to another registrant from the place of manufacture without registering as a distributor. However, if the manufacturer ships the controlled substance from the place of manufacture to a warehouse located elsewhere and then ships from the warehouse to another registrant, the manufacturer must register as a distributor.

Activities that are closely allied with the registered activity

require separate registration are called, coincident

and which do not

activities.

described in the regulations. As a general rule, if the activity is inseparable from the registered activity and carried on at the same physical location and is not the dominant activity, a separate registration is not

These coincident

activities are

necessary.

EXEMPTION FROM REGISTRATION FOR EMPLOYEES AND AGENTS OF REGISTRANTS An employee or agent of a person who is registered to engage in any of the above independent activities is exempt from registration. Thus an employee of a registered manufacturer need not personally register to handle controlled substances in the usual course of employment.

Most pharmacists

are not individually registered.

macy, rather than the pharmacist,

pharmacist pharmacist

is

is

As we

shall see, the phar-

usually the registrant, and, provided the

acting within the scope of his usual duties at the pharmacy, the

falls

within this agent or employee exemption and need not personally

register.

Some

practitioners act in a dual capacity

of a hospital

who If

who occasionally

engages

—for example, a physician employee

in private practice or a

nurse practitioner

employed by a hospital part-time and also maintains a private the employed physician or nurse practitioner (assuming the nurse is

in a state that authorizes

nurse practitioners

practice.

practices

to initiate prescriptions for controlled

Registration

by Activity

39 Notes

substances) issues a prescription for a private patient, the prescriber is not acting in the capacity of an employee or agent and is required to have a personal registration for such activity.

ACTIVITIES

AND COINCIDENT

ACTIVITIES

Manufacture

To manufacture

defined by the C.S.A. as engaging in activities that include compounding, or processing of a drug or other substance by extraction or synthesis as well as packaging or repackaging of such substance or labeling or relabeling its container. Except, the term manufacture does not include preparation, compounding, packaging, or labeling of a drug or substance in conformity with state or local law by a practitioner as an incident to is

the production, preparation,

the administration or dispensing of a drug in the course of professional practice. 21 U.S.C. 802(14)

Pharmacist Exemption

A pharmacist may "manufacture" without registering as a manufacturer an aqueous or oleaginous solution or solid dosage form containing a narcotic-controlled substance not exceeding 20% of the complete solution or mixture. 21 C.F.R. 1307.12

Comment: Obviously, many

of a pharmacist's activities are indistinguishable

from those of a manufacturer. In one sense, a pharmacist filling a prescription is a "custom manufacturer." In order to distinguish between these two activities, the law defines the various acts that constitute manufacturing and then proceeds to exempt from registration as manufacturers practitioners dispensing or administering to their patients, e.g., filling a prescription. A practitioner who compounds a mixture containing a controlled substance and administers it to a patient is also within this exemption and thus is not required to register as a manufacturer.

Another exemption allows pharmacists

to

manufacture not

solution of controlled substances and distribute

it

to

more than

a

20%

another registrant. However,

if

pharmacist wished to make up a stock solution or mixture containing more than 20% of a narcotic-controlled substance for distribution to another registrant, or if a significant part of his business (over 5%) consisted in distributing this stock solution to others, he would be required to register as a manufacturer. Of course, a pharmacist can dispense to an ultimate user such a solution or an even stronger one pursuant to a valid prescription. Coincident Activities. A person registered to manufacture any controlled substance may distribute that substance but not other controlled substances. Such a person may also conduct chemical analysis and preclinical research on those substances without additional registration for those activities. The physical location of the coincident activity must be the same as that of the registered activitv. a

—

—

21 C.F.R. 1301.22(b)(l)(2)

Distribute

To

distribute

means

trolled substance.

A

to deliver, other than by administering or dispensing, a con-

distributor

is

one

who

delivers. 21 U.S.C. 802

40

Federal Controlled Substance Act

Notes

Comment: No as

we have

coincident activities are recognized by the regulations. However, pharmacy may on occasion act as a distributor (see Separate

seen, a

Registration for Separate Sites section in this chapter). to

a distributor, 1.

it

may do

The person

to

so provided:

whom the controlled substances are distributed is registered

—

handle such substances or another pharmacy. to

2.

a pharmacy chooses without registering as

If

in limited distribution of controlled substances

engage

for instance, a registered physician, dentist,

Adequate records are maintained. If a schedule II drug is distributed, federal must be prepared (see Chapter 7). The total annual amount distributed by the pharmacy to other registrants computed by dosage units does not exceed 5% of the total amount distributed and dispensed by the pharmacy. If it does, the pharmacy must register order forms

3.

as a distributor. 21 C.F.R. 1307.11

Comment: Most

drug wholesalers. This exemption for pharconform an existing practice, i.e., distribution of small macies to to amounts between registrants. However, when distribution becomes a significant then in effect the pharmacy becomes part of a pharmacy's business over 5% a wholesaler and must register as a distributor. There are significant disadvantages for a retail pharmacy to consider before rushing out to register as a distributor. The anticipated profits from a limited distributorship may not justify the substantial investment involved in such a dual registration. For instance, distributors are required to install elaborate security devices and to construct a secure storage environment for their controlled substances. Such elaborate preis

distributors are

designed

—

—

cautions are normally not consistent with the day-to-day operations of a

retail

pharmacy. Additionally, dual registration entails two sets of records maintained separately for each activity as well as separate reporting periods. An average pharmacy contemplating such a dual capacity should anticipate a major reorganization of its personnel and procedures as well as a significant capital investment in new security construction.

Dispense

To

means

substance to the ultimate user. In broader than most definitions adopted by state laws. Its includes prescribing, compounding, packaging, and labeling the substance to prepare it for delivery to the patient or research subject. Therefore when a registered physician prescribes a controlled substance for a patient, he is dispensing. If the physician administers the drug to the patient or furnishes the drug to the dispense

to deliver a controlled

general, this definition

is

patient for later self-administration, he a patient with a controlled substance

tioner

is,

is

dispensing.

upon

A

pharmacy

that furnishes

the lawful prescription of a practi-

of course, also dispensing. 21 U.S.C. 802(10)

To

fully

the term

understand the meaning of the term dispense

it is

necessary to define

practitioner.

Practitioner Defined

A practitioner is "a physician,

dentist, veterinarian, scientific investigator, phar-

macy, hospital, or other person licensed, registered, or otherwise permitted, by the United States or the jurisdiction in which he practices or does research, to

Registration

41

by Activity

Notes

conduct research with respect to, administer, or use in teaching or chemical analysis, a controlled substance in the course of professional practice or research." distribute, dispense,

21 U.S.C. 802(20)

Comment: The

relationship

between the

states

and the

federal

government with

respect to controlled substance handling, licensing, and registration appears is due to overlapping claims of jurisby those who jealously guard "state rights" from perceived federal incursions and usurpation. With certain exceptions, as in the military, it is the state that initially licenses the

confusing. This appearance of confusion diction

determining that he possesses the necessary qualifications. For is not necessarily licensed to practice in Nevada. The state license to practice gives the practitioner the right to use and dispense drugs in treatment of the patient. If the practitioner wishes to dispense certain drugs, i.e., controlled substances, in the treatment of patients, the practitioner must, in addition to possessing a state license, apply for registration with the federal government. In some instances the practitioner is licensed by the state to administer certain drugs. For example, an optometrist is licensed in some states to use certain legend drugs for diagnosis, but is not licensed to prescribe such drugs for the patient. Not all practitioners apply for such registration. If a practitioner does not intend to use controlled substances in his or her practice, there would be no need to register. Most practitioners, however, do dispense some controlled substances in their professional practice and, therefore, are required to apply for

practitioner after

instance, a pharmacist or a physician licensed to practice in California

registration.

The Drug Enforcement Agency of the federal government is required to regpersons whose license to practice issued by the state entitles the licensee

ister all

to

dispense controlled substances in the practice of the licensed profession.

state, for instance, in

One

addition to licensing physicians, dentists, and veterinar-

ians, also licenses a healing arts professional called a

"naturopath"

to

controlled substances in treatment of patients. Naturopaths have

use certain little

or

no

formal medical education and are often compared to lay mid wives. Since the state licenses these persons to dispense controlled substances, the DEA is required to accept them for registration. As we have seen, an increasing number of states are extending prescribing privileges to physician assistants practitioners.

If

and nurse

the licensing state authorizes these persons to initiate prescrip-

tions for controlled substances, the

DEA

is

required to accept

them

as practi-

tioners. 21 U.S.C. 834(f)

Sometimes the

DEA refuses

to register

controlled substances. This refusal

by the state to dispense almost always based on some personal

a person licensed

is

malfeasance of the applicant and not upon the state's authority to license. The Attorney General (acting through his agency, the DEA), is empowered to deny an application for registration if such registration would be "inconsistent with the public interest." 21 U.S.C. 823(f)

"In determining the public interest, the following factors shall be considered:"

The 1.

statute then

lists five

such

The recommendation

factors:

of the state licensing authority.

42

Federal Controlled Substance Act

Notes

The The The

2.

3.

4.

applicant's experience. applicant's conviction record, both state

and federal. and local controlled sub-

applicant's compliance with state, federal,

stance statutes.

Such other conduct as may threaten the public health and safety. Comment: The statute is inartfully drawn. Surely the above factors that are to be considered "in determining the public interest," have nothing to do with the public interest at all, but are concerned with flaws in the character and conduct of the applicant. Presumably when an applicant's prior conduct and past defalcations have been particularly egregious, the DEA would find that granting registration to such an individual would be inconsistent with the public interest. The "public interest" remains undefined. The obvious purpose of the statute is to provide the DEA with the statutory authority to deny registration to an applicant who has technically fulfilled state requirements for licensure but whose past conduct with controlled substances exposed the public to an unreasonable risk of diversion. Less obvious is the intent expressed in the last factor. What, precisely, is meant by "conduct as may threaten public health and safety?" The language is broad enough to encompass acts that bear no relationship whatsoever to abuse or diversion of controlled substances. For instance, grouped under the title "Crimes against Public Health and Safety" in the California Penal Code and made ap5.

plicable to areas within federal jurisdiction within that state are the following

crimes: 1.

Failing to close railway gates (Penal

2.

Dumping waste

Code

369(d)).

3.

matter on a public highway (Penal Code 374(b)). Failing to relinquish a party line when informed it is needed for an emer-

4.

gency call (Penal Code 384). Exposing meat for sale falsely representing

it

to

be kosher (Penal Code

383(b)).

Releasing a balloon with a burning candle attached to

5. It

would be a mistake

it

(Penal

Code 384(g)).

to allow the facetious aspects of the illustration to

obscure

the gravity of the claim.

Make no mistake about it. When the authority to deny registration is limited only by the requirement that a finding be made that the applicant has engaged in conduct that is vaguely characterized by the statute as conduct that "may be a threat to public health and safety," then the authority to deny registration is largely discretionary. Amorphous standards and criteria provide reservoir hosts for the arbitrary exercise of authority.

Of course the power

to

deny an application

for registration is

discretionary. Before taking such action the Attorney General

not totally

(DEA) must pro-

vide the applicant with an administrative hearing which, in turn,

is

subject to

a limited judicial review. 21 U.S.C. 824(c)

As

a practical matter, this right to

judicial

review reads better than

it

an administrative hearing and subsequent The procedure affords the disappointed

plays.

little protection. The cost of the procedure, hiring counsel to guide one through a labyrinthine administrative procedure and judicial review, calculated in terms of money, time, and aggravation is appalling and tends to discourage even the stoutest of heart. In fairness, these factors that allow the Attorney General to deny an application for registration have been in existence with respect to manufacturers and distributors for some time. However, the resources of an individual to challenge a

applicant precious

Registration

by

43

Activity

Notes

governmental agency cannot be realistically compared drug manufacturer or commercial enterprise.

An 1.

may

application for registration

The applicant has

be refused

to those available to a

it:

any information

materially falsified

in the application for

registration. 2.

The applicant has been convicted law relating

3.

of a felony

under the C.S. A. or any other

to controlled substances.

The applicant has had

his state license

suspended, revoked, or denied. 21 U.S.C. 824(a)

Notice, too, that a practitioner

may

be an

artificial legal

entity

such as

a hospital

The

or a pharmacy, as distinct from the employees of the hospital or pharmacy.

pharmacy

is

usually the registrant. Pharmacist employees are exempt from reg-

istration as are

who practice solely as employees of Exemption from Registration for Employees and Agents

pharmacists and physicians

a hospital registrant (see

of Registrants section in this chapter).

Coincident Activities. A person registered to dispense may conduct research and with such substances. However, such activities do not include conducting a narcotic treatment program, which requires separate registration. instructional activities

Practitioners

Exempt from Registration

Affiliated Persons. Persons

pharmacy but do not

who have an ownership

interest in a hospital or

directly participate in the operation of the business

need

not register separately.

Agents and Employees. Just as a truck driver for a registered "distributor" is not required to register personally, a pharmacist or a nurse who works solely as an employee of a hospital registrant is not required to register personally with the

DEA. 21 C.F.R. 1301.24

Practitioners Practicing

Only

practices only in a hospital that

need not apply

registered with the

an additional personal registration. However, there are imon the use of this exemption:

for

portant limitations 1.

The employed physician (without

a personal

DEA

write prescriptions for controlled substances to be

2.

outside of the hospital. Such a prescription cannot be hospital

A physician who DEA as a practitioner

in Registered Institutions.

is itself

pharmacy

is itself

filled

registration) filled

may

not

by a pharmacy

by the hospital pharmacy either

if

the

registered as a practitioner.

The employed physican may administer or dispense controlled substances only while acting in the course of his usual employment in the hospital. 21 C.F.R. 1301.24(b)

Comment: These

limitations

on the authority

of a nonregistered physician are

designed for a hospital that does not have a pharmacy licensed for outpatient dispensing and an employed physician who does not practice on his own outside the hospital. For example, a nonregistered itinerant emergency room physician may administer a controlled substance to a patient from hospital "ward stock." In that case the hospital's registration as a practitioner

matter,

most physicians maintain

is

sufficient.

As a

practical

a personal registration as a practitioner so that

they can avoid the restriction this exemption places on their activities. Many modern hospital pharmacies, in order to be able to fill discharge medication

44

Federal Controlled Substance Act

Notes

prescriptions as well as prescriptions brought in by

from the hospital as pharmacy

register

members

of the public,

practitioners.

Interns, Residents, Foreign-Trained Physicians, and Physicians Employed by the Veterans Administration. These nonregistered persons who are employees of a V.A. hospital may dispense, administer, and prescribe provided: 1.

2. 3.

State law allows such person to prescribe.

Such prescribing is done in the usual course of employment in the hospital. The hospital has authorized the intern, resident, or foreign-trained physician to prescribe and designates a specific internal code that identifies the prescriber. The internal code is a suffix to the institution's DEA registration number separated by a hyphen. 21 C.F.R. 1301.24

Comment: An

intern, resident, or foreign-trained physician practicing in a Veterans Administration hospital enjoys a broader scope of practice than the same person would in a state or private institution. The exemption for such unregis-

tered V.A. hospital practitioners allows controlled substances.

The

an internal hospital code that 123456-A17). The

them

to prescribe

hospital's registration identifies the

as well as to administer

number

exempt

is

used together with such as (APO

practitioner,

three letters and six numerals represent the V.A. hospital's number, the last letter and numerals represent the hospital's internal code identifying the exempt practitioner. Upon receipt of such a prescription, a pharmacist must first of all determine if state law allows such an unlicensed practitioner to prescribe. Federal law cannot grant prescribing authority to such unlicensed individual practitioners outside the perimeters of the federal institution unless permitted by state law. In general, most states have granted these unlicensed individuals the limited

DEA

first

registration

right to prescribe provided the prescription

is

issued within the scope of the

practitioner's practice at the V.A. hospital.

Each V.A. hospital is required to maintain a current list of practitioners and code to enable pharmacists to verify the prescribing authority of such a practitioner. their assigned

21 C.F.R. 1301.24(c)(5)

Authorized Prescribers Who Are Members of the Military, Bureau of Prisons, or Public Health Service. Governmental employees, e.g., physicians in the military service, official

may prescribe,

administer,

and

dispense in the usual course of their

duties without securing a registration number.

Such employees may

not

purchase controlled substances. They may issue prescriptions as part of their official duties, but such prescriptions must state the branch of the service, e.g., U.S. Coast Guard, and the prescriber's service number. In lieu of a service number a Public Health official uses his social security number. 21 C.F.R. 1301.25

Comment: Of course, if the prescriber were to act in a private capacity, he would be required to comply with state laws and to secure a registration number. Masters of Ocean Vessels and Aircraft. Under the general supervision of a medical officer, a master of a vessel may possess and dispense controlled substances. 21 C.F.R. 1301.28

Comment: This out a medical

general exemption applies to oceangoing vessels with and withprovides procedures for stocking controlled sub-

officer. It also

stances in emergency field kits for industrial firms.

Registration

45

by Activity

Notes

Research

As we have seen, listed on schedules

may conduct research on substances without registering separately as a researcher. Research for substances listed in schedule I always requires separate registration, as does research in connection with a narcotic treatment or maintenance program. This category of registration, since the 1984 amendment, is now almost exclusively occupied by the nonpractitioner researcher conducting independent registered practitioners

II

through

V

research activities, say, at a university or private laboratory.

Coincident Activities. Those not requiring separate registration are: distribupersons named in the research protocol, manufacture, if stated in the

tion to

research protocol, chemical analysis, preclinical research, and instructional

activities.

Instructional Activities

Conducting instructional activities with substances listed in schedules through V requires registration. No coincident activities are recognized.

II

Narcotic Treatment Programs

The term narcotic treatment program means a program engaged in maintenance and/or detoxification treatment with narcotic drugs. The term "maintenance treatment" means the dispensing, for a period in excess of twenty-one days, of a narcotic drug in the treatment of an individual for dependence upon heroin or other morphinelike drugs. The term "detoxification treatment" means the dispensing, for a period not in excess of one hundred and eighty days, of a narcotic drug in decreasing doses to an individual in order to alleviate adverse physiologic or psychologic effects incident to withdrawal from the continuous or sustained use of a narcotic drug and as

a

method

of bringing the individual to a narcotic drug-free state within

such period. As amended

Oct. 19, 1984

Public

Law

98-509

practitioner engaged in a narcotic treatment program must This registration is in addition to and separate from the practitioner's registration to dispense controlled substances. Each treatment site must be separately registered if controlled substances are stored at the site. Coincident Activities. A registrant conducting a narcotic treatment program

Comment: Every register separately.

may

dispense and, in accordance with an approved program, conduct

clinical

research.

Research with Schedule

I

Substances

In order to register to conduct research with controlled substances listed in schedule I, an applicant must submit for approval a detailed protocol describing

the project, the identities and qualifications of the participating investigators, the security arrangements, the institutional affiliation, and an approved I.N.D. 21 C.F.R. 1303.33

I

Coincident Activities. A person registered to research a basic class of schedule substances may import or manufacture that basic class as set forth in the research

46

Federal Controlled Substance Act

Notes

may

protocol and analysis

on

distribute to others

authorized to research or perform chemical

that basic class pursuant to such protocol. 21 C.F.R. 1301.22(3)

Chemical Analysis Conducting a chemical analysis of controlled substances

in

any schedule

re-

quires registration. 21 C.F.R. 1301.22(8)

Coincident Activities. These include the right to manufacture and import such substances for chemical analysis or instructional purposes and to distribute to other registrants authorized to conduct chemical analysis and to law enforcement agencies exempt from registration, to export such substances to persons conducting analysis in other countries. 21 C.F.R. 1301.23(4)

Importing Controlled Substances Self-explanatory. Coincident activities include distribution from place of importation.

Exporting Controlled Substances Self-explanatory. There are

no recognized coincident

activities.

Compounder

A compounder is a person who while engaged in a narcotic treatment program mixes, prepares, packages, or changes the dosage form of a narcotic

schedules

II

through

V

for

drug

listed in

use in another narcotic treatment program. 21 C.F.R. 1301.02(d)

Comment: gram's

A

narcotic treatment

activities include

pounder who

is

program must register as a compounder if the pronarcotics for use in the program. A comwith the program and who is compounding for

compounding

not affiliated

or distributing to narcotic program sites must be registered as a manufacturer or a distributor and comply with the requirements generally applicable to those registration classifications.

ACTIVITIES EXEMPT

FROM REGISTRATION

Law enforcement personnel and civil defense officials are exempt from regwhen handling controlled substances a part of their official duties. Law

istration

enforcement laboratories are not exempt and must

register. 21 C.F.R. 1301.26-.27

SEPARATE REGISTRATIONS FOR SEPARATE SITES The general rule is that if controlled substances are manufactured, distributed, or dispensed from separate locations by one manufacturer, distributor, or prac-

Registration

by

Activity

47 Notes

titioner, a

separate registration

is

pharmacy must have separate

required for each location. For example, a chain

registrations for each location. 21 C.F.R. 1301.23(1)

Exceptions 1.

exception is made for a physician who maintains several offices. If the physician does not maintain a supply of controlled substances at a branch office and does not administer or dispense from chat office, he may write a prescription from the branch office without obtaining a separate regis-

An

tration for

it.

21 C.F.R. 1301.23(3)

Comment: Consider

Separate

this exception.

site registration is

required

each professional practice from which controlled substances are "dispensed." The definition of the term dispense includes the act of prescribing. The federal government thus found itself in the ludicrous position of requiring an individual practitioner to register every site from which he regularly prescribed, even though no controlled substances were administered, maintained, or dispensed on the site. What to do? The regulations solve the problem in a delightfully bureaucratic manner. The regulation provides that branch offices "shall be deemed not to be places where controlled substances are dispensed." The practitioner may be prescribing from the branch office, and the act of prescribing is dispensing, except in this instance when we deem it is not. Such a solution is very much like hanging a sign on a horse saying, "The federal government has deemed this animal while occupying this particular pasture to be a cow." The rule to remember is: If there is a supply of controlled substances on site, or if the practitioner regularly administers or dispenses such substances from the site, the site must have a separate registration. Another exception is made for sales offices where controlled substances are sold but none are kept other than display samples. for

2.

21 C.F.R. 1301.23(2)

3.

Recognizing that good patient care requires the availability of certain controlled substances for emergency use at long-term care facilities, the DEA allows storage of controlled substances in emergency kits at those facilities provided:

b.

The source of supply is a registered hospital pharmacy or practitioner. The supplier maintains accurate records and performs a periodic phys-

c.

The

a.

ical

inventory. state

agency regulating such

such emergency

and conditions

kits

facilities

and has adopted

has approved the storage in

rules regarding security, access,

of administration. 45 F.R. 40576

Chapter

4

APPLICATIONS FOR REGISTRATION

FORMS There are three basic forms

Form Form Form

1.

2. 3.

for registration currently in use:

225,

to

manufacture or distribute

224,

to

dispense (for hospitals, physicians, pharmacies, etc).

363, to

conduct a

narcotic treatment

program or to be a compounder 21 C.F.R. 1301.32

ANNUAL REGISTRATION No

person

may engage

in

any

activity for

which

registration

a certificate of registration is issued. Application for registration Comment: This is a favorite examination question.

is

is

required until

not sufficient.

After a person has been registered for one year, renewal or reregistration forms are issued annually by the DEA. Exception: In 1984, the CSA was amended and now provides that while manufacturers and distributors must register annually, dispensers may be granted a

which

registration

is

valid for three years. 21 U.S.C. 827(g)

Every registrant

is

required to advise the

any transfer or discontinuance

DEA

at least 14 days in advance of

of business. 21 C.F.R. 1307.14

APPLICATION FOR REGISTRATION AS A PRACTITIONER Plate

1 is

a fascimile of

DEA

form 224, the application

for registration as a

practitioner.

Applicant Investigation

When an application for registration has been received, DEA conducts an investigation of the applicant.

the regional office of

the

some

warrant a more complete investimeans checking with the state agency (Board of Pharmacy, Board of Dental Examiners) to determine if the applicant is indeed licensed by the state to conduct the activity for which reg-

Comment: Unless

there are

facts that

gation, this preregistration investigation usually

istration

is

sought.

49

—

> z KZO if e

• 8 o s a

< E

u-

I-

o co H Z

rg

J

£d

Efl

S

c

M

o

K ^ 8

E"-oi z

c

I

ISS

STA

3

D o _ FINE

FURNI

E

>

>

A

.2

s

"

£

"S YEARS.

ujg,

E

5

R < 3 M ?»o F 1- H;

E




?

91

O t

£

O 5

.000

WH

$30

i£

it

3

~°

oJ>

Z

o «

D ° 8 at

a,

e

-S

H a r

».

E

is

v.

b

M

a e

aa

F

B

«

£


?Z«332c1

a»— o "T « u s ; S 5-9 "

3 ^ 2 £ z o

o

o

CC UJ

2

Z

-

.

UI rr

-

«

t; tj

«i

D D

tj

.c c o

-

•55

Ui en

£

"-

?£

C "

a

"^

tj«-;

CJ

CJ


CD

as

-,

CD CO

HJ

j ct.

CL.

"P-D

CC UJ co

Li-

03

Z DC < 3X O > O LU

ss co

IS Z

c CO

,

.2=5.

o o

f PH*r SlC/fTKl

QUANTlTi UNLESS checked OR DENTIST DE A MUMMER

Complete Medication

Rn

rrl

on

4/10/84

- G26 nwi«e iiEPORE DISPENSING

1AV342 1257 NOTE TO PHARMACIST VA FORM OCT 197S 10-2577d

1

PRESCRIPTION FORM

Plate 9 3.

