9024 Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 201, 330, and 358

[Docket Nos. 96N–0420, 92N–454A, 90P–

0201, and 95N–0259]

RIN 0910–AA79

Over-The-Counter Human Drugs;

Proposed Labeling Requirements

AGENCY: Food and Drug Administration,

HHS.

ACTION: Proposed rule.

SUMMARY: The Food and Drug

Administration (FDA) is proposing to

establish a standardized format for the

labeling of over-the-counter (OTC) drug

products. FDA has determined that

because the design and format of

labeling information varies considerably

among OTC drug products, consumers

often have difficulty reading and

understanding the information

presented on OTC drug product

labeling. The proposal is intended to

enable consumers to better read and

understand OTC drug product labeling

and to apply this information to the safe

and effective use of OTC drug products.

This document supersedes the agency’s

proposed rule regarding the use of

interchangeable terms, published in the

Federal Register of March 4, 1996

(hereinafter referred to as the March

1996 proposal), and responds to the

comments that were submitted to FDA

as a result of that proposal (Docket No.

92N–454A). Accordingly, this document

formally withdraws the March 1996

proposal. Finally, this proposal would

preempt State and local rules that

establish different or additional format

or content requirements.

DATES: Submit written comments by

June 27, 1997. Submit written

comments on the information collection

requirements by March 31, 1997.

ADDRESSES: Submit written comments

to the Dockets Management Branch

(HFA–305), Food and Drug

Administration, 12420 Parklawn Dr.,

rm. 1–23, Rockville, MD 20857. Submit

written comments on the information

collection requirements to the Office of

Information and Regulatory Affairs,

Office of Management and Budget

(OMB), New Executive Office Bldg., 725

17th St. NW., rm. 10235, Washington,

DC 20503, ATTN: Desk Officer for FDA.

FOR FURTHER INFORMATION CONTACT:

Diana M. Hernandez, Center for Drug

Evaluation and Research, Division of

OTC Drug Products (HFD–560), Food

and Drug Administration, 5600 Fishers

Lane, Rockville, MD 20857, 301–827–

2222.

SUPPLEMENTARY INFORMATION:

I. Introduction

Under the Federal Food, Drug, and

Cosmetic Act (the act), OTC drug

products must be safe and effective in

order to be marketed. The agency is

conducting a comprehensive review of

these drug products, which are available

to consumers without a prescription. As

a result of this review, the agency has

required specific language to be

included in the labeling of many OTC

drug products, describing the uses,

directions, warnings, drug interaction

precautions, active ingredients, and

other information, so that consumers

can use these products safely and

effectively.

As a result of escalating health care

costs and the increasing availability of

OTC drug products, some of which were

once available only by prescription,

more consumers are engaging in selfmedication. Thus, it is increasingly

important that consumers read and

understand the information on drug

product labeling.

On January 6, 1993, the agency issued

final regulations to help consumers read

and understand the information on food

product labeling (58 FR 2079). The new

regulations, which provide for a

standardized graphic presentation for

food nutrients, were issued in response

to the Nutrition Labeling and Education

Act of 1990 (the 1990 amendments)

(Pub. L. 101–535, November 8, 1990).

The 1990 amendments directed the

Secretary of Health and Human Services

to issue implementing regulations to:

* * * require the required information to

be conveyed to the public in a manner which

enables the public to readily observe and

comprehend such information and to

understand its relative significance in the

context of a total daily diet.

(Section 2(b)(1)(A) of the 1990 amendments)

This new, standardized format allows

the consumer to judge the significance

of the level of a particular nutrient in a

particular food in the context of the total

daily diet.

FDA believes it is equally important

for consumers to be able to make

reasoned decisions about the drugs they

take. On August 24, 1995 (60 FR 44182),

FDA proposed a comprehensive

program to increase the distribution and

quality of easy to read and easy to

understand written information about

prescription drugs to patients. Recently

enacted legislation provides that various

private entities will work to transform

these goals into a satisfactory program.

FDA is now proposing to improve the

way that information on the labeling of

OTC drug products is communicated.

The design, format, and placement of

required labeling information varies

considerably among OTC drug products.

As a result, consumers often have

difficulty finding, reading, and

understanding this labeling information.

Modifying and simplifying the manner

in which the information is presented

can improve the legibility and

understandability of OTC drug product

labeling. FDA is, therefore, proposing to

establish a standardized format for the

labeling of all marketed OTC drug

products. This action is intended to

enable consumers to better read and

understand OTC drug product labeling

and to apply this information to the safe

and effective use of OTC drug products.

The agency is proposing five types of

labeling changes for OTC drug products.

First, the proposal would require that

OTC drug product labeling include

standardized headings and subheadings

presented in a standardized order, as

well as standardized graphical features

such as the Helvetica type style,

minimum standards for type size,

leading (i.e., space between two lines of

text), kerning (spacing between letters),

upper and lower case letters, and

graphical highlights.

Second, the proposal would permit

manufacturers, packers, or distributors

to delete specific terms, referred to for

purposes of this rulemaking as

‘‘connecting terms,’’ that are currently

required in OTC drug product labeling.

Holders of approved new drug

applications (NDA’s), antibiotic drug

applications, and abbreviated new drug

and antibiotic drug applications

(referred to collectively in this

document as ‘‘marketing applications’’)

who wish to delete a ‘‘connecting term’’

in their labeling would also be

permitted to delete the ‘‘connecting

term’’ in accordance with 21 CFR

314.70. Typically, such terms are found

within quotation marks in OTC drug

monographs and in specific regulations.

Deletion of these terms would only be

permitted where deletion would not

change the meaning of the information.

Deletion of these terms would not be

required but, rather, would be permitted

as needed to simplify the presentation

of labeling information (which is

usually presented in a lengthy

paragraph format), so that

manufacturers, packers, distributors, or

applicants can comply with the

proposed, easier to read format.

Third, the proposal would expand the

list of ‘‘interchangeable terms’’ found in

the current regulations (§ 330.1(i) (21

CFR 330.1(i))), to facilitate the use of

more concise, easier to understand
Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules 9025

statements on the labeling of OTC drug

products. Expanding the list of

interchangeable terms would provide

manufacturers, packers, distributors, or

applicants with a broader choice of

terms for a particular statement on the

labeling. This proposed rule addresses

the same interchangeable terms (as well

as additional interchangeable terms)

that were proposed on March 4, 1996

(61 FR 8450). Thus, this proposal

formally withdraws the March 1996

proposal.

Fourth, the proposal would amend

specific warning language required

under current monographs and

regulations (the pregnancy-nursing

warning, the ‘‘keep out of reach of

children’’ warning, and the overdose/

accidental ingestion warning (§§ 201.63,

201.314(a) and (g)(1) (21 CFR 201.63,

201.314(a) and (g)(1)), and 330.1(g)) to

make the warnings easier to understand

and more concise.

Finally, in order to ensure that OTC

drug product labeling is easier to read

and understand, and to ensure the safe

and effective use of OTC drug products,

FDA is proposing to preempt State and

local rules that establish different or

additional format or content

requirements than those in this

proposed rule. The agency believes that

such State and local requirements for

OTC drug labeling would undermine

the agency’s objectives of ensuring the

safe and effective use of OTC drug

products through the use of a uniform

easy-to-read format for all OTC drug

product labeling.

II. Regulatory Scheme for OTC Drug

Product Labeling

A. Current Statutory and Regulatory

Requirements

The act and FDA’s implementing

regulations require specific information

on the labeling of all OTC drug

products. FDA regulations, including

OTC drug monograph regulations,

require information on the labeling of

OTC drug products by product type

(e.g., antacid, bronchodilator).

Additionally, manufacturers,

distributors, and packers may place the

information required under OTC drug

monographs in any format and order, as

long as the information complies with

the appropriate monograph and other

applicable regulations. OTC drug

products marketed under a marketing

application must be labeled in

accordance with the labeling approved

in the application. As a result, the

format of required labeling information

varies considerably among OTC drug

products.

Under section 502 of the act (21

U.S.C. 352), a drug is misbranded if the

labeling does not contain: The name and

place of business of the manufacturer,

packer, or distributor and a statement of

the quantity of contents in terms of

weight, measure, or numerical count

(section 502(b)); the established name, if

any, of the drug, and the established

name of each active ingredient if the

drug is fabricated from two or more

ingredients (section 502(e)); and

adequate directions for use and

adequate warnings against unsafe use

(section 502(f)). In addition, a drug is

misbranded if its labeling is false or

misleading in any particular (section

502(a)), or if it is dangerous to health

when used in the dosage or manner, or

with the frequency or duration

prescribed, recommended, or suggested

in the labeling (section 502(j)).

The act also addresses the

prominence and conspicuousness of

drug product labeling. Section 502 of

the act states that:

A drug * * * shall be deemed to be

misbranded—

* * * * * * *

(c) If any word, statement, or other

information required by or under authority of

this Act to appear on the label or labeling 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.

FDA has implemented the general

labeling requirements under section 502

of the act in part 201 of the regulations

(21 CFR part 201). Section 201.1 sets

forth requirements with respect to the

name and place of business of the

manufacturer, packer, or distributor.

Section 201.5 defines adequate

directions for use as ‘‘directions under

which the layman can use a drug safely

and for the purposes for which it is

intended.’’ Adequate directions include

a statement of all the manufacturer’s

intended uses of the drug (frequently

termed ‘‘Indications’’), quantity of dose,

route or method of administration, and

the frequency, duration, and timing of

administration (§ 201.5). Section 201.10

sets forth requirements for ingredient

information required by section 502(e)

of the act.

Section 201.17 sets forth requirements

concerning the location of expiration

dating, which is required under the

current good manufacturing practice

(CGMP) regulations (§ 211.137 (21 CFR

211.137)). Section 201.18 requires a lot

number ‘‘capable of yielding the

complete manufacturing history of the

package.’’ A related CGMP regulation

(§ 211.132 (21 CFR 211.132)) that

applies to most OTC drug products

requires a labeling statement alerting

consumers to certain tamper-resistant

packaging features (§ 211.132(c)).

Sections 201.60 through 201.62 define

and set forth requirements for the

principal display panel of OTC drug

product labeling. The principal display

panel is defined as the part of a label

that is most likely to be displayed,

presented, shown, or examined under

customary conditions of display for

retail sale. The information required to

be on the principal display panel

includes a statement of identity of the

drug and the net quantity of contents of

a drug. The statement of identity must

include the established name of the

drug, as well as the pharmacological

category or principal intended action of

the drug. If the drug is a mixture and has

no established name, its general

pharmacological actions or its principal

intended actions must be stated

(§ 201.61(b)). Under § 330.1(c)(1) (21

CFR 330.1(c)(1)), the statement of

identity of a drug covered by an OTC

drug monograph shall be the term or

phrase used in the applicable

monograph.

Under section 502(e)(3) of the act, the

established name of a drug is generally

derived from its official title in an

official compendium. When the

established name for a single or a

multiple ingredient drug product is

stated in terms of the active

ingredient(s), the active ingredient(s)

will appear on the principal display

panel. However, when a multiple

ingredient product does not have an

established name, the active ingredients

are not required to be placed on the

principal display panel (§ 201.61(b)),

but may be prominently placed on the

back or side panel in accordance with

section 502(e) of the act and §§ 201.10

and 201.15. Under § 330.1(j), the agency

recommends that the labeling of a

product contain the quantitative amount

of each active ingredient, expressed in

terms of the dosage unit stated in the

directions for use (e.g., tablet,

teaspoonful).

Current regulations also address the

format of OTC drug product labeling,

but do not require a specific print size

or print style. For example,

implementing regulations in § 201.15

describe a number of situations in

which the agency considers information

on a drug product’s label as lacking the

prominence and conspicuousness

required by section 502(c) of the act. For

example, a statement may lack the

prominence and conspicuousness

required by section 502(c) of the act by

reason of, among others, ‘‘[s]mallness or

style of type in which such word,
9026 Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules

statement, or information appears,

insufficient background contrast,

obscuring designs or vignettes, or

crowding with other written, printed, or

graphic matter’’ (§ 201.15(a)(6)).

Section 201.61(c) requires that the

statement of identity of an OTC drug

product shall be in boldface type on the

principal display panel, in a size

reasonably related to the most

prominent printed matter on such

panel, and in lines generally parallel to

the base on which the package rests as

it is designed to be displayed. In some

instances, the agency has required that

warnings for certain OTC

bronchodilator drug products shall

appear in boldface type (§ 341.76(c)(6)(i)

and (c)(6)(ii) (21 CFR 341.76(c)(6)(i) and

(c)(6)(ii))).

In the Federal Register of March 13,

1995 (60 FR 13590), the agency issued

final regulations (part 328 (21 CFR part

328)) that require the principal display

panel of all alcohol-containing OTC

drug products intended for oral

ingestion to state the percentage of

alcohol present in a product. Section

328.50(d) specifies that this information

must appear in a size ‘‘reasonably

related to the most prominent printed

matter on the panel or label on which

it appears * * *.’’ This requirement is

based on the agency’s belief that

consumers, especially those who wish

to avoid or limit alcohol ingestion, need

to be able to readily determine the

alcohol content of OTC drug products at

the time of purchase (60 FR 13590 at

13592).

Section 330.1(g) currently requires

that the labeling of all OTC drugs

contain the warning: ‘‘Keep this and all

drugs out of the reach of children’’ and

requires that drugs contain specific

language outlining procedures to follow

in case of accidental overdose for drugs

administered orally, and in case of

accidental ingestion for drugs

administered topically or rectally.

Sections 201.63 and 330.2 (21 CFR

330.2) require a warning for persons

who are pregnant, or are breast feeding

a baby, on the labeling of all OTC drugs

intended for systemic absorption.

In addition to the warnings required

under OTC drug monographs, the

agency has specific warning

requirements for certain ingredients in

OTC drug products. Some examples are

the Reye’s syndrome warning for OTC

aspirin and aspirin-containing drug

products in § 201.314(h) and the

warnings for water-soluble gums and

related ingredients in § 201.319. These

regulations mandate specifically worded

warning statements for drugs containing

sodium, mineral oil, wintergreen oil,

ipecac syrup, acetophenetidin,

salicylates, OTC drugs intended for

minor sore throats, and guar gum, and

address safety concerns associated with

these ingredients and conditions. (See,

e.g., §§ 201.64, 201.302, 201.303,

201.308, 201.309, 201.314, 201.315, and

201.319.) For example, § 201.315

requires in certain circumstances the

following warning for OTC products

intended for the temporary relief of

minor sore throats:

‘‘Warning—Severe or persistent sore throat

or sore throat accompanied by high fever,

headache, nausea, and vomiting may be

serious. Consult physician promptly. Do not

use more than 2 days or administer to

children under 3 years of age unless directed

by physician.’’