In addition to the prescriber's signature, his or typed on the prescription.

DISPENSING A SCHEDULE

II

name stamped, handprinted,

SUBSTANCE

Except in an emergency, a pharmacist suant to a written prescription.

may

dispense a C-II substance only pur21 C.F.R. 1306.11

Such prescriptions cannot be

refilled.

21 C.F.R. 1306.12

Only a pharmacist may fill a prescription for controlled substances. "Intern" pharmacists are allowed to fill such prescriptions if permitted under state law. Unlicensed employees

Emergency Oral

An

emergency

1.

An

2.

No

3.

It is

may

not.

C-II Prescriptions

means

the prescriber has determined that:

immediate administration of a schedule the patient's care.

II

substance

is

necessary for

proper alternative treatment is available. not reasonably possible for the prescriber to present a written pre-

scription prior to dispensing.

.

89

Prescriptions

Notes All three determinations

that a schedule

II

must have been made

substance

may

to qualify as

be dispensed upon an

an emergency so

oral prescription. 21 C.F.R. 290.10

In a valid emergency, the prescriber may transmit an oral prescription to the pharmacy. The oral prescription must contain all the information required for a 7

written prescription (except, obviously, the prescriber s signature). Upon receiving an emergency oral prescription for a schedule II substance the pharmacist must: 1.

2.

Reduce the oral prescription to writing. Unless the prescriber is known to the pharmacist, make a reasonable determine his authority,

i.e.,

that

he

is

effort to

in fact a registered practitioner.

The amount prescribed and dispensed may be only enough to last the patient through emergency and should be noted on the prescription. Within 72 hours, the prescriber must deliver or deposit in the mail a written prescription covering the emergency quantity dispensed. The prescription must the

have the words "Authorization

for

Emergency Dispensing" written on

its

and be

face

dated as of the date of the oral order. If the prescriber fails to provide such a covering prescription, the pharmacist shall promptly notify the DEA. 21 C.F.R. 1306.11

Comment: scriber, the

by

After receiving an oral emergency prescription from an unknown pre-

pharmacist should

at least

attempt to verify the individual's identity

a "call back", i.e., calling the prescriber at the prescriber's office listed in a

number orally given by the individual at the time of preOf course, if the prescriber is calling from the patient's house, a call the office would not help. What is required is a good faith effort on the part of

directory (not at the scribing).

to

the pharmacist to verify identity. Partial Filling of a C-II Prescription If

a

pharmacist

is

unable

to

completely

fill

(temporarily low on stock, for example), he

a prescription for a C-II substance

may

dispense a partial amount. The

pharmacist must: 1

Note the

fact of

such

partial filling on the face of the prescription, giving

and quantity supplied. Complete the entire order within 72 hours. the date

2.

is unable to complete the order within 72 hours, he must notify secure a new prescription. and the prescriber to the rule that a partial filling must be completed in 72 an exception There is hours. Extended partial fillings of prescriptions are allowed for patients who are residents of long-term care facilities (nursing homes). For these patients, prescriptions may be filled in small quantities for up to 60 days, provided a record is kept of each such partial dispensing.

If

the pharmacist

Comment:

seems

make good sense

to allow partial filling of prescriptions reduces the amount of the drug physically on in such more lax than in, say, an acute care may be where security facility the hand in hospital, while at the same time allowing such patients to receive any price breaks from quantity purchasing. It

to

situations. Partial filling

DISPENSING A SCHEDULE III OR IV SUBSTANCE A prescription for a controlled substance listed in schedules be oral or written.

If

the prescription

is

transmitted orally,

it

III,

IV, or

V may

must contain

all

of

Federal Controlled Substance Act

90 Notes

the information required for a prescription of a schedule

II

substance except, of

course, the prescriber's signature. 21 C.F.R. 1306.21

Upon

receipt of such

an

oral prescription, the pharmacist

must reduce

the pre-

scription to writing.

Refills

A

III or IV substance may be refilled if authorized such a prescription may not be refilled: (a) more than more than six months after the date of issue, whichever occurs first.

prescription for a schedule

by the

prescriber. However,

five times, or (b)

21 C.F.R. 1306.21

—Computer Records

Record of Authorized Refills

A record of each refill must be entered on

the back of the prescription, and include dispensing pharmacist and (2) date of dispensing. Or, if the pharmacy has an automated record system for patient medication profiles, etc., refill information may be stored in that provided the pharmacy ts authorized by

the: (1) initials of the

the

DEA

to

maintain computerized records.

The regulations covering computerized refill records for schedule III and IV substances in pharmacies distinguish between systems that can provide a printout and those that cannot. If the system provides a daily printout of controlledsubstance refill data, the printout must be verified, dated, and signed by the dispensing pharmacist within 72 hours of dispensing. If the system does not provide a daily printout, the pharmacy must maintain a bound log book in which the dispensing

pharmacist records that he has reviewed the day's entries into the

computer and

that they are accurate. The pharmacist must sign the log book each day. 21 C.F.R. 1306.22(b)

pharmacy maintains

its records on a computer, it must have an auxiliary information if the computer malfunctions. All information must be available on both the manual and computerized systems. Comment: In other words, a pharmacy cannot have some of its records available If

a

system to determine

refill

on computer and others on the back Partial Filling of

Schedule

III

of prescriptions.

and IV Prescriptions

There are no special time requirements for completing the partial filling as II substances. Each partial filling must be recorded in the same manner as a refill. Of course, a partial refilling may not be completed after six months from the date of original filling.

there are for schedule

21 C.F.R. 1306.23

DISPENSING A SCHEDULE V SUBSTANCE The

FDA

has determined that some schedule

the counter without a prescription.

When

V

substances

the substance

is

may be

sold over

not a prescription

must comply with certain rules established by the DEA regarding such sales (see Records of Sales of Nonprescription Schedule V Substances, Chapter 7). In general, these restrictions limit the amount and frequency of sale and the age and identity of the purchaser and require the dispenser to record the sales in a bound book.

item, the pharmacist

91

Prescriptions

Notes

When

the substance

is

a prescription item

—

i.e., it

Federal law prohibits sale without a prescription" a prescription apply as for schedules III and IV.

A

prescription for a schedule

refilled

V

substance

bears the legend "Caution: the same requirements for

—

may

be written

or oral

and may be

with the prescriber's authorization an unlimited number of times. 21 C.F.R. 1306.31

LABELING THE CONTAINER OF PRESCRIPTION MEDICATION With two exceptions

(labeling a container for mailing

and dating the

label of

on the any controlled substance dispensed by a pharmacy pursuant to a prescription is the same regardless of the schedule classification of the substance. The required information is:

a container containing a refilled prescription), the information required label of a container of

1.

2. 3.

Name and address of pharmacy Name of patient Name of prescriber (Note: If the

medication

is

and is to be must be included on

a non-narcotic

mailed to the patient, then the prescriber's address

the label; see Mailing the Prescription Drug, Chapter

2.)

4.

Directions for use

5.

Serial

6.

Date of filling if schedule II, date of initial filling if schedule III or IV Comment: Requiring the date of initial filling for schedule III or IV substances continues to cause problems. The tendency, of course, is to date

number

of prescription

on the date of dispensing to comply with the FDCA. The alleged purpose behind this curious rule is to enable an inspector to determine if the substance is being dispensed beyond the six-month period allowed for refills of prescriptions for C-III and C-IV substances. Prescriptions for schedule II substances cannot be refilled. Because the FDA requires the pharmacist to date the label on the date filled, presumably the container label of a refilled C-III or C-IV substance must contain two dates (the date of original filling, required by the DEA, as well as the date of refilling, required by the FDA). Neither rule has any apparent relation to public or patient safety but appears to be solely for the label

administrative convenience.

Cautionary Statements

— Schedules

II, III,

and IV

The FDA under its general authority to regulate the labeling of drugs in commerce has added the requirement that prescription medication containers dispensed

to the ultimate user that contain

schedule

II,

III,

or IV substances

carry the following language: "Caution: Federal law prohibits the transfer of this drug to

any person other than

the person for

whom

it

was prescribed." 21 C.F.R. 290.5

The approved Spanish translation is: "Precaucion: La ley Federal prohibe el de esta droga a otra persona que no sea el paciente para quien fur recetada."

transferir

21 C.F.R. 201.16

The Spanish version is required for drugs dispensed in Puerto Rico. (With respect to the adequacy of an English language warning for a patient who neither speaks nor reads English see Cautionary Statements Foreign Languages, Chap-

—

ter 2).

92

Federal Controlled Substance Act

Notes

— Schedule

Exemptions from Labeling Requirements

II

Unit doses dispensed to a patient in a nursing home or other long-term care facility are exempt from container labeling requirements provided: 1.

2. 3.

4.

Not more than a seven-day supply is dispensed at one time. The drug is not in the possession of the patient prior to use. There is appropriate security maintained by the institution. The pharmacist has adopted a system that identifies the supplier, the product, the patient, the directions for use,

and cautionary statements. 21 C.F.R. 1306.14

Controlled substances dispensed by an individual practitioner directly to the ultimate user need not be labeled. 21 C.F.R. 1306.11

Why

Comment:

should the same drugs dispensed in the same amount by an

individual practitioner be treated differently than those dispensed by a phar-

macist? The answer must be political expediency because surely the of diversion

and

same

risks

dangers to health exist irrespective of the identity of the dis-

penser. Controlled substances dispensed by an institutional practitioner, such as a hospital,

pursuant user

(i.e.,

to

a

an order for medication for immediate administration to the ultimate bed patient) are exempt from labeling requirements.

LABELING THE MEDICATION CONTAINER FOR SCHEDULE IV SUBSTANCES The information required on the III

label of a

or IV controlled substances dispensed

tion

is

the

medication

same is

a

then

the date

on the

AND

medication container of schedule

by a pharmacy pursuant

as for a container of schedule

refill,

III

II

to a prescrip-

substances. However,

label of the refill is

if

the

the date or original

or initial dispensing.

In the case of an institutionalized patient, the labeling requirements do not apply provided no more than a 34-day supply is furnished, the patient does not have possession of the substance prior to administration, there is an institutional security system in effect, and the medication is dispensed in unit doses or some other system providing identical information.

TRANSFERRING PRESCRIPTIONS BETWEEN PHARMACIES The following

rules apply only to prescriptions for schedule

111,

IV,

and

V substances.

Purpose of Transfer

When a patient with a refillable prescription wishes to have the remaining authorized refills dispensed by another pharmacy, a procedure has been established to allow for the exchange of prescription information. Pharmacists' Responsibilities

The

transfer

must be communicated between two licensed pharmacists. The

transferring pharmacist must: 1.

2.

3.

Write

"VOID" on

the original prescription.

Record on the back the name, address, and DEA number of the pharmacy to which transferred and the date of transfer. Record the name of pharmacists transferring and receiving such information.

Prescriptions

93 Notes

The 1.

receiving pharmacist must:

Write

all

of the information required for a prescription as well as the

word

"transfer" on the face of the prescription. 2.

3.

Record the date of original prescription, original number of authorized refills,

date of original dispensing,

of last

refill.

number

of refills remaining,

Record the name, address, and DEA number and the name of the pharmacist.

Both pharmacies must maintain these records the last

of the transferring

for

two years

and date

pharmacy

after the date of

refill.

21 C.F.R. 1306.26

Chapter

Jy

DISPOSAL OF CONTROLLED SUBSTANCES

A

pharmacy desiring

to

dispose of controlled substances other than by

re-

turning them to the distributor must forward a letter to the regional field office of the DEA requesting disposal instructions and DEA form 41, the registrant's

inventory of drugs surrendered (Plate 10). The DEA will return form 41 and will specify the approved manner of disposal for example, dispose of the drugs in front of two witnesses, forward the drugs to a state agency, hold until the DEA can witness destruction, or ship to

—

the

DEA.

When a pharmacy basis, e.g., officer

when

is

required to dispose of controlled substances on a regular

a supply of drugs in a hospital

upon request

will establish a

is contaminated, the regional procedure for routine disposal by the reg-

istrant.

95

.

96

OMB No

Federal Controlled Substance Act

DRUG ENFORCEMENT ADM NIST R* T REGISTRANTS INVENTORY OF DRUGS SURRENDERED

DEPARTMENT OF JUSTICE

Approval 1117 0007

The following schedule

is

/

I

an inventory of controlled substances which

is

I

:

PACKAGE No

'

here jy surrendered to you

for proper disposition.

FROM:

(Include

Name,

Street. City, State

and ZIP Code

in

space provided below) Signature o> applicant or authorized agent

r

~l

Registrant's

L

DEA Number

_J Registrant'* Telephone

NOTE

Registrants will

fill

in

Columns

1, 2. 3,

Number

and 4 Only.

CONTENTS Number

(Number of

of

grams, tablet:

Con-

ounces or

tainers

other units per container

)

Con-

FOR DEA USE ONLY

trolled

Substance

Content.

DISPOSITION

(Each Unit)

2

1

3

QUANTITY GMS.

S

4

6

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

J

16

DEA Form (Mar

1980)

•

41

Previous edition

may be

used.

Plate 10

MGS.

See instructions on reverse side

97

Disposal of Controlled Substances

Number

NAME OF DRUG OB PREPARATION

CONTENTS

Con

(Number of

trolled

grams, tablets,

stance

Con-

ounces or other units per con-

Con-

tainers

tainer)

3

2

1

FOR DEA USE ONLY

Sub

of

QUANTITY DISPOSITION

tent

(Each

GMS

Unit)

4

MGS

6

5

7

17

11

19

a 21

22

23

24

The controlled substances surrendered

(2)

accordance with Title 21 of the Code cf Federal Regulations. Section 1307.21

in

packages purporting to contain the drugs

in

Destroyed

as

listed

on

this

inventory and have been

*

"(1

.

have beer, received

Forwarded tape -sealed without opening,

)

indicated and the remainder forwa'ded tape-sealed after verifying contents. (3) Forwarded tape-sealed after verifying contents

DATE

DESTROYED

19

BY:

WITNESSED BY

•• Strike out lines not applicable.

INSTRUCTIONS 1.

List the name of the drug in column 1. the number of containers in column 2. the size of each container in column 3. and in column 4 the controlled substance content of each unit described in column 3. e.g.. morphine sulfate tabs.. 3 pkgs.. 100 tabs 1/4 gr. (16 ml) or morphine sulfate tabs.. 1 pkg.. 83 tabs.. 1/2 gr. (32 m*.). etc. .

2. 3.

AU

packages included on a single line should be identical

in

name, content and controlled substance

strength.

quadruplicate Mail two (2) copies of this form to the Special Agent in Charge, under separate roier Enclose one additional copy in the shipment with the drugs. Retain one copv for your records One copy will be returned to \ ou as a receipt. No further receipt will be furnished to you unless specifically requested. Any furhter inquiries concerning these drugs should be addressed tr. the DE \ District Office which Prepare this form

in

serves your area. 4.

5.

is no provision for payment for drugs surrendered. This records of unwanted items.

There

is

merely a service rendered to registrants enabling them to clear their slocks and

Drugs should be shipped tape-sealed via prepaid expres' or registered mail DEA District Office which serves your area.

to Special

Agent In Charge. Drug Enforcement Administration, of the

PRIVACY ACT INFORMATION AUTHORITY:

Section 307 of the Controlled Substances Act of 1970

PURPOSE: To document

DEA ROUTINE USES:

(PL 91-513).

the surrender of controlled substances which have been forwarded by registrants to

for disposal.

This form

is

required by Federal Regulations for the surrender o' unwanted Controlled Substances.

Disclosures of information from this system are

made

to the following categories of users for the

purposes stated.

EFFECT

A

Other Federal law enforcement and regulatory agencies

B

State and local law enforcement and regulatory agencies

Failure to

document

the surrender of

for law

fc

laiv

unwanted Controlled Substances may

Controlled Substances Act.

Plate 10 Continued

enforcement and regulatory purposes

enforcement and regulatory purposes result in

prosecution fo' violation ol the

Chapter

1U

NATIVE AMERICAN CHURCH

is used by members of the Native American The Supreme Court of the United States has determined that regulation of their use of peyote is an unjustified intrusion by the state into their religion and violates their rights under the First Amendment.

Peyote, a schedule

Church

I

substance,

in religious ceremonies.

members of this church may possess this substance without being registered. Persons distributing or manufacturing the substance for them must, however, be registered and conform to the applicable laws. Accordingly, the

99

11

Chapter

VIOLATIONS OF THE CSA

PENALTIES Because there is a broad spectrum of crimes associated with drug abuse, the range of penalties for violations of the CSA is very wide. For instance, for simple unlawful possession of a controlled substance, the penalties range from immediate probation, with expungement of the offender's criminal record upon satisfactory completion of the probation, to up to one year's imprisonment and/ or a 5,000 dollar fine.

Under the Harrison Narcotic Act the maximum penalty that could be exacted was death (for sale of heroin to a minor). Under the present CSA, the maximum criminal penalty is life imprisonment and a 200,000 dollar fine for persons engaged

in a

continuing criminal enterprise.

The wide range of punishments is intended to allow the courts to distinguish between persons engaged in drug trafficking and those with lesser violations. There

is

a provision in the

law that allows

for a pre-sentence investigation after

conviction to determine whether the offender

is

"dangerous" or a "special

of-

fender" based on prior convictions, a pattern of dealing unlawfully in controlled substances, or membership in a conspiracy. Once such a special offender status has been fixed, the court may add up to 25 years of imprisonment onto the normal penalty for the offense. An example of the severity of the possible penalty that might be imposed on a practitioner is

It

shall be

found

in 21 U.S.C. 842.

unlawful for any person

.

.

.

to refuse or fail to

make, keep or furnish any record,

report, notification, declaration, order or order form, statement, invoice, or information required

under

this

subchapter

.

.

.

Any

person

who

violates this section

.

.

.

shall be subject to a civil

penalty of not more than $25,000.00. If the violation was committed knowingly, such person shall ... be sentenced to imprisonment of not more than one year and/or a $25,000 fine.

keep records may not be a crime, but will subject the If, however, the practitioner knowingly keep records, the same act becomes a crime, and the practitioner may

The negligent

failure to

practitioner to a substantial civil penalty. railed to

be fined as well as imprisoned.

The same

act that violates a provision of the federal

provision of state

CSA may violate

a similar

law. Each jurisdiction may prosecute and punish separately

without regard to the other.

imposed by the criminal law, both state who is licensed by the state to administer or dispense person and who convicted of violation of the CSA will unand is substances controlled In addition to incurring the penalties federal, a

101

102

Federal Controlled Substance Act

Notes

doubtedly be subject

to administrative disciplinary action to revoke,

suspend,

or restrict his authority to possess controlled substances.

CONTROLLED SUBSTANCE REGISTRANT PROTECTION ACT OF

1984

Congress has recognized that persons lawfully handling controlled subi.e., registrants and their agents, run a greater risk of burglaries and robberies than the general public. In an attempt to dissuade potential burglars and robbers, Congress enacted the Controlled Substance Registrant Protection Act, which raised the federal penalties for such crimes to a fine of up to 25,000 dollars and up to twenty years' imprisonment or both. If the crime results in significant bodily injury or death, penalty can run to life imprisonment. stances,

Chapter

1Z

ADMINISTRATIVE INSPECTIONS

HISTORY The Constitution

of the United States protects

all

citizens

from unreasonable

searches and seizures. In order to conduct a search or seize persons or things, law enforcement officers must first secure a warrant from a judge or magistrate.

The Fourth Amendment to the Constitution provides that a search warrant be issued only upon a sworn statement that a crime has been committed. The statement must also state where the officers will search and what they expect to find and seize or

whom they expect

to arrest.

a person consents to a search, a search warrant

If

An

administrative inspection

is

is not necessary. not a search within the meaning of the Fourth

Amendement. Comment: There

are significant legal differences between the two procedures. The following material is intended to highlight those differences. At times the procedures overlap and a practitioner may lose significant legal rights by failing to to

understand the nature of the proceeding. Accordingly practitioners are urged seek counsel at an early stage in any investigation, inspection, or search. The

cardinal principal to his

mouth

remember

is:

The

fish is

still

swimming

that did not

open

for the bait.

WHAT MAY

BE INSPECTED

AND WHEN

may be made of any controlled premises. A conpremises includes the place of business of any registrant, any place where controlled substances are stored, or a vehicle if the substances are in transit. It also includes any place where records of controlled substances are stored or maintained. The following may be inspected:

An

administrative inspection

trolled

2.

and forms required to be kept as well as physical inventory and prescriptions. Container, labels, and all equipment used to manufacture, distribute, or

3.

dispense controlled substances. Security systems.

1.

All records, reports,

An administrative warrant inspection may be made only in a reasonable manner and during regular business hours. Of course, this does not mean that the inspection must take place at the convenience of the owner or that the owner is required to remain open for the convenience of the inspectors. Comment: The owner

is

authority of the inspection. to arrange for

entitled to a receipt for It is

photocopying of

all

materials seized under

on a detailed any seized documents.

wise to

insist

receipt or, preferably,

103

104

Federal Controlled Substance Act

Notes

INSPECTION BY CONSENT

A DEA

inspector

may make an

inspection of a "controlled premises"

provided

the inspector:

owner

or person in charge his purpose.

1.

States to the

2.

Displays his credentials.

3.

Displays a Notice of Inspection.

4.

Receives informed consent of the

A

warrant

is

not necessary

if

owner

or person in charge.

the person in charge of the controlled premises

consents to the inspection or search.

The owner or the person

The consent the

owner

1.

is

The

owner

of the

entitled to

charge of the controlled premises will be asked

in

to sign a Consent to Inspection, to

which appears on the Notice of Inspection form. the inspection must be "informed." To be informed,

know:

real reason the inspector

is

there.

(Is

it

a routine inspection, or is the

inspector investigating alleged diversion?) 2.

What the inspector intends

3.

That the consent of the owner may be withdrawn

to inspect. at

any time during the

inspection and that the inspection must cease at that time. 4. 5.

That consent is purely voluntary. That anything found, including any statements made by the owner, may used against the owner in a civil or criminal trial.

be

21 C.F.R. 1316.05

//,

after the

owner or person

the inspection, the inspection

in

charge understands these rights, he then consents

may commence.

If

to

the person inspected does not under-

stand these rights, evidence developed during the inspection may not be admissible against the person in a subsequent trial. If, after an explanation of his rights, the owner, registrant, or person in charge refuses to consent to the inspection, the inspector must leave the premises and secure an administrative warrant of inspection.

INSPECTION BY ADMINISTRATIVE WARRANT If

the

owner or person in charge must apply to a judge for

inspector

refuses to consent to an inspection, the a warrant.

The

application contains the

following information:

1.

Name and

2.

A

3.

4.

1.

address of premises to be inspected. statement of authority to inspect, including a statement that such an inspection is necessary to insure compliance with the CSA. A statement as to the nature and extent of inspection including a request to seize specified items (e.g., prescriptions samples, or records. A statement of prior inspection history. Comment: Three points should be made: It is

not necessary to attempt a consensual inspection before applying for

Administrative Inspections

105 Notes

a warrant for an administrative inspection. Many law enforcement officers believe that the time lapse between the denial of consent and the securing of a warrant may result in a destruction of potentially incriminating evi-

2.

3.

dence. In applying for an administrative warrant, unlike a search warrant, it is not necessary to allege that a crime has been committed or to state "probable cause." One need only state that there is a valid public interest to secure compliance with the CSA. If the owner or person in charge still refuses inspection with a warrant,

he

is

subject to immediate arrest.

Chapter

ID

THEFT OF CONTROLLED SUBSTANCES

AND ORDER FORMS Upon

discovery of a theft of controlled substances, the registrant must: Report the DEA and the local police.

theft to the

The report to the DEA is made on form 106 (Plate 11) and shows the store name, address, and DEA number, the type of theft, any internal store coding on containers, the branch of local police notified, and the amount of controlled substances stolen. The report is made in triplicate. One copy is retained by the registrant (pharmacy or practitioner) with its drug acquisition and dispersal records, and two copies are forwarded to the DEA. Comment: The most common error of individual practitioners and pharmacies after a theft is to neglect to report to the DEA on form 106. The practitioner has probably filled out a detailed report and inventory for the local police as well as the insurance carrier. Neither of these

is

an acceptable record of

loss.

Form

106 must be kept with the acquisition and dispersal records, separate from other

business records, for two years. Upon discovery of the loss or theft of federal order forms, used or unused, the registrant

must promptly

notify the

bers of the stolen order forms,

if

DEA

of the theft

and report the

serial

num-

known. 21 C.F.R. 1305.12

107

U.S.

DEPARTMENT OF JUSTICE

/

DRUG ENFORCEMENT ADMINISTRATION

OMB APPROVAL

REPORT OF THEFT OR LOSS OF CONTROLLED SUBSTANCES

\o

I

117 0001

Federal Regulations require registrants to submit a detailed report of any theft or loss of Controlled Substances to the Drug

Enforcement Administration. Complete the front and back of this form in tiipUcate. Forward the Office. Retain the triplicate copy for your records. 1.

NAME AND ADDRESS OF REGISTRANT

3.

PRINCIPAL BUSINESS OF REGISTRANT (Check 1

I

2

|

L)

Pharmacy

31

Practitioner

4

[

1

J

CODE

ZIP

one)

4.

2

Manufacturer/Distributor

2

DEA REGISTRATION NUMBER Itr.

DEA

and duplicate copies to the nearest

(Include ZIP Code)

5.

7 digit suffix

prefix

Regional

PHONE NO.

(Include Area Code)

COUNTY IN WHICH REGISTRANT IS LOCATED

Other

DATE OF THEFT OR LOSS

6.

original

7.

NUMBER OF THEFTS OR LOSSES REGISTRANT EXPERIENCED IN LAST 12 MONTHS

WAS THEFT OR LOSS REPORTED TO

8.

POLICE

,-.

,—.

Jno

LJyes

NAME AND ADDRESS OF POLICE DEPARTMENT

9.

1

0.

TYPE OF THEFT OR LOSS [Check One and complete 1

2 3

1

J

I

J

I

I

items below as appropriate)

Night Break — In (complete Item 11 below)

4

[

|

Customer

Armed Robbery (complete Item 12 below)

5

1

I

Other (specify)

Employee Theft

6

NIGHT BREAK-IN, WHAT WAS THE POINT OF ENTRY?

11. IF

J

Lost

in

IF LOST IN TRANSIT. COMPLETE THE FOLLOWING: Name of Common Carrier B. Name

D.

Was

13.

the carton received at

7

E. If so,

D

YES

of Consignee

did

it

(If

YES,

HOW

C. Consignee's

appear to be tampered with 7

(Z)yes

WHAT IDENTIFYING MARKS. SYMBOLS OR

16a. IF

17.

by the customer

NO

F.

Qno

Was

7

7

)

DEA

Registration

Number

State regulatory agency notified 7

Qyes

Qno

OFFICIAL CONTROLLED SUBSTANCES ORDER FORMS WERE STOLEN, GIVE NUMBERS.

14. IF

15.

all

Qno

Qyes

Transit (complete Item 13 below)

ARMED ROBBERY, WAS ANYONE INJURED

12. IF

D

A.

Pilferage

CASH WAS TAKEN, WHAT AMOUNT

PRICE CODES

WERE ON THE LABELS OF THESE CONTAINERS

?

16b.

IF

?

(Insert

MERCHANDISE WAS TAKEN. VALUE

WHAT SECURITY MEASURES HAVE BEEN TAKEN TO PREVENT FUTURE THEFTS OR LOSSES

your pricing codes)

7

?

PRIVACY ACT INFORMATION

AUTHORITY:

Section 301 of the Controlled Substances Act of 1970 (PL 91-513)

PURPOSE: Report

ROUTINE USES:

theft or loss of Controlled Substances

The Controlled Substances Act Registration Records produces special reports as required for statistical analytical purposes. Disclosures of information from this system are made to the following categories of users for the purposes stated:

A. Other Federal law enforcement and regulatory agencies for law enforcement and regulatory purposes B. State and local law enforcement and regulatory agencies for law enforcement and regulatory purposes C.

EFFECT:

Persons registered under the Controlled Substances Act (Public the registration of customers and practitioners

Failure to report theft or loss of controlled substances

may

Law 91-513)

result in penalties

under Section 402 and 403 of the Controlled

Substances Act.

PEA Form (Apr. 1981)

106

Previous editions are

Plate 11

for the purpose of verifying

OBSOLETE.

LIST

NAME OF SUBSTANCE OR PREPARATION EX:

EMPIRIN

++ 3

OF CONTROLLED SUBSTANCES LOST DOSAGE FORM AND STRENGTH

NAME OF CONTROLLED SUBSTANCE IN PREP CODEINE

TOTAL NET WT. (Gml.l OF QUANTITY CONTROLLED INGREDIENT

30 Mg Tab.

100

3

1.

2. 3.

4. 5.

6. 7.

8. 9.

10.

11. 12.

13. 14. 15.

16 17. 18.

19.

20. 21.

22 23. 24.

25. 26.

27.

28 29 30. 31. 32. 33. 34.

35. 36. 37.

FOR DEA REGIONAL USE ONLY AMPHETAMINES BARBITURATES COCAINE CODEINE DIHYDROCO DEI NONE DILAUDID

METHADONE METHAMPHETAMINE

GRAMS I

certify that the foregoing information

correct to the best of belief.

Sii mature

MORPHINE

NUMORPHAN OPIUM

Title

OXYCODONE PETHIDINE

OTHER

(Lilt)

Dc

te

Plate 11 Continued

my

is

knowledge and

Chapter lrr

PACKAGING AND MAILING A CONTROLLED SUBSTANCE PRESCRIPTION

PACKAGING A CONTROLLED SUBSTANCE Any preparation for human use that consists in whole or in part of any controlled and that is in a dosage form intended for oral administration shall be packaged in a child-resistant container. For a discussion of the Poison Prevention Packaging Act of 1970 and the application of that act to prescribers as well as pharmacists, see the Poison Prevention and Packaging Act section in Chapter 2.

substance

15 U.S.C. 1471-76

16 C.F.R. 1700

Comment: The Poison Prevention Packaging Act

of 1970 considers all controlled substances as requiring special packaging, accordingly all prescription medication containing these substances unless exempted by direction of the prescriber or patient must be dispensed in these containers. {See supra: P. P. P. A. part 1, pgs 51-54.)

MAILING A CONTROLLED SUBSTANCE Regulations of U.S. Postal Service 39CFR.124.5, 124.364-5. Domestic Mail

Manual

Between Registrants Controlled substances may be mailed, presumably in any amount, between persons exempt from registration. There must be an inner container that is properly labled and securely sealed. There must be a plain outer container or the inner container must be overwrapped in plain paper with no markings to indicate the contents. registrants or

Between

a Registered Practitioner

and

a Patient

Prescription medications containing narcotic drugs to certain veterans.

may

not be mailed, except

by the Veteran's Administration

Ill

112

Federal Controlled Substance Act

Notes

Prescription medicines containing non-narcotic controlled substances may be mailed from a registered practitioner or dispenser to an ultimate user. The inner container must be properly labeled and securely sealed and placed in a plain outer container or overwrapped in plain paper with no markings indicating the contents of the package. 21 U.S.C. 801

Comment: Originally, postal regulations placed quantity limitations upon the amount of controlled substances that could be mailed to an ultimate user. Those restrictions

have been removed. Substantial quantities of controlled substances alternative competing carriers which do not impose the

now move through

restricitons of the U.S. Postal Service.

—

—

APPENDIX A Selected Portions of the Food, Drug,

Cosmetic Act,

Title 21,

SUBCHAPTER II— DEFINITIONS § 321 Definitions; generally

For the purposes of this chapter (g)(1) The term "drug" means (A) articles recognized in the official United States

Pharmacopoeia, official Homoeopathic Pharmacopoeia of the United States, or official National Formularly, or any supplement to any of them; and (B) articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and (C) articles (other than food) intended to affect the structure or any function of the body of man or other animals; and (D) articles intended for use as a component of any article specified in clauses (A), (B), or (C) of this paragraph; but does not include devices or their components, parts, or accessories.

a

(2) The term "counterfeit drugs" means drug which, or the container or labeling

of which, without authorization, bears the trademark, trade name, or other identify-

ing mark, imprint, or device, or any likeness thereof, of a drug manufacturer, processor, packer, or distributor other than the person or persons who in fact manufactured, processed, packed, or distributed such drug and which thereby falsely purports or is represented to be the product of, or to have been packed or distributed by, such other drug manufacturer, processor, packer, or distributor. (h) The term "device" (except when used in paragraph (n) of this section and in sections 331(i), 343(f), 352(c), and 362(c) of this title) means an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or ac-

cessory,

which

is

recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them, (1)

United States

and Code

(2) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or (3) intended to affect the structure or any function of the body of man or other animals, and

which does not achieve any

of

its

principal

intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its principal intended purposes. (i) The term "cosmetic" means (1) articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance, and (2) articles intended for use as a component of any such articles; except that such term shall not include soap. "official compendium" the official United States Pharmacopoeia, official Homeopathic Pharmacopoeia of the United States, official National Formulary, or any supplement to any of (j)

The term

means

them. (k)

The term "label" means

a display of

written, printed, or graphic matter

upon

the immediate container of any article; and a requirement made by or under authority of this chapter that any word, statement, or other information appear on the label

be considered to be complied with unless such word, statement, or other information also appears on the outside container or wrapper, if any there be, of the

shall not

retail

package of such article, or is easily through the outside container or

legible

wrapper. (1) The term "immediate container" does not include package liners. (m) The term "labeling" means all labels and other written, printed, or graphic mat-

113

—

—

114

Appendix

—

A

Notes ter (1)

upon any

article

or any of

tainers or wrappers, or (2)

such

its

con-

accompanying

article.

If an article is alleged to be misbranded because the labeling or advertising is misleading, then in determining whether

(n)

the labeling or advertising is misleading there shall be taken into account (among

other things) not only representations made or suggested by statement, word, design, device, or any combination thereof, but also the extent to which the labeling or advertising fails to reveal facts material in the light of such representations or material with respect to consequences which may result from the use of the article to which the labeling or advertising relates under the conditions of use prescribed in the labeling or advertising thereof or under such conditions of use as are customary or usual. (o) The representation of a drug, in its labeling, as an antiseptic shall be considered to be a representation that it is a germicide, except in the case of a drug purporting to be, or represented as, an antiseptic for inhibitory use as a wet dressing, ointment, dusting powder, or such other use as involves prolonged contact with the body. (p)

The term "new drug" means

not generally recognized,

by

among

scientific training

experts

and and

ex-

perience to evaluate the safety effectiveness of drugs, as safe and effective for use under the conditions prescribed, recommended, or suggested in the labeling thereof, except that such a drug not so recognized shall not be deemed to be a "new drug" if at any time prior to June 25, 1938, it was subject to the Food and Drugs Act of June 30, 1906, as amended, and if at such time its labeling contained the same representations concerning the conditions of its use; or (2) Any drug (except a new animal drug or an animal feed bearing or containing a new animal drug) the composition of which is such that such drug, as a result of investigations to

determine

its

and

effectiveness for use under such conditions, has become so recognized, but which has not, otherwise than in such investigations, been used to a safety

material extent or for a material time under such conditions. (t)(l)

The term "color additive" means which

a

material (A)

stance

is

a dye, pigment, or other sub-

made by

except that such term does not include any material which the Secretary, by regula-

determines is used (or intended to be used) solely for a purpose or purposes other than coloring. (2) The term "color" includes black, white, and intermediate grays. tion,

(3) Nothing in subparagraph (1) of this paragraph shall be construed to apply to

any pesticide chemical,

soil or plant nuother agricultural chemical solely because of its effect in aiding, retarding, or otherwise affecting, directly or indirectly, the growth or other natural physiological processes of produce of the soil and thereby affecting its color, whether before or after

trient, or

harvest. (u) (s)

The term "safe" as used in paragraph and in sections 348, 360b,

of this section

and 376

of this

health of

(1) Any drug (except a new animal drug or an animal feed bearing or containing a new animal drug) the composition of which is such that such drug is

qualified

otherwise derived, with or without intermediate or final change of identity, from a vegetable, animal, mineral, or other source, and (B) when added or applied to a food, drug, or cosmetic, or to the human body or any part thereof, is capable (alone or through reaction with other substance) of imparting color thereto;

a process of synthesis or

similar artifice, or extracted, isolated, or

(v)

man

title,

has reference to the

or animal.

Repealed. Pub. L. 91-513,

title II,

§

701(a), Oct. 27, 1970, 84 Stat. 1281.

(w) The term "new animal drug" means any drug intended for use for animals other than man, including any drug intended for

use in animal feed but not including such animal feed, the composition of which is such drug is not generally recognized, among experts qualified by scientific training and experience to evaluate the safety and effectiveness of animal drugs, as safe and effective for use under (1)

that such

the conditions prescribed, recommended, or suggested in the labeling thereof; except that such a drug not so recognized shall not be deemed to be a "new animal drug" if at any time prior to June 25, 1938, it was subject to the Food and Drug Act of June 30, 1906, as amended, and if at such time its labeling contained the same representations concerning the conditions of its use; or (2) the composition of which is such that such drug, as a result of investigations to determine its safety and effectiveness for use under such conditions, has become so recognized but which has not, otherwise than in such investigations,

been used

to a material extent or

for a material time

under such condi-

tions; or (3)

which drug is composed wholly or any kind of penicillin, strep-

partly of

)

Appendix

A

115 Notes

tomycin, chlortetracycline, chloramphenicol, or bacitracin, or any derivative

ized or required by regulations promulgated under the provisions of sections 344,

thereof, except when there is in effect a published order of the Secretary declaring such drug not to be a new animal

356, 357, or 376 of this

drug on the grounds that (A) the require-

or concealing any punch, die, plate, stone, or other thing designed to print, imprint,

ment

of certification of batches of such drug, as provided for in section 360b(n) of this title, is not necessary to insure that the objectives specified in paragraph (3)

thereof are achieved

and

(B) that neither

subparagraph (1) nor (2) of this paragraph (w) applies to such drug. § 331. Prohibited acts

The following acts and the causing thereof are prohibited: (a) The introduction or delivery for introduction into interstate commerce of any food, drug, device, or cosmetic that is adulterated or misbranded. (b) The adulteration or misbranding of any food, drug, device, or cosmetic in in-

commerce. The receipt in

terstate (c)

commerce

of

otherwise.

keeping

title.

selling,

disposing

of,

or

in possession, control, or custody,

or reproduce the trademark, trade name, or other identifying mark, imprint, or device of anothpr or any likeness of any of the foregoing upon any drug or container or labeling irtereof so as to render such drug a counterfeit drug. (3) The doing of any act which causes a drug to be a counterfeit drug, or the sale or dispensing, or the holding for sale or dispensing, of a counterfeit drug. (j) The using by any person to his own advantage, or revealing, other than to the

Secretary or officers or employees of the Department, or to the courts when relevant in

any judicial proceeding under this chapany information acquired under au-

ter,

The introduction or delivery for introduction into interstate commerce of any article in violation of section

344 or 355 of

this title. (e) The refusal to permit access to or copying of any record as required by sec-

tion 350a or 373 of this

357, 360, 360b, 360c, 360d, 360e, 360f, 360h,

379 of this title concerning any method or process which as a

360i, 360j, 374, 376, or

trade secret (k)

(d)

title;

or the failure

establish or maintain any record, or make any report, required under section 350a, 355(i) or (j), 357(d) or (g), 360b(j), (1), or (m), 360e(f), or 360i of this title, or the to

refusal to permit access to or verification or copying of any such required record.

The

refusal to permit entry or inspection as authorized by section 374 of this title.

The manufacture within any Territory any food, drug, device, or cosmetic that

(g)

of

Making,

thority of section 344, 348, 350a, 355, 356, interstate

any food, drug, device, or cosmetic that is adulterated or misbranded, and the delivery or proffered delivery thereof for pay or

(f

(2)

adulterated or misbranded. The giving of a guaranty or undertaking referred to in section 333(c)(2) of this title which guaranty or undertaking is false, except by a person who relied upon a guaranty or undertaking to the same effect signed by, and containing the name and address of, the person residing in the United States from whom he received in good faith the food, drug, device, or cosmetic; or the giving of a guaranty or un-

is

(h)

dertaking referred to in section 333(c)(3) of this title which guaranty or undertaking is false. (i)(l) Forging, counterfeiting, simulating, or falsely representing, or without proper

authority using any mark, stamp, tag, label, or other identification device author-

The

is

entitled to protection.

alteration,

mutilation, destruc-

removal of the whole or any part of the labeling of, or the doing of any other act with respect to, a food, drug, device, or cosmetic, if such act is done while such article is held for sale (whether or not the first sale) after shiption, obliteration, or

ment such

commerce and results in being adulterated or mis-

in interstate

article

branded.

The using, on the labeling of any drug any advertising relating to such drug or device, of any representation (1)

or device or in

or suggestion that approval of an application with respect to such drug or device is in effect under section 355, 360e, or 360j(g) title, as the case may be, or that such drug or device complies with the provisions of such section.

of this

(m) The sale or offering for sale of colored oleomargarine or colored margarine, or the possession or serving of colored oleomargarine or colored margarine in violation of subsections (b) or (c) of section 347 of this title.

(n) The using, in labeling, advertising or other sales promotion of any reference to any report or analysis furnished in compliance with section 374 of this title. (o) In the case of a prescription drug distributed or offered for sale in interstate commerce, the failure of the manufacturer, packer, or distributor thereof to maintain for transmittal, or to transmit, to any practitioner licensed by applicable State law to administer such drug who makes written

—

116

Appendix

A

Notes request for information as to such drug, true and correct copies of all printed matter which is required to be included in any

package in which that drug is distributed or sold, or such other printed matter as is approved by the Secretary. Nothing in this paragraph shall be construed to exempt any person from any labeling requirement imposed by or under other provisions of this

contents injurious to health; or (4) if (A) it bears or contains, for purposes of coloring only, a color additive which is unsafe within the meaning of section 376(a) of this title, or (B) it is a color additive the intended use of which in or on drugs or devices is for purposes of coloring only and is unsafe within the meaning of section 376(a) of this or (5) if it is a new animal drug which unsafe within the meaning of section 360b of this title; or (6) if it is an animal feed bearing or containing a new animal drug, and such animal feed is unsafe within the meaning of section 360b of this title. title;

chapter. (p) The failure to register in accordance with section 360 of this title, the failure to provide any information required by sec-

tion 360(j) or 360(k) of this title, or the failure to provide a notice required by section 360(j)(2) of this (q)(l)

The

title.

failure or refusal to (A)

comply

with any requirement prescribed under section 360h or 360k(g) of this title, or (B) furnish any notification or other material or information required by or under section 360i or 360j(g) of this title. (2) With respect to any device, the submission of any report that is required by or under this chapter that is false or misleading in any material respect. (r) The movement of a device in violation of an order under section 344(g) of this title or the removal or alteration of any mark or label required by the order to identify the device as detained. (s) The failure to provide the notice required by section 350a(b) or 350a(c), the failure to make the reports required by section 350a(d)(l)(B), or the failure to meet the re-

quirements prescribed under section 350a(d)(2).

and devices

A drug or device shall be adulterated

deemed

to

be

Poisonous, insanitary, etc., ingredients; adequate controls in manufacture

(1) If

it

whole or in part of any decomposed substance; or

consists in

filthy, putrid,

or

if it has been prepared, packed, or held under insanitary conditions whereby it may have been contaminated with filth,

(2)(A)

or whereby it may have been rendered injurious to health; or (B) if it is a drug and the methods used in, or the facilities or con-

used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirements of this chapter as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess; or (3) if its container is composed, in whole or in part, of any poisonous or deleterious substance which may render the trols

(b)

Strength, quality, or purity differing

from

official

compendium

If it purports to be or is represented as a drug the name of which is recognized in an official compendium, and its strength

differs from, or its quality or purity falls below, the standard set forth in such compendium. Such determination as to strength, quality, or purity shall be made in accordance with the tests or methods of assay set forth in such compendium, except that whenever tests of methods of assay have not been prescribed in such compendium, or such tests or methods of assay as are prescribed are, in the judgment of the Secretary, insufficient for the making of such determination, the Secretary shall bring such fact to the attention of the appropriate body charged with the revision

of such

§ 351. Adulterated drugs

(a)

is

compendium, and

if

such body

fails

within a reasonable time to prescribe tests or methods of assay which, in the judgment of the Secretary, are sufficient for purposes of this subsection, then the Secretary

promulgate regulations prescribing appropriate tests or methods of assay in accordance with which such determination as to strength, quality, or purity shall be made. No drug defined in an official compendium shall be deemed to be adulterated shall

under this subsection because it differs from the standard of strength, quality, or purity therefor set forth in such compendium, if its difference in strength, quality, or purity from such standard is plainly stated on its label. Whenever a drug is recognized in both the United States Pharmacopoeia and the Homoeopathic Pharmacopoeia of the United States it shall be subject to the requirements of the United States Pharmacopoeia unless it is labeled

and offered for sale as a homoeopathic drug, in which case it shall be subject to the provisions of the Homoeopathic Pharmacopoeia of the United States and not to those of the United States Pharmacopoeia.

—

—

—

Appendix

A

117 Notes

Misrepresentation of strength, where drug is unrecognized in

(c)

etc.,

If it

is

not subject to the provisions of its

strength differs from, or its purity or quality falls below, that which it purports or is represented to possess. (d)

solely for investigational

use, paragraph (1)(B) shall not apply with

compendium subsection (b) of this section and

and intended

III

Mixture with or substitution of another substance

a drug and any substance has been mixed or packed therewith so as to reduce its quality or strength or (2) substiIf it is

respect to such device during the period ending on the ninetieth day after the date of the promulgation of the regulations prescribing the procedures and conditions required by section 360j(g)(2) of this title. (B) In the case of a device subject to a regulation promulgated under subsection (b) of section 360e of this title, paragraph (1) shall not apply with respect to such device during thp period ending (i) on the last day of the thirtieth calendar month beginning after the month

(1)

tuted wholly or in part therefor.

in

which the classification of the device III became effective under section

in class

Devices not in conformity with performance standards

(e)

or purports to be or is represented device which is subject to a performance standard established under section 360d of this title unless such device is in all respects in conformity with such standard.

360c of this title, or (ii) on the ninetieth day after the date of the promulgation of such regulation,

If it is,

as, a

(f)

Certain class

III

devices

(1) If it is a class III

whichever occurs (g)

Banned devices

If it is

(h)

device

later.

a

banned

device.

Manufacture, packing, storage, or installation of device not in

which is required by a regulation promulgated under subsection (b) of section 360e of this title to have an approval under such section of an application for premarket approval and which is not exempt from section 360e of this title under section 360(g) of this title, and (h)(1) for which an application for premarket approval or a notice of completion of a product development protocol

conformity with applicable requirements or conditions

(A)(i)

If it is

a device

and the methods used

in,

or the facilities or controls used for, its manufacture, packing, storage, or installation are not in conformity with applicable requirements under section 360j(f)(l) of this title or an applicable condition prescribed

by an order under section

360j(f)(2) of this

title.

was not

filed with the Secretary within the ninety-day period beginning on the date of the promulgation of such regulation, or (II) for which such an application was filed and approval of the application has been denied or withdrawn, or such a notice was filed and has been declared not completed or the approval of the device

under the protocol has been withdrawn; (B)(i) which was classified under section 360c(f) of this

title

into class

III,

which under section 360e(a) of this title is required to have in effect an approved application for premarket approval, and which is not exempt from section 360e of this title under section 360j(g) of this title, and (ii) which does not have such an application in effect; or

under section III, which under such section is required to have in effect an approved application under section 360e of this title, and which does not have such an application in effect. (C)

which was

comply with requirements under which device was exempted for Failure to

(i)

investigational use a device for which an exemption has been granted under section 360j(g) of this title for investigational use and the person who was granted such exemption or any investigator who uses such device under such exemption fails to comply with a requirement prescribed by or under such If it is

section.

§ 352.

Misbranded drugs and devices

A drug or device misbranded (a)

shall

be deemed to be

False or misleading label

If its

labeling

is

false or

misleading in any

particular.

classified

Package form; contents of label

360j(l) of this title into class

(b)

(2)(A) In the case of a device classified this title into class

If in package form unless it bears a label containing (1) the name and place of business of the manufacturer, packer, or distributor; and (2) an accurate statement of the quantity of the contents in terms of weight, measure, or numerical count: Pro-

under section 360c(f ) of

Appendix A

118 Notes vided,

That under clause

(2) of this

subsec-

be permitsmall packages

tion reasonable variations shall

and exemptions as to be established, by regulations prescribed by the Secretary.

ted,

shall

on any labeling on which a name for such drug or ingredient is used) is printed prominently and in type at least half as large as that used thereon for any proprietary name or designation for such drug or ingredient: Provided, That to the extent that compliance

Prominence of information on label

(c)

any word, statement, or other information required by or under authority of this chapter to appear on the label or laIf

is not prominently placed thereon with such conspicuousness (as compared with other words, statements, designs, or devices, in the labeling) and in such terms as to render it likely to be read and understood by the ordinary individual under customary conditions of purchase and use.

beling

(d)

Habit forming substances

for use by man and contains any quantity of the narcotic or hypnotic substance alpha eucaine, barbituric acid, betaeucaine, bromal, cannabis, carbromal, chloral, coca, cocaine, codeine, heroin, If it is

marihuana, morphine, opium, paraldehyde, peyote, or sulphonmethane; or any chemical derivative of such substance, which derivative has been by the Secretary, after investigation, found to be, and by regulations designated as, habit forming; unless its label bears the name and quantity or proportion of such substance or derivative and in juxtaposition therewith the statement "Warning May be habit form-

—

ing." (e)

Designation of drugs or devices by established

(1) If

it is

names

a drug, unless (A) its label bears,

to the exclusion of

any other nonproprie-

name (except the applicable systematic chemical name or the chemical formula), (i) the established name (as defined in subtary

paragraph

(3))

of the drug,

if

such there be,

and (ii) in case it is fabricated from two or more ingredients, the established name and quantity of each active ingredient, including the quantity, kind, and proportion of any alcohol, and also including, whether active or not, the established name and quantity or proportion of any bromides, ether, chloroform, acetanilid, acetpheneti-

din, amidopyrine,

antipyrine, atropine, hyoscine, hyoscyamine, arsenic, digitalis, digitalis glucosides, mercury ouabain strophanthin, strychnine, thyroid, or any derivative or preparation of any such substances, contained therein; Provided, That the requirement for stating the quantity of the active ingredients, other than the quantity of those specifically named in this paragraph, shall apply only to prescription drugs; and (B) for any prescription drug the established name of such drug or ingredient, as the case may be, on such label (and

with the requirements of clause (A)(ii) or clause (B) of this subparagraph is impracticable, exemptions shall be established by regulations promulgated by the Secretary. (2) If it is a device and it has an established name, unless its label bears, to the exclusion of any other nonproprietary name, its established name (as defined in subparagraph (4)) prominently printed in type at least half as large as that used thereon for any proprietary name or designation for such device, except that to the extent compliance with the requirements of this subparagraph is impracticable, exemptions shall be established by regulations promulgated by the Secretary. (3) As used in subparagraph (1), the term "established name", with respect to a drug or ingredient thereof, means (A) the applicable official

name designated pursuant

to section 358 of this

title,

or (B),

if

there

is

no such name and such drug, or such ingredient, is an article recognized in an official compendium, then the official title thereof in such compendium, or (C) if neither clause (A) nor clause (B) of this subparagraph applies, then the common or usual name, if any, of such drug or of such ingredient: Provided further, That where clause (B) of this subparagraph applies to an article recognized in the United States

Pharmacopeia and in the Homoeopathic Pharmacopoeia under different official titles, the official title used in the United States Pharmacopeia shall apply unless it labeled and offered for sale as a eopathic drug, in which case the is

title

used

in

homoofficial

Homoeopathic Pharmacopoeia

shall apply. (4) As used in subparagraph (2), the term "established name" with respect to a device means (A) the applicable official name of the device designated pursuant to section 358 of this title, (B) if there is no such name and such device is an article recognized in an official compendium, then the official title thereof in such compendium, or (C) if neither clause (A) nor clause (B) of this subparagraph applies, then any common or

usual (f )

name

of such device.