The agency has issued other warnings

and caution statements for certain

ingredients in OTC drugs in part 369 (21

CFR part 369) as ‘‘interpretative

statements.’’ These warnings and

cautions are ‘‘suggested,’’ because

manufacturers are not required to use

the specific text of the warnings on their

products. These warnings are based on

safety considerations associated with

the ingredients to which they apply.

Products that do not contain a similar

warning to those suggested in part 369

are deemed to be misbranded under

section 502(f) of the act.

The important warning information,

as well as the other required or

recommended labeling information,

does not appear in the same location, in

the same sequence, or in the same print

size in the labeling of OTC drug

products. The agency has determined

that consumers would be able to use

OTC drug products more effectively if

this information appeared with

sufficient prominence (at or above a

specified minimum print size) and in a

uniform location in the labeling of all

OTC drug products. Such labeling

uniformity is a major goal of this

proposal.

B. Requirements for Labeling of Drugs

Covered by an OTC Monograph

In addition to being subject to the

general and specific labeling

requirements, OTC drugs marketed

under a final OTC drug monograph are

subject to specific labeling requirements

contained in the monograph. The

general criteria for establishing adequate

labeling for OTC drugs under a

monograph are set forth in

§ 330.10(a)(4)(v) (21 CFR

330.10(a)(4)(v)). Under these criteria,

labeling of OTC drugs must be clear and

truthful, not misleading, and must state

the intended uses, warnings, side

effects, and adverse reactions associated

with a product in ‘‘such terms as to

render them likely to be read and

understood by the ordinary individual,

including individuals of a low reading

comprehension level, under customary

conditions of purchase and use.’’

The labeling requirements established

in OTC drug monographs cover various

categories of drug information,

including the statement of identity,

indications, directions, warnings, and

drug interaction precautions. However,

the specific information required to

appear under these categories varies

according to the therapeutic class, active

ingredients covered by the monograph,

and safety concerns. In addition, the

labeling information is not required to

appear in the same location, in the same

sequence, or in the same print size.

Thus, the format varies among drug

products covered by the same OTC drug

monographs. This proposal is intended

to provide a uniform format so that

consumers will be able to use OTC drug

products more safely and effectively.

In the Federal Register of May 1, 1986

(51 FR 16258), FDA amended its policy

(known as the exclusivity policy) for the

labeling of OTC drug products

(§ 330.1(c)) to allow the use of alternate,

industry provided terminology in the

‘‘indications’’ section of OTC drug

product labeling. The rule established

three alternatives for stating the

indications for use in OTC drug product

labeling. The label and labeling of OTC

drug products are required to contain, in

a prominent and conspicuous location,

either: (1) The specific wording on

indications for use established under an

OTC drug monograph, which may

appear within a boxed area designated

‘‘APPROVED USES;’’ (2) other wording

describing such indications for use that

is truthful and not misleading, which

shall neither appear within a boxed area

nor be designated ‘‘APPROVED USES;’’

or (3) the approved monograph language

on indications, which may appear

within a boxed area designated

‘‘APPROVED USES,’’ plus alternative

language describing indications for use

that is truthful and not misleading,

which shall appear elsewhere in the

labeling. The rule states that all required

OTC drug labeling other than

indications for use (e.g., statement of

identity, and warnings) must appear in

the specific wording established under

an OTC drug monograph where exact

language has been established and

identified by quotation marks in an

applicable monograph or by regulation

(§ 330.1(c)(vi)).

C. Requirements for Labeling of Drugs

Not Marketed Under an OTC Drug

Monograph or a Marketing Application

Some OTC drug products are not

currently marketed under an approved
Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules 9027

marketing application or a final OTC

drug monograph. Many of these OTC

drug products will become the subject

of final monographs and, as discussed

in section VI. of this document, they

will then be subject to the labeling and

format requirements in this proposed

rule. Other products in this category

that are, or become, the subject of

pending marketing applications, would

be required to submit labeling with their

application in compliance with this

rule.

III. The Need for Improved Labeling

Design for OTC Drug Products

The labeling requirements for OTC

drug products set forth specific wording

for the information presented (e.g.,

directions for use, warnings, etc.) to

consumers to ensure the safe and

effective use of OTC drug products. FDA

has examined representative examples

of currently marketed OTC drug product

labeling and has found that the design

and format of labeling information

varies considerably among these

products. The agency has determined

that consumers would have less

difficulty reading and understanding the

information if the labeling included

uniform headings and subheadings

presented in a standardized order,

utilizing a minimum type size and other

graphical features, and if certain

required information could be made

more concise.

While some manufacturers of OTC

drug products have taken significant

steps to improve the presentation of

information on OTC drug product

labeling, many of these products still

have labeling that is difficult to read. In

addition, consumers often have

difficulty comparing the labeling on

different products and deciding which

product to purchase, because the

information is not presented in the same

format.

The agency has determined that a

standardized format for OTC drug

product labeling would improve

legibility and understandability and

enable consumers to become more

familiar with the type and location of

specific important labeling information,

thus increasing consumer knowledge

about the safe and effective use of OTC

drug products. A standardized format

would also improve the ability of

consumers to compare products, thereby

helping consumers select the

appropriate product to meet their needs.

In reaching this determination, the

agency has considered the increased use

of OTC drug products in the

marketplace and the changing patterns

of use of these products by consumers.

The agency also has considered

comments that it has received from

consumers expressing their concerns

with the legibility and understandability

of OTC drug product labeling.

Additionally, the agency has reviewed

literature studies that confirm

consumers’ concerns with current OTC

drug product labeling. These studies

recommend ways to improve legibility

and understandability, discuss the

importance of adherence to the

‘‘directions for use’’ and ‘‘warnings’’

sections of the labeling, and report on

preventable adverse drug reactions from

OTC drug products.

In the August 16, 1995 (60 FR 42578),

Federal Register notice the agency

sought comment on to what extent OTC

drug labeling influences consumer

judgements and behavior. No data or

comments were submitted in response

to this request. The agency also

conducted a review of the literature on

this issue. Although there is voluminous

literature on the effects of labels on a

variety of consumer products, there is

little information about the influence of

label variations regarding OTC drug

products. Because the agency believes

that this information is important and

relevant to this proposed rule, the

agency again seeks comment or

submission of data or research relating

to OTC drug labeling and its influence

on consumer behavior and

comprehension of label information.

During the comment period the

agency intends to conduct research on

the revised format compared to existing

labeling. This research will focus on

consumer reading and comprehension

of the information from the revised

format, compared to existing labeling. It

will also examine consumers’ reading of

OTC drug labels under a variety of

conditions for a variety of consumers

(e.g., at various literacy levels). It will

also examine the impact of new OTC

label designs on comprehension of the

intended messages. The research will

also explore consumer judgments about

OTC drug products for the intended

population. Additionally, the agency

intends to collect data relevant to

overall judgments of the relative value

of revisions in the OTC drug labeling

format. The agency intends to seek

public comment on the results relevant

to the development of standardized

format and content requirements prior

to finalizing these provisions. After this

rule becomes final, the agency intends

to examine the consumer behavioral

effects and the public health impact of

imposed OTC drug labeling.

A. Changing Patterns of OTC Drug Use

OTC drug products are readily

available and may be used without

medical supervision. In recent years,

more potent drugs have been switched

from prescription to OTC status (e.g.,

cimetidine, naproxen sodium,

ketoprofen, nicotine polacrilex, nicotine

transdermal system, and minoxidil

topical) and new uses have been

approved for certain OTC drugs (e.g.,

acid reducer claims for several drug

products, and hair growth claims for

topical minoxidil). This trend of

switching from prescription to OTC

status is expected to increase in the

future as the safety profile of many drug

products becomes more established.

Additionally, consumers are becoming

more actively involved in their own

health care. As a result, consumers are

more likely to practice self-diagnosis

and self-medication with OTC drug

products. Thus, it is increasingly

important that OTC drug product

labeling provide consumers with

uniform and understandable

information for the safe and effective

use of these products.

One important factor contributing to

the increased use of OTC drug products

has been rising health care costs.

Hospital charges, physician fees, and

the costs of prescription medications

and other health-related products and

services are higher and have risen faster

than the associated costs of selfmedication with OTC drug products.

Today, four times as many health

problems are treated by consumers with

OTC drug products instead of seeing a

physician, and 60 to 95 percent of all

illnesses are initially treated with some

form of self-care, including selfmedication with OTC drug products

(Ref. 1). Although 60 percent of the

medications purchased by consumers in

the United States are OTC, these

purchases account for less than 2

percent of the U.S. health-care dollar,

making it likely that, as a low-cost

alternative, OTC drug use will continue

to grow (Ref. 1).

Another significant factor

contributing to the increased use of all

drugs, including OTC drug products, is

the advancing age of many consumers.

The elderly comprise 12 to 17 percent

of the population but consume about 30

percent of all medications (Ref. 1). The

elderly are projected to consume as

much as 50 percent of all medications

by the year 2000 (Ref. 1).

B. Difficulties With Current Labeling

Although significant strides have been

made in improving the legibility and

understandability of OTC drug product

labeling, there are still many products

with labeling that is difficult to read.

The agency has received numerous

reports from consumers, health
9028 Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules

professionals, patient advocacy

organizations, literacy experts, and

others stating their concerns about

current OTC drug product labeling.

Reports in the literature document

similar concerns (Refs. 2 and 3).

Type size, letter and line spacing,

contrast, print and background color,

and type style are all factors that

contribute to poor legibility of

information (Refs. 3, 4, and 5). A recent

study examined the effects of type size

(vertical letter height) and horizontal

letter compression on the legibility of

OTC drug product labeling in persons

60 years of age and older (Ref. 3). The

subjects were tested using three

marketed OTC analgesics. The

researchers found that a significant

number of the elderly population could

not adequately see the print on certain

OTC product labels due in part to the

small type sizes and high degree of

horizontal compression (Ref. 3).

Another study evaluated the visual

acuity needed to read 25 marketed OTC

drug product labels (Ref. 2) The authors

found that the majority of labels

required a visual acuity much greater

than what is considered normal (Ref. 2).

Another study found that 26.2 percent

of the test subjects indicated difficulty

reading print on product labels, even

though over 90 percent of those tested

reported always or sometimes reading

the label (Ref. 6).

Visual acuity alone, however, is not

the only consideration, because persons

with normal vision report having

trouble reading OTC drug product

labeling (Ref. 3). Much of the

informational text in OTC drug product

labeling is specifically required by

regulation and, on many products, the

required text may be extensive. The

information is often presented in a

paragraph format that is unappealing to

the eye and may cause the reader to lose

interest.

In contrast, warnings in outline layout

may have greater eye appeal, be easier

to process, and be more effective than

warnings in paragraph form (Ref. 7). An

outline format may provide the reader

with spatial cues as to the organization

of the text and is likely to increase

attention to the message (Ref. 7).

Without the modifications presented in

this proposed rule, it would be

extremely difficult to organize labeling

text to provide the spacial cues

necessary to increase the appeal and

visibility of the messages.

C. Problems With Adherence and

Preventable Adverse Drug Reactions

OTC drug products are safe and

effective when used as directed in the

labeling. However, because of the

changing patterns of OTC drug use, the

potential for adverse drug reactions and

misuse of OTC drug products is

increasing. Although much of the data

on the incidence of adverse drug

reactions, including hospital or

physician visits due to these reactions,

does not distinguish between

prescription and OTC drugs,

inappropriate use of drug therapy

generally is a major concern (Refs. 6, 8,

and 9). Studies indicate that the elderly

sometimes take OTC drug products for

the wrong reasons (Ref. 10). This misuse

has been attributed to the lack of

information or misinformation from

various sources (Refs. 3 and 11).

Additionally, the possibility of

adverse drug interactions has increased

because more new medications (as a

result of prescription-to-OTC switches)

are now available OTC and there are

new OTC combination drug products for

multiple symptoms. Consumers may not

be aware that a particular prescription

drug product that they are taking is in

the same drug class as an OTC drug

product that they are also taking. For

example, a number of nonsteroidal antiinflammatory drugs (NSAID) are

marketed both as high-dose prescription

anti-inflammatory arthritis treatments as

well as lower dose OTC pain relievers/

fever reducers. Patients who selfmedicate with an OTC analgesic who

are also taking a prescription NSAID

place themselves at risk for NSAIDinduced gastrointestinal problems (Ref.

12). Making OTC drug product labeling

information easier to read and

understand could ensure that patients

become aware of this important

information and avert potential

problems.

D. FDA’s Requests for Public Comment

During the past several years, many

consumers have written to FDA to

express concern about the legibility and

understandability of OTC drug product

labeling. Many individuals, especially

the elderly, are concerned with small

print size, print style, and lack of color

contrast. Consumers stated that poor

labeling legibility may cause them to

select an improper dose, and, thus, may

result in unsafe or ineffective use of the

product. Consumers have also

submitted comments to FDA about the

print size of OTC drug product labeling

in response to various OTC drug

product rulemakings.

Additionally, the agency received a

citizen petition requesting that FDA

adopt regulatory standards for the size

and style of print used for OTC drug

product labeling. In response to

consumer comments and the citizen

petition, the agency published two

requests for public comments in the

Federal Register that related to the

legibility and understandability of OTC

drug product labeling. In addition, in an

effort to solicit more information and

views on specific aspects of OTC drug

product labeling design that would

improve communication to consumers,

FDA held a public hearing on

September 29, 1995. A discussion of the

citizen petition, requests for comment,

and the public hearing follows.

1. Citizen Petition and March 6, 1991,

Request for Comments

Pharmacists Planning Service, Inc.,

petitioned FDA (Docket No. 90P–0201)

to adopt regulatory standards for

optimum size and style of print used for

OTC drug product labeling. The petition

stated that regulatory standards are

needed to maximize readability of the

print for persons with deteriorating

vision, and because most people

(especially the elderly) are unable to

read the small print that currently

appears on some OTC drug product

labeling.