Directions for use and warnings on label

its labeling bears (1) adequate directions for use; and (2) such adequate warnings against use in those pathological

Unless

conditions or by children where its use may be dangerous to health, or against unsafe dosage or methods or duration of admin-

Appendix

A

119 Notes

istration or application, in

such manner and

Health-endangering

(j)

form, as are necessary for the protection of users: Provided, That

where any

require-

when used

as

prescribed

of clause (1) of this subsection, as applied to any drug or device, is not necessary

dangerous to health when used in the dosage or manner, or with the frequency or duration prescribed, recom-

for the protection of the public health, the

mended, or suggested

ment

Secretary shall promulgate regulations exempting such drug or device from such re-

quirement.

If it is

(k)

Insulin not properly certified

If it is,

(g)

Representations as recognized drug;

packing and labeling; inconsistent requirements for designation of drug purports to be a drug the name of is recognized in an official compendium, unless it is packaged and labeled as prescribed therein: Provided, That the method of packing may be modified with the consent of the Secretary. Whenever a drug is recognized in both the United States Pharmacopoeia and the Homoeopathic Pharmacopoeia of the United States, it shall be subject to the requirements of the United States Pharmacopoieia with respect to packaging and labeling unless it is labeled If it

which

and offered for sale as a homoeopathic drug, in which case it shall be subject to the provisions of the Homoeopathic Pharmacopoeia of the United States, and not those of the United States Pharmacopoeia: Provided further, That, in the event of inconsistency between the requirements of this subsection and those of subsection (e) of this section as to the name by which the drug or its ingredients shall be designated, the requirements of subsection (e) of this section shall prevail. drugs; packing and

labeling If it has been found by the Secretary to be a drug liable to deterioration, unless it is packaged in such form and manner, and its label bears a statement of such precau-

tions, as the Secretary shall

by regulations

require as necessary for the protection of the public health. No such regulation shall be established for any drug recognized in an official compendium until the Secretary shall have informed the appropriate body charged with the revision of such compendium of the need for such packaging or labeling requirements and such body shall have failed within a reasonable time to prescribe such requirements.

(i)

Drug; misleading container; imitation; offer for sale under another name

(1) If it is a drug and its container is so made, formed, or filled as to be misleading; or (2) if it is an imitation of another drug; or (3) if it is offered for sale under the name

of another drug.

or purports to be, or

as a drug

is

composed wholly

represented or partly of

insulin, unless (1) it is from a batch with respect to which a certificate or release has

been issued pursuant to section 356 of this title, and (2) such certificate or release is in effect with respect to such drug. (1)

Antibiotic drugs improperly certified or purports to be, or

is represented use in animals other than man) composed wholly or partly of any kind of penicillin, streptomycin, chlortetracycline, chloramphenicol, bacitracin, or any other antibiotic drug, or any If it is,

as a

drug (except

a

drug

for

derivative thereof, unless (1) it is from a batch with respect to which a certificate or release has been issued pursuant to section 357 of this title, and (2) such certificate or release is in effect with respect to such drug: Provided, That this subsection shall not apply to any drug or class of drugs exempted by regulations promulgated

under section

357(c) or (d) of this

title.

(m) Color additives; packing and labeling

intended use purpose of coloring only, unless its packaging and labeling are in conformity with such packaging and labeling requirements applicable to such color of

(h) Deteriorative

in the labeling

thereof.

If it is

a color additive the

which

is

for the

additive, as

may

tions issued

under section 376 of

be contained in regulathis title.

drug advertisements: established name; quantitative formula; side effects, contraindications, and effectiveness; prior approval; false advertising; labeling; construction of the Convention on Psychotropic

(n) Prescription

Substances In the case of any prescription drug distributed or offered for sale in any State,

unless the manufacturer, packer, or distributor thereof includes in all advertisements and other descriptive printed matter issued or caused to be issued by the manufacturer, packer, or distributor with respect to that drug a true statement of (1) the established name as defined in subsection (e) of this section, printed prominently and in type at least half as large as that used for any trade or brand name thereof, (2) the

Appendix

120

A

Notes

formula showing quantitatively each ingredient of such drug to the extent required for labels tion,

and

under subsection (e) of this secsuch other information in brief

(3)

summary

relating to side effects, contrain-

dications,

and effectiveness as shall be reregulations which shall be issued

quired in by the Secretary in accordance with the procedure specified in section 371(e) of this title: Provided, That (A) except in extraordinary circumstances, no regulation issued under this subsection shall require prior approval by the Secretary of the content of any advertisement, and (B) no advertisement of a prescription drug, published after the effective date of regulations issued under this subsection applicable to advertisements of prescription drugs, shall with respect to the matters specified in this subsection or covered by such regulations, be subject to the provisions of sections 52 to 57 of title 15. This subsection (n) shall not be applicable to any printed matter which the Secretary determines to be labeling as defined in section 321(m) of this title. Nothing in the Convention on Psychotropic Substances, signed at Vienna, Austria, on February 21, 1971, shall be construed to prevent drug price communications to consumers.

Drugs or devices from nonregistered

(0)

Restricted devices not carrying requisite accompanying statements in advertisements and other descriptive printed matter

(r)

establishments

was manufactured, prepared, propagated, compounded, or processed in an establishment in any State not duly registered under section 360 of this title, if it was not included in a list required by section 360(j) of this title, if a notice or other information respecting it was not provided as required by such section or section 360(k) of this title, or if it does not bear such symbols from the uniform system for identification of devices prescribed under section 360(e) of this title as the Secretary by regulation requires. If it

In the case of any restricted device distributed or offered for sale in any State,

unless the manufacturer, packer, or distributor thereof includes in all advertisements and other descriptive printed matter issued or caused to be issued by the manufacturer, packer, or distributor with respect to that device (1) a true statement of the device's established name as defined in subsection (e) of this section, printed prominently and in type at least half as large as that used for any trade or brand name thereof, and (2) a brief statement of the intended uses of the device and relevant warnings, precautions, side effects, and contraindications and, in the case of specific devices made subject to a finding by the Secretary after notice and opportunity for comment that such action is necessary to protect the public health, a full description of the components of such device or the formula showing quantitatively each ingredient of such device to the extent required in regulations which shall be issued by the Secretary after an opportunity for a hearing. Except in extraordinary circumstances, no regulation issued under this paragraph shall require prior approval by the Secretary of the content of any advertisement and no advertisement of a restricted device, published after the effective date of this paragraph shall, with respect to the matters specified in this paragraph or covered by regulations issued hereunder, be subject to the provisions of sections 52 through 55 of title 15. This paragraph shall not be applicable to any printed matter which the Secretary determines to be labeling as defined in section 321 (m) of this title.

(s)

Devices subject to performance standards not bearing requisite labeling

(p)

Packaging or labeling of drugs in violation of regulations

drug and its packaging or labeling an applicable regulation issued pursuant to section 1472 or 1473 of If it is

is

a

in violation of

a device subject to a performance standard established under section 360d of this title, unless it bears such labeling as may be prescribed in such performance If it is

standard.

title 15. (t)

Devices for which there has been a failure or refusal to give required

devices using false or misleading advertising or used in violation of regulations

(q) Restricted

notification or to furnish required

material or information

and there was a failure or comply with any requirement prescribed under section 360h of this title respecting the device, or (2) to furnish any material or informaiton required by or under section 360i of this title respecting If it is

In the case of

any

restricted device dis-

tributed or offered for sale in any State, if (1) its advertising is false or misleading in

any particular, or (2) it is sold, distributed, or used in violation of regulations prescribed under section 360(j) of this title.

a device

refusal (1) to

the device.

—

Appendix

A

121 Notes

§ 353.

Exemptions

in case of drugs

and

devices (a)

Regulations for goods to be processed, labeled, or repacked elsewhere

The Secretary is directed to promulgate regulations exempting from any labeling or packaging requirement of this chapter drugs and devices which are, in accordance with the practice of the trade, to be processed, labeled, or repacked in substantial quantities at establishments other than those where originally processed or packed, on condition that such drugs and devices are not adulterated or misbranded under the provisions of this chapter upon removal from such processing, labeling, or repacking establishment.

by physician; exemption from labeling and prescription requirements; misbranded drugs; compliance with narcotic and marihuana laws

containing the name and address of the dispenser, the serial number and date of the prescription or of its filling, the name of the prescriber, and, if stated in the prescription, the name of the patient, and the directions for use and cautionary statements, if any, contained in such prescription. This exemption shall not apply to any drug dispensed in the course of the conduct of a business of dispensing drugs pursuant to diagnosis by mail, or to a drug dispensed in violation of

(1)

A

drug intended

for

use by

man

(A) is a habit-forming drug to which section 352(d) of this title applies; or (B) because of its toxicity or other potentiality for harmful effect, or the

method of its use, or the collateral measures necessary to its use, is not safe for use except under the supervision of a practitioner licensed by law to administer such drug; or limited by an approved appliunder section 355 of this title to use under the professional supervision of a practitioner licensed by law to ad(C) cation

is

minister such drug; shall

be dispensed only

upon

a written

prescription of a practitioner licensed by law to administer such drug, or (ii) upon an oral prescription of such practitioner which is reduced promptly to writing and filed by the pharmacist, or (iii) by refilling any such written or oral prescription if such refilling is authorized by the prescriber either in the original prescription or by oral order which is reduced promptly to writing and filed by the pharmacist. The act of dispensing a drug contrary to the provisions of this paragraph shall be deemed to be an act which results in the drug being misbranded while held for sale. (2) Any drug dispensed by filling or re-

written or oral prescription of a by law to administer such drug shall be exempt from the requirements of section 352 of this title, except subsections (a), (i)(2) and (3), (k), and (1) of said section, and the packaging requirements of subsections (g), (h), and (p) of said section, if the drug bears a label filling a

practitioner licensed

of this sub-

The Secretary may by regulation resubject to sections 352(d) and

(3)

title from the requirements of paragraph (1) of this subsection when such requirements are not necessary for the pro-

355 of this

tection of the public health.

A drug which is subject to paragraph of this subsection shall be deemed to be

(4) (1)

misbranded sing

its

if

at

any time prior

to dispen-

label fails to bear the statement

"Caution: Federal law prohibits dispensing without prescription". A drug to which paragraph (1) of this subsection does not apply shall be deemed to be misbranded if at any time prior to dispensing its label bears the caution statement quoted in the preceding sentence. (5) Nothing in this subsection shall be construed to relieve any person from any requirement prescribed by or under authority of law with respect to drugs now included or which may hereafter be included within the classifications stated in sections 4721, 6001, and 6151 of title 26, or to marihuana as defined in section 4761 of title

26.

§ 355. (i)

(1)

move drugs

(b) Prescription

which

paragraph

section.

(a)

New

drugs

Necessity of effective approval of application

No

person shall introduce or deliver for introduction into interstate commerce any new drug, unless an approval of an application filed pursuant to subsection (b) of this section is effective with respect to such drug. (b) Filing application;

contents

Any person may file with the Secretary an application with respect to any drug subject to the provisions of subsection (a) of this section. Such person shall submit to the Secretary as a part of the application (1) full reports of investigations which have

been made drug is safe is

to for

show whether

or not such use and whether such drug

effective in use; (2) a full

list

of the articles

used as components of such drug; (3) a full statement of the composition of such drug; (4) a full description of the methods used in, and the facilities and controls used for,

—

Appendix

122

A

Notes the manufacture, processing, and packing of such drug; (5) such samples of such drug and of the articles used as components thereof as the Secretary may require; and (6) specimens of the labeling proposed to be used for such drug.

Period for approval of application; period for, notice, and expedition of hearing; period for issuance of order

(c)

Within one hundred and eighty days an application under this subsection, or such additional period as may be agreed upon by the Secretary and

after the filing of

the applicant, the Secretary shall either

approve the application if he then none of the grounds for denying approval specified in subsection (1)

finds that

(d) of this section applies, or (2) give the applicant notice of an opportunity for a hearing before the Secretary under subsection (d) of this section on the question whether such application is approvable. If the applicant elects to accept the opportunity for hearing by written request within thirty days after such notice, such hearing shall commence not more than ninety days after the expiration of such thirty days unless the Secretary and the applicant otherwise agree. Any such hearing shall thereafter be conducted on an expedited basis and the Secretary's order thereon shall be issued within ninety days after the date fixed by the Secretary for filing final

briefs. (d)

Grounds

for refusing application;

approval of application; "substantial evidence" defined If the Secretary finds, after due notice to the applicant in accordance with subsection (c) of this section and giving him an opportunity for a hearing, in accordance with said subsection, that (1) the investigations, reports of which are required to be submitted to the Secretary pursuant to subsection (b) of this section, do not include

adequate

tests

applicable to

drug

is

by

all

methods reasonably

show whether

safe for use

or not such under the conditions

prescribed, recommended, or suggested in the proposed labeling thereof; (2) the results of such tests show that such drug is

unsafe for use under such conditions or do not show that such drug is safe for use under such conditions; (3) the methods

used

in,

and the

facilities

and controls used

the manufacture, processing, and packing of such drug are inadequate to preserve its identity, strength, quality, and purity; (4) upon the basis of the information submitted to him as part of the application, or upon the basis of any other information for,

him with respect to such drug, he has insufficient information to determine whether such drug is safe for use under such conditions; or (5) evaluated on the basis of the information submitted to him as part of the application and any other information before him with respect to such drug, there is a lack of 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; or (6) based on a fair evaluation of all material facts, such labeling is false or misleading in any particular; he shall issue an order refusing to approve the application. If, after such notice and opportunity for

before

hearing, the Secretary finds that clauses (1) through (6) do not apply, he shall issue an order approving the application. As used in this subsection and subsection (e) of this section, the term "substantial evidence" means evidence consisting of adequate and well-controlled investigations, including clinical investigations, by experts qualified by scientific training and experience to evaluate the effectiveness of the drug involved, on the basis of which it could fairly and responsibly be concluded by such experts 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 labeling or

proposed labeling thereof.

Withdrawal of approval; grounds; immediate suspension upon finding imminent hazard to public health The Secretary shall, after due notice and

(e)

opportunity for hearing to the applicant, withdraw approval of an application with respect to any drug under this section if the Secretary finds (1) that clinical or other experience, tests, or other scientific data show that such drug is unsafe for use under the conditions of use upon the basis of which the application was approved; (2) that new evidence of clinical experience, not contained in such application or not available to the Secretary until after such application

was approved, or tests by new methods, or tests by methods not deemed reasonably applicable when such application was approved, evaluated together with the evito the Secretary when the application was approved, shows that such drug is not shown to be safe for use under the conditions of use upon the basis of which the application was approved; or (3) on the basis of new information before him

dence available

with respect to such drug, evaluated together with the evidence available to him when the application was approved, that there is a lack of substantial evidence that the drug will have the effect it purports or

— —

Appendix

A

123 Notes

represented to have under the conditions of use prescribed, recommended, or suggested in the labeling thereof; or (4) that the application contains any untrue statement of a material fact: Provided, That if the Secretary (or in his absence the officer acting as Secretary) finds that there is an imminent hazard to the public health, he may suspend the approval of such application immediately, and give the applicant

is

prompt notice of

his action and afford the applicant the opportunity for an expedited hearing under this subsection; but the authority conferred by his proviso to suspend the approval of an application shall not be delegated. The Secretary may also, after due notice and opportunity for hearing to the applicant, withdraw the approval of an application with respect to any drug under this section if the Secretary finds (1) that the applicant has failed to establish a system for maintaining required records, or has repeatedly or deliberately failed to maintain such records or to make required reports, in accordance with a regulation or order under subsection (j) of this section or to comply with the notice requirements of section 360(j)(2) of this title, or the applicant has refused to permit access to, or copying or verification of, such records as required by paragraph (2) of such subsection; or (2) that on the basis of new information before him, evaluated together with the evidence before him when the application was approved, the methods used in, or the facilities and controls used for, the manufacture, processing, and packing of such drug are inadequate to assure and preserve its identity, strength, quality, and purity and were not made adequate within a reasonable time after receipt of written notice from the Secretary specifying the matter complained of; or (3) that on the basis of new information before him, evaluated together with the evidence before him when the application was approved, the labeling of such drug, based on a fair evaluation of all

material facts, particular and

is

false or

misleading in any

was not

corrected within a reasonable time after receipt of written notice from the Secretary specifying the mat-

complained of. Any order under this subsection shall state the findings upon which it is based.

ter

(i)

Exemptions of drugs for research; discretionary and mandatory conditions; direct reports to Secretary

may, within the discretion of the Sec-

tions

among other conditions relating to the protection of the public health, provide

retary,

for conditioning

such exemption upon

the submission to the Secretary, beclinical testing of a new drug is undertaken, of reports, by the manufacturer or the sponsor of the investigation of such drug, of preclinical tests (including tests on animals) of such drug adequate to justify the proposed clinical test(1)

fore

any

ing; (2) the manufacturer or the sponsor of the investigation of a new drug proposed to be distributed to investigators for clinical testing obtaining a signed agreement from each of such investigators that patients to whom the drug is administered will be under his personal supervision, or under the supervision of investigators responsible to him, and that he will not supply such drug to any other investigator, or to clinics, for administration to human beings; and (3) the establishment and maintenance of such records, and the making of such reports to the Secretary, by the manufacturer or the sponsor of the investigation of such drug, of data (including but not limited to analytical reports by investigators) obtained as the result of such investigational use of such drug, as the Secretary finds will enable him to evaluate the safety and effectiveness of such drug in the event of the filing of an application pursuant to subsection (b) of

this section.

Such regulations shall provide that such exemption shall be conditioned upon the manufacturer, or the sponsor of the investigation, requiring that experts using such drugs for investigational purposes certify to such manufacturer or sponsor that they will inform any human beings to whom such drugs, or any controls used in connection therewith, are being administered, or their representatives, that such drugs are being used for investigational purposes and will obtain the consent of such human beings or their representatives, except where they deem it not feasible or, in their professional judgment, contrary to the best interests of such human beings. Nothing in this subsection shall be construed to require any clinical investigator to submit directly to the Secretary reports on the investigational use of drugs.

The Secretary shall promulgate regulations for exempting from the operation of

§ 360c. Classification of devices intended for human use

the foregoing subsections of this section drugs intended solely for investigational

(a)

use by experts qualified by scientific training and experience to investigate the safety

and effectiveness

of drugs.

Such regula-

Classes of devices

(1)

There are established the following

classes of devices intended for

(A) Class

I,

human

General Controls

use:

—A

—

—

—

—

Appendix A

124 Notes

(i) A device for which the controls authorized by or under section 351, 352, 360, 360f, 360h, 360i, or 360j of this title or any combination of such sections are sufficient to provide reasonable assurance of the safety and effec-

tiveness of the device. (ii) A device for which insufficient information exists to determine that

the controls referred to in clause

are

(i)

sufficient to provide reasonable assur-

ance of the safety and effectiveness of the device or to establish a performance standard to provide such assurance, but because it (I) is not purported or represented to be for a use in supporting or sustaining human life or for a use which is of substantial importance in pre-

venting impairment of health, and

human

(II) does not present a potential unreasonable risk of illness or injury,

is

to

be regulated by the controls

ferred to in clause

re-

(i).

Performance Standards A device which cannot be classified as a class I device because the controls authorized by or under sections 351, 352, (B) Class

II,

360, 360f, 360h, 360i, and 360j of this title by themselves are insufficient to provide

reasonable assurance of the safety and effectiveness of the device, for which there is sufficient information to establish a performance standard to provide such assurance, and for which it is therefore necessary to establish for the device a performance standard under section 360d of this title to provide reasonable assurance of its safety and effectiveness. (C) Class III, Premarket Approval device which because (i) it (I) cannot be classified as a class I device because insufficient information exists to determine that the controls authorized by or under sections 351, 352, 360, 360f, 360h, 360i, and 360j of this title are sufficient to provide reasonable assurance of the safety and effectiveness of the device and (II) cannot be classified as a class II device because insufficient information exists for the establishment of a performance standard to provide reasonable assur-

—

ance of its safety and effectiveness, and (ii)(I) is purported or represented to be for a use in supporting or sustaining human life or for a use which is of substantial importance in preventing impairment of human health, or (II) presents a potential unreasonable risk of illness or injury, is

to

be subject,

tion 360e of this

in

accordance with secto premarket ap-

title,

proval to provide reasonable assurance of

its

safety

and

effectiveness.

not sufficient information to establish a performance standard for a device to provide reasonable assurance of its safety and effectiveness, the Secretary may conduct such activities as may be necessary to develop or obtain such information. (2) For purposes of this section and sections 360d and 360e of this title, the safety and effectiveness of a device are to be deIf

there

is

termined (A) with respect to the persons for the device is represented or

whose use

intended, (B) with respect to the conditions of use prescribed, recommended, or suggested in the labeling of the device, and (C) weighing any probable benefit to health from the use of the device against any probable risk of injury or illness from

such use. (3)(A) Except as authorized by subparagraph (B), the effectiveness of a device is, for purposes of this section and sections 360d and 360e of this title, to be determined, in accordance with regulations promulgated by the Secretary, on the basis of

well-controlled investigations, including clinical investigations where appropriate, by experts qualified by training and experience to evaluate the effectiveness of the device, from which investigations it can fairly and responsibly be concluded by qualified experts 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. (B) If the Secretary determines that there exists valid scientific evidence (other than evidence derived from investigations described in subparagraph (A)) (i)

which

is

sufficient to

effectiveness of a device, (ii)

from which

it

can

determine the

and fairly

and

re-

sponsibly be concluded by qualified experts 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, then, for purposes of this section and sections 360d and 360e of this title, the Secretary may authorize the effectiveness of the device to be determined on the basis of such evidence. (b) Classification (1)

panels

For purposes of

(A) determining which devices infor human use should be subject to the requirements of general controls, performance standards, or premarket ap-

tended

proval,

and

—

—

—

Appendix

A

125 Notes

providing notice to the manufacturers and importers of such devices to enable them to prepare for the application of such requirements to devices manufactured or imported by them, (B)

the Secretary shall classify

all

(other than devices classified

§ 360e. Premarket approval

A

before May 28, 1976, or both. Section 14 of the Federal Advisory Committee Act shall not apply to the duration of a panel established under this paragraph. (2) The Secretary shall appoint to each panel established under paragraph (1) persons who are qualified by training and experience to evaluate the safety and effectiveness of the devices to be referred to the panel and who, to the extent feasible, possess skill in the use of, or experience in the

development, manufacture, or utilization of such devices. The Secretary shall make appointments to each panel so that each panel shall consist of members with adequately diversified expertise in such fields as clinical

and administrative medicine, enand physical sciences,

gineering, biological

and other related professions. In addition, each panel shall include as nonvoting members a representative of consumer interests and a representative of interests of the device manufacturing industry. Scientific, trade, and consumer organizations

be afforded an opportunity to nominate individuals for appointment to the panels. No individual who is in the regular shall

and

full-time

employ

engaged

in the administration of this chap-

ter

may be

a

of the United States

member

of

any panel. The

Secretary shall designate one of the members of each panel to serve as chairman thereof. (3)

Panel

members

(other than officers or

States), while attending meetings or conferences of a panel or otherwise engaged in its business, shall be entitled to receive compensation at rates to be fixed by the Secretary, but not at rates exceeding the daily equivalent of the rate in effect for grade GS-18 of the General Schedule, for each day so engaged, including travel time; and while so serving away

employees of the United

their homes or regular places of business each member may be allowed travel expenses (including per diem in lieu of subsistence) as authorized by section 5703(b) of title 5, for persons in the Government

from

service

employed

intermittently.