The petition requested that FDA

adopt regulatory standards for the

following reasons: (1) Medication

misuse and abuse are serious and costly

problems to patients, health providers,

health care insurance plans, and

Federal, State, and local governments;

(2) prescription drugs continue to be

switched to OTC status along with their

attendant side effects and cautions on

use; (3) OTC drugs are marketed in

containers of all shapes and sizes, and

the labeling bears instructions, cautions,

and side effects associated with their

use; and (4) most people, particularly

the elderly, are unable to read the small

print, which often includes vital

information.

The petition also stated that:

more than 240,000 older adults were

hospitalized due to adverse drug reactions,

mixing OTC drugs, which are available

through sources other than a qualified health

professional, and through lack of medical/

pharmaceutical information on the proper

method of administration of these

medications.

The petition asserted that FDA

regulatory standards could result in a

$10 billion savings in hospital costs.

In response to this petition, and in an

effort to determine what further steps

needed to be taken, FDA published a

notice to seek public comments on the

feasibility of regulatory standards for the

print size and style of OTC drug product

labeling (hereinafter referred to as the

March 1991 notice) (56 FR 9363, March

6, 1991). FDA also requested comments

on whether any new labeling

requirements would have a substantial

economic impact on manufacturers.
Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules 9029

FDA requested specific comments on

the following issues:

(1) Are current print, sizes, types,

colors, contrasts, and backgrounds of

OTC drug product labeling adequate in

providing readable information for

individuals with normal eyesight and

for those with poor or deteriorating

eyesight?

(2) Should there be a mandatory

minimum print size or other readability

standard and, if so, what should it be?

If the answer is yes, should this be

established through a regulation or a

guideline?

(3) Should a package insert or larger

carton be mandatory if a minimum print

size standard is implemented and,

because of package size, the

manufacturer is unable to meet the

specifications?

(4) What impact would a Federal

legibility/readability regulation have on

State laws that relate to ‘‘slack-fill?’’

(5) What relevant data are available

and what studies have been performed

to determine optimum print size,

background, and contrast for package

products?

(6) What adverse effects have been

documented that are associated with the

inability or failure to read labels on OTC

drug products?

(7) Will the Nonprescription Drug

Manufacturers Association’s (NDMA’s)

guidelines be effective and have a

positive impact on labeling and, if so,

are these guidelines adequate so that a

Federal regulation or guideline is not

needed?

FDA received 57 comments on the

March 1991 notice (see Docket No. 90P–

0201). About half of these comments

were from consumers and favored larger

or more readable print. Congressional

representatives, professional

organizations, manufacturers, health

professionals, health departments,

universities, a nursing home, a hospital,

and a trade association expressed strong

support for new FDA regulations. In

contrast, a professional organization, a

trade association, and several OTC drug

product manufacturers preferred limited

regulation or guidelines.

Some comments attached studies or

documents on readability. One

document discussed the loss of visual

acuity with increased age, and

concluded that size, color, and

background of OTC product labeling are

important. One study involving 36

students and 29 elderly subjects

concluded that the results showed that

labeling of small bottles need not be

restricted to bottle surface area, but can

be incorporated on wings and tags

attached to the label.

One comment, which favored

voluntary guidelines, included a

number of suggestions concerning

inserts, slack-fill laws, and larger

packages. The comment submitted a

publication that analyzed print size and

style used in publications and listed 30

suggested guidelines for print, including

type selection, size, line leading,

proportional spacing, line width,

columns, paragraphing, etc. The

comment also submitted parts of a text

that discussed legibility, color, surface,

spatial arrangement, and position of

printing.

NDMA, a trade group representing

manufacturers of OTC drug products,

agreed that efforts should be made to

enhance labeling legibility, and

submitted several references dealing

with print size and style. NDMA stated

that it had established a Special Task

Force on Label Readability and had

distributed guidelines to its membership

as part of industry’s voluntary program

to enhance readability of OTC drug

product labeling. NDMA also stated that

it had held a briefing session for the

entire industry, which was open to the

public, to explain and help implement

the guidelines.

NDMA stated that its guidelines

provide for enhanced readability of OTC

drug product labeling by addressing

improvements in print size, type, style,

colors, contrasts, and backgrounds.

NDMA’s guidelines, in 1991,

recommended a minimum of 4.5 point

type, where package size and copy

requirements prohibit larger print.

(These guidelines were revised in 1995,

however, to recommended 6 point type,

with 4.5 type as an absolute minimum

in very small packages where space

does not allow 6 point type.) NDMA

claimed, however, that it is

unreasonable to assume that all labeling

can be made easily readable to all

persons with poor or deteriorating

eyesight.

NDMA also stated that there is a need

for national uniformity in slack-fill laws

because multiple State laws could be

inconsistent or contradictory with each

other and with Federal requirements for

print size.

One comment submitted an

investigative survey of consumers’

ability to read OTC drug product

labeling printed with the minimum type

sizes recommended by NDMA’s

guidelines. According to the comment,

the survey demonstrates that a

significant proportion of the adult

population over 20 years of age is not

able to read OTC drug product labeling

with 4.5 point minimum type size, and

that only 48 percent of the public who

currently purchase OTC medications are

able to read labels with the 4.5 point

minimum type size. People over 51

years of age have the most trouble

reading labels with the 4.5 point type

size—only 32 percent were able to read

it—and only 63 percent of people under

age 51 were able to read the labels.

The comment asserted that although

80 percent of all those surveyed were

able to read 6 point reverse type size

(which was NDMA’s suggested

minimum type size for white print on

colored background), only 68 percent of

the people over 51 were able to read the

6 point reverse type size. Thus, the

comment recommended that FDA not

accept NDMA’s guidelines on minimum

type size until further research and

testing of consumers’ ability to read

labels are completed.

2. Public Hearing and August 16, 1995,

Request for Comments

In an effort to solicit more information

and views on specific aspects of OTC

drug product labeling design that would

improve the communication of labeling

information to consumers, FDA

published a notice in the Federal

Register (August 16, 1995 (60 FR

42578)), announcing a public hearing on

OTC drug product labeling issues. The

notice stated that the hearing would

address consumer use, legibility and

consumer comprehension of OTC drug

product labeling, OTC drug product

labeling design features, and behavioral

issues. The notice requested comments

from the public about whether FDA

should set standards for type size, color,

contrast, type style, spacing, white

space, uppercase and lowercase letters,

and boldface letters.

FDA stated in the notice that a

standardized format would help

consumers know what information to

look for and where to find it. The

agency requested comments on the

communication benefits that a uniform,

standardized OTC drug product labeling

format would provide to consumers.

The agency also requested comments

about what features should be made

consistent on a standardized labeling

format (e.g., order of information, major

headings or subheadings for

information, the use of lines or boxes

around information, and certain labeling

statements).

Recognizing that proposing a

standardized format could necessitate

revisions to many of the existing

monographs, FDA published a

subsequent notice in the Federal

Register of September 14, 1995 (60 FR

47752), requesting comments on the

process that should be followed by FDA

to ensure that any revisions would be
9030 Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules

completed in an efficient and expedient

manner.

The public hearing was held on

September 29, 1995, and included

presentations from 22 panelists

including representatives from

government agencies, universities,

industry associations, consumer

associations, and corporations. The

agency accepted written comments on

the notice and the docket until October

30, 1995. Following the public hearing,

the agency’s Nonprescription Drugs

Advisory Committee held a public

meeting to further discuss OTC drug

labeling issues. (Transcripts of the

Advisory Committee meeting are

available from the Freedom of

Information Staff (HFI–35), Food and

Drug Administration, 5600 Fishers

Lane, Rockville, MD 20857.) A summary

of the presentations made at the public

hearing and the comments submitted in

response to the notice follows:

a. NDMA’s comments. NDMA

supported FDA’s initiative to improve

OTC drug product labeling, and stated

that:

[b]y establishing mandatory standard

headings and subheadings and a mandatory

standard order for these headings,

simplifying warnings, reducing duplicative

and complex wording, and assuring a label

that will be uniform throughout the United

States, FDA can help to reduce label clutter

and promote greater consumer use of label

information.

NDMA recommended that FDA adopt

uniform headings and subheadings for

‘‘mandatory information’’ pertaining to

active ingredients, actions, uses,

directions, and warnings, and that FDA

adopt a standardized order for these

headings and subheadings. NDMA also

recommended that FDA combine

contraindications, warnings,

precautions, adverse reactions, and

other similar information under one

general heading titled ‘‘Warnings.’’ In

addition, NDMA recommended that the

following subheadings be included

under the ‘‘Warning’’ heading: Complete

contraindications; warnings that depend

upon a doctor’s advice based on the

physical condition of the consumer;

warnings that relate to pregnancy and

nursing, concurrently taking other

drugs, or dietary restrictions; in-use

precautions; warnings for topical

products; and warnings concerning the

use of the terms ‘‘doctor’’ or ‘‘health

professional.’’

NDMA recommended a 6 point or

greater type size, or 4.5 point as an

‘‘absolute minimum.’’ NDMA also

recommended the use of bullet points,

but did not support mandatory

pictograms. NDMA endorsed FDA’s

current practice of not requiring

symbols or pictograms but rather

permitting their voluntary use in

addition to required warning language.

In addition, NDMA recommended that

FDA make available an expanded list of

alternative words and phrases for OTC

labeling terminology.

NDMA also recommended that FDA

mandate a uniform national system

because multiple State laws could be

inconsistent or contradictory with each

other and with Federal requirements.

NDMA stated that dual, national and

State labeling regulations, could confuse

the public, undermine the credibility

and effectiveness of FDA, create costly

and burdensome barriers to interstate

commerce, and expose companies to

potential product liability suits. NDMA

stated that ‘‘[n]ational uniformity is

consistent with principles of federalism

and will prevent the prospect of fifty

‘mini-FDA’s’ applying a plethora of

differing and inconsistent standards that

would hinder implementation of FDA’s

own regulatory scheme.’’

Finally, NDMA urged FDA not to

amend any monographs for OTC drug

ingredients as part of this rulemaking

because ‘‘to do so would lengthen the

regulatory process and possibly

undermine support for a prompt and

efficient relabeling process.’’

b. Other comments. Other comments

from individuals, drug companies, and

professional associations generally

supported FDA’s efforts to improve the

legibility and understandability of OTC

drug product labeling, and most

comments supported FDA’s

recommendation for a standardized

format. Many comments endorsed

NDMA’s recommendations. Most

comments did not support a

monograph-by-monograph review of

OTC drug products to determine what

labeling revisions should be made.

Several comments supported the use

of color, boxed warnings, pictorials,

high contrast, and symbols. Some

comments stated that specifying font

size is not enough, and that FDA should

specify stroke width, color, letter-line

spacing, types of fonts, line height, and

compression. Other comments

recommended that FDA propose

standards for the frequency of words,

sentence length, and word length. One

comment recommended that ornate

typefaces, italics, and capitalization of

entire words should be prohibited, and

that FDA should establish clear

standards for leading, contrast, and

substrate (i.e., material and finish of the

label).

Several comments provided

suggestions on how to address the

readability and legibility concerns of the

elderly population. One comment

requested that a bold black box

containing the drug’s expiration date,

lot number, and other important

information, such as major drug

interactions or warnings, be

prominently displayed in the labeling of

OTC drug products. One comment

stated that, although larger type is

preferable, the legibility of text in small

copy can be enhanced by using

highlighted words, delineation, and

paragraphing, without actually

increasing text size. The comment stated

that the stronger the contrast between

the color of the text and the color of the

background, the easier it is for the

elderly to read the text.

One comment recommended 12 point

type as the smallest type size for elderly

people. Because the comment

recognized that 12 point type is not

possible for many OTC drug product

labels, the comment urged FDA to

consider a sliding scale of typeface sizes

based on the size of the product

package. One comment stated that 48

percent of adults are not able to read the

4.5 point type, and recommended that

the type be at least 6 point.

Several comments asserted that OTC

drug product labeling needs to be

simplified, so that adults with a low

reading comprehension will be able to

understand the information. One

comment stated that FDA should

require a consumer mailing address on

all OTC drug product labels so that

consumers can write to the company

with questions. The comment stated

that FDA should not require a toll free

phone number because it would be an

unreasonable cost burden for small

companies.

A comment submitted on behalf of the

Uniform Code Council, administrator of

the Universal Product Code (U.P.C.),

stated that if FDA were to mandate a

smaller U.P.C. symbol, it would make

product scanning more difficult and

would require product manufacturers to

relabel at an enormous cost.

A comment from the Cosmetic,

Toiletry, and Fragrance Association

(and endorsed by NDMA) stated that

cosmetic drugs that do not bear dosage

limitations should not be required to list

active ingredients before the inactive

ingredients. The comment contended

that the names of most of the active

ingredients contained in such products

do not have any meaning to most

consumers, except in specific situations

where those consumers have been

advised by a doctor to avoid a specific

ingredient or want to do so for other

reasons. The comment stated, however,

that even in those situations, such

consumers are accustomed to examining
Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules 9031

the list of ingredients to look for that

ingredient.

IV. Efforts to Improve the Design of

OTC Drug Product Labeling

A. FDA Efforts

On August 17, 1995, FDA met with

NDMA, at NDMA’s request, to discuss

proposed labeling changes for OTC drug

products. At this meeting, NDMA

representatives presented a proposal for

text simplification (i.e., the use of words

understood by persons of low

comprehension, and a reduction in the

number of words through text

consolidation) of the pregnancy-breast

feeding warning and the drug

interaction precaution statement for

OTC drug monograph ingredients.

In February 1996, FDA conducted a

focus group study to investigate

participant’s perceptions of risks and

benefits of prescription and OTC drugs

(Ref. 13). The study looked specifically

at how the participants react to different

wording, claims, and statements

contained in prescription and OTC drug

product labeling. In addition, the study

looked at the format and order of the

information contained in the labeling.

Participants confirmed that it would be

beneficial to emphasize side effects and

warnings, either by using bullets, bold

type, block lettering, or larger type.

Although there was no consensus about

the best placement order for the

information, the participants agreed that

‘‘simple’’ directions would be

beneficial. In addition, participants

stated that they wanted labeling

information to be in ‘‘plain English’’ so

they could better understand what the

ingredients were, and how the drug

works. Participants stated that this

increased knowledge would help to

alleviate their concerns of any health

risk from taking the drug.

B. States’ Efforts

In addition to FDA’s efforts, the State

of California has taken steps to improve

the readability of OTC drug product

labeling. On September 12, 1990, the

Governor of the State of California

signed a bill (AB 2713) to amend the

Health and Safety Code regarding the

labeling of OTC drug products. Section

1 of the bill states that printed materials

on labels and notices packaged with

OTC drug products may be difficult to

read, presenting a potential danger to

the health and safety of customers.

Section 2 of the bill adds the

following to the State’s Health and

Safety Code: (1) Manufacturers of

nonprescription drugs that are sold in

the State of California shall evaluate and

may modify the labeling of

nonprescription drugs to maximize the

readability and clarity of label

information, in both the cognitive and

visual sense; (2) NDMA shall report on

a quarterly basis to, and seek advice

periodically from, the California State

Department of Health Services,

consumer groups, health professionals,

and drug manufacturers regarding the

progress made by the nonprescription

drug industry with respect to the

readability and clarity of labeling

information; and (3) the Director of the

California State Department of Health

Services shall report to the legislature

regarding the progress made by the

nonprescription drug industry with

respect to the readability and clarity of

labeling information. The effective

period of the bill has now lapsed.

C. Industry Efforts

NDMA has taken steps to improve

OTC drug product labeling. NDMA

endorsed the California legislation and,

recognizing the difficulty in reading

OTC drug product labeling, appointed a

task force on labeling to: (1) Explore the

issues associated with label readability,

and (2) evaluate the need and

opportunity to make labels more easily

read and understood by the public. The

task force made recommendations on

options to achieve such labeling,

including type-size, print, style, color,

contrast, package inserts, and special

larger size packages.

NDMA has also worked with FDA in

an effort to improve the legibility of

OTC drug product labeling. NDMA

issued ‘‘Label Readability Guidelines’’

that identify specific technical factors

that can be addressed to improve the

readability of OTC drug product labels.

These guidelines cover major elements

of readability pertaining to layout and

design (e.g., information placement,

hyphenation, uppercase/lowercase

letters, paragraphs) and typography and

printing (e.g., type size and style,

contrast, printing process, color). The

guidelines state that no single factor can

determine readability by itself because

the total effect of all factors must be

considered. Because OTC drug product

labeling is still difficult to read and

understand, despite the voluntary

guidelines, NDMA has urged FDA to

adopt new regulations.

FDA has also worked individually

with a number of companies in their

efforts to improve labeling readability

and understandability.

V. Description of the Proposed Rule

The proposed rule would establish a

standardized labeling format for all OTC

drug products and require

manufacturers to revise the format and

content of current OTC drug product

labeling. The proposed rule would not,

however, apply to the format or content

of the principal display panel. The

proposed rule would establish Federal

preemption of State and local laws,

rules, regulations, or other requirements

for OTC drug product labeling content

or format that are different from or in

addition to those required by FDA. As

proposed, this preemption would not

include statutory or common law causes

of action in tort, based on the format or

content of OTC drug product labeling.

The agency is, however, specifically

requesting comment on several aspects

of the scope of the preemptive effect of

this regulation.

A. Scope

The proposed format and general

content requirements would apply to

OTC drug products that are the subject

of a pending marketing application,

OTC drug products marketed under an

existing final OTC drug monograph, and

OTC drug products marketed under an

approved marketing application. The

proposed requirements would also

apply to marketed products pending

under the monograph review process

when the applicable monograph is

finalized.

The proposed rule would not apply to

any drug labeled as being homeopathic

and which is also listed in the

Homeopathic Pharmacopeia of the

United States (H.P.U.S.). The labeling of

such products is addressed in FDA’s

Compliance Policy Guide 7132.15,

‘‘Conditions Under Which Homeopathic

Drugs May Be Marketed.’’

As discussed in section II. of this

document, OTC drug products marketed

under a final OTC drug monograph are

subject to the specific labeling

requirements contained in the

monograph (21 CFR part 330). The

agency is proposing that where an OTC

drug product is the subject of an

applicable final monograph or

regulation that contains content and

format requirements that conflict with

proposed § 201.66, then the format and

content requirements in § 201.66 must

be followed. For example, where a final

monograph states that the indications

for use must be listed under the heading

‘‘Indications,’’ such a monograph

provision would be superseded by

proposed § 201.66(c)(3) requiring that

indications for use must be listed under

the heading ‘‘Uses.’’

In the January 15, 1997, Federal

Register (62 FR 2218), the agency issued

a final rule requiring a specific warning

statement in the labeling of drug

products in solid dosage form that

contain iron or iron salts as an active
9032 Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules

ingredient. Although the agency

currently is not aware of any marketed

OTC drug products that would require

such a statement, the agency recognizes

that there may be conflicts with the

provisions set forth in this proposed

rule and the iron final rule. Conforming

amendments regarding iron-containing

drug products would be proposed and

finalized prior to the implementation of

the provisions set forth in this proposed

rule.

B. Definitions

Proposed § 201.66(b) would define

‘‘active ingredient’’ as:

any component that is intended to furnish

pharmacological activity or other direct effect

in the diagnosis, cure, mitigation, treatment,

or prevention of disease, or to affect the

structure or any function of the body of

humans or other animals. The term includes

those components that may undergo

chemical change in the manufacture of the

drug product and be present in the drug

product in a modified form intended to

furnish the specified activity or effect.

This definition is consistent with the

definition of active ingredient in

§ 210.3(b)(7) for the CGMP regulations.

As set forth in section 502(e)(3) of the

act, proposed § 201.66(b) would define

‘‘established name’’ of a drug or active

ingredient as the applicable official

name designated under section 508 of

the act (21 U.S.C. 358), or, if there is no

designated official name and the drug or

active ingredient is recognized in an

official compendium, the official title of

the drug or active ingredient in such

compendium, or if there is no

designated official name and the drug or

active ingredient is not recognized in an

official compendium, the common or

usual name of the drug or active

ingredient.

Proposed § 201.66(b) would define

‘‘ingredient’’ as any substance in the

drug product, whether added to the

formulation as a single substance or in

admixture with other substances. This

definition is consistent with the

definition of ingredient in § 201.10(b).

C. Content Requirements

As discussed in sections II.A. and II.B.

of this document, the act and

implementing regulations require that

certain information (such as the

established name of the active

ingredients, the statement of identity,

adequate directions for use, and

adequate warnings against unsafe use)

appear in OTC drug product labeling.

OTC drug monographs require that

specific information be included in the

labeling of OTC drug products,

depending on the therapeutic class and

active ingredients covered by the

monograph. The agency has also issued

regulations that require specific OTC

drug products to bear certain warnings.

Drugs marketed under an approved

marketing application must the labeled

in accordance with the labeling

approved in that application.

Because the content and format of

OTC drug product labeling varies

depending on the drug product,

consumers often have difficulty finding,

reading, and understanding the

information. As discussed in section III.

of this document, the agency has

solicited comments from industry in

order to develop a standardized format

that would facilitate the readability and

understandability of the information

presented in OTC drug product labeling.

Based on these comments and other

information currently available to the

agency, the agency is proposing, in

§ 201.66(c)(1) through (c)(7), that the

outside container or wrapper of the

retail package (or the immediate

container label if there is no outside

container or wrapper) of OTC drug

products contain the labeling

information required in final OTC drug

monographs or in approved marketing

applications in the order listed in

paragraphs (c)(1) through (c)(7), with the

appropriate headings and subheadings

listed below. The agency is also

proposing that the interchangeable

terms and the connecting terms listed in

proposed § 330.1(i) and (k) shall apply

both to the OTC drug monographs set

forth in part 331 et seq., and to the OTC

drug product labeling requirements

provided in part 201. In the case of OTC

drugs marketed under a new drug or

antibiotic drug application, the use of

the these terms to change approved

labeling, and the use of the proposed

format to change approved labeling,

would have to be accomplished in

accordance with § 314.70.

Proposed § 201.66(c)(1) would require

the section heading ‘‘Active Ingredient

(In Each [insert type of dosage unit]):’’

or ‘‘Active Ingredients (In Each [insert

type of dosage unit]):’’, followed

immediately by the established name of

each active ingredient. For example, the

heading would read, ‘‘Active Ingredient

(In Each Tablet):’’. Other dosage units

could include capsule, suppository, or

per 5 milliliter (mL) dose or per

teaspoon. For other products marketed

without discrete dosage units (e.g., most

topicals), the section heading would

read ‘‘Active Ingredient’’ or ‘‘Active

Ingredients’’. The quantity, proportion,

or concentration of each ingredient per

dosage unit, if contained in or if

required to appear in the labeling,

would appear after the established name

of each active ingredient. The agency

believes that specifying the amount or

concentration of active ingredient per

dosage unit would provide consumers

with information they need to

understand how much active ingredient

is contained within each unit in the

package. This information would allow

consumers to make better product

comparisons and to have greater

information regarding proper dosing,

thereby ensuring safe and effective use.

Section 502(e) of the act requires that

drug product labeling contain the

established name of each active

ingredient for drugs fabricated from two

or more ingredients. OTC products that

are fabricated from two or more

ingredients are not currently required to

contain a statement of the quantity of

each active ingredient unless the

product contains one of the ingredients

specifically listed in section 502(e)(1) of

the act. Current regulations recommend

that the labeling of OTC drug products

contain the quantitative amount of each

active ingredient per dosage unit in the

‘‘Directions for Use’’ section of the

labeling (§ 330.1(j)). Given the

customary conditions under which most

consumers of OTC drugs must make a

product selection decision, the agency

believes that the quantity of each active

ingredient within a dosage unit should

appear prominently on the labeling. In

order for consumers to distinguish

among products within a

pharmacological category, and select the

appropriate product to meet their needs,

such information is essential and

therefore may be required under

sections 201, 502, 505, 507, and 701 of

the act (21 U.S.C. 321, 352, 355, 357,

and 371). The agency specifically

invites comments from the public on

this point.

Proposed § 201.66(c)(2) would require

that all OTC drug product labeling

include the heading ‘‘Purpose:’’ or

‘‘Purposes:’’, followed by an accurate

statement of the general

pharmacological category(ies) or the

principal intended action(s) of the drug,

or, where the drug consists of more than

one ingredient, the general

pharmacological categor(ies) or the

principal intended action(s) of each

active ingredient. The information

contained after the ‘‘Active

Ingredient(s)’’ and ‘‘Purpose’’ heading

would be required to be consistent with

the information provided in the

applicable OTC drug monographs.

For products that contain more than

one active ingredient, the information

would be required to be presented in

such a way as to make it obvious to the

reader which active ingredients are

associated with each purpose listed. The

proposed rule would require that the

‘‘Active Ingredient’’ heading and
Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules 9033

information be presented immediately

adjacent and to the left of the ‘‘Purpose’’

heading and information (proposed

§ 201.66(d)(5)). The agency is also

proposing that where there is more than

one active ingredient, the active

ingredients be listed in alphabetical

order (proposed § 201.66(d)(5)).

An example of how labeling

requirements proposed in § 201.66(c)(1)

and (c)(2) would appear follows:

Active Ingredients (In Each Tablet): Purpose:

Chlorpheniramine Maleate 2 mg .......... Antihistamine

Dextromethorphan 15 mg ..................... Cough suppressant

Pseudoephedrine HCl 30 mg ............... Nasal decongestant

In the example, there are three active

ingredients, listed in alphabetical order,

followed by the amount of each

ingredient per dosage unit, and the

purpose for each active ingredient. The

purpose is presented in such a way as

to make it obvious to the reader which

active ingredients are associated with

each purpose listed.

Section 201.64 (to become effective on

April 22, 1997) will require that OTC

drug products intended for oral

ingestion that contain 5 milligrams or

more of sodium per single

recommended dose, state the sodium

content per dosage unit on the labeling.

Section 201.64(b) will require that the

sodium content per dosage unit be listed

on a separate line after the heading

‘‘Sodium Content’’ as the last statement

in the ingredients section. In the

Federal Register of April 22, 1996 (61

FR 17807), the agency proposed similar

provisions for the labeling of products

containing more than specified amounts

of calcium, magnesium, and potassium,

per single dose.

The agency requests comment on the

presentation of this information within

the proposed labeling format. For

example, information regarding the

quantity of sodium, calcium,

magnesium, and potassium, could be

listed under the heading entitled

‘‘Dietary Information.’’ Alternatively,

this information could be listed under

the heading ‘‘Other Information,’’

discussed below. The agency recognizes

that the placement of this information

within the proposed labeling format

may require a conforming amendment

to § 201.64. FDA intends to include

dietary information on the various

formats that will be tested during the

comment period.

Proposed § 201.66(c)(3) would require

that all OTC drug product labeling

include the section heading ‘‘Use:’’ or

‘‘Uses:’’, followed by the indication(s)

for the drug product. An example of

how this would appear on the labeling

is as follows: ‘‘Use: Aids in the

prevention of dental cavities’’

(§ 355.50(b)). Another example would

be:

Uses: For the temporary relief of these cold symptoms

* sneezing * nasal congestion, stuffiness

* runny nose * cough

Proposed § 201.66(c)(4) would require

that all OTC drug product labeling

include the heading ‘‘Warning:’’ or

‘‘Warnings:’’, followed by one or more

of the specific warning subheadings

(proposed § 201.66(c)(4)(i) through

(c)(4)(viii)), if applicable.

Proposed § 201.66(c)(4)(i) would

require, where appropriate, the

subheading ‘‘Warning:’’ or ‘‘Warnings:’’,

followed by any specific warnings that

are required for certain products. Such

warnings are currently required to

appear as the first warning(s) under the

heading ‘‘Warnings’’, such as the Reye’s

syndrome warning for aspirin and

aspirin-containing drug products that

reads ‘‘WARNING: Children and

teenagers should not use this medicine

for chicken pox or flu symptoms before

a doctor is consulted about Reye

syndrome, a rare but serious illness

reported to be associated with aspirin’’

(§ 201.314(h)(1) and (h)(2)). This section

would also require that, where

appropriate, the subject of the warning

be specified in the subheading before

the word ‘‘Warning’’, for example,

‘‘Allergy Warning:’’ and ‘‘Alcohol

Warning:’’ for certain OTC analgesics.