III

device

section; or

by subsection

(2)

of this section) into the classes established by subsection (a) of this section. For (f)

the Secretary shall establish panels of experts or use panels of experts established

class

(1) which is subject to a regulation promulgated under subsection (b) of this

such devices

the purpose of securing recommendations with rspect to the classification of devices,

General requirement

(a)

which

is

a class

is

device because

III

of section 360c(f ) of this

title,

required to have, unless exempt under

section 360j(g) of this title, an approval under this secfion of an application for pre-

market approval. (b)

Regulation to require premarket approval

(1)

In the case of a class

III

device which

(A) was introduced or delivered for introduction into interstate commerce for

commercial distribution before

May

28,

1976; or (B) is

(i)

livered,

of a type so introduced or de(ii) is substantially equiva-

and

lent to another device within that type,

the Secretary shall by regulation, promulgated in accordance with this subsection, require that such device have an approval under this section of an application for premarket approval. (2)(A) A proceeding for the promulgation of a regulation under paragraph (1) respecting a device shall be initiated by the publication in the Federal Register of a notice of proposed rulemaking. Such notice shall contain (i) the proposed regulation; (ii) proposed findings with respect to the degree of risk of illness or injury designed to be eliminated or reduced by requiring the device to have an approved application for premarket approval and the benefit to the public from use of the device; (iii) opportunity for the submission of comments on the proposed regulation and the proposed findings; and (iv) opportunity to request a change in the classification of the device based on new information relevant to the classification of the device. (B) If, within fifteen days after publication of a notice under subparagraph (A), the Secretary receives a request for a change in the classification of a device, he shall, within sixty days of the publication of such notice and after consul-

under by order pub-

tation with the appropriate panel

section 360c of this

title,

lished in the Federal Register, either deny the request for change in classification or give notice of his intent to initiate

such a change under section 360(e)

of this (3)

title.

After the expiration of the period

—

126

Appendix

—

A

Notes

ment of this subparagraph may be met by the submission of complete information concerning the location of one or more such devices readily available to examination and testing; (F) specimens of the labeling proposed to be used for such device; and (G) such other information relevant to

for comment on a proposed regulation and proposed findings published under paragraph (2) and after consideration of comments submitted on such proposed regulation and findings, the Secretary shall (A) promulgate such regulation and

publish in the Federal Register findings

on the matters referred

to in

paragraph

or (B) publish a notice terminating the proceeding for the promulgation of the regulation together with the reasons for such termination. If a notice of termination is published, the Secretary shall (unless such notice is issued be-

the subject matter of the application as the Secretary, with the concurrence of the appropriate panel under section 360c of this title, may require.

(2)(A)(ii),

cause the device is a banned device under section 360f of this title) initiate a proceeding under section 360(e) of this title

to reclassify the device subject to the

proceeding terminated by such notice. (4)

The Secretary, upon his own initiupon petition of an interested

ative or

may by regulation amend or revoke any regulation promulgated under person,

this subsection. A regulation to amend or revoke a regulation under this subsection shall be promulgated in accordance with the requirements prescribed by this subsection for the promulgation of the regulation to be amended or revoked.

(c)

Application for premarket approval

Any

person

may

with the Secretary an application for premarket approval (1)

for a class

III

device.

file

Such an application

for a device shall contain

(A) full reports of all information, published or known to or which should rea-

sonably be known to the applicant, concerning investigations which have been made to show whether or not such device

is

safe

and

effective;

(B) a full statement of the components, ingredients, and properties and of the principle or principles of operation, of such device; (C) a full description of the methods

used used and,

in,

for,

and the

facilities and controls the manufacture, processing,

when

lation of,

relevant, packing and such device;

instal-

(D) an identifying reference to any performance standard under section 360d of this title which would be applicable to any aspect of such device if it were a class II device, and either adequate information to show that such aspect of such device fully meets such performance standard or adequate information to justify any deviation from such standard; (E) such samples of such device and of

components thereof as the Secretary may reasonably require, except that where the submission of such samples able or

unduly burdensome,

impracticthe require-

is

(2) Upon receipt of an application meeting the requirements set forth in paragraph (1), the Secretary shall refer such application to the appropriate panel under section 360c of this section for study and for submission (within such period as he may establish) of a report and recommendation respecting approval of the application, together with all underlying data and the reasons or the basis for the recommendation. (B) is not generally available to or generally used by other physicians or dentists (or other specially qualified persons so designated).

(c)

Trade secrets

Any information reported to or otherwise obtained by the Secretary or his representative

under section

360c, 360d, 360e,

title or under or (g) of this section which is exempt from disclosure pursuant to subsection (a) of section 552 of title 5 by reason of subsection (b)(4) of such section shall be

360f, 360h, 360i, or 374 of this

subsection

(f)

considered confidential and shall not be disclosed and may not be used by the Secretary as the basis for the reclassification of

a device

under section 360c of this

class

to class

III

II

title

from

or as the basis for the

establishment or amendment of a performance standard under section 360d of this title for a device reclassified from class III to class II, except that such information may be disclosed to other officers or employees concerned with carrying out this chapter or when relevant in any proceeding under this chapter (other than section 360c or 360d of this title). (d)

Notices and findings

Each notice of proposed rulemaking under section 360c, 360d, 360e, 360f, 360h, or 360i of this title, or under this section, any other notice which is published in the Federal Register with respect to any other action taken under any such section and which states the reasons for such action, and each publication of findings required to

be

made

in

connection with rulemaking

under any such section (1)

sons

the

shall set forth

manner in which interested

may examine

perdata and other infor-

—

— ——

Appendix

A

127 Notes

mation on which the notice or findings based, and (2) the period within which interested persons may present their comments on the notice or findings (including the need therefor) orally or in writing, which period shall be at least sixty days but may not exceed ninety days unless the time is extended by the Secretary by notice published in the Federal Register stating good cause therefor. is

Restricted devices

(e)

(1) The Secretary may by regulation require that a device be restricted to sale, distribution, or use

(A) only upon the written or oral authorization of a practitioner licensed by law to administer or use such device, or (B)

upon such other conditions

Secretary

may

as the

prescribe in such regula-

tion, if,

because of

its

potentiality for harmful

effect or the collateral

to

its

measures necessary

use, the Secretary determines that

there cannot otherwise be reasonable assurance of its safety and effectiveness. No condition prescribed under subparagraph (B) may restrict the use of a device to persons with specific training or experience in

use or to persons for use in certain faunless the Secretary determines that such a restriction is required for the safe and effective use of the device. No such condition may exclude a person from using a device solely because the person does not have the training or experience to make him eligible for certification by a certifying board recognized by the American Board of Medical Specialties or has not been certified by such a Board. A device subject to a regulation under this subsection is a re-

its

cilities

stricted device. (2) The label of a restricted device shall bear such appropriate statements of the restrictions required by a regulation under paragraph (1) as the Secretary may in such

regulation prescribe. (f)

Good manufacturing

practice

requirements (1)(A)

The Secretary may,

with subparagraph

(B),

in

accordance

prescribe regula-

tions requiring that the methods used in, and the facilities and controls used for, the

manufacture, packing, storage, and installation of a device conform to current good manufacturing practice, as prescribed in such regulations, to assure that the device will be safe and effective and otherwise in compliance with this chapter. (B) Before the Secretary may promulgate any regulation under subparagraph (A) he shall—

(i) afford the advisory committee established under paragraph (3) an opportunity to submit recommendations to him with respect to the regulation pro-

posed

to

be promulgated, and

afford opportunity for an oral hear-

(ii)

ing.

The Secretary

shall

provide the advisory

committee a reasonable time to make its recommendation with respect to proposed regulations undpr subparagraph (A). (2)(A) Any person subject to any requirement prescribed by regulations under paragraph (1) may petition the Secretary for an exemption or variance from such requirement. Such a petition shall be submitted to the Secretary in such form and manner as he shall prescribe and shall (i)

in the case of a petition for

emption from

an ex-

a requirement, set forth

the basis for the petitioner's determination that compliance with the requirement is not required to assure that the device will be safe and effective and otherwise in compliance with this chapter, (ii) in the case of a petition for a variance from a requirement, set forth the methods proposed to be used in, and the facilities and controls proposed to be used for, the manufacture, packing, storage, and installation of the device in lieu of the methods, facilities, and controls prescribed by the requirement, and (iii) contain such other information as the Secretary shall prescribe. (B) The Secretary may refer to the advisory committee established under para-

graph (3) any petition submitted under subparagraph (A). The advisory committee shall report its recommendations to the Secretary with respect to a petition referred to it within sixty days of the date of the petition's referral. Within sixty days after (i)

the date the petition

to the Secretary

was submitted

under subparagraph

(A),

or (ii)

if

was

the petition

referred to an

advisory committee, the expiration of the sixty-day period beginning on the date the petition was referred to the advisory committee, whichever occurs later, the Secretary shall by order either deny the petition or (C)

approve

it.

The Secretary may approve

an exemption for a if he determines that compliance with such require(i)

a petition for

device from a requirement

ment

is not required to assure that the device will be safe and effective and otherwise in compliance with this chapter,

and (ii)

from

a petition for a variance for a device a

requirement

if

he determines that

Appendix A

128 Notes

methods to be used in, and the faand controls to be used for, the manufacture, packing, storage, and in-

scribed by the requirement are sufficient to assure that the device will be safe and

advisory committee to serve as its chairman. The Secretary shall furnish the advisory committee with clerical and other assistance. Section 14 of the Federal Advisory Committee Act shall not apply with respect to the duration of the advisory committee established under this paragraph.

and otherwise with this chapter.

(g)

the

cilities

stallation

of the device in lieu of the

methods, controls, and

effective

facilities pre-

compliance

in

order of the Secretary approving a pevariance shall prescribe such conditions respecting the methods used in, facilities and controls used for, the manufacture, packing, storage, and installation of the device to be granted the variance under the petition as may be necessary to assure that the device will be safe and effective and otherwise in compliance with this chapter. (D) After the issuance of an order under

and the

subparagraph

(B) respecting a petition, the

have an opportunity for an informal hearing on such order. (3) The Secretary shall establish an advisory committee for the purpose of advising and making recommendations to him with respect to regulations proposed to be petitioner shall

promulgated under paragraph

(1)(A)

and

the approval or disapproval of petitions submitted under paragraph (2). The advi-

sory committee shall be

members

composed

of nine

members

pointed from persons

shall

Two

of the

who are officers or

members

shall

be ap-

who are representative of interests of the device manufacturing industry; two of the members shall be appointed from persons who are representative of the interests of physicians and other health professionals; and two of the members shall be representative of the interests of the general pub-

pointed from persons

lic.

of the advisory committee who are not officers or employees of the United States, while attending conferences or meetings of the committee or otherwise engaged in its business, shall be entitled to

Members

receive compensation at rates to be fixed Secretary, which rates may not exceed the daily equivalent of the rate in effect for grade GS-18 of the General Schedule, for each day (including travel time) they are

by the

and while so serving away homes or regular places of business each member may be allowed travel so engaged;

from

their

expenses, including per diem in lieu of subsistence, as authorized by section 5703 of title 5 for persons in the Government service

employed

intermittently.

shall designate

protection of the public health and safety ethical standards, the discovery and development of useful devices in-

and with

tended for human use and to that end to maintain optimum freedom for scientific investigators in their pursuit of that purpose. (2)(A) The Secretary shall, within the one hundred and twenty-day period beginning on May 28, 1976, by regulation prescribe procedures and conditions under which devices intended for human use may upon application be granted an exemption from the requirements of section 352, 360, 360d, 360e, 360f, 360i, or 376 of this title or subsection (e) or (f ) of this section or from any combination of such requirements to per-

mit the investigational use of such devices

by experts qualified by scientific training and experience to investigate the safety and (B)

be ap-

employees of any State or local government or of the Federal Government. (B)

(1) It is the purpose of this subsection to encourage, to the extent consistent with the

effectiveness of such devices.

as follows:

(A) Three of the

for devices for

investigational use

An

tition for a

Exemption

The Secretary

one of the members of the

to

The conditions prescribed pursuant

subparagraph (A)

shall include the fol-

lowing: (i) A requirement that an application be submitted to the Secretary before an exemption may be granted and that the application be submitted in such form

and manner

as the Secretary shall spec-

ify. (ii) A requirement that the person applying for an exemption for a device assure the establishment and maintenance of such records, and the making of such reports to the Secretary of data obtained as a result of the investigational use of the device during the exemption, as the Secretary determines will enable him to assure compliance with such conditions, review the progress of the investigation, and evaluate the safety and effectiveness of the device. (iii) Such other requirements as the Secretary may determine to be necessary for the protection of the public health and

safety.

(C) Procedures and conditions prescribed pursuant to subparagraph (A) for an exemption may appropriately vary de-

pending on

(i)

exemption,

(ii)

jects that are to

and duration of be conducted under such

the scope

clinical testing to

the

number

of

human

sub-

be involved in such testing,

—

—

—

—

Appendix

A

129 Notes

(iii)

the need to permit changes to be made device subject to the exemption dur-

in the

ing testing conducted in accordance with a clinical testing plan required under paragraph (3)(A), and (iv) whether the clinical testing of such device is for the purpose of developing data to obtain approval for the commercial distribution of such device. (3) Procedures and conditions prescribed

pursuant to paragraph (2)(A) shall require, as a condition to the exemption of any device to be the subject of testing involving human subjects, that the person applying for the exemption (A) submit a plan for any proposed clinical

and

testing of the device

a report of

prior investigations of the device (including,

where appropriate,

adequate to

justify the

tests on animals) proposed clinical

testing (i) to the local institutional review committee which has been established in accordance with regulations of the Secretary to supervise clinical testing of devices in the facilities where the pro-

posed

clinical testing is to

be conducted,

or (ii)

to the Secretary,

(I)

if

no such committee

(II)

exists, or the Secretary finds that the proc-

by such committee is inadequate (whether or not the plan for such testing has been approved by such committee), ess of review

for

review for adequacy to

commencement of such

justify the

unplan and report are submitted to the Secretary, submit to the Secretary a summary of the plan and a report of prior investigations of the device (including, testing; and,

less the

where appropriate,

tests

on animals);

promptly notify the Secretary (under such circumstances and in such manner as the Secretary prescribes) of approval by a local institutional review committee of any clinical testing plan submitted to it in accordance with subparagraph (A); (C) in the case of a device to be distributed to investigators for testing, obtain signed agreements from each of such investigators that any testing of the device involving human subjects will be under such investigator's supervision and in accordance with subparagraph (D) and submit such agreements to the Secretary; and (D) assure that informed consent will be obtained from each human subject (or his representative) of proposed clinical testing involving such device, except where subject to such conditions as the Secretary may prescribe, the investigator conducting or supervising the proposed clinical testing of the device determines in writing that there (B)

exists a life threatening situation involving

the human subject of such testing which necessitates the use of such device and it is not feasible to obtain informed consent from the subject and there is not sufficient time to obtain such consent from his representative.

The determination required by subparagraph (D) shall be concurred in by a li-

who is not involved in the human subject with respect which such determination is made un-

censed physician testing of the to

less

to

immediate use of the device

save the

lite

of the

human

is

required

subject of such

testing and there is not sufficient time to obtain such concurrence. (4)(A) An application, submitted in accordance with the procedures prescribed by regulations under paragraph (2), for an exemption for a device (other than an exemption from section 360f of this title) shall be deemed approved on the thirtieth day after the submission of the application to the Secretary unless on or before such day the Secretary by order disapproves the ap-

and notifies the applicant of the disapproval of the application. (B) The Secretary may disapprove an application only if he finds that the investigation with repect to which the application is submitted does not conform to procedures and conditions prescribed under regulations under paragraph (2). Such a notification shall contain the order of disapproval and a complete statement of the reasons for the Secretary's disapproval of the application and afford the applicant opportunity for an informal hearing on the disapproval order. (5) The Secretary may by order withdraw an exemption granted under this subsection for a device if the Secretary determines that the conditions applicable to the device under this subsection for such exemption are not met. Such an order may be issued only after opportunity for an informal hearing, except that such an order may be issued before the provision of an opportunity for an informal hearing if the Secretary determines that the continuation of testing under the exemption with respect to which the order is to be issued will result in an unreasonable risk to the public health. plication

(h)

Release of information respecting safety

and effectiveness

The Secretary shall promulgate regunder which a detailed summary of information respecting the safety and effectiveness of a device which information was submitted to the Secretary and which was the basis for (1)

ulations

(A)

an

order

application for

under

section

approving an premarket approval for

360e(d)(l)(A) of this

title

130

Appendix

A

Notes the device or denying approval of such an application or an order under section 360e(e) of this title withdrawing approval of such an application for the device, (B) an order under section 360e(f )(6)(A) of this title revoking an approved protocol for the device, an order under sectitle declaring a protocol for the device completed or not completed, or an order under section 360e(f)(7) of this title revoking the ap-

tion 360e(f)(6)(B) of this

proval of the device, or (C) an order approving an application under subsection (g) of this section for an exemption for the device from section 360f of this title or an order disapproving, or withdrawing approval of, an application for an exemption under such subsection for the device,

be made available to the public upon issuance of the order. Summaries of infor-

shall

mation made available pursuant to this paragraph respecting a device shall include information respecting any adverse effects on health of the device. (2) The Secretary shall promulgate regulations under which each advisory com-

mittee

under section shall make availdetailed summary of

established

360e(g)(2)(B) of this

title

able to the public a information respecting the safety and effectiveness of a device which information was submitted to the advisory committee and which was the basis for its recommendation to the Secretary made pursuant to section 360e(g)(2)(A) of this title. A summary of information upon which such a

recommendation

is

based

shall

be made

available pursuant to this paragraph-.

—

—

APPENDIX B Selected Portions of the Controlled

Substance Act, States

Title 21,

Code

CHAPTER 13— DRUG ABUSE PREVENTION AND CONTROL

merce immediately prior

This subchapter

is

section 304m;

A

title

Controlled substances manufactured intrastate cannot be differentiated from controlled substances manufactured and distributed interstate. Thus, it is not feasible to distinguish, in terms of controls, between controlled substances (5)

referred to in sections title; title

40

42 sections 242, 261.

Introductory Provisions

§ 801. Congressional findings and declarations: controlled substances

The Congress makes the following and declarations:

such posses-

(4) Local distribution and possession of controlled substances contribute to swelling the interstate traffic in such substances.

Subchapter Referred to in Other Sections 951, 952, 958, 962, 965 of this

to

sion.

SUBCHAPTER I- -CONTROL AND ENFORCEMENT

Part

United

find-

ings

and distributed

manufacturered and distributed interstate and controlled substances manufactured and distributed intrastate. (6) Federal control of the intrastate incidents of the traffic in controlled substances is

essential to the effective control of the

interstate incidents of

Many

such

traffic.

of the drugs included within this subchapter have a useful and legitimate medical purpose and are necessary to

The United States is a party to the Single Convention on Narcotic Drugs, 1961, and other international conventions

maintain the health and general welfare of the American people. (2) The illegal importation, manufacture,

designed

and possession and improper use of controlled substances have a substantial and detrimental effect on the health and general welfare of the American peo-

§ 802. Definitions

(1)

distribution,

ple.

A

major portion of the traffic in conthrough interstate and foreign commerce. Incidents of the traffic which are not an integral part of the interstate or foreign flow, such as manu(3)

trolled substances flows

and possession, nonetheless have a substantial and direct effect upon interstate commerce because facture, local distribution,

(A) after manufacture, many controlled substances are transported in interstate

commerce,

controlled substances distributed locally usually have been transported in interstate commerce immediately before (B)

their distribution,

(C)

controlled

(7)

to establish effective control over international and domestic traffic in controlled substances.

As used in this subchapter: (1) The term "addict" means any

indi-

vidual who habitually uses any narcotic drug so as to endanger the public morals, health, safety, or welfare, or who is so far addicted to the use of narcotic drugs as to have lost the power of self-control with reference to his addiction. (2) The term "administer" refers to the direct application of a controlled substance to the body of a patient or research subject

by(A) a practitioner (or, in his presence, his authorized agent), or (B) the patient or research subject at the direction and in the presence of the

by

practitioner.

substances possessed

whether such application be by injection, inhalation, ingestion, or any other means. (3) The term "agent" means an authorized person who acts on behalf of or at the

com-

direction of a manufacturer, distributor, or

and

commonly flow through

interstate

131

—

132

Appendix B

Notes dispenser; except that such term does not include a common or contract carrier, pubic warehouseman, or employee of the carrier or warehouseman, when acting in the usual and lawful course of the carrier's or warehouseman's business.

having, a potential for abuse because of its depressant or stimulant effect on the central nervous system or its hallucinogenic effect.

The term "Drug Enforcement Administration" means the Drug Enforcement Administration in the Department of Jus-

substance to an ultimate user or research subject by, or pursuant to the lawful order of, a practitioner, including the prescribing and administering of a controlled substance and the packaging, labeling or compounding necessary to prepare the substance for such delivery. The term "dispenser" means a practitioner who so delivers a controlled substance to an ultimate user or research subject. (11) The term "distribute" means to deliver (other than by administering or dispensing) a controlled substance. The term "distributor" means a person who so de-

(4)

tice.

(5) The term "control" means to add a drug or other substance, or immediate precursor, to a schedule under part B of this subchapter, whether by transfer from an-

other schedule or otherwise. (6) The term "controlled substance" means a drug or other substance, or immediate precursor, included in schedule I, II, III, IV, or V of part B of this subchapter. The term does not include distilled spirits, wine, malt beverages, or tobacco, as those terms are defined or used in subtitle E of

Revenue Code of 1954. (7) The term "counterfeit substance" means a controlled substance which, or the the Internal

container or labeling of which, without authorization, bears the trademark, trade name, or other identifying mark, imprint, number, or device, or any likeness thereof, of a manufacturer, distributor, or dispenser other than the person or persons who in fact manufactured, distributed, or dispensed such substance and which thereby falsely purports or is represented to be the product of, or to have been distributed by, such other manufacturer, distributor, or dispenser. (8) The terms "deliver" or "delivery" mean the actual, constructive, or attempted transfer of a controlled substance, whether or not there exists an agency relationship. (9) The term "depressant or stimulant

substance" means

which contains any quantity any of the salts of acid; or (ii) any derivative of acid which has been desig-

(A) a drug of

(i)

barbituric acid or

barbituric barbituric

nated by the Secretary as habit forming

under section 352(d) of this title; or (B) a drug which contains any quantity of (i) amphetamine or any of its optical isomers; (ii) any salt of amphetamine or any salt of an optical isomer of amphetamine; or (iii) any substance which the Attorney General, after investigation, has found to be, and by regulation designated as, habit forming because of its stimulant effect on the central nervous systems; or (C) lysergic acid diethylamide; or (D) any drug which contains any quantity of a substance which the Attorney General, after investigation, has found to have, and by regulation designated as

(10)

The term "dispense" means

to de-

liver a controlled

livers a controlled substance. (12) The term "drug" has the meaning given that term by section 321(g)(1) of this title.

(13)

The term "felony" means any Fed-

eral or State offense classified

by applicable

Federal or State law as a felony. (14) The term "manufacture" means the production, preparation, propagation, compounding, or processing of a drug or

other substance, either directly or indirectly or by extraction from substances of natural origin, or independently by means of chemical synthesis or by a combination of extraction and chemical synthesis, and includes any packaging or repackaging of such substance or labeling or relabeling of its container; except that such term does not include the preparation, compounding, packaging, or labeling of a drug or other substance in conformity with applicable

law by a practitioner as an incident to his administration or dispensing of such drug or substance in the course of his professional practice. The term "manufacturer" means a person who manufactures a drug or other substance. State or local

(15) The term "marihuana" means all parts of the plant Cannabis sativa L., whether growing or not; the seeds thereof; the resin extracted from any part of such plant; and every compound, manufacture, salt, derivative, mixture, or preparation of such plant, its seeds or resin. Such term does not include the mature stalks of such plant, fiber produced from such stalks, oil or cake made from the seeds of such plant, any other compound, manufacture, salt, derivative, mixture, or preparation of such

mature

stalks (except the resin extracted therefrom), fiber, oil, or cake, or the sterilized seed of such plant which is incapable of germination. (16) The term "narcotic drug" means any of the following, whether produced di-

—

— —

—

Appendix B

133 Notes

by extraction from subvegetable origin, or independ-

rectly or indirectly

States, the District of

stances of ently by means of chemical synthesis, or by a combination of extraction and chemical

monwealth

synthesis:

(B)

derivative, or preparation of

opium, coca

leaves, or opiates. (C) A substance (and any compound, manufacture, salt, derivative, or preparation thereof) which is chemically identical with any of the substances referred to in clause (A) or (B).

of Puerto Rico, the Trust Ter-

ritory of the Pacific Islands,

and the Canal

Zone. (25)

Opium, coca leaves, and opiates. A compound, manufacture, salt,

(A)

Columbia, the Com-

person

The term "ultimate user" means a who has lawfully obtained, and

who possesses, a controlled substance for his own use or for the use of a member of his household or for an animal owned by him or by a member of his household. (26) The term "United States", when used in a geographic sense, means all places and waters, continental or insular, subject to the jurisdiction of the United States.

Such term does not include decocainized coca leaves or extracts of coca leaves which extracts do not contain cocaine or ecgonine. (17) The term "opiate" means any drug or other substance having an addictionforming or addiction-sustaining liability similar to morphine or being capable of conversion into a drug having such addiction-forming or addiction-sustaining

li-

ability.

(18) The term "opium poppy" means the plant of the species Papaver somniferum L., except the seed thereof. (19)

The term "poppy straw" means

parts, except the seeds, of the

poppy,

all

opium

after mowing. The term "practitioner" means

a physician, dentist, veterinarian, scientific investigator, pharmacy, hospital, or other person licensed, registered, or otherwise permitted, by the United States or the jurisdiction in which he practices or does research, to distribute, dispense, conduct research with respect to, administer, or use in teaching or chemical analysis, a controlled substance in the course of profes(20)

sional practice or research. (21) The term "production" includes the manufacture, planting, cultivation, growing, or harvesting of a controlled substance. (22) The term "immediate precursor" means a substance

which the Attorney General has found to be and by regulation designated (A)

as being the principal

compound

used,

produced primarily for use, in the manufacture of a controlled substance; (B) which is an immediate chemical intermediary used or likely to be used in the manufacture of such controlled substance; and (C) the control of which is necessary to prevent, curtail, or limit the manufac-

or

ture of such controlled substance. (23) The term "Secretary", unless the context otherwise indicates, means the Sec-

retary of Health

and

Human

Services.