Proposed § 201.66(c)(4)(ii) would

require, where appropriate, the words

‘‘Do Not Use:’’, followed by any

contraindications for the use of the

product. These contraindications are

‘‘absolute’’ and are intended specifically

for situations where consumers are

urged not to use the product unless a

prior diagnosis has been established by

a physician or for situations in which

consumers are urged not to use the

product under any circumstances

regardless of whether a doctor or health

professional is consulted. ‘‘Absolute’’

contraindications under this subheading

would include the need for a diagnosis

of asthma prior to the use of an OTC

bronchodilator drug product,

monoamine oxidase inhibitor

interactions, or allergies to active or

inactive ingredients when there is no

specific allergy warning heading. For

example, this subheading would contain

the following for OTC bronchodilator

drug products (§ 341.76(c)(1)): ‘‘Do Not

Use: this product unless a diagnosis of

asthma has been made by a doctor.’’

And this subheading would contain the

following statement for a nasal

decongestant drug product: ‘‘Do Not

Use: this product if you are now taking

a prescription monoamine oxidase

inhibitor (MAOI) (certain drugs for

depression, psychiatric or emotional

conditions, or Parkinson’s disease), or

for 2 weeks after stopping the MAOI

drug. * * * ’’ (§ 341.80(c)(1)(D)).

Another example, for eyewash drug

products, would be, ‘‘Do Not Use:’’

followed by the warning ‘‘Obtain

immediate medical treatment for all

open wounds in or near the eyes’’

(§ 349.78(c)(2)).

Proposed § 201.66(c)(4)(iii) would

require, where appropriate, the words

‘‘Ask a Doctor Before Use’’ immediately

followed by one or more specific

warning subheadings (proposed

§ 201.66(c)(4)(iii)(A) through

(c)(4)(iii)(C)), as appropriate. These

specific warnings are intended for

situations where consumers should not

use the product until a doctor is

consulted. Warnings under this heading
9034 Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules

include those that contain phrases such

as ‘‘unless directed by a doctor,’’

‘‘without first consulting your doctor,’’

and ‘‘except under the advice and

supervision of a doctor.’’

Proposed § 201.66(c)(4)(iii)(A) would

require, where appropriate, the words

‘‘If You Have:’’, followed by any

warnings for persons with certain

preexisting conditions (excluding

pregnancy, which is discussed under

proposed § 201.66(c)(4)(vi) and

warnings for use in persons

experiencing certain symptoms).

Examples of preexisting conditions that

would be included are disease states or

conditions, such as ‘‘If You Have: heart

disease, high blood pressure, thyroid

disease, diabetes, or difficulty in

urination due to enlargement of the

prostate gland’’ (§ 341.80(c)(1)(i)(C)).

This example, when presented under

the proposed format, would appear as

follows:

Ask a Doctor Before Use:

If You Have:

* Heart disease

* High blood pressure

* Thyroid disease

* Diabetes

* Difficulty in urination due to enlargement of the prostate gland

Proposed § 201.66(c)(4)(iii)(B) would

require, where appropriate, the words

‘‘If You Are:’’, followed by any drug/

drug interaction warnings and drug/

food interaction warnings. An example

of when this warning would be used is:

Ask a Doctor Before Use:

If You Are:

* Taking sedatives or tranquilizers

* On a sodium restricted diet

Proposed § 201.66(c)(4)(iii)(C) would

require, as an alternative, and where

appropriate, the words ‘‘If You:’’,

followed by a combination of the

warnings in paragraphs (c)(4)(iii)(A) and

(c)(4)(iii)(B) of this section. For example,

this heading would be appropriate if

there is only one disease state or

condition and one drug/drug interaction

or drug/food interaction. An example is:

Ask a Doctor Before

Use:

If You:

* Have kidney disease

* Are taking other drugs

Proposed § 201.66(c)(4)(iv) would

require, where appropriate, the words

‘‘When Using This Product:’’, followed

by the side effects that the consumer

may experience, and the substances or

activities to avoid while using the

product (for example, alcohol, operating

machinery, or driving a car). An

example is:

When Using This Product:

* Use caution when driving a motor vehicle or operating machinery

Proposed § 201.66(c)(4)(v) would

require, where appropriate, the words

‘‘Stop Using This Product If:’’ followed

by any signs of toxicity and other

serious reactions that would necessitate

the immediate discontinuation of use of

the product, followed by the words

‘‘Ask a doctor. These may be signs of

a serious condition.’’ An example is:

Stop Using This Product If:

* Nervousness, dizziness, or sleeplessness occurs.

Ask a doctor. These may be signs of a serious condition.
Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules 9035

The last two sentences would be

required to be highlighted by bold type

and indented under the ‘‘Stop Using

This Product If:’’ heading. Alternatively,

if there is only one sign of toxicity or

serious reaction, this statement would

read:

Stop Using This Product If: * * *

Ask a doctor. This may be a sign of

a serious condition.

Proposed § 201.66(c)(4)(vi) would

provide that any required warnings that

do not fit within one of the categories

of warnings listed in proposed

201.66(c)(4)(i) through (c)(4)(v),

(c)(4)(vii), and (c)(4)(viii) must appear as

a separate subsection, without a heading

or subheading, after the information

appearing under proposed

§ 201.66(c)(4)(v). For example, a ‘‘For

external use only’’ warning would

appear after the information in the

‘‘Stop Using This Product If:’’ section.

Proposed § 201.66(c)(4)(vii) would

require, where appropriate, the warning

statement for women who are pregnant

or breast-feeding a baby, as set forth in

§ 201.63 and as amended in this

proposal. The agency is proposing to

amend the pregnancy-nursing section

heading and warning statement in

response to comments submitted by

NDMA (see Docket No. 95N–0259) and

to make the warning more concise and

understandable. The revised warning

statement in § 201.63 would state ‘‘If

pregnant or breast-feeding, ask a health

professional before use.’’ The revised

section heading would state

‘‘Pregnancy-breast feeding warning.’’

Proposed § 201.66(c)(4)(viii) would

require, where appropriate, the ‘‘keep

out of reach of children’’ warning and

the accidental overdose or ingestion

warning, as set forth in §§ 201.314(a)

and (g)(1), 330.1(g), and as amended in

this proposal. The agency is proposing

to amend the ‘‘keep out of reach of

children’’ and the accidental overdose

or ingestion warning statements to make

them more concise and understandable.

Furthermore, the agency is proposing

to delete the recommendation to contact

a poison control center because poison

control centers do not exist in every

State, and thus are not always accessible

to all consumers. Instead, the revised

recommendation reflects the idea that

consumers generally may receive advice

on overdose situations by contacting

other medical professionals who may be

more readily available to the consumer.

The revised overdose warning

statements in § 330.1(g) would state:

‘‘The labeling of drugs used by oral

administration shall also state: ‘In case

of overdose, get medical help right

away.’’’ If required, the labeling for all

drugs used topically, rectally or

vaginally, and not intended for oral

ingestion, shall state: ‘‘If swallowed, get

medical help right away.’’ However, for

the specific category of topical drugs

that are intended for oral use, the

agency recognizes that the statement ‘‘If

swallowed, get medical help right

away,’’ may be confusing to consumers

who might think that any swallowing of

the product during normal use may be

dangerous. Therefore, to clarify to

consumers that excessive amounts of

the product should not be swallowed,

labeling of topical drugs which are

intended for oral use shall state, ‘‘If

more than used for * * * is accidentally

swallowed, get medical help right

away’’ (see final rule for OTC anticaries

drug products, 61 FR 52285 at 52286,

October 7, 1996). The agency is also

proposing to amend § 201.314(a) and

(g)(1) to conform to this new, more

concise, overdose warning.

The revised ‘‘keep out of reach of

children’’ warning statements in

§§ 201.314(a) and (g)(1), and 330.1(g)

would state: ‘‘Keep out of reach of

children.’’ The agency is proposing to

require this statement to be in bold

print.

The agency also intends to revise

§§ 369.20 and 369.21 to conform to

these revised warning statements at or

before the time that this proposed rule

is finalized.

Proposed § 201.66(c)(5) would require

that all OTC drug product labeling

include the word ‘‘Directions:’’,

followed by the appropriate directions

for use. The proposal would require that

the directions conform with the

appropriate final OTC drug monograph

or the approved application.

Proposed § 201.66(c)(6) would

require, where appropriate, that OTC

drug product labeling include the

heading ‘‘Other Information:’’ followed

by additional information that is not

included under proposed § 201.66(c)(1)

through (c)(5), but is required by or is

optional under an applicable OTC drug

monograph or is required under an

approved marketing application. If

included, this information would be

required to immediately follow the

‘‘Directions’’ for use section on the

label. An example of such required

labeling, for pediculicide drug products,

is the statement required by § 358.650(e)

that describes different types of lice.

Another example of such optional

labeling is in the monograph for

anticaries fluoride treatment rinses

(§ 355.50(f)(1)), which permits, but does

not require, the statement:

Other Information:

* The combined daily use of a fluoride preventative treatment

rinse and a fluoride toothpaste can help reduce the incidence

of dental cavities.

Proposed § 201.66(c)(7) would require

that the labeling for all OTC drug

products that are also cosmetics (as

defined by section 201(i) of the act)

include the words ‘‘Other Ingredients:’’

or ‘‘Inactive Ingredients:’’, followed by

the cosmetic and/or inactive ingredients

that are required to be stated on the

label under § 701.3 (21 CFR 701.3).

Current § 701.3(d) provides that

‘‘[w]here a cosmetic product is also a

drug, the declaration shall first declare

the active drug ingredients as required

under section 502(e) of the act, and shall

then declare the cosmetic ingredients.’’

The new standardized format would list

the active ingredients before the ‘‘Other

Ingredients’’ or ‘‘Inactive Ingredients,’’

but separated by the other required

labeling information (i.e., ‘‘Purpose(s),’’

‘‘Use(s),’’ ‘‘Warning(s),’’ and

‘‘Direction(s)’’).

Although many manufacturers,

packers, and distributors voluntarily

include a list of inactive ingredients on

the labeling of OTC drug products, OTC

drug products (that are not also

cosmetics) are not currently required to

list inactive ingredients on their

labeling. In order to standardize the

location of this information (if

included), FDA is proposing that for

OTC drug products that are not also

cosmetics, the labeling must include the

words ‘‘Inactive Ingredients:’’, followed

by the inactive ingredients.

FDA has also received a citizen

petition (96P–0318, CP1) requesting that

existing regulations be changed to

require placement of expiration dating

on the immediate container of OTC drug

products in a visible location so that the
9036 Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules

date is legible throughout the use of the

product and to adequately adapt the

expiration dating to the way consumers

use the products, particularly for drug

products distributed in tubes. FDA is

seeking public comment on whether

current regulations should be revised to

require expiration dating to appear in a

specific location with specific legibility

requirements on both the outer and

immediate container packaging,

especially for products marketed in

tubes.

D. Format Requirements

The act and current regulations do not

establish a standardized format for OTC

drug product labeling. In addition, the

agency has determined that some OTC

drug product labeling may be difficult to

read and understand. The agency

understands the need for a flexible

application of graphical techniques to

achieve an acceptable level of

readability for OTC drug product

labeling. However, in order to ensure

that labeling information is conveyed in

a manner that enables the public to

readily notice and comprehend such

information, the agency is proposing to

set minimal standards and requirements

for certain key graphic elements of the

format of OTC drug product labeling

(except for the labeling on the principal

display panel). Type size, letter and line

spacing, contrast, print and background

color, and type style are all factors that

may contribute to poor readability and

low comprehension of information

(Refs. 3, 4, and 5). To provide further

assistance to industry, the agency may,

in the future, issue a guidance

document to provide additional useful

guidance on labeling format. The agency

is proposing to revise the labeling

format as follows:

Proposed § 201.66(d)(1) would require

that all headings and subheadings must

be in upper and lower case letters, and

must be highlighted by bold type that

prominently distinguishes the headings

and subheadings from other

information. FDA is also proposing to

permit the use of shading or other color

contrast to highlight headings and

subheadings. FDA is proposing to

require upper and lower case letters

because the agency has tentatively

determined that words in all upper case

letters are harder to read. Consequently,

the agency is also proposing to amend

other regulations that explicitly require

the use of all upper case letters (see

§§ 201.63(e), 201.319(b), and

358.650(d)(1)). At the time of

publication of the final rule, the agency

intends to revise other labeling

information that is required to appear in

all capital letters to conform with the

proposed requirement for the use of

upper and lower case letters. FDA

would not permit the use of ‘‘reverse

type’’ (i.e., white or neutral color type

on a darker color background) as a form

of highlighting because this type of

graphic technique is known to have

poorer readability than regular type.

The agency is proposing to require

that a horizontal line separate each

section of information under the major

headings listed in § 201.66(c)(1) through

(c)(7). For example, a thin hairline

would follow the active ingredient/

purpose, warnings, directions, other

information, etc. The agency believes

that horizontal lines will distinctively

separate each section of important

information to make it more

conspicuous and easier to read.

Proposed § 201.66(d)(2) would require

that the letter height or type size for

headings and subheadings in proposed

§ 201.66(c)(1) through (c)(7) shall be no

smaller than 6 point type. The agency is

also proposing that the letter height or

type size for all other OTC drug product

labeling information (including, but not

limited to, information on the outside

container or wrapper, the immediate

container label (if different), and the

package insert (if any)) also shall be no

smaller than 6 point type. The proposed

minimum 6 point type requirement

would not apply to the manufacturer’s

name and address or the labeling on the

principal display panel. The format and

content requirements for the principal

display panel are set forth under

§§ 201.60 and 201.62. The agency

requests comments on whether FDA

should establish minimum type size

requirements for the principal display

panel.

Based on the data and comments

discussed in section III. of this

document, FDA believes that the

minimum type size requirements would

benefit a substantial number of

consumers who have difficulty reading

the labeling on OTC drug products. The

agency is, however, specifically

requesting comment on whether to

require that a package insert, or similar

accompanying material, printed in a

larger point size (such as 10 point type),

be included with every OTC drug

product. This requirement would help

ensure the safe and effective use of OTC

drug products by segments of the

population (such as the elderly) who

may be unable to read 6 point type.

In addition, the agency does not

believe that the proposed minimum

type size would require applicants,

manufacturers, packers, or distributors

to increase the size of OTC drug product

containers.

The agency is proposing to allow

manufacturers, packers, or distributors

to delete specific ‘‘connecting terms’’

(that do not change the meaning of the

information) that are currently required

in OTC drug product labeling. Holders

of approved marketing applications who

wish to delete a ‘‘connecting term’’ in

their labeling may do so in accordance

with § 314.70. The ability to delete these

terms would permit applicants,

manufacturers, packers, and distributors

to format their labeling to fit more

legible information into the proposed

bulleted format. Thus, FDA believes that

the deletion of ‘‘connecting terms’’

would in a number of instances

compensate for the increased demands

on label space that may result from the

increased minimum type size.

FDA recognizes that there may be

some containers and packages that may

not be able to accommodate 6 point

type, even with the new proposed

format. The agency believes, however,

that the available surface area of the

labeling on a number of these products

could be increased without changing the

size of the current container or package.

For example, the labels affixed to some

bottled drug products may be

lengthened and widened to increase the

surface area of the label without

changing the size of the container. Also,

the agency believes that the information

presented on boxed drug products can,

in some instances, be rotated 90 degrees

in order to accommodate the proposed

minimum type size without changing

the dimensions of the package. The

agency expects manufacturers, packers,

distributors, and applicants to take all

possible steps to increase the available

surface area of the labeling, without

changing the size of the container or

package, in order to accommodate the

proposed type size. In addition, the

agency is specifically inviting comment

on whether it should require

manufacturers, packers, distributors,

and applicants to use alternative

packaging designs, such as extending a

single side panel of a package, to

increase available labeling space.

The agency also requests comment on

whether to require a performance

standard for the labeling on containers

and packages that may be too small to

accommodate 6 point type, and on the

important elements such a performance

standard should contain. A performance

standard would use performance-based

measuring techniques, rather than

precise minimum requirements on the

size, appearance, and format of a

product’s labeling, to ensure that the

labeling is readable and understandable.

For example, a performance standard

could involve measuring a label’s
Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules 9037

readability based on a validated test of

visual acuity (e.g., whether x number of

persons with y visual acuity can read

the labeling when it is z inches from the

eye under specified or controlled

lighting conditions).

Proposed § 201.66(d)(3) would require

that all headings, subheadings, and

information set forth in proposed

§ 201.66(c)(1) through (c)(7) shall be

legible and clearly presented. The

proposal would permit the use of

shading or color contrast in order to

increase the prominence and

conspicuousness of the text. Shading or

color contrast, however, would not be

permitted to highlight or emphasize

specific text or portions of text unless

otherwise provided in an approved

marketing application, final monograph,

or an applicable regulation (e.g., current

requirements for bold print in §§ 341.76

and 341.80, and requirement for box

and red letters in § 201.318(c)(1)).

The proposal would require that the

headings, subheadings, and information

be presented in the Helvetica type style,

which is an easy-to-read type style, and

would require at least 1 point leading

for the headings, subheadings, and

information set forth in proposed

§ 201.66(c)(1) through (c)(7). The

proposal also specifies, as a minimal

kerning requirement, that letters should

not touch. FDA believes that setting

minimal requirements for upper and

lower case type styles, leading, and

kerning would enhance the readability

of the proposed 6 point type.

Proposed § 201.66(d)(4) would require

the use of bullet points to distinguish

each piece of information found under

each heading and subheading. For

example, if there is more than one ‘‘use’’

for an OTC drug product, then the

information required under the section

heading ‘‘Uses’’ would be set off by a

bulleted point before each unique piece

of information. If more than one

bulleted phrase is placed on the same

horizontal line, the end of one bulleted

phrase would be required to be

separated from the beginning of the next

bulleted phrase by at least two square

em’s (i.e., two squares of the size of the

letter ‘‘M’’). The agency is not proposing

to specify a graphical icon for bulleted

points. The proposed rule would not

require the inactive ingredients or other

cosmetic ingredients (proposed

§ 201.66(c)(7)) to be set off by bullet

points.

Proposed § 201.66(d)(6) would require

that the general labeling information

required under the heading ‘‘Warnings’’

shall be continuous and not separated in

any way, in order to increase the

readability of this important

information. For example, where the

required labeling information is

presented on two panels, the warning

section shall be contained as a whole on

one panel and not divided such that

some information is on one panel and

the rest is on another panel.

The agency is maintaining its current

policy regarding the voluntary use of

symbols and pictograms (see pregnancynursing warning, at 47 FR 54750,

December 3, 1982 (§ 201.63(a)). The

agency currently permits the voluntary

use of symbols and pictograms, but does

not permit symbols or pictograms to be

used as a substitute for a required

warning; they may only be used in

addition to it. The agency, however,

would not permit the use of a symbol

or pictogram that is confusing or

misleading, e.g., one that directs

attention away from required labeling

information or one that is ambiguous or

could easily be misunderstood by

consumers.

Examples of prototype OTC drug

product labeling are attached in

Appendix A. Example 1 demonstrates

the general format and style

contemplated by the proposed rule,

including the proposed headings and

subheadings, in the order proposed, as

well as the proposed type style,

hairlines, and bolding. Example 2

depicts OTC drug labeling for

chlorpheniramine maleate, based on the

applicable monograph, using the format

and content specifications set forth in

the proposed rule. The headings are

presented in 8 point type, which is

larger than the minimum type size

proposed by the agency. The

information is presented using an

ordinary package size for this type of

product. Example 3 depicts OTC drug

labeling for a combination cough/cold

product, based on the applicable

monographs, using the proposed format

and content specifications. Example 4

demonstrates how the same information

shown in Example 3 can be presented

directly on the package label for an 8

ounce bottle of syrup.

Examples 5 and 6 depict OTC drug

labeling for a topical acne product and

for a stannous fluoride product,

respectively, based on the applicable

monographs and using the format and

content specification set forth in this

proposed rule. The information is

presented using an ordinary package

size for each of these products.

Example 7 demonstrates OTC drug

labeling for a chlorpheniramine maleate

product, based on the applicable

monograph, using the proposed

amendment to the ‘‘exclusivity policy’’

set forth in § 330.1(c)(2) and described

in Section V.I. of this document. Note

that the approved information from the

monograph is surrounded by a hairline

forming a box and that the boxed area

is entitled ‘‘FDA Approved

Information.’’ The additional

information in this example is optional.

Example 8 demonstrates OTC drug

labeling for a combination cough/cold

product, based on the applicable

monographs, using the proposed

content and format specifications,

except that the ‘‘Directions’’ section is

presented before the ‘‘Warnings’’

section, and the directions for use are

highlighted. The agency specifically

requests comment on the order of

appearance of the ‘‘Directions’’ and

‘‘Warnings’’ sections, as well as whether

to require highlighting of the

information contained in the

‘‘Directions’’ section.

Example 9 demonstrates OTC drug

labeling for a chlorpheniramine maleate

product, based on applicable

monographs, using the proposed

content and format specifications,

except that the order is different than

that proposed. The agency specifically

requests comments on this, and other

alternative for the order of information.

Each of these examples also makes

use of proposed § 330.10(i) and (k) by

deleting certain ‘‘connecting terms’’ and

by substituting certain ‘‘interchangeable

terms’’ as would be permitted by this

proposed rule.

Finally, the agency is proposing that

the new format will not apply to the

product’s immediate container, unless

the product is sold without an outer

package or wrapper. The agency

believes that were it to require the

proposed labeling format, and the

information that would be presented

within that format, to appear on the

immediate container of all marketed

OTC drug products, many products as

currently marketed could not conform

with the proposed requirements. The

agency does not intend to require

applicants, manufacturers, packers, and

distributors to increase the container

size of their products in order to

conform to the proposed new format.

The agency recognizes, however, that

dual labeling of products that are sold

with outer packages or wrappers is

beneficial because consumers may

discard the outer package. For that

reason, the agency is proposing that the

letter height or type size for all other

OTC drug product labeling information

(except for the principal display panel)

be no smaller than 6 point type. Thus,

important information that is required

to appear on the immediate containers

of OTC drug products will be more

legible to the consumer. The agency

invites specific comment on whether

additional elements of the proposed
9038 Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules

new format, such as certain required

headings, presentation of information in

a standardized order, or the use of a

bullet point format, should also be

required for the immediate container

labels of all OTC drug products.

E. Location

Proposed § 201.66(e) provides that the

labeling information required under

§ 201.66(c)(1) through (c)(7) must be the

first information that appears on the

back or side panel of the outside

container or wrapper of the retail

package (or the immediate container

label if there is no outside container or

wrapper) of all marketed OTC drug

products. FDA is specifying the location

of this important information in order to

enable consumers to become

knowledgeable about OTC drugs and

familiar with the type and location of

specific information on OTC drug

product labeling. Increased knowledge

and familiarity with important

information would help to ensure the

safe and effective use of OTC drug

products.

The agency is requiring that this

labeling information appear in a

uniform location in order to facilitate

consumer familiarity with OTC drug

product labeling information. Although

current regulations require that the

‘‘statement of identity’’ and ‘‘net

quantity of contents’’ appear on the

‘‘principal display panel’’ (see

§§ 201.60, 201.61, 201.62)), important

warning information does not appear in

a uniform location in the labeling of

various OTC drug products (as

discussed in section III. of this

document).

F. Exemptions and Deferrals

Some requirements in proposed

§ 201.66 may be inapplicable or

impracticable for certain products. For

example, it may be impracticable for a

product, because of its attributes, to

meet all of the labeling format

requirements. Under proposed

§ 201.66(f), manufacturers, packers,

distributors, or applicants may submit

written requests to FDA to be exempted

from one or more specific requirements

in proposed § 201.66(a) through (e).

Requests for exemptions would be

required to be submitted in the form of

a citizen petition under 21 CFR 10.30 of

this chapter and should be clearly

identified on the envelope as a ‘‘Request

for Exemption from § 201.66 (OTC

Labeling Format).’’ The request for

exemption would be required to include

documentation that demonstrates why

the requirements are inapplicable or

impracticable for this product. Such

requests would be required to include

documentation that demonstrates that

the manufacturer has used all other

graphical techniques to enhance

readability, and has complied with as

many of the format requirements in

proposed § 201.66 as practicable. The

agency seeks comment on whether there

are particular types of products or

packages that should be granted a

regulatory exemption or should be

required to meet a performance

standard.

In addition, FDA on its own initiative

may, based on the particular

circumstances presented, exempt or

defer any or all of the requirements set

forth in these sections.

G. Interchangeable Terms

At the public hearing held by FDA on

September 29, 1995, several comments,

including NDMA comments,

recommended that FDA consider

amending its regulations to permit the

use of synonyms that would promote

greater comprehension among people

with low or moderate literacy skills (see

Docket No. 95N–0259). In response to

these requests, the agency is proposing

to amend current § 330.1(i) to include

additional terms that may be used

interchangeably in any of the labeling

established for OTC drug products

(including the OTC drug product

labeling regulations in part 201, and

parts 331 through 358), provided such

use does not alter the meaning of the

labeling that has been established and

identified in an applicable monograph

or by regulation. The proposal would

not permit the titles of the headings and

subheadings specified by the agency in

proposed § 201.66(c)(1) through (c)(7) to

be changed through the use of

interchangeable terms, through the

deletion of connecting terms, or in any

other manner.

These interchangeable terms would be

cross-referenced in proposed

§ 201.66(g). Expanding the current list of

interchangeable terms would permit the

formulation of easier to understand and

more concise messages on the labeling

of OTC drug products.

Because the part of speech (i.e.,

adjectives, nouns, adverbs, verbs, etc.) is

not always the same for words that can

be used in different ways, the contextual

message conveyed by using certain

substituted words may dramatically

change the overall meaning of the

labeling statement. Consequently, when

using any interchangeable word, the

meaning must not be changed.

Although these additional terms are

based primarily on NDMA’s

recommendations, the agency is

proposing some additional terms that

were not included on NDMA’s list of

recommended terms. In addition, FDA

is not proposing all of NDMA’s

suggestions in this proposal. One

example of an NDMA recommendation

that FDA is not proposing is NDMA’s

recommendation that the word ‘‘call’’

should be proposed as an

interchangeable term with the current

word ‘‘contact.’’ The agency, however,

is proposing ‘‘ask’’ instead of ‘‘call’’

because FDA does not want to limit

other forms of ‘‘contact’’ (i.e., visit, or

see).

Another example of an NDMA

recommendation that FDA is not

including in this proposal is the

recommended phrase ‘‘use only on

skin’’ as an interchangeable term with

the current phrase ‘‘for external use

only.’’ The agency is not proposing this

phrase because it is not interchangeable

for topical ophthalmic or vaginal

products. In addition, the phrase could

be confusing for products intended to be

used on cuts or abrasions.

In the March 1996 proposal, FDA

proposed to amend § 330.1(i) to provide

for interchangeable terms for the

phrases ‘‘unless directed by a doctor’’ or

‘‘except under the advice and

supervision of a physician.’’ Labeling

information about not using an OTC

drug product under these circumstances

appears in different OTC drug

monographs in different language, but

conveys the same message (see, for

example, §§ 341.76(c)(2), 331.30(c)(1)

and (c)(4) through (c)(7), 349.75(c)(2),

341.72(c)(3) and (c)(4), 346.50(c)(7)(ii),

341.72(c)(6)(i) through (c)(6)(iii),

358.750(c)(2)(ii), (c)(3), and (c)(4)). In

addition, the phrase ‘‘unless directed by

a doctor’’ has been used more recently

and most frequently. The agency

determined that all of these phrases

could be interpreted in the same way

(e.g., ‘‘* * * unless a doctor tells you’’)

and that this simpler phrase may be

better understood by consumers than

some of the other phrases. Thus, the

agency proposed to amend § 330.1(i) to

include the phrase ‘‘unless a doctor tells

you’’ as an alternative for these other

phrases where they appear in the

labeling of OTC drug products.

The proposal also stated that, in a few

instances, the words ‘‘or your child’s

doctor’’ would be permitted as part of

this phrase. The agency requested

comments on whether it would be

preferable to say ‘‘your’’ child’s doctor

or ‘‘the’’ child’s doctor, or whether it

does not make any difference which

wording is used.

FDA received three comments

supporting the proposal. NDMA

recommended that FDA reconsider its

proposal to adopt ‘‘unless a doctor tells

you’’ because NDMA stated that the
Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules 9039

phrase was ‘‘colloquial, awkward and

incomplete in its instructional intent.’’

(See Docket No. 92N–454A.) Another

comment also urged FDA not to adopt

the phrase ‘‘unless a doctor tells you,’’

because the phrase could lead to

ambiguity and confusion. The

comments alternatively recommended

that FDA adopt the phrases ‘‘unless told

to do so by a doctor,’’ ‘‘unless you first

ask a doctor,’’ ‘‘without checking with a

doctor,’’ or ‘‘without asking a doctor.’’