The term "State" means any State, territory, or possession of the United (24)

(27)

The term "maintenance treatment"

means

the dispensing, for a period in excess of twenty-one days, of a narcotic drug in the treatment of an individual for dependence upon heroin or other morphinelike

drugs.

The term

"detoxification treatment" the dispensing, for a period not in excess of twenty-one days, of a narcotic drug in decreasing doses to an individual in order to alleviate adverse physiological or psychological effects incident to withdrawal from the continuous or sustained use of a narcotic drug and as a method of bringing the individual to a narcotic drugfree state within such period. (28)

means

(29)

The term "Convention on Psychomeans the Convention

tropic Substances"

on Psychotropic Substances signed at Vienna, Austria, on February 21, 1971; and the term "Single Convention on Narcotic Drugs" means the Single Convention on Narcotic Drugs signed at New York, New York, on March 30, 1961. Part B Authority To Control; Standards and Schedules § 811. Authority and criteria for classification of substances

Rules and regulations of Attorney General; hearing

(a)

The Attorney General shall apply the provisions of this subchapter to the controlled substances listed in the schedules established by section 812 of this title and to any other drug or other substance added to such schedules under this subchapter. Except as provided in subsections (d) and (e) of this section, the Attorney General

may by

rule

add to such a schedule or transfer between such schedules any drug or (1)

other substance

if

he

(A) finds that such drug or other substance has a potential for abuse,

and (B) makes with respect to such drug or other substance the findings prescribed by subsection (b) of section 812

134

Appendix B

Notes of this

title

such drug

schedule be placed; or

for the

is

to

in

which

removal from schedules

(2) remove any drug or other substance

from the schedules if he finds that the drug or other substance does not meet the requirements for inclusion in any schedule.

Rules of the Attorney General under this subsection shall be made on the record after opportunity for a hearing pursuant to the rulemaking procedures prescribed by subchapter II of chapter 5 of title 5. Proceedings for the issuance,

amendment,

or repeal of

such rules may be initiated by the Attorney General (1) on his own motion, (2) at the request of the Secretary, or (3) on the petition of any interested party. (b)

remove

a

drug or other subdrug or other sub-

and

after gathering the necessary data, request scientific and medical recommendations, as to whether such drug or other substance should be so controlled or removed as a controlled substance. In making such evaluation and recommendations, the Secre-

from the Secretary a

and

his

tary shall consider the factors listed in par-

agraphs

(2), (3), (6), (7), and (8) of subsection (c) of this section and any scientific or medical considerations involved in

(1), (4), and (5) of such subThe recommendations of the Secshall include recommendations with

paragraphs

section.

retary

respect to the appropriate schedule,

if

any,

under which such drug or other substance should be listed. The evaluation and the recommendations of the Secretary shall be made in writing and submitted to the Attorney General within a reasonable time. The recommendations of the Secretary to the Attorney General shall be binding on the Attorney General as to such scientific and medical matters, and if the Secretary

recommends

making any finding under subsection under subsection (b)

of this section or

of section 812 of this

title, the Attorney General shall consider the following factors with respect to each drug or other substance proposed to be controlled or removed from the schedules:

(1) Its

actual or relative potential for

abuse. (2) Scientific

evidence of

cological effect,

The

(3)

if

its

pharma-

known.

state of current scientific

knowledge regarding the drug or other substance. (4) Its

history

and current pattern of

abuse.

(6)

stance entirely from the schedules,

evaluation,

(a)

The scope, duration, and

signifi-

cance of abuse.

The Attorney General shall, before initiating proceedings under subsection (a) of stance or to

In

(5)

Evaluation of drugs and other substances

this section to control a

Factors determinative of control or

(c)

that a drug or other substance not be controlled, the Attorney General shall not control the drug or other substances. If the Attorney General determines that these facts and all other relevant data constitute substantial evidence of potential for abuse such as to warrant control or substantial evidence that the drug or other substance should be removed entirely from the schedules, he shall initiate proceedings for control or removal, as the case may be, under subsection (a) of this section.

What,

if

any, risk there

is

to the

public health. (7) Its

psychic or physiological de-

pendence liability. (8) Whether the substance

is an imsubstance already controlled under this subchapter.

mediate precursor of

a

(d) International treaties,

conventions,

and protocols requiring

control;

procedures respecting changes in drug schedules of Convention on Psychotropic Substances (1) If control is required by United States obligations under international treaties, conventions, or protocols in effect on October 27, 1970, the Attorney General shall issue an order controlling such drug under the schedule he deems most appropriate to carry out such obligations, without regard to the findings required by subsection (a) of this section or section 812(b) of this title and without regard to the procedures prescribed by subsections (a) and (b) of this

section.

(2)(A) Whenever the Secretary of State receives notification from the SecretaryGeneral of the United Nations that information has been transmitted by or to the

World Health Organization, pursuant to article 2 of the Convention on Psychotropic Substances, which may justify adding a drug or other substance to one of the schedules of the Convention, transferring a drug or substance from one schedule to another, it from the schedules, the Secretary of State shall immediately transmit the notice to the Secretary of Health and Human Services who shall publish it in the

or deleting

Federal Register and provide opportunity to interested persons to submit to him comments respecting the scientific and medical evaluations which he is to prepare respecting such drug or substance. The Secretary

—

Appendix B

135 Notes

of Health

and

Human

Services shall prepare for transmission through the Secretary of State to the World Health Organization

ceedings for scheduling the drug or substance, pursuant to subsections (a) and (b) of this section, to apply to such con-

such medical and scientific evaluations as may be appropriate regarding the possible action that could be proposed by the World Health Organization respecting the drug or substance with respect to which a notice was transmitted under this subparagraph.

trols.

(B) Whenever the Secretary of State receives information that the Commission on

Narcotic Drugs of the United Nations proposes to decide whether to add a drug or other substance to one of the schedules of the Convention, transfer a drug or substance from one schedule to another, or delete it from the schedules, the Secretary of State shall transmit timely notice to the Secretary of Health and Human Services of such information who shall publish a summary of such information in the Federal Register and provide opportunity to interested persons to submit to him comments respecting the recommendation which he is to furnish, pursuant to this subparagraph, respecting such proposal. The Secretary of Health and Human Services shall evaluate the proposal and furnish a recommendation to the Secretary of State which shall be binding on the representative of the United States in discussions and negotiations relating to the proposal. (3) When the United States receives notification of a scheduling decision pursuant to article 2 of the Convention on Psychotropic Substances that a drug or other substance has been added or transferred to a schedule specified in the notification or receives notification (referred to in this subsection as a "schedule notice") that existing legal controls applicable under this subchapter to a drug or substance and the controls required by the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 301 et seq.] do not meet the requirements of the sched-

Convention in which such drug or substance has been placed, the Secretary of Health and Human Services after conule of the

sultation with the Attorney General, shall first determine whether existing legal con-

under this subchapter applicable to the drug or substance and the controls required by the Federal Food, Drug, and Cosmetic Act, meet the requirements of the schedule specified in the notification or schedule notice and shall take the following trols

action:

(A) If such requirements are met by such existing controls but the Secretary of Health and Human Services nonetheless believes that

more

(B) If such requirements are not met by such existing controls and the Secretary of Health and Human Services con-

curs in the scheduling decision or schedule notice transmitted by the notification, the Secretary shall recommend to the At-

torney General that he initiate proceedings for scheduling the drug or substance under the appropriate schedule pursuant to subsections (a) and (b) of this section. (C) If such requirements are not met

by such existing controls and the Secretary of Health and Human Services does not concur in the scheduling decision or schedule notice transmitted by the notification, the Secretary shall (i)

if

he deems that additional con-

necessary to protect the public health and safety, recommend to the Attorney General that he initiate proceedings for scheduling the drug or substance pursuant to subsections (a) trols are

and

(b) of this section, to apply such additional controls; (ii)request the Secretary of State to transmit a notice of qualified acceptance, within the period specified in the Convention, pursuant to paragraph 7 of article 2 of the Convention, to the Secretary-General of the United Na-

tions; (iii) request the Secretary of State to transmit a notice of qualified acceptance as prescribed in clause (ii) and request the Secretary of State to ask for a review by the Economic and Social Council of the United Nations, in accordance with paragraph 8 of article 2 of the Convention, of the scheduling

decision; or (iv) in the case of a schedule notice, request the Secretary of State to take appropriate action under the Conven-

tion to initiate proceedings to

remove

the drug or substance from the schedules under the Convention or to transfer the drug or substance to a schedule under the Convention different from the one specified in the schedule notice.

(4)(A) If the Attorney General determines, after consultation with the Secretary of Health and Human Services, that proceedings initiated under recommendations

made under paragraph (B) or (C)(i) of paragraph (3) will not be completed within the 1

stringent controls

should be applied to the drug or substance, the Secretary shall the Attorney General that

recommend he

to

initiate pro-

So

in

original.

"subparagraph".

Probably should be

—

136

Appendix B

Notes time period required by paragraph 7 of article 2 of the Convention, the Attorney General, after consultation with the Secretary and after providing interested persons opportunity to submit comments respecting the requirements of the temporary order to be issued under this sentence, shall issue a temporary order controlling the drug or substance under schedule IV or V, whichever is most appropriate to carry out the minimum United States obligations under paragraph 7 of article 2 of the Convention. As a part of such order, the Attorney General shall, after consultation with the Secretary, except such drug or substance from the application of any provision of part C of this subchapter which he finds is not required to carry out the United States obligations under paragraph 7 of article 2 of the Convention. In the case of proceedings initiated under subparagraph (B) of paragraph (3), the Attorney General, concurrently with the issuance of such order, shall request the Secretary of State to transmit a notice of qualified acceptance to the Secretary-General of the United Nations pursuant to paragraph 7 of article 2 of the Convention. A temporary order issued under this subparagraph controlling a drug or other substance subject to proceedings initiated under subsections (a)

and

(b) of this section shall

expire

upon

the effective date of the application to the

drug or substance of the controls resulting from such proceedings. (B) After a notice of qualified

acceptance

of a scheduling decision with respect to a

drug or other substance

is

transmitted to

the Secretary-General of the United tions in accordance with clause (ii) or

Na(iii)

of paragraph (3)(C) or after a request has

been made under clause (iv) of such paragraph with respect to a drug or substance described in a schedule notice, the Attorney General, after consultation with the Secretary of Health and Human Services and after providing interested persons opportunity to submit comments respecting the requirements of the order to be issued under this sentence, shall issue an order controlling the drug or substance under schedule IV or V, whichever is most appropriate to carry out the minimum United State obligations ticle

under paragraph 7

of ar-

2 of the Convention in the case of a

which a notice of qualified acceptance was transmitted or whichever the Attorney General determines is appropriate in the case of a drug drug or substance

for

or substance described in a schedule notice. As a part of such order, the Attorney General shall, after consultation with the Secretary, except such drug or substance from the application of any provision of part C

which he finds is not required to carry out the United States obligations under paragraph 7 of article 2 of the Convention. If, as a result of a review under paragraph 8 of article 2 of the Convention of the scheduling decision with respect to which a notice of qualified acceptance was transmitted in accordance with clause (ii) or (iii) of paragraph (3)(C)

of this subchapter

the decision is reversed, and the drug or substance subject to such decision is not required to be controlled under schedule IV or V to carry out the minimum United States obligations under paragraph 7 of article 2 of the (i)

(ii)

Convention, the order issued under this subparagraph with respect to such drug or substance shall expire upon receipt by the United States of the review decision. If, as a result of action taken pursuant to action initiated under a request transmitted under clause (iv) of paragraph (3)(C), the drug or substance with respect to which such action was taken is not required to be controlled under schedule IV or V, the order issued under this paragraph with respect to such drug or substance shall expire upon receipt by the United States of a notice of the action taken with respect to such drug or substance under the Convention. (C) An order issued under subparagraph (A) or (B) may be issued without regard to the findings required by subsection (a) of this section or by section 812(b) of this title and without regard to the procedures prescribed by subsection (a) or (b) of this section. (5) Nothing in the amendments made by the Psychotropic Substances Act of 1978 or the regulations or orders promulgated

thereunder shall be construed to preclude requests by the Secretary of Health and Human Services or the Attorney General through the Secretary of State, pursuant to other applicable provisions of the Convention, for review of scheduling decisions under such Convention, based on new or additional information.

article 2 or

(e)

Immediate precursors

The Attorney General may, without regard to the findings required by subsection (a)

of this section or section 812(b) of this

and without regard to the procedures prescribed by subsections (a) and (b) of this section, place an immediate precursor in the same schedule in which the controlled substance of which it is an immediate precursor is placed or in any other schedule with a higher numerical designation. If the Attorney General designates a substance as an immediate precursor and places it in a schedule, other substances shall not be title

—

Appendix B

137 Notes

placed in a schedule solely because they are its

precursors.

(f)

Abuse

tion (a) of this section.

potential

If, at the time a new-drug application is submitted to the Secretary for any drug having a stimulant, depressant, or hallucinogenic effect on the central nervous system, it appears that such drug has an abuse potential, such information shall be forwarded by the Secretary to the Attorney

General.

Non-narcotic substances sold over the counter without a prescription;

(g)

dextromethorphan

metic Act [21 U.S.C. 301 et seq.], be lawfully sold over the counter without a prescription. (2) Dextromethorphan shall not be deemed to be included in any schedule by

reason of enactment of this subchapter unless controlled after October 27, 1970 pursuant to the foregoing provisions of this

§ 812. Schedules of controlled substances

There are established five schedules of controlled substances, to be known as schedules I, II, III, IV, and V. Such schedules shall initially consist of the substances listed in this section. The schedules estabthis section shall

be updated and

republished on a semiannual basis during the two-year period beginning one year after October 27, 1970, and shall be updated and republished on an annual basis thereafter.

§ 825 Labeling (a)

and packaging

Symbol

be unlawful to distribute a consubstance in a commercial container unless such container, when and as required by regulations of the Attorney General, bears a label (as defined in section 321 (k) of this title) containing an identifying symbol for such substance in accordance with such regulations. A different symbol shall be required for each schedule of conshall

It

trolled

trolled substances. (b)

Unlawful distribution without identifying symbol

It

of

shall

The Secretary shall prescribe regulations under section 353(b) of this title which shall provide that the label of a drug listed in schedule II, III, or IV shall, when dispensed to or for a patient, contain a clear, concise

warning that it is a crime to transfer the drug to any person other than the patient. Containers to be securely sealed

(d)

be unlawful to distribute conschedule I or II, and narcotic drugs in schedule III or IV, unless shall

trolled substances in

the bottle or other container, stopper, covwrapper thereof is securely sealed as required by regulations of the Attorney General. ering, or

§ 827. Records and reports of registrants (a)

Inventory

Except as provided in subsection

(c)

of

this section

first engages manufacture, distribution, or dispensing of controlled substances, and every second year thereafter, make a complete and accurate record of all stocks thereof on hand, except that the regu-

thereafter as such registrant in the

Establishment

by

label

(1) every registrant under this subchapter shall, on May 1, 1971, or as soon

section.

lished

Warning on

(c)

It

(1) The Attorney General shall by regulation exclude any non-narcotic substance from a schedule if such substance may, under the Federal Food, Drug, and Cos-

(a)

by regulations of the Attorney General, the identifying symbol required under subsec-

be unlawful for the manufacturer

any controlled substance

to distribute

(as defined in section 321 (m) of this title) of such substance contains, when and as required

such substance unless the labeling

lations prescribed

under

this section shall

permit each such biennial inventory (following the initial inventory required by this paragraph) to be prepared on such registrant's regular general physical inventory date (if any) which is nearest to and does not vary by more than six months from the biennial date that would otherwise apply; (2) on the effective date of each regulation of the Attorney General controlling a substance that immediately prior to such date was not a controlled substance, each registrant under this subchapter manufacturing, distributing, or dispensing such substance shall make a complete and accurate record of all stocks thereof on hand; and (3) on and after May 1, 1971, every registrant under this subchapter manufacturing, distributing, or dispensing a controlled substance or substances shall maintain, on a current basis, a complete and accurate record of each such substance manufactured, received, sold, delivered, or otherwise disposed of by him, except that this paragraph shall not require the maintenance of a perpetual inventory.

—

138

Appendix B

Notes visions of paragraph (1)(B),

(b) Availability of records

Every inventory or other record required this seciton (1) shall be in accordance with, and contain such relevant information as may be required by, regulations of the Attorney General, (2) shall (A) be maintained separately from all other records of

under

the registrant, or (B) alternatively, in the case of nonnarcotic controlled substances, be in such form that information required by the Attorney General is readily retrievable from the ordinary business records of the registrant, and (3) shall be kept and be available, for at least two years, for inspection and copying by officers or employees of the United States authorized by the Attorney General. (c)

(2),

or

(3)

of this

subsection. (d)

Periodic reports to Attorney General

Every manufacturer registered under title shall, at such time such form as the Attorney

section 823 of this

or times

and

in

General may require, make periodic reports to the Attorney General of every sale, de-

by him of any conand each distributor shall

livery or other disposal trolled substance,

make such reports with respect to narcotic controlled substances, identifying by the number assigned under this subchapter the person or establishment (unless exempt from registration under section 822(d) of this title) to whom such sale, delivery, or other disposal was made. registration

Nonapplicability

The foregoing provisions shall not

(e)

of this section

apply

(1)(A) with respect to

any narcotic con-

trolled substance in schedule

II,

III,

IV,

or V, to the prescribing or administering of such substance by a practitioner in the lawful course of his professional practice unless such substance was prescribed or administered in the course of maintenance treatment or detoxification treatment of an individual; or (B) with respect to nonnarcotic controlled substances in schedule

or V, to any practitioner

II,

III,

IV,

who

dispenses such substances to his patients, unless the practitioner

is

regularly

engaged

in

charging his patients, either separately or together with charges for other professional services, for substances so dispensed; (2)(A) to the use of controlled substances, at establishments registered under this subchapter which keep records with respect to such substances, in research conducted in conformity with an exemption granted under section 355(i) or 360b(j) of this title;

use of controlled substances, establishments registered under this subchapter which keep records with respect to such substances, in preclinical research or in teaching; or (3) to the extent of any exemption granted to any person, with respect to all or part of such provisions, by the Attorney General by or pursuant to regulation on the basis of a finding that the application of such provisions (or part thereof) to such person is not necessary for carrying out the purposes of this sub(B) to the

at

chapter.

the Convention on Psychoshall be construed as superseding or otherwise affecting the pro-

Nothing

in

tropic Substances

Reporting and recordkeeping requirements of drug conventions

In addition to the reporting

and record-

keeping requirements under any other provision of this subchapter, each manufac-

under section 823 of this with respect to narcotic and nonnarcotic controlled substances manufactured by it, make such reports to the Attorney General, and maintain such records, as the Attorney General may require to enable the United States to meet its obligations under articles 19 and 20 of the Single Convention on Psychotropic Substances. The Attorney General shall administer the requirements of this subsection in such a manner as to avoid the unnecessary imposition of duplicative requirements under this subchapter on manufacturers subject to the requirements of this subsection. turer registered title shall,

(f)

Investigational uses of drugs;

procedures Regulations under sections 355(i) and 360(j) of this title, relating to investigational

use of drugs, shall include such procedures as the Secretary, after consultation with the

Attorney General, determines are necessary to insure the security and accountability of controlled substances used in research to which such regulations apply. § 828. (a)

Order forms

Unlawful distribution of controlled substances

It shall be unlawful for any person to distribute a controlled substance in sched-

ule I or II to another except in pursuance of a written order of the person to

whom

such substance is distributed, made on a form to be issued by the Attorney General in blank in accordance with subsection (d)

and regulations prescribed by him pursuant to this section. of this section

—

Appendix B

139 Notes

(b)

Nonapplicability of provisions

Nothing shall

apply

in subsection (a) of this section to

(1) the exportation of such substances from the United States in conformity

with subchapter

II

of this chapter;

the delivery of such a substance to common or contract carrier for carriage in the lawful and usual course of its business, or to or by a warehouseman for storage in the lawful and usual course of its business; but where such carriage or storage is in connection with the distribution bv the owner of the substance to a third person, this paragraph shall not relieve the distributor from compliance with subsection (a) of this (2)

or

by a

section.

Preservation and availability

(c)

(1)

Every person

who

in

pursuance of an

order required under subsection

(a) of this section distributes a controlled substance

shall preserve

such order

of the United States duly

authorized for that purpose by the Attorney General, and by officers or employees of States or their political subdivisions who are charged with the enforcement of State or local laws regulating the production, or regulating the distribution or dispensing, of controlled substances and who are authorized under such laws to inspect such orders. (2) Every person who gives an order required under subsection (a) of this section shall, at or before the time of giving such order, make or cause to be made a duplicate thereof on a form to be issued by the Attorney General in blank in accordance with subsection (d) of this section and regulations prescribed by him pursuant to this section, and shall, if such order is accepted, preserve such duplicate for a period of two years and make it available for inspection and copying by the officers and employees mentioned in paragraph (1) of this subsec-

tion. (d)

Issuance

(1)

(2) The Attorney General may charge reasonable fees for the issuance of such forms

such amounts as he may prescribe for the purpose of covering the cost to the United States of issuing such forms, and

in

other necessary activities in connection therewith. (e)

Unlawful

acts

be unlawful for any person to obtain by means of order forms issued under this section controlled substances for any purpose other than their use, distribution, dispensing, or administration in the conduct of a lawful business in such substances or in the course of his professhall

It

sional practice or research.

(Pub. L. 91-513, 84 Stat. 1259.)

title II,

§ 308, Oct. 27, 1970,

§ 829. Prescriptions

for a period of

two years, and shall make such order available for inspection and copying by officers and employees

furnish such form to any person with intent thereby to procure the distribution of such substances.

The Attorney General

shall issue

forms pursuant to subsections (a) and (c)(2) of this section only to persons validly registered under section 823 of this title (or exempted from registration under section 822(d) of this title). Whenever any such form is issued to a person, the Attorney General shall, before delivery thereof, insert therein the name of such person, and it shall be unlawful for any other person (A) to use such form for the purpose of obtaining controlled substances or (B) to

(a)

Schedule

Except

II

substances

when dispensed

directly

by

practitioner, other than a pharmacist, to

a

an

no controlled substance in which is a prescription drug as determined under the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 301 et seq.], ultimate user,

schedule

may

II,

be dispensed without the written pre-

scription of a practitioner, except that in

emergency situations, as prescribed by the Secretary by regulation after consultation with the Attorney General, such drug mav be dispensed upon oral prescription in accordance with section 503(b) of that Act [21 U.S.C. 353(b)]. Prescriptions shall be retained in conformity with the requirements of section 827 of this title. No prescription for a controlled substance in schedule II may be refilled. (b)

Schedule

Except

III

and IV substances

when dispensed

directly

by a an

practitioner, other than a pharmacist, to

ultimate user, no controlled substance in schedule III or IV, which is a prescription drug as determined under the Federal

Food, Drug, and Cosmetic Act [21 U.S.C. 301 et seq.], may be dispensed without a written or oral prescription in conformity with section 503(b) of that Act [21 U.S.C. 353(b)]. Such prescriptions may not be filled or refilled more than six months after the date thereof or be refilled more than five times after the date of the prescription unless renewed by the practitioner. (c)

Schedule

V

substances

controlled substance in schedule V which is a drug may be distributed or dis-

No

pensed other than

for a

medical purpose.

140

Appendix B

Notes (d)

should be so considered because of abuse potential, he shall so advise the

Non-prescription drugs with abuse

seq.]

potential

its

Whenever it appears to the Attorney General that a drug not considered to be a prescription drug under the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 301 et

Secretary and furnish to data relevant thereto, (Pub. L. 91-513, 84 Stat. 1260.)

title II,

him

all

available

§ 309, Oct. 27, 1970,

APPENDIX C Labeling Directed Toward Patient 21 C.F.R. 310.500-310.526,

March

effective date

29, 1974

§ 310.501 Preparations for contraception; labeling directed to the patient. (a) Oral contraceptives. (1) The Commissioner of Food and Drugs concludes that the safe and effective use of oral contraceptive drug products requires that patients be fully informed of the benefits and risks involved in the use of these drugs.

Information in lay language concerning effectiveness, contraindication, warnings, precautions, and adverse reactions shall be furnished to each patient receiving oral contraceptives. This information shall be given to the patient by the dispenser in the

form of

a brief

summary of certain essential

information included in each package dispensed to each patient, and in a longer, detailed labeling piece in or

accompanying

each package dispensed to each patient. Patient labeling for drug products dis-

pensed

acute-care hospitals or long-

in

will be considered to have been provided in accordance with this section if provided to the patient before

term-care

facilities

administration of the first oral contraceptive and every 30 days thereafter, as long as the therapy continues. (2)

The

brief

summary

shall specifically

include the following: (i) A statement that oral contraceptives are effective, but that any failure to take

them in accordance with the recommended dosage increases the chance of pregnancy.

A

statement of the specific items of (ii) history to be told the physician that would lead the physician not to prescribe oral contraceptives

(i.e.,

the contraindications to

use). (iii) A statement that oral contraceptives should be taken only under the continued

supervision of a physician. (iv) A listing of the serious side effects of

such as thrombophlepulmonary embolism, myocardial in-

oral contraceptives, bitis,

farction, retinal artery thrombosis, stroke,

benign hepatic adenomas, induction of fetal abnormalities, and gallbladder disease. (v)

A

statement in the form of a boxed

cigarette smoking increases the risks of serious side effects on the heart and blood vessels from oral contraceptive use, and advising women who use oral contraceptives not to smoke. (vi) A statement of the most common side effects, such as nausea and vomiting,

warning that

weight change, change in menses, and breast tenderness. (vii) A statement that the estrogen in oral contraceptives has been found to cause breast cancer and other cancers in certain animals and that these findings suggest that oral contraceptives may also cause cancer in humans but that studies to date in women taking currently marketed oral contraceptives have not confirmed that oral contraceptives cause cancer in humans. (viii) A statement that oral contraceptives are of no value in the prevention or treatment of venereal disease. (ix) A statement calling attention to the detailed patient labeling and a recommendation that it be carefully read. (3) The detailed patient labeling shall be a separate printed leaflet independent of any additional materials. It shall specifically include the following: (i) Name of the drug. (ii) Name and place of business of the manufacturer, packer, relabeler or distrib-

utor.

A

statement that oral contraceptives (iii) are effective but can cause certain serious side effects. (iv) A statement that oral contraceptives should be taken only under the continued

supervision of a physician. (v) A statement of the effectiveness of oral contraceptives, including the differ-

141

Appendix C

142 Notes

ences in effectiveness among different types and the relationship between effectiveness and estrogen dosage. (vi) A summary of the effectiveness of other methods of contraception.

A boxed warning stating that cigasmoking increases the risk of serious side effects on the heart and blood vessels from oral contraceptive use and advising (vii)

rette

women who

use oral contraceptives not to

smoke.

from various contraceptive methods (oral contraceptives in smokers, oral contraceptives in nonsmokers, IUD, condom or diaphragm, condom or diaphragm with abortion in the event of pregnancy, no contraception but abortion in the event of pregnancy, and no contraception or abortion).

A

statement of the specific items of be told the physician which would lead the physician not to prescribe (xiii)

history

to

(viii) A warning regarding the serious side effects of oral contraceptives, including the relative risk (where known) faced by users compared to nonusers and the relationship of the side effects to age, smok-

oral contraceptives

and other conditions. The side effects mentioned shall include thrombophlebitis, pulmonary embolism, retinal artery throm-

myocardial infarction, family history of

ing,

bosis, stroke (the relation of these to estro-

gen dose

be mentioned), myocardial infarction, benign hepatic adenomas, induction of fetal abnormalities, and gallbladder disease. The following shall be mentioned: (a) Estrogens have been shown to cause cancer in animals, which showing justifies the inference that estrogens may cause cancer in humans; (b) there is strong evidence that estrogen use increases the risk of endometrial cancer in postmenopausal women; (c) there is some evidence that sequential oral contraceptive (which are no longer marketed) may increase the risk of endometrial cancer in women; (d) studies of an association between oral contraceptives and breast cancer are largely negative except for a suggestion of increased risk (one study) in women with benign breast disease, and there is no evidence of an increased risk of uterine cancer in users of oral contraceptives other than shall

sequentials. (ix) A statement of common side effects, including nausea and vomiting, weight change, darkening of the skin, changes in menses, and a statement of other serious side effects, including worsened migraine, and worsened heart or kidney disease due

to fluid retention,

growth of uterine

fibroid

tumors, depression, jaundice, delayed return to fertility, blood pressure elevation, decreased glucose tolerance and elevated blood lipids. (x) A statement of reported side effects not definitely related to oral contraceptive use.

crease the flow. (xii)

the contraindica-

(xiv) A statement of specific items of history that might cause the physician to sug-

gest another

method

(e.g., risk factors for

breast cancer or past history of fibrocystic disease or abnormal mammogram, gall-

bladder disease) or would require the physician's special attention (e.g., migraine, asthma, epilepsy, heart or kidney disease, fibroids, history of depression).

(xv) A statement that jaundice, depression, breast lumps, and the particular warning signals of thromboembolic disease, thrombotic disease, and ruptured hepatic adenoma, should be reported to the physician. (xvi) A statement of how to take oral contraceptives properly and what to do in the event of one or two missed periods. (xvii) A statement cautioning the patient

that this

drug has been prescribed for the and that the drug

particular individual only

must not be given to others. (xviii) The date, identified as such, of the most recent revision of the labeling prominently placed immediately after the last section of such labeling. (4) For those oral contraceptive drug products with approved new drug applications for indications in addition to contraception, both the brief summary and de-

tailed patient labeling may identify these other indications. If the other indications are identified, the labeling must specifically include a statement that the information in the patient labeling relative to contraindications, the dangers of oral contraceptives, and the safe use of the drug are also applicable when these drugs are used for these other indications. (5) The detailed patient labeling shall be printed in accordance with the following

specifications:

A

statement cautioning the patient to consult her physician before resuming the use of the drug after childbirth, especially if she intends to breastfeed the baby, pointing out that the hormones in the drug are known to appear in the milk and may de(xi)

(i.e.,

tions to use).

A

comparison of the

(i)

The minimum

letter size

(lower-case

equivalent) shall be not less than '/i6 inch in height. (ii) The body copy shall contain 1 -point leading and noncondensed type, and shall not contain any light face type or small capletter

"o" or

its

ital letters.

risk of

death

(6)

Patient labeling for each oral contra-

Appendix C

143 Notes

ceptive drug product shall be provided to the retailer by the manufacturer, packer, relabeler, or distributor as follows: (i) The brief summary patient labeling

be included in each package intended be dispensed to the patient. (ii) The detailed patient labeling shall be included in or shall accompany each package intended to be dispensed to the patient. (iii) In the case of oral contraceptive drug products in bulk packages intended for shall to

multiple dispensing, a sufficient number of patient labeling pieces shall be included in or shall accompany each bulk package to assure that both pieces can be furnished

with each package dispensed to every patient. Each bulk package shall be labeled with instructions to the dispenser to include both patient labeling pieces (the brief summary to be in the package and the detailed labeling piece either in or accompanying the package) with each package dispensed to the patient. This section does not preclude the manufacturer or labeler from distributing additional patient labeling

pieces to the dispenser. (7) An oral contraceptive drug product that is not labeled as required by paragraph of this section and that is either introduced or delivered for introduction into interstate commerce, or held for sale after shipment in interstate commerce is misbranded under section 502 of the act. However, an oral contraceptive drug product packaged before the effective date of this (a)

not misbranded if adequate numbers of copies of the detailed patient labeling required by this paragraph are furnished to wholesalers or retailers to permit any retail purchaser after the effective date to obtain such labeling with the product. The requirement that any oral contraceptive drug product be dispensed with detailed patient labeling, as applied to physicians, shall not be effective for supplies in their possession on the effective date, but shall apply only to supplies received

paragraph

is

thereafter. (8) The Food and Drug Administration has available patient labeling for oral contraceptive drug products that includes information responsive to all the items specified in paragraphs (a) (2) and (3) of this section. The labeling has been published in the Federal Register and updated versions will continue to be published as guides when changes occur. Any person may rely

on the newest version of this labeling as complying with paragraphs (a) (2) and (3) of this section after the effective date of this

paragraph. (9) Holders of

new drug

applications for

drug products that are subject to paragraph (a) of this section must submit supplements under § 314.8(d) of

oral contraceptive

provide for the labeling required by paragraphs (a) (2) and (3) of this section on or before April 3, 1978. The labeling may be put into use without advance approval by the Food and Drug Administhis chapter to

tration.

APPENDIX D Test Questions 1.

In order to lawfully prescribe controlled substances, the prescriber a.

b. c.

a

a

4.

A

be:

and b are correct and c are correct a, b, and c are correct none are correct

1.

2. 3.

2.

must

Licensed by the local jurisdiction to prescribe controlled substances. Registered as an individual practitioner. Registered as an institutional practitioner.

podiatrist registrant, in order to

scription for Empirin

cramps. The signature

and codeine, is

"Take

1

accommodate

a patient, writes a pre-

C-III, to relieve

the patient's stomach

every 4 hours (pain)." The pharmacist has

no other information. a. The pharmacist may lawfully dispense the prescription. b. The podiatrist may lawfully write such a prescription for this condition. The podiatrist has probably violated the local medical practice act. c. d. The podiatrist, because he was registered, has not violated the CSA. e. The pharmacist may not lawfully dispense this prescription.

3.

A

and d are correct and d are correct and d are correct and c are correct and c are correct

1.

a, b,

2.

a

3.

c

4.

e

5.

a

pharmacist receives three prescriptions from three prescribers, each for a The prescriptions are properly executed and bear the fol-

different patient.

lowing names of prescribers as well as their registration numbers. a. Dr. John Drake, M.D. DEA #AD4132647. b. Dr. Pamela Paul, M.D. DEA #AP7461193. c. Dr. Carlos Ramiros, M.D. DEA #AC5243162. 1.

2. 3.

4. 5.

DEA

number numbers a and number registration valid c is a a and c are valid registration numbers b is a valid registration number a

is

a valid

b are valid

registration

DEA

registration

145

146

Appendix

D

Notes 4. Dr.

John Smith, M.D., and

reception area. Both leave

Before leaving, Dr. Smith

Jones

calls for a refill of

leaves the office,

tells

Dr. Richard Roe share an office suite and town on Wednesday to attend a convention.

tells

Norma Nurse,

R.N., his office nurse, "If Mrs.

her Darvon prescription,

it's

the receptionist, "It's okay to

OK."

Dr. Roe, as

renew any

of

my

he

pre-

make a list of those you approve." Thursday, Mrs. Jones asks Fred Farmosis, the pharmacist at Acme Drug Store, to refill her Darvon prescription. Fred looks up the prescription and determines that the drug is C-IV and that the prescription was written one month previously. The prescription was for a 30-day supply. No refills were authorized on the written prescription. He calls Dr. Smith's office. "Who is this speaking?" he asks. scriptions. Just

On

"This is Dr. Smith's nurse, Norma." "Mrs. Jones is here at my pharmacy. She would like her prescription for Darvon refilled. Would you ask Dr. Smith for authority?" he asks. "Dr. Smith has approved a refill of that prescription," Norma replies. "May I refill it more than once? I won't have to bother you if it's OK." "Sure, you may refill it every month," Norma replies and hangs up. John Black calls Dr. Roe and advises the receptionist he is a patient of Dr. Roe. The receptionist advised him Dr. Roe is out of town. "That's terrible news," he says." Look, this is an emergency. I'm leaving

town. Dr. Roe told me he would phone my pharmacy and leave a prescription for ephedrine and Seconal with the Rex Pharmacy. I only need twenty. Please call them." The receptionist agrees. She calls Rex Pharmacy and says, "This is Dr. Richard Roe's office. Our address is 123 Main Street. His DEA number is AR4327563. Dr. Roe has prescribed for John Black #20 ephedrine and Seconal, Lily, take

"Any

1

a

day as directed."

pharmacist, Joe Green, asks. "Dr. Roe didn't say anything about refills." "Okay. What kind of a practice does Dr. Roe have? refills?" the

I

don't think I've had

any prescriptions from him before." "He's an internist." a.

b. c.

a.

"Okay. Well, I'll get this right out." Dr. Smith may authorize his nurse to transmit his refill authorization. Nurse Norma acted within the scope of her authority. Fred Farmosis may refill the prescription and dispense it based on Norma's authorization. 1.

a

is

correct

2.

b

is

correct

3.

c is correct

4.

a, b,

5.

a

Fred

and c are correct and c are correct

may

refill

the prescription each succeeding

month without

addi-

tional authorization. b. c.

Fred Fred

may refill the prescription only once. may refill the prescription without additional

times. 1.

a

is

correct

2.

b

is

correct

3.

c is correct

4.

none

of the above

authorization five

.

Appendix

D

147 Notes

Select the correct statement: a.

b.

c.

d.

5.

Pharmacist Green may lawfully fill the prescription for John Black. Pharmacist Green may lawfully fill the prescription provided only that John Black's statement to the receptionist is true. Pharmacist Green may not lawfully fill the prescription. Pharmacist Green may fill the prescription provided only that he calls back the prescriber's office and verifies it is an emergency.

The Controlled Substance Act requires the separate

registration of each person lawfully handling controlled substances as well as separate registration for each activity. Which, if any, of the following statements are true? a. An employee or agent of a registrant must register if he or she physically handles controlled substances in the course of employment. b. A manufacturer must obtain a separate registration as a distributor if he

c.

ships directly to a wholesaler. A pharmacy is not required to register as a distributor provided only that it distributes schedule II substances pursuant to a valid federal order form and maintains adequate records of all other substances. 1.

a

is

true

2.

b

is

true

3.

c is true

4.

b and c are true none of the above

5.

6.

A physician is employed and practices only as an emergency room physician Which, if any, of the following statements are true? the physician administers or dispenses controlled substances, he must register personally with the DEA. The physician may administer controlled substances to patients as well

for a registered hospital. a.

b.

If

as write prescriptions for such patients which may be filled by the hospital pharmacy provided it is registered as a pharmacy with the DEA. c.

The physician may administer or dispense controlled substances from the hospital stock in an emergency even if the patient is not a hospital patient.

7.

d.

None

e.

All of the above.

of the above.

Pharmacies that are also registered as distributors must comply with security regulations. ures, pick the

one that

is

the following not required.

c.

Storage area with perimeter security, Electronic alarm system. Self-closing and locking doors.

d.

Key

e.

Controlled accessibility.

a.

b.

8.

From

Which

of the following activities

c.

Commission Commission Commission

d.

Failure to report a

b.

e.

of precautionary security

i.e.,

patrolled by an

may

result in

an employee being barred

of a crime. of a crime involving moral turpitude. of a misdemeanor involving controlled substances.

above

1

All of the

2.

and e b, c, and e c, d, and e b, c, d, and

4. 5.

armed guard.

to controlled substances?

drug diversion to his employer. Unlawful use of a controlled substance.

3.

strict

meas-

control.

from working with or with access a.

list

c

e

148

D

Appendix

Notes 9.

The authority is

a.

b. c.

d. e.

10.

remove

to place or

a

drug

in a controlled

substance schedule

vested in the:

FDA DEA FDA

DEA

and

jointly

Attorney General Secretary of Health and

Which

Human

Resources

of the following statements accurately describes the authority of a

registered institutional practitioner? a.

An institutional

practitioner

may

furnish, package, label,

and administer

controlled substances to the ultimate user. b.

An

institutional practitioner

age, label, c.

11.

An

institutional practitioner

its

other drugs for storage.

1.

a

is

correct

2.

b

is

correct

3.

c is correct

4.

b and

c are correct

5.

a

and

c are correct

Which

may

furnish, administer, dispense, pack-

and prescribe controlled substances.

of the following

may

is insufficient

disperse controlled substances

grounds

among

an application

to refuse

for

registration? a.

b. c.

d. e.

12.

A

Conviction in a state court of a misdemeanor. Falsifying information on the application. Conviction of felony involving controlled substances. Revocation or suspension of state license. None of the above. physician

who

employed by

is

i.e.,

DEA

but

who

a hospital,

may:

not personally registered with the

a registered institutional practitioner,

is

a.

Prescribe controlled substances for patients provided the prescriptions are filled at the hospital's registered pharmacy.

b.

Prescribe controlled substances for patients provided the prescriptions may be filled only by the hospital pharmacy if it is not registered as a practitioner.

c.

Administer, dispense, and prescribe for patients; such prescriptions may be filled by any registered pharmacy provided the prescriber uses the

DEA number. Administer only controlled substances from the hospital's stock but not furnish such medications for a patient to take home. hospital's

d.

13.

A physician with individual scribe for a patient a.

b.

registration only

methadone

in

which

may

may

administer to and/or pre-

of the following cases?

Administer or prescribe for analgesia when medically indicated. Administer only as part of a detoxification process while the patient is seeking entry into a narcotic treatment program and for no longer than three days.

c.

Administer for maintenance for an addict being treated by the physician for a broken leg in a hospital. 1.

a

is

correct

2.

b

is

correct

3.

c is correct

4.

a

5.

All of the

and

c are correct

above

Appendix

D

149 Notes

14.

Which, a.

b.

c.

15.

if

any, of the following statements concerning the

FDCA

are true?

drug advertising is supervised by the FDA. All drugs presently on the market have been approved by the FDA as safe and effective. All drugs currently on the market must be manufactured in accordance with good manufacturing practices. All

1.

a

is

true

2.

b

is

true

3.

c is true

4.

All of the

5.

None

Which one

of the following

FDCA? A drug a.

It is

b.

It

above above

of the

is

adulterated

is

not "adulteration" within the

meaning

of the

if:

packed under unsanitary conditions.

varies from compendial standards without stating such variations

on

its label.

contains an unsafe color additive.

c.

It

d.

It fails

e.

Its

to state the

container

is

name

of manufacturer.

composed

of deleterious matter

which may leech

into

contents. 16.

Which of the following will

drug

to

be classified as a

"new drug"?

Prescribing the drug for a condition not indicated on

b.

Combining two substances neither of which is a new drug. Changing the proportion of substances in a drug.

c.

d. e.

17.

not cause a

a.

The

b. c.

d. e.

labeling.

Claiming a new therapeutic indication for the drug. Suggesting a new route of administration for an existing drug without changing claims of efficacy or safety. label

include a.

its

The The The and The The

on

a manufacturer's stock bottle containing

legend drugs must

of the following information.

all

recommended

or usual dose.

quantity or proportion of each active ingredient. names of all inactive ingredients except flavorings, color additives, trace substances. lot

and control number.

legend.

Certain information, though,

may

be omitted

if

the container

is

too small

and may instead be included in the labeling. The information which may be omitted from a unit dose container is: 1. c and e 2. a and b 3. b, d, and e 4. a, c, and d 5. a, c, and e 18.

The following information normally appears on a prescription. Select the one item that need not appear on the label of the container dispensed by the pharmacist according to the FDCA. 1. Name and address of pharmacy

number

2.

Serial

3.

Date of

4. 5.

Name Name

filling

of patient

of prescriber

150

Appendix

D

Notes 19.

Under

the following a.

b.

drug may be dispensed by

certain circumstances, a legend

macist in a plain container,

A A

list

the

i.e.,

one

that

is

a phar-

not child-resistant. Select from

drug that must be specially packaged.

drug dispensed to an inpatient in a hospital. drug dispensed pursuant to a prescription which

states,

"Dispense

in plain container" c.

d. e.

A drug packaged as a unit dose. Sublingual doses of nitroglycerin. Prednisone tablets

in a container

containing less than 105

mg

of the

drug.

20.

Which

of the following household substances proof packaging? a.

Sulfuric acid

b.

Potassium hydroxide Toluene Turpentine Methyl alcohol

c.

d. e.

21.

Under

certain circumstances, a pharmacist

may

may be

sold in non-child-

mail prescription drugs to

the ultimate user using the U.S. Postal Service. Which,

if

any, of the

fol-

lowing statements are correct? a. Drugs, except controlled substances, dispensed pursuant to prescription may be mailed out of state to the patient. b. A 100-day supply of Librium my be mailed to the patient by the pharmacist dispensing a prescription with the signature, "t. 1 q.i.d." c. In an emergency declared by the prescriber, a schedule II narcotic substance in an amount reasonably necessary to sustain the patient during such emergency provided the prescriber complies with all legal requirements may be mailed to the patient. d. All controlled substances mailed by a practitioner to the ultimate user must be securely sealed with a plain outer wrapping, and the container label must contain the name and address of the prescriber.

and d are

correct

1.

a, c,

2. 3.

b and d are correct c and d are correct

4.

a

5.

a, b,

and d are correct and d are correct

FDA

a.

becomes aware of a misbranded product, even though any poon health caused by the product would be reversible, it may: Institute an action to seize the misbranded articles.

b.

Institute a class

III

c.

Institute a class

II

d.

Institute a class

I

e.

Maintain a criminal action against the manufacturer.

22. If the

tential effects

and b are correct and e are correct a, d, and e are correct a and d are correct c and e are correct

1.

a

2.

a, c,

3. 4.

5.

procedure. procedure. recall procedure. recall

recall

Appendix

D

151 Notes

23.

A

small hospital that does not employ a full-time pharmacist must comply with which of the conditions to participate in the federal Medicare program? a.

The

b.

A member of the hospital

must employ

d.

pharmacist as a consultant. must meet with the consultant regularly. All prescription medications must be filled by the consultant and stored only on the hospital premises. The hospital must adopt a policy of stop orders for all dangerous med-

e.

The

c.

hospital

a

staff

ications.

hospital

must have

a

pharmacy and therapeutics committee which

holds regular monthly meetings.

24.

and e are correct and e are correct and d are correct d, and e are correct and d are correct

1.

a, b, c

2.

a, b, d,

3.

a, c,

4.

b, c,

5.

a, b,

A

pharmacist who serves as a consultant to a skilled nursing facility must perform which of the following functions for the facility to qualify for participation in the federal Medicare program? a. Make periodic visits to the facility to supervise drug handling. b. Review each patient's drug regimen during each visit at least quarterly. c. Report to the medical director any irregularity in a patient's drug regid.

e.

men. Review at least monthly each patient's drug regimen, and file a written monthly report with the therapeutics committee as well as the facility's medical director and administrator. Serve on the pharmacy and therapeutics committee of the facility and orally report their findings to the facility's administrator.

and e only are correct and e only are correct and e only are correct d, and e only are correct

1.

a, c, d,

2.

a, b, c,

3.

a, d,

4.

b, c,

5.

None

of the above

order forms are used by a pharmacy to secure a supply of schedule drugs. Which of the following statements, if any, are correct? An order form may be completed by any licensed pharmacist employee

25. Federal II

a.

of a registered practitioner pharmacy. b.

c.

order form may be used to secure schedule II and III substances provided the substances are available from the same wholesaler. Unless registered as a distributor, a pharmacy registered as a practitioner may not fill a federal order form for C-ll substances from another prac-

An

titioner.

d.

One copy

of the federal order

the supplier.

Upon

form and transmits e.

A

form

is

transmitted by the pharmacy to

pharmacy completes the DEA. pharmacy must complete the shipment of

receipt of the drugs, the a

copy

supplier, wholesaler, or

to the

drugs ordered on a federal order form within 30 days. 1.

a

and

2.

b

is

e are correct

correct

3.

b and d are correct

4.

a

5.

None

and

c are correct

of the

above

152

Appendix

D

Notes 26.

Pharmacies are required to maintain certain records with respect to controlled substances. Which, if any, of the following statements are true? a. The day a pharmacy first dispenses a controlled substance, the pharmacy must take a beginning inventory. b.

c.

27.

A pharmacy must

include in

its

inventory controlled substances that

have been ordered and invoiced but not received. Newly scheduled drugs are inventoried on the date of the next inventory or within 60 days of being added to the list of controlled substances, whichever occurs first. 1.

a is correct

2.

b

3.

c is correct

4.

a

5.

b and

Which

correct

is

and b are

correct

c are correct

three of the following four

methods

for filing prescriptions are ap-

proved? a.

Two

drawers: drawer

1

containing

all

controlled substances, with C-III,

CTV b.

c.

and C-V prescriptions marked with a red "C" in the lower right corner; drawer 2 containing prescriptions for all other drugs Two drawers: drawer 1 containing C-II prescriptions only; drawer 2 containing all others, with C-III, C-IV, and C-V marked with red "C" Two drawers: drawer 1 containing all prescriptions for noncontrolled drugs; drawer 2 all controlled drug prescriptions, with red "C" on all C-II prescriptions

d.

28.

Three drawers: drawer 1 with C-II; drawer 2 with C-III, C-IV and C-V; drawer 3 with all other noncontrolled substance prescriptions 1.

a, b,

2.

a, c,

3.

a, b,

4.

b, c,

and c are correct and d are correct and d are correct and d are correct

Some C-V drugs may be

sold without a prescription. Records of such sales

must be maintained by the pharmacy. All but one of the following items must be maintained by the pharmacy respecting such sales. Which one? a.

Name

b.

Address of purchaser

c.

Age

d. e.

29.

A

of purchaser

of purchaser

Name and quantity of substance Name or initials of dispensing pharmacist

calls the pharmacy where you are employed and asks if it is him to send #20 Percodan tablets home with a patient and if so what he must do with respect to labeling the medication and record keeping.

physician

legal for

Pick the correct response from the following. Yes, you may furnish the patient with 20 tablets from your office supply. You need not label the container nor maintain any specific records other than general business records. Yes, you may furnish the patient with 20 tablets. You must label the b. container with the patient's name, your name, and directions for use. Your office records, i.e., federal order forms, are adequate. Yes, you may furnish the patient with 20 tablets. Because the medication c. is a narcotic, you must maintain in addition to your records of acquisition a.

name and address of the patient, what drug you furnished, the date, and the quantity furnished. You need not label the

a record of the

container. d.

Why

don't you

call a

lawyer or the

DEA?

Appendix

D

153 Notes

30.

Which

of the following

is

not a

requirement for a written prescription for a

C-II substance? It

b.

It

c.

d. e.

31.

must bear the full name and address of the patient. must bear the name, address, and DEA number of the prescriber. It must be written in ink, typewriter, or indelible pencil by the prescriber. It must be dated on the day of issue. It must be manually signed on the date of issue.

a.

A C-II substance may be dispensed upon oral order provided the pharmacist and prescriber follow a strict procedure. Identify any errors in procedure: The pharmacist and physician determine Ml emergency exists, the paa. tient needs the medication, no alternative is available, and a written prescription

is

not practical.

b.

The pharmacist receiving the

c.

In addition to information required for a written prescription, less the

oral order reduces

it

to writing.

on the prescription "Authorization for Emergency Dispensing." Even though the prescription is for a larger amount, the pharmacist may dispense only enough to last through the emergency. The pharmacist must note on the prescription the amount of partial filling. Within 72 hours, the prescriber must deliver a written prescription covering the medication prescribed with the words "Authorization for Emergency Dispensing" written on it. signature, the pharmacist writes

d.

e.