NDMA also recommended that FDA

not adopt the phrase ‘‘your doctor’’ or

‘‘your child’s’’ doctor because ‘‘it is

limiting and should be dropped in favor

of ‘a doctor’ or ‘the child’s doctor’.’’

NDMA recommended that FDA adopt

this broader language because a

designated caretaker may administer an

OTC drug product in the absence of a

parent. Finally, NDMA recommended

that FDA permit interchangeable terms

defined in the OTC drug review to also

be interchangeable with the same terms

found in marketing applications.

Another comment recommended that

for OTC drug products intended for use

in conditions involving the feet (e.g.,

athletes foot, corns, calluses, etc.) the

term ‘‘podiatrist’’ be added as an

allowable interchangeable alternative to

‘‘doctor’’ or ‘‘physician’’ because many

consumers consult their podiatrist

rather than their usual doctor or

physician for foot related conditions.

Because this proposed rule addresses

the same interchangeable terms (as well

as additional interchangeable terms),

this proposed rule responds to the

comments submitted to Docket No.

92N–454A. Therefore, the agency is,

with this notice, formally withdrawing

the March 1996 proposal.

FDA has carefully considered the

comments and is proposing that the

current terms, ‘‘unless directed by a

doctor’’ and ‘‘except under the advice

and supervision of a physician’’ be

interchangeable with ‘‘unless told to do

so by a doctor.’’ In addition, the agency

is proposing that the phrases ‘‘before a

doctor is consulted,’’ ‘‘without first

consulting your doctor,’’ or ‘‘consult

your doctor before * * *’’ may be

interchanged with ‘‘unless first told to

do so by [the child’s doctor] a doctor.’’

The agency agrees with NDMA’s

comment that ‘‘a doctor’’ or ‘‘the child’s

doctor’’ is preferable to ‘‘your doctor’’ or

‘‘your child’s doctor.’’

The agency disagrees with the

comment that recommended that the

term ‘‘podiatrist’’ be interchangeable

with ‘‘doctor’’ or ‘‘physician’’ for OTC

drug products intended for use in

conditions involving feet (e.g., athlete’s

foot, corns, callouses, etc.). The agency

does not believe that ‘‘podiatrist’’ would

be an appropriate substitution for

‘‘physician’’ for all OTC drug products

intended for use involving feet. Because

the agency has determined that there

may be specific limited instances where

the term ‘‘or podiatrist’’ may be

appropriate, however, current

regulations do provide that ‘‘or

podiatrist’’ may be used in addition to

the word ‘‘doctor’’ when a wart remover

product is labeled with the specific

indication found in § 358.150(b)(2).

FDA agrees with NDMA’s

recommendation that FDA permit

interchangeable terms defined in the

OTC Drug Review to be interchangeable

with the same terms found in approved

marketing applications for OTC drug

products. Applicants or holders of

approved marketing applications for

OTC drug products who wish to include

an interchangeable term in their labeling

would be required, however, to include

the interchangeable term in the

marketing application or supplemental

application in accordance with § 314.70.

The agency recognizes that a large

percentage of OTC drug products are

purchased at retail stores where a

pharmacist is present. FDA also

recognizes that pharmacists are

knowledgeable about OTC drug

products and are trained to counsel and

give advice about these products.

Although the agency is not proposing

the terms ‘‘doctor’’ and ‘‘pharmacist’’ as

interchangeable terms, the agency

believes the phrase ‘‘doctor or

pharmacist,’’ as in ‘‘Ask your doctor or

pharmacist,’’ may be appropriate

guidance on OTC drug product labeling

for certain products. The agency seeks

comment on whether the phrase ‘‘or

pharmacist’’ should be included on OTC

drug labeling and, if so, on what section

of the labeling, and for which products.

H. Connecting Terms

OTC drug product regulations

currently contain statements or clauses

that are in quotation marks. Information

that is presented in a monograph in

quotation marks is required to appear in

the labeling exactly as it appears in the

monograph (except to the extent an

interchangeable term may apply). In

order for these statements or clauses to

fit into the new format, including the

required minimum type size, certain

words within the quotation marks may

have to be deleted. Therefore, proposed

§ 330.1(k) includes a list of connecting

terms that may be deleted from the

labeling of OTC drug products required

under OTC drug product regulations,

including monograph regulations, when

labeling is revised to comply with

§ 201.66, and when such deletion does

not alter the meaning of the OTC drug

product labeling requirements.

The agency is proposing to permit

manufacturers, packers, or distributors

to delete these connecting terms because

these terms generally do not affect the

meaning of the labeling, but are required

in current regulations to ensure that

sentences are grammatically correct.

Holders of approved marketing

applications who wish to delete a

‘‘connecting term’’ from their labeling

may delete the ‘‘connecting term’’ in

accordance with § 314.70. The agency is

proposing this approach to simplify

language and to enhance readability for

consumers. In addition, the deletion of

such connecting words would enable

the currently required OTC drug

product labeling language to fit into the

new format without revising all of the

current regulations. These connecting

terms would be cross-referenced in

proposed § 201.66(g). Manufacturers

who choose to delete these connecting

terms in the manner described would

still be deemed to be using the exact

monograph language where monograph

language is specified in quotation

marks. The agency recognizes that the

proposed list does not include all

connecting words that could be deleted

and invites comment on additional

terms.

I. ‘‘FDA Approved Information’’

Designation

The agency is also proposing to

amend § 330.1(c)(2) regarding the use of

the designation ‘‘APPROVED USES’’ or

other similar designation when a

manufacturer, packer, or distributor

utilizes the exact language as it appears

in an applicable monograph or

regulation to state the indications for

use. Section 330.1(c), in its present

form, allows manufacturers some

flexibility in describing the indications

for use that are established in applicable

monographs or regulations

(§ 330.1(c)(2)(i) to (c)(2)(iii)). All other

required OTC labeling, including

required warnings, must be stated in the

exact language established and

identified (by quotation marks) in an

applicable monograph or regulation

(§ 330.1(c)(2)(vi)). Manufacturers,

packers, or distributors who choose to

delete connecting terms or use

interchangeable terms in the manner

described in this proposal would still be

deemed to be using the exact

monograph language where monograph

language is specified in quotation

marks. The agency is not proposing to

change these elements of its

‘‘exclusivity policy’’ (see 51 FR 16258).

The agency is, however, proposing to

amend § 330.1(c)(2) to make it
9040 Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules

consistent with the labeling format

proposed in this notice. Specifically, the

agency would continue to invite

manufacturers, packers, or distributors

to use the exact language of a

monograph or applicable regulation to

describe the indications for use.

Manufacturers, packers, or distributors

who use such exact language to describe

the indications for use would have the

option of placing a box around all

labeling information that has been

established in an applicable final

monograph or regulation, and to

designate the boxed area, ‘‘FDA

Approved Information.’’ To be

consistent with the standardized format

being proposed, no other designation

would be permitted, and the designation

would appear in bold text with upper

and lower cases letters (rather than in

upper case letters). Manufacturers,

packers, or distributors would not be

permitted to use a boxed area around

the ‘‘Uses’’ heading, but would be

required to put a box around all of the

information that is established in an

applicable final monograph or

regulation.

Manufacturers, packers, or

distributors would also continue to have

the option of using other truthful and

nonmisleading statements to describe

the indications for use, subject to the

provisions of sections 301(d) (21 U.S.C.

331(d)), 502, and 505(a) of the act. As

in the existing regulation, labeling that

uses other truthful and nonmisleading

statements to describe the indications

for use could not be boxed and could

not contain the ‘‘FDA Approved

Information’’ designation (see

§ 330.1(c)(2)(ii)).

The agency recognizes that while it

may be limiting the manner in which a

manufacturer, packer, or distributor can

make use of the boxed labeling

technique, the agency is also proposing

additional interchangeable terms and

connecting terms. The agency believes

that these proposed interchangeable

terms and connecting terms would

provide manufacturers, packers, and

distributors more flexibility in using

exact language (where exact language

has been established or identified by

quotation marks in an applicable

monograph or regulation) to describe

the indications for use. Therefore,

manufacturers, packers, and distributors

would have more opportunities to make

use of the ‘‘FDA Approved Information’’

designation and box.

The agency is also considering

whether it should instead take the step

of deleting altogether the provisions for

boxed labeling in § 330.1(c)(2). The

agency seeks comment on this point.

J. Preemption

1. Need for Federal Regulation and

Preemption

FDA has tentatively determined that

to ensure that OTC drug product

labeling conveys all material

information to the consumer, and that

the labeling conveys this information in

a manner that is likely to be read and

understood by the consumer, State and

local rules that would establish different

or additional format or content

requirements than those in this

proposed rule should be preempted.

The agency believes that a

standardized format, and a single set of

rules regarding the appearance and

content of OTC drug labeling, will

significantly improve the ability of

consumers to read and understand OTC

drug labeling. The agency expects that

as consumers become familiar with the

format, they will more readily recognize

and focus on important information

contained in the labeling regarding the

use of the product. NDMA, the primary

trade association representing

nonprescription drug manufacturers,

likewise has reached the conclusion that

by establishing ‘‘a label that will be

uniform throughout the United States,

FDA can help to reduce label clutter and

promote greater consumer use of label

information.’’

With the number and variety of drug

products available OTC, it is the norm

that consumers face a range of choices

when selecting an OTC drug product.

However, all OTC products within the

same pharmacological class or with the

same principal intended drug action are

not identical. Thus, uniformity will

allow consumers to easily compare

various OTC drug products, without

having to take into account potentially

confusing, and even misleading,

differences in format or style. By

helping consumers to easily and

meaningfully distinguish among drug

products, the agency believes it will

increase the likelihood that consumers

will select appropriate products for their

needs.

A single format for all drug products,

wherever sold, will minimize confusion

while enhancing the readability and

understandability of OTC drug labeling.

Within a short period of time after

implementation of the final rule,

consumers will become familiar with

the revised format and will be able to

use it similarly to the way that they now

use nutritional labeling on foods.

State and local requirements for OTC

drug labeling format or content that

differ from or add to those established

by the proposed rule would interfere

with FDA’s proposed method and

objectives. The proposed regulations are

intended to allow consumers to glance

at virtually any OTC drug product

labeling anywhere in the country and

find information in a format they

recognize, presented in a manner that is

easily read and understood.

Consequently, the likelihood of safe and

effective use of OTC drug products

would be increased. A State or local

requirement that differs from the

proposed rule with respect to any of the

standard format elements could frustrate

the basis and purposes of the proposed

regulations.

For example, changing the order in

which required information must

appear, or the size or graphic ‘‘look’’ of

the area in which drug information will

be contained, could confuse consumers

and limit the intended effectiveness of

the proposed format. Even if each State

required only one small variation in the

format, the resulting 50 different

requirements throughout the country

could undermine the goals the agency

believes may be achieved through a

uniform OTC drug labeling format.

In addition to the need for OTC label

standardization and the adverse effect

State and local requirements would

have on it, State and local requirements

could impose additional economic and

distributional burdens on industry that

ultimately would be borne by

consumers. State requirements at

variance with the Federal law would

force manufacturers to develop unique

sets of labeling or stop altogether the

supply of OTC drug products to the

residents of the jurisdiction involved.

Moreover, were manufacturers required

to tailor their products to different

jurisdictions, they would likely face

increased printing and distribution

costs, leading to higher OTC drug prices

for consumers and, therefore, more

limited access for some consumers to

safe and effective drugs.

The imposition of different or

additional State or local labeling

requirements could also make it

difficult for some products to fit all of

the FDA required labeling information

within the proposed format, and may

cause more products to have to seek an

exemption from the new format.

Finally, the agency has tentatively

determined that State or local interests

in regulating OTC drug product labeling

format or content would be modest

when compared to the benefits of a

national program. The agency to date

has found little evidence to suggest that

States or localities have a significant

interest in controlling the format or

content of OTC drug labeling. Moreover,

the agency has tentatively determined

that the benefits of clear, concise, and
Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules 9041

consistent information that all

consumers will receive as a result of this

regulation would ordinarily outweigh

the value of unique or unusual

informational requirements for State or

local consumers.

In sum, the agency has tentatively

determined that for most consumers

there are no inherent differences

between States that would justify a need

for different State regulation.

Implementation of specialized rules

could come at the expense of nationally

uniform OTC drug labeling, and could

ignore other national interests and

priorities addressed by the proposed

rule.

2. Scope of Proposed Preemption

The agency is proposing to preempt

only those State and local requirements

that would directly threaten the national

uniformity sought to be achieved by the

proposed rule, or otherwise directly

interfere with the attainment of the

agency’s objectives outlined in this

proposed rule. The agency has

tentatively determined that State or

local laws, regulations, or rules that

establish or continue in effect additional

or different requirements with respect to

any of the elements of format or content

addressed in the proposed rule could

have a deleterious effect on the goals

sought in this proposed rule. Thus,

under the proposed preemption

provision, a State or locality may not

establish or continue in effect

requirements different from or in

addition to the agency’s requirements

with respect to the format (including

headings, subheadings, order, boxing or

title, lines and spacing, type size, color

and contrast, and other format

requirements in the proposed rule) or

the content of OTC drug labeling. The

agency also intends the preemption to

apply to requirements that a State or

locality may view as improving an

agency requirement, such as requiring a

larger minimum type size than 6 point

and other minimum standards for

graphical features. States or localities

would similarly be prohibited from

requiring more (or less) spacing between

lines or letters, or requiring that the

information appear in a different order

or with different subheadings, or that

additional information be included.

As proposed, the scope of this

preemption would exclude statutory or

common law causes of action in tort,

based on the format or content of OTC

drug product labeling. Because there

may be situations in which information

about potential harm from an OTC drug

product may not be available to FDA

until after an individual consumer may

have been harmed, the agency does not

want to preclude compensation through

tort actions in all cases related to OTC

drug product labeling. The agency

specifically seeks comment on this

exclusion.

The agency recognizes that in rare

instances a State or local government

may find a compelling need to issue a

law, regulation, or ordinance relating to

the format or content of OTC drug

labeling. For example, there may be

certain populations of patients in

defined areas of the country who may be

more sensitive to a particular aspect of

an OTC drug product, and who would

need to be warned of that aspect in

order to ensure the safe and effective

use of the product. Accordingly, the

proposed rule contains a procedure for

States and local governments to petition

for an exemption from the preemption.

Finally, the agency specifically seeks

comment on whether State or local

warning statements that are different

from, or that would be in addition to,

those required by FDA should be

preempted by this rule.

3. Legal Authority for Federal

Preemption

The preemption doctrine is rooted in

the Supremacy Clause of the United

States Constitution (U.S. Const., Art. VI,

Cl. 2). Under the Supremacy Clause of

the Constitution, State law may be

preempted by Federal law in a number

of ways (U.S. Const., Art. VI, Cl. 2.).

Congress may preempt State law by so

stating in express terms (Jones v. Rath

Packing Co., 430 U.S. 519 (1977).

Section 521 of the act (21 U.S.C. 360k),

for example, contains an express

preemption provision applicable to

devices.

Federal preemption may also be based

on any of several ‘‘implied preemption’’

principles. First, preemption may be

found ‘‘where the scheme of federal

regulation is sufficiently comprehensive

to make reasonable the inference that

Congress ‘left no room’ for

supplementary state regulation’’

(Hillsborough County v. Automated

Medical Laboratories, Inc., 471 U.S. 707,

713 (1985), quoting Rice v. Santa Fe

Elevator Corp., 331 U.S. 218, 230

(1947)), or where ‘‘the federal interest is

so dominant that the federal system will

be assumed to preclude enforcement of

state laws on the same subject’’ (Rice,

331 U.S. at 230; see Hines v.

Davidowitz, 312 U.S. 52 (1941)).

Federal preemption may also be

found where Federal law conflicts with

State law. Such conflict may be

demonstrated either where ‘‘compliance

with both federal and state [law] is a

physical impossibility’’ (Florida Lime

and Avocado Growers, Inc. v. Paul, 373

U.S. 132, 142–143 (1963)), or where

State law ‘‘stands as an obstacle to the

accomplishment and execution of the

full purposes and objectives of

Congress’’ (Hines, 312 U.S. at 67).

State law is also preempted if it

interferes with the methods by which a

Federal law is designed to reach its

goals. (See Int’l Paper Co. v. Ouellette,

479 U.S. 481, 494 (1987); Michigan

Canners & Freezers Ass’n v. Agricultural

Marketing & Bargaining Bd., 467 U.S.

461, 477–478 (1984).)

A statutorily authorized regulation

may preempt a State or local law under

any of these implied preemption

theories. (See City of New York v. FCC,

486 U.S. 57, 63–64 (1988); Louisiana

Public Service Comm’n v. FCC, 476 U.S.

355, 368–369 (1986).) That is, ‘‘federal

regulations have no less preemptive

effect than federal statutes.’’ (See

Fidelity Federal Savings & Loan

Association v. de la Cuesta, 458 U.S.

141, 153–154 (1982).) Thus, a federal

agency, acting within the scope of its

delegated authority, may preempt State

or local laws that conflict with or

frustrate the purposes of the agency’s

regulations. (See City of New York, 486

U.S. at 64.) In addition, an agency may,

under certain circumstances, determine

that its authority over an area of

regulation is exclusive and expressly

preempt State regulation in that area. Id.

If the agency’s choice to preempt

‘‘represents a reasonable

accommodation of conflicting policies

that were committed to the agency’s

care by statute [the regulation will stand

unless] it appears from the statute or its

legislative history that the

accommodation is not one that Congress

would have sanctioned.’’ (See United

States v. Shimer, 367 U.S. 374, 383

(1961).)

FDA’s proposed regulations are

within the scope of its delegated

authority. (See section VII. of this

document, ‘‘Legal Authority.’’)

Furthermore, conflicts between State

and local OTC labeling laws, with

different or additional requirements

than those of the Federal law, justify

FDA’s preemption of such laws.

Although Congress did not expressly

preempt State law in this area, the

agency’s action is appropriate because

different or additional State and local

laws would significantly interfere with

both the goals of Federal law and the

methods by which the Federal law is

designed to achieve those goals.

Conflicting State and local laws for

OTC drug labeling could undermine the

agency’s objectives to ensure greater

legibility and comprehension of OTC

drug labeling and to help ensure safe

and effective use of OTC drug products.
9042 Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules

Although States and localities may have

an interest in developing their own

requirements in the area of OTC drug

product labeling, the agency has

tentatively determined that the national

standard set forth in this proposal is

tailored to meet the agency’s goal of

ensuring safe and effective use of OTC

drug products, and that the need for a

national standard outweighs the

interests of individual States and

localities.

VI. Proposed Implementation Plan

The agency is proposing the following

implementation plan for the proposed

labeling format and content provisions.

This proposed implementation plan is

intended to minimize the economic

impact on the regulated industry, while

providing consumers with the benefit of

more readable and understandable OTC

drug product labeling at the earliest

reasonable date. The proposed

implementation plan provides

implementation dates that vary

according to the regulatory status of the

particular OTC drug product. A product

whose labeling does not comply with

the proposed format and content

provisions on or after the applicable

implementation date would be liable to

regulatory action.

The agency generally provides an

implementation date of 1 year after the

date of publication of the final

monograph in the Federal Register for

the use of labeling prescribed under a

final OTC drug monograph (monograph

labeling provisions). Accordingly, the

agency is proposing that the

implementation date for the new

labeling format and content provisions

for OTC final monographs, published on

or after the effective date of the final

rule based on this proposal, would be

the implementation date for the

applicable final OTC monograph.

However, the agency encourages

manufacturers, packers, and distributors

of products pending under the

monograph review process to

voluntarily implement the new labeling

format when they print new labels.

Because the labeling changes for

information required under the final

monograph and these new labeling

format changes would be effective at the

same time, manufacturers would only

need to make one label printing to

incorporate final monograph

information into the new labeling

format. In addition, implementation of

the provisions of the final rule would be

less burdensome because the agency

and the industry will have gained

information and experience from the

planning, preparing, and printing of

labeling in the new format for other

products covered by either marketing

applications or existing final

monographs at the time of publication

of the final rule. Accordingly, less time

should be required for firms to bring

OTC drug products pending under the

monograph review process into

compliance with the new labeling

format requirements.

For an OTC combination product for

which one component is pending under

monograph review and another

component is the subject of a final OTC

drug monograph on or after the effective

date of the final rule based on this

proposal, the agency is proposing that

the implementation date for the new

labeling format and content provisions

would be the earlier of 2 years after the

effective date of the final rule based on

this proposal or the effective date of the

final OTC drug monograph applicable to

the component under review. For an

OTC combination drug product for

which more than one component is

pending under the OTC drug

monograph review on or after the

effective date of the final rule based on

this proposal, the agency is proposing

that the implementation date of the new

format and content provisions would be

the date on which any one of the

components first becomes the subject of

an effective OTC drug monograph.

For an OTC drug product that is the

subject of a pending marketing

application on or after the effective date

of the final rule based on this proposal,

the agency is proposing that the

implementation date would be

immediately (concurrent with initial

product marketing) upon approval of

the application. Manufacturers of such

products would submit draft labeling in

the proposed new format for review as

part of the application.

For an OTC product with a low level

of distribution (i.e., products with

annual sales of less than $25,000), the

agency is proposing that manufacturers

comply with the new labeling format

and content requirements within 3 years

of the effective date of the final rule

based on this proposal.

For all other OTC drug products,

including those products marketed

under a final OTC drug monograph, or

an approved application, before the

effective date of the final rule based on

this proposal, the agency is proposing

an implementation date of 2 years after

the effective date of the final rule based

on this proposal. By the applicable

implementation date, applicants would

be required to submit to FDA necessary

changes in their product’s labeling that

would bring the product’s labeling into

compliance with the new standardized

format requirements. The agency is

proposing these dates to provide

manufacturers with sufficient time to

design and print new labeling and

deplete existing stocks of products with

old labeling.

Labeling changes to OTC drug

products marketed pursuant to a

marketing application would be made in

accordance with § 314.70. Section

314.70(b) requires that FDA approve a

supplement for a labeling change, prior

to marketing any product with the

labeling change, except for changes

described in § 314.70(c)(2) or (d). Under

§ 314.70(c)(2), a supplement must be

submitted at the time the change is

made, and does not require agency

preapproval if the change, among other

things, is to add or strengthen a

contraindication, warning, precaution,

adverse reaction, or statement on

overdose, or to add or strengthen an

instruction about dosage and

administration that is intended to

increase the safe use of the product, or

to delete a false or misleading indication

or claim. Under § 314.70(d) a

supplement is not required for a change

in labeling concerning, among others,

the description of the drug product, how

it is supplied, or for an editorial or

similar minor change in the labeling.

Instead, the change need only be

described in the next annual report.

Products that are marketed pursuant to

an OTC drug monograph are not

required to submit labeling to the

agency.

The agency intends to work closely

with sponsors of products that switch

from prescription only status to OTC

status prior to the implementation of the

final rule on incorporating the new

format and content requirements into

the products’ labeling. With respect to

products currently marketed OTC

pursuant to a marketing application, the

agency is interested in receiving

comment on whether changes made

pursuant to the provisions set forth in

this proposed rule should be made

under § 314.70(b), (c), or (d).

The agency intends to make the final

rule based on this proposal effective 30

days after the date of its publication in

the Federal Register.

The proposed rule would not apply to

any homeopathic drug products which

are listed in the H.P.U.S. The labeling of

such products is addressed in FDA’s

Compliance Policy Guide 7132.15

entitled ‘‘Conditions Under Which

Homeopathic Drugs May Be Marketed.’’

VII. Legal Authority

FDA’s legal authority to modify and

simplify the manner in which certain

information is presented in OTC drug

product labeling derives from sections
Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules 9043

201, 502, 505, 507, and 701 of the act.

Regulating the order, appearance, and

format of OTC drug product labeling is

consistent with the agency’s authority to

ensure that drug labeling convey all

material information to the consumer

(21 U.S.C. 321(n) and 352(a)), and that

the labeling communicate this

information in a manner that is ‘‘likely

to be read and understood by the

ordinary individual under customary

conditions of purchase and use’’ (21

U.S.C. 352(c)). Regulating the content of

OTC drug product labeling is consistent

with FDA’s authority to ensure that the

products are safe and effective for use

(sections 201(n) and (p), 502, 505, and

507 of the act).

More specifically, the act authorizes

FDA to regulate the marketing of drug

products, including drugs composed

wholly or partly of any antibiotic drug,

to ensure that they are safe and effective

for their intended uses (sections 201(p),

505(d), and 507 of the act). A major

element of FDA’s authority to ensure the

safe and effective use of drug products

is through FDA’s review, approval, and

monitoring of drug product labeling.

Determinations about safety and

effectiveness are to be made with

respect to the conditions prescribed,

recommended, or suggested in the

labeling (sections 201(p) and 505(d) of

the act).

Under section 505(d) and (e), FDA

also must refuse to approve a new drug

application, and may withdraw

approval for a product, if the product’s

labeling is false or misleading in any

particular. Moreover, under section

502(a) of the act, a drug product is

deemed to be misbranded if its labeling

is false or misleading in any particular.

In determining whether the labeling of

a drug is false or misleading, the agency

must take into account not only the

representations or suggestions made in

the labeling, but also the extent to

which the labeling fails to reveal

material facts about the consequences

that may result when the product is

used according to its labeling or under

the customary or usual conditions of use

(section 201(n) of the act).

The act also provides that a drug

product is misbranded, and liable to

regulatory action, if:

any word, statement, or other information

required by or under authority of this Act to

appear on the label or labeling 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.

(Section 502(c))

Implementing regulations in § 201.15

describe a number of situations in

which the agency considers information

on a drug product’s label as lacking the

prominence and conspicuousness

required by section 502(c) of the act. For

example, a labeling statement may lack

the prominence and conspicuousness

required by section 502(c) of the act by

reason of, among others, ‘‘[s]mallness or

style of type in which such word,

statement, or information appears,

insufficient background contrast,

obscuring designs or vignettes, or

crowding with other written, printed, or

graphic matter’’ (§ 201.15(a)(6)).

The agency may also take regulatory

action to ensure that OTC drug products

contain ‘‘adequate directions for use’’

and ‘‘adequate warnings’’ against unsafe

or dangerous uses (section 502(f) of the

act).

Finally, section 701(a) of the act

authorizes FDA to issue regulations for

the efficient enforcement of the act (see

Weinberger v. Hynson, Westcott and

Dunning, Inc., 412 U.S. 609 (1973); see

also National Association of

Pharmaceutical Mfrs. v. FDA, 637 F.2d

877 (2d Cir. 1981); National

Confectioners Association v. Califano,

569 F.2d 690 (D.C. Cir. 1978)).

The agency has tentatively concluded

that a standardized format, with certain

content requirements, for OTC drug

products is necessary to fulfill the

requirements of the act that information

required to appear on the label or

labeling of an OTC drug product be

placed with such conspicuousness and

prominence (as compared with other

printed matter) as to render it likely to

be read by the ordinary individual

under customary conditions of use

(section 502(c) of the act), and that the

information be presented in a manner

designed to communicate all material

facts about the safe and effective use of

the product to the consumer (section

502(a) of the act). The proposed

regulations are also consistent with the

agency’s authority to ensure that OTC

drug products are labeled with

directions for use and warning

statements that are adequate to guide

the consumer in the safe and effective

use of these products (section 502(f) of

the act).

The currently available information,

as summarized in section III. of this

document, supports the conclusion that

a standardized format and certain

content requirements for all OTC drug

products would help minimize the

potential for consumers to be confused

or misled when comparing products

within the same pharmacologic class.

As the number and variety of drug

products available OTC continues to

increase, consumers ‘‘under customary

conditions of use’’ are frequently

presented with a range of seemingly

similar products. Given the complexity

of the information contained on the

label of an OTC drug, a standardized

format and certain content requirements

are necessary in order for the consumer

to readily and meaningfully compare

OTC drug products.

Finally, the agency believes that a

standardized format and certain content

requirements are essential to help

ensure that consumers are able to

recognize and understand important

information about an OTC drug’s proper

use, its contraindications, and the

adverse effects and safety hazards

associated with its use. As discussed in

greater detail in section III. of this

document, many consumers have

complained that OTC drug labels are

difficult to understand and, among other

things, that the print size on the labels

is too small.

Thus, the agency’s authority to ensure

that material facts regarding the safe and

effective use of an OTC drug product are

adequately presented to the consumer

derives directly from the agency’s

authority under sections 201, 502, 505,

and 507 of the act. These provisions,

combined with the agency’s authority

under section 701(a) of the act to issue

regulations for the efficient enforcement