1.

2. 3.

4. 5.

There are no errors in procedure a is erroneous b and c are erroneous c and d are erroneous d and e are erroneous

32.

The CSA requires the label on a container of controlled substances dispensed by a pharmacy to contain certain information. Which of the following is not required to appear on the label? Name, address, and phone number of pharmacy. a. b. Name of patient and name of prescriber. c. Date of filling if C-II; date of initial filling if C-III, C-IV and V. Directions for use and serial number of prescription. d. The words "Caution: Federal law prohibits the transfer of this drug to e. any person other than the person for whom it was prescribed."

33.

The following statements refer to prescriptions for controlled substances in schedules III, IV, and V. Which statement is not true? a. A prescription for a C-III, C-IV, or C-V substance may originate as an oral or written order. b.

Such

a prescription

may be

refilled

no more than

five

times within any

six-month period. c.

Refills of

such a prescription must be recorded

either:

on the back

of the

prescription, with the initials of the dispensing pharmacist and the date, or if the pharmacy has an automated system with a daily printout, the

pharmacist must review, sign, and date the printout within 72 hours of dispensing. d.

A pharmacy maintaining its refill records on an automated system must maintain an auxiliary system.

e.

A

partial refilling of a C-III or

after six

months from the date

C-IV substance of issue.

may

not be completed

154

Appendix

D

Notes 34.

A DEA

inspector

may make an

inspection of a registered pharmacy.

The

following statements apply to such an inspection. Select the statement that is

a.

not true.

Before an administrative warrant of inspection

may be

spector must have been barred from inspection by the

issued, the in-

owner

or phar-

owner

or phar-

macist in charge. b.

An

inspection by consent requires that the pharmacy

macist in charge give informed consent to the inspection. c.

If

a pharmacist in charge

macist d.

is

Consent

entitled to to

is

know

asked

to

consent to an inspection, the phar-

the real reason for the inspection.

an inspection may be terminated

at

any time by the phar-

macist in charge. e.

Anything found on the premises as well as any statements made by the owner or pharmacist in charge during the inspection can be used against the pharmacist or

owner

in a later criminal trial.

APPENDIX E Test

Answers Question

Correct

Answer

Texf Pages

1

1

17-18, 81-85

2

5

17-18, 81-85

3

1

4

5, 3, c

82 18,

81-85, 90

5

5

38-39

6

d

38, 43

7

a

52

8

4

52-55 61

9

d

10

5

51

11

a

12

b

41-43 43-44

13

5

86

14

3

15

d

16

a

4

8-9 8-10 13-17 9-13 21-23 24-26 24-26 26-27, 111-112 30-31 32-34 32-34 63-69 72-73

3

74

17

5

18

4

19

c

20

c

21

4

22 23 24

2

25 26

27 28 29

5 5 5

c

75

c

77-78 86-88 88-89 91-93 81-93 103-105

30

c

31

4

32

a

33 34

b a

155

INDEX

Acquisition of controlled substances, records of, 73, 74 See also specific schedules of controlled substances Activities

coincident. See Controlled Substance

Act registration of, 37, 38

chemical analysis, 46 compounding, 46 dispensing, 40-44

labeling directed toward patient,

141-143

distributing, 39-40

patient information required for, 22, 23, 141 Controlled Substance Act, 131-140

exporting, 46

importing, 46 instructing, 45

manufacturing, 12, 37 narcotic treatment programs, 45 research, 45, 46 Addiction, treatment of, 86. See also Narcotic treatment program(s) Addihve(s), color, 8, 10, 31 Adulteration, acts constituting, 8 color additives as, unsafe, 8

compendial standards and, variation from, 8 cosmetics and, 30 misbranding and, distinguished from, 9 Adverse reactions, reports of, 16 Agents, registration of, exemption from, 43 Alcohol tax, 31 Annual registration, 37, 49 See also Registration Attorney, power of, 67

Business(es), corporate form,

insulation as, 57 discontinuance of, procedures 68 inspection of, 103-105 records of, separation of, 75 See also Record(s) theft from, 107-109 transfer of, 57

Coincident activities. See Controlled Substance Act Color additives, unsafe, 8 Compounder, defined, 46 order forms used by, 69 records required of, 78 registration of, 46 Computer records. See Record(s) Conrraceptive(s), 23, 24

for,

Cautionary statements. See Warning(s) Central record keeping, 72. See also Record(s) Chaney vs. Heckler, 19

addiction and, 86 administrative inspections and, 103 consent revocation, 104 consent to, 103 hours of, 103 place of, 103 warrants for, 104-105 applicant investigation and, 49, 52 business and, 57 corporations, 57 inspections of, 103-105 order form discontinuance, 68 records separation and, 75 theft from, 107-109 transfer of, 57 See central record keeping and. Record(s) "closed system" and, 35 coincident activities and, chemical analysis, 46

compounding, 46 dispensing, 43 distributing, 40 exporting, 45 general considerations, 39 importing, 45 instruction, 45 manufacturing, 39 narcotic treatment program, 45 research, 45 diprenorphine, 54, 69 dispensing and. See Dispensing dispersals and, records of, 74 disposal of substances, 95 diversion of substances and, duty to report, 55 Drug Enforcement Administration and, functions of, 35 guidelines of, 85

number

verification and, 82

on schedules of, 61 employee(s) and, access to records, 54 effects of treaties

dismissal

of,

54-55

statements by, 54-55 etorphine hydrochloride and, 54, 69 Food and Drug Administration and, administrative inspections and, 103-105 functions of, 35 general considerations, 35 individual practitioner and. See false

Practitioner(s), individual

See Controlled Substance Act, administrative

inspections.

inspections and institutional practitioner and.

See

Pracririoner(s), institutional

inventory, perpetual, 77 required, 72-73 separate, 73 invoices and, retention of, 74-75 long-term care facility and, registration exemption, 47 mail and, between practitioner and patient, 111

between

registrants, 111

manufacturer's quotas and, 63 records submission required, 60 narcotic treatment program and, acceptance of controlled substances, 55-57 control of, 55 records of, 78 Native American Church and, 99 nurse practitioner and, authority of, 82 order forms and, additional uses of, 68 completion of, 66 disposition of executed forms, 68 endorsement of, 69 errors on, 68 execution of, 63 power of attorney and, 66, 67 theft of, 107-109 over-the-counter (OTC) substances and, 60 penalties for violation of, 101-102 pharmacist and, as practitioner, 17, 40, 82 responsibility of, 81-82, 85

157

158

Index

Controlled Substance Act (Continued) pharmacy and. See Pharmacy physician assistants and, authority of, 82 practitioner and. Sec Practitioner(s) prescriptions and, authority to issue, '

Dispensing, compendial standards and, 8

91,

methods

formalities of, transfer

between

See also specific schedules schedules for, procedures for, 61 security requirements and, for manufacturers and distributors,

52-55

treatment programs,

55-57 for practitioners, 49-52

separate activities, 38 symbols required, 61 treaties, effect of, 61

verification of registration

number,

82 violations of, 101-102 Cosmetics, adulteration defined, 29 labeling of, 29, 30

of,

30

manufacturer registration, 29 misbranding of, 30 tamper-resistant packaging of, 31

of

refills,

limitations

of, 90,

on frequency

91

90 Poison Prevention Packaging Act and, 20-24 unapproved use and, 19

Federal Trade Commission, authority of, 10, 11

Food and Drug Administration,

Distributor(s), activities separate from,

73 coincident activities and, 39 defined, 39 pharmacy as, 52 records of, 70, 74 registration of, application for, 52 requirements of, 40 security of premises and personnel of,' 52, 54 separate inventories of, 73 Drug(s), advertising, 24 compendial standards and, 8 counterfeit, defined, 7 defined, 7 diprenorphine and, 7 disposal of, 95 etorphine hydrochloride and, 54, 69 informed consent and, 19, 20

new drug procedures

container label, 21, 22, 90, 92 for schedule II oral substances, 89, 91

narcotic, treatment

See also

requirement Definition(s),

for, 20,

programs

of, 8, 10, 11, 26,

New

for,

55

75

drug application(s)

packaging of, poison prevention and, 20, 24-26

87

compounder, 46

cosmetics, 29 devices, 27 dispense(r), 37, 40, 71 distribute, 39

drug, 7 counterfeit, 7

new, 13 label, 3

labeling, 4

pharmacy, 72 practitioner(s), 40

individual, 71 institutional, 71

prescription, 20, 81 special packaging, 25

Department of Justice, United Drug Enforcement

States,

therapeutic claims and, 7 See also Controlled Substance Act Drug Enforcement Administration, disposal of controlled substances and, 95 drug advertising and, shared responsibility for, 10, 35 functions of, 35 guidelines for fraud detection, 85 inspections by, 104-105. See also Controlled Substance Act, administrative inspections and registration denial by, 41, 42 Drug Price Competition and Patent Term Restoration Act of 1984, 6 Durham-Humphrey Amendment, 4

for, 28,

Emergency

29

defined, 27

Medical Device and, 6

Amendment

on sale of, 29 and effectiveness of,

of 1976

restrictions

safety

6,

28

Diagnosis, by mail, 20 mail order prescription and, 20 pharmacist's knowledge of, 19

Diprenorphine, 54, 69 order forms for, 69

enforcement and

recall

procedures

of, 31

investigational drugs and, authority

over, 14-15

new drug

application and, authority over, 15-17

and, authority over,

13,

14

unapproved drug use and, policy regarding, 19

Food, Drug and Cosmetic Act,

3-6,

113-130

Drug Price Competition and Patent Term Restoration Act and, 6

Durham-Humphrey Amendment

of

1951 and, 4

Kefauver-Harris Amendments of 1976 and, 6 Orphan Drug Act of 1983 and, 6 Foreign languages, labeling and, 13 patient information and, 23, 24, 91 Foreign trained physician(s), authority of, 44

Good manufacturing establishment failure to

practice, of, 5

comply with, 8

Habit-forming drugs, warnings

Administration and, 35 Device(s), classification of, 28

procedures

cosmetics and, authority over, 29 diagnosis by mail and, policy regarding, 20-21 dispensing prescribers and, policy regarding, 21 Drug Enforcement Agency and, responsibility shared with, 35, 45

23

established, 10

new, sales

reminder, 24 controlled substances and, shared authority over, 35, 45

patient drug labeling and, 12-13, 22-

and, 14-15 of,

advertising and, authority over, 10, 24

new drugs

intent to market as, 7

name

refill

for,

partial, 89,

investigational

Date, of prescription, for

Etorphine hydrochloride, order forms for, 54, 69 Exporting, registration required 10, 46

substances

registrants, 92

See also Prescription^) records and. See Record(s) registration and. See Registration repackaging, 39, 79 schedules and, establishment of, 59

for narcotic

141

See

specific schedules of controlled

74 86-88

Act,

Established name of drug, 10 Estrogen, patient information and, 23,

92

of controlled substances.

tor,

Drug and Cosmetic

Federal 31

defined, 37, 40, 71 labeling and, exemption from, 20,

81 tiling

ut

oral prescriptions, of

schedule II substances, 88-89 pharmacist's duties, 89 prescriber's duties, 84 Employee(s), arrest or court records of, access to, 54 diversion of substances by, reporting of, 55 registration of, exemption from, 38, 43 Enforcement procedures, of Controlled Substance Act, 101-105

regarding, 4,9 Hospital(s), alcohol tax

exemption and,

31, 32

chart orders, 81 contraceptives furnished by, 23

dangerous drug control by, 33 drug standards of, 33 labeling of drugs in, exemptions affecting, 23, 25, 32, 33, 92

long-term care facilities and, requirements for, 47 Medicare participation in, 32

Index poison prevention packaging and, exemption affecting, 25 practitioners practicing in, 43, 44 foreign-trained, 44 institutional, 40, 71 prescriptions written in, authority of

employees and, 44 records required of, 32, 33, 76, 77 registration as, 43

numbers

for,

44

security in, regulations regarding, 51 : 52 Veterans Administration, authority of, 44 prescription formalities, 87, 88

Individual practitioner. See Practirioner(s), individual

Informed consent,

19,

20

Inspections, administrative, authority for,

103

consent

to, 72,

104

places subject to, 103

time

of,

103

waiver of warrants for, 72 warrants for, 104-105 Institutional practitioner. See Practitioner(s), institutional

Insulin, certification of, 10

Interns, authority of, 43

Inventory(ies), date of, 73

methods

159

contents of, 12, 13 contraceptives, 22, 23 Food and Drug Administration authority over, 13 for estrogens, 22, 141 for prescription only requirement, 13 in foreign languages, 13 new drugs, 15 patient information and, 11 prescribing for unapproved use and, 18-20 symbols required for, 61 tamper-resistant packages and, 8 for prescription medication container, cautionary statements, 23, 91 contents of, 20-22, 86-89 dating of, 21, 91, 92 for controlled substances, 91, 92 for estrogens, 23, 141 foreign languages and, 23 hospital requirements for, 33 mailing requirements for, 11, 26 patient information and, 22 prescriber exemption and, 21, 22, 77 unit dose exemption and, 92 Labeling directed toward patient, 141144 Long-term care facilities, requirements for,

47

73 perpetual, 77 of,

requirements

for,

72

new drug

Investigational 14-15

Mailing, of controlled substances, 2627, 111-112

procedures,

Judicial review, administrative

determinations and, right

to,

42

administrative warrants and, applications for, 104

Kefauver-Harris

Amendments

of 1976,

6

Label(s), for cosmetics, for,

requirements

29-31

for devices, restricted, 28-29 for

manufacturer's drug container, adequate directions for use and,

advertisements as part contents of, 9-12

of, 10,

for,

29

for

39

responsibility of, 25, 26

vs.

Parke-Davis, Co., 19

Narcotic treatment program(s), coincident activities of, 45, 46 detoxification treatment and, defined, 45 emergency treatment and, 86 for narcotic addicts, 35 maintenance treatment and, defined, 45 records required for, 78 registration required for, for activities, 37 for practitioner, 43 restrictions on treatment, 86 Native American Church, 99 Naturopaths, 41 Negligence, foreign-language labeling as, 24 "special packaging" omission as, 26 unapproved use as, 19 New devices, classification of, 28, 29 premarket testing of, 28 New drug applicarion(s), 15-17

adverse reaction reports and, 16 confidentiality of data, 15

continuing reports required

for, 16 defined, 13 for controlled substances, manufacturer's reports of, 61 investigational, 14 procedures for, 14 Nurse(s), authority of, as prescribers, 17, 82 to transmit prescriptions, 18, 84 Nurse practitioners, authority of, 17, 82

Order forms for controlled substances, endorsement procedure, 69 execution filled filled

of,

66

by compounder, 69 by researcher, 69

loss or theft of, 69

necessity for, 68 power of attorney and, 66, 67 required, 63 retention of, 69

returning substances and, 68 transfer of business and, 68 Orphan Drug Act of 1983, 6 Out-of-state prescriber, authority

of,

17, 18

Over-the-counter drugs, 8

practices, 5

defined, 3 distinguished from "labeling,"

exemption exemption

as, 27,

poison prevention and,

24

control of, 11 3,

4

pharmacy, 27

for prescription drug,

registration requirements of, 10 Medical Device Amendment, 6 Medical devices. See Device(s) Medicare, conditions for participation,

32

11

federal caution legend, 11

disclosure policy and, 9 habit-forming substances legend, 9 investigational new drug, 14, 15 symbols required for, 61 full

for, 9, 14, 15

Labeling, for manufacturer's drug container, adequate directions

and, 11

of devices, premarketing procedures

pharmacy exemption

11

warnings

Manufacrure(r), adverse reaction reports required, 16 of controlled substances, activities of, 34 application procedure for, 52 coincident activities of, 39 defined, 39 distributor as, 38 information required of, 60 quotas for, 63 records of, 78 registration of, 37, 39 security requirements for, 52, 5455 of cosmetics, registration of, 29

policy of law, 9

Mulder

personnel requirements for, 32 pharmacy committees and, requirements for, 33 physical facility requirements, 32, 33

Methadone, 86 Misbranding, acts constituting, 9 for devices, 9-11, 28 adulteration distinguished from, 9 of cosmetics, 30, 31

Packaging, for mailing, 26, 27, 111-112 of cosmetics, 29 of drugs, 8, 9-13, 24 patient information and, 8. See also Patient information Poison Prevention Packaging Act and, 24-26 tamper-resistant requirements and, 8, 29 Patient information, brochure for drugs, 22, 23, 141 cautionary statements and, 22, 23, 91

1

160

Index

Patient information (Continual) directions tor use, 22

adequate, display

of,

4,

1

9

exemptions from, prescriber's, 21 prescription drug, 11 for contraceptives, 22, 23, 141

for cosmetics, 30-32 for devices, 28,

languages, 23, 24, 91 informed consent and, 14, 15 tamper-resistant packaging and, 8 unapproved use of drugs and,

in foreign

prescribing for, 18-20 warnings, transfer of, 91 Pharmacy, administrative inspection of, 103-105 as distributor, 38-39, 40, 52, 68

another registrant, 68

as manufacturer, 27, 39, 75

business

of,

employee exemption and,

38, 43

prescription transfer and, 92-93 of,

maintenance

requirements

for,

of,

72

72

theft of, 92-93

registration of, 37, 49 refusal of, 41-43

security requirements for, 51 theft reporting by, 107

Physician assistants, authority of, to prescribe, 14, 17, 41, 82 to transmit prescriptions, 84 Poison Prevention Packaging Act, child resistant container and, defined, 25 exemptions from, 25 hospital application of, 25 household substances subject to, 26 misbranding and, 10 products subject to, 24 Power of attorney, 67 Practirioner(s), at separate site practices, 38, 47

coincident activities of, 43 defined, 40, 41 discontinuing business as, 68

exemptions from registration, 43 foreign-trained physicians as, 44 hospital as, 40 in

issue of, authority

naturopaths as, 41 nurse practitioner as,

refills of,

82 17, 40

bureau of prisons, 44

in institutions, 43. See also

Practitioner(s), institutional

individual, addiction treatment by,

86 administering drugs by, 41 administrative inspections of, 103105 branch office exemption for, 47 coincident activities of, 43 defined, 40, 77 dentists as, 40, 71

discontinuance or transfer of business by, 57, 60 dispensing by, 21, 41 disposal of controlled substances by, 95 distinguished from institutional practitioner, 71

emergency prescriptions by, 88-89

purpose

physician assistants as, 14, 17, 41, 82 physicians as, 17, 40, 71

85,

81

authorization 90

for, 18, 82-

responsibility for, 81 transfer of,

between pharmacies, 92-

93 Public health

and

safety,

concept

of,

42

podiatrists as, 17, 40, 71

prescribing authority of, 17, 40, 71, 81 prescribing formalities for, 86-88

prescribing limitations on, 43 records maintained by, 77, 78 security requirements for, 78 veterinarian as, 17, 40, 71

inspections and, 103-105 alcohol tax exemption for, 31, 32 coincident activities of, 45 defined, 40, 41 foreign-trained physician as, 44 in

to, 14, 17, 40,

85

of,

mail order, 20-21 pharmacist's responsibility for, 85 records of, dispersal and, 74

17, 40,

institutional, administrative

discontinuing, 68 transfer of, 57 defined, 72

records

registration, 43 foreign-trained physicians as, 44 interns as, 44 investigation of, 49, 103-105 labeling exemption for, 92

out-of-state prescribers as,

29

for estrogens, 23, 141

to

exemptions from

Veterans Administration hospitals, 44, 51

Purchase

restrictions, 41,

45

Quotas, manufacturer's, 63

Recall procedures, 31 Record(s), acquisition of, 70, 73 adverse reaction reports, 16 central record keeping, 69, 72

dispersal, 75 of

compounders, 78

of distributors, 40, 78 of individual practitioners, disposal

individual practitioners and, 43 interns as, 44 labeling requirements for, 92 Medicare participation and, 32-39

physicians in employment and, 44 records maintained by, 32-34, 76, 77 registration number for, 82 registration of, 49, 50 repackaging by, 79 security requirements for, 51, 52 theft reporting by, 51 interns as, 44 investigation of, 49 masters of ocean vessels and aircraft as, 44 military as, 44 pharmacist as, 17, 40 pharmacy as, 40 podiatrist as, 17, 40

of,

95

required, 47, 77-78 theft of, 107 of institutional practitioners,

acquisition of, 76

dispersals of, 76, 77 disposals of, 95 internal codes and, 44

inventories and, 76 Medicare participation and, 32-33 repackaging exemptions and, 79 requirements for, 76 theft of, 107 of long-term care facilities, 47

of manufacturer, 78 of narcotic treatment

of

pharmacy, as

programs, 78

distributor, 40

dispersal of, 74

disposal

registration of, 41

refusal of, 41-43

95

of,

for

emergency prescriptions, 88-89

for

schedule

V

substances, 75

of inventories, 72

scientific investigators as,

40

of order forms, 69, 72, 75

security requirements applicable to,

of partial filling, 89 of prescription transfers, 92, 93

51 theft reporting by, 51

of prescriptions, 18, 72, 74, 89, 90 of separate activities, 73, 75

Prescription(s), authority to issue, 14,

refills, computer generated, 72 requirements for, 90 of returned drugs, 75 order forms, 63-69. See also Order forms for controlled substances

of

17, 40, 81

of Public Health Service

employees, 44 scope of practice and,

17, 81

verification of, 82

authority to transmit, 18, 82-85 defined, 81 devices and, 29

readily retrievable, 74

Durham-Humphrey Amendment

separate, requirements for, 46, 73

and, 4

emergency, filing

repackaging and, exemption from, 79 theft of, 51, 54

Registrant(s), mailing between, 27, 111

85, 88-89

methods

for,

74

for controlled substances.

See

Controlled Substance Act; specific schedules of controlled substances for methadone, 86 formalities of, 18, 86-91

Registrant Protection Act, 102 Registration, activities requiring, 10, 37 annual, 37, 49 applications for, 50, 53, 56 certificate of, 51

chemical analyses and, 46 denial of, 40-43

Index exemptions from, for

exemptions, 92 order forms for. See Controlled Substance Act prescriptions for, date of, 87, 89

affiliated

persons, 43 for agents, 43 for for

branch offices, 47 bureau of prisons, 44 employees,

for interns, for

law enforcement personnel, 46

masters of ocean vessels and aircraft, 44 for military, 44 for Public Health Service employees, 44 for sales offices, 47 for separate sites, 47

of

and research

37,

substances, acquisition

70, 76 criteria for,

60

dispensing

of,

programs,

37,

46 of separate sites, 38, 46 period of, 37 verification of, 82 Repackaging, 39, 79 45,

and, 90

criteria for,

60

dispensing

of,

of,

See Controlled

Substance Act prescriptions prohibited for, 59

Act

substances, acquisition of,

59

dispensing

of,

88-89

dispersals, records of, 74

labeling of, 9, 91-92

between

registrants,

Treaties, effect of, 61

Unapproved use

Scope of

of drugs, as negligence, 18-20 informed consent and, 20

manufacturer's responsibility Unit dose, labeling and, 12, 92

19

90

Vermont & 110th Street Medical Arts Pharmacy vs. State Board of Pharmacy, 85-86 Veterans Administration hospitals, agents and employees of, 44 prescription formalities in, 87, 88

for,

Warning(s), for habit-forming drugs,

75

practice, 17, 18, 81

9

Security requirements, for distributors, 40, 52-54 for manufacturers, 52-54 for narcotic treatment

programs, 55-

57 for pharmacies, 40, 51-52 for practitioners, 51, 77, 78 Site registration, record retention 69, 72

in,

91

record book

59

criteria for,

74

exemption from, 92 nonprescription, 75 prescriber authority for, 82-85 prescriptions for, formalities of, 8690 refills of,

II

of,

labeling of, 91

substances, acquisition

See also Controlled Substance

of prescriptions 92-93

invoices for, 74

63 for.

about, 91

practitioner dispensed, 92

70

of manufacturers, 10, 29, 37, 39

order forms

89-90

Schedule IV substances, criteria for, 60 See also Schedule III substances Schedule V substances, acquisition of,

of importers, 37, 46

criteria for,

Theft, of controlled substances, 51-54 of order forms, 69, 107-109 Therapeutic claims, 7 Transfer, of business, 57 of prescription drugs, warnings

dispersals of, records of, 74 labeling of, dating, 91

methods

31

Thalidomide disaster of 1962, 5 of,

returns, procedure for, 75

of exporters, 37, 46

Schedule 63

III

8,

fraudulent, 82-85

46

of narcotic treatment

47

formalities of, 86-89

of distributors, 37, 39, 40

I

Schedule

prescriptions, filing

57

of cosmetic manufacturers, 29

Schedule

partial filling of, 89

refills

45

new number,

compounder,

Tamper-resistant packaging, Test answers, 155 Test questions, 145-154

See also Controlled Substance Act

for

activities, 37,

for, 46,

Sulfanilamide disaster of 1937, 3 Symbols for controlled substances, 61

fraudulent, 82-85

for long-term care facilities, 47

obtaining

separate registration

Skilled nursing facilities, 33

formalities of, 86-88

38, 43

44

for instructional

Sites,

emergency oral, 88-89 filing methods for, 74

for coincident activities, 38, 39 for

161

at,

for investigational for prescription

new

drug, 15

drug legend,

5, 11

for prohibition of transfer, 91

tampering evidence, misbranding and, 9 for

8,

9

Warrants, for administrative inspection, authority for, 103104 consent to, 72, 104

4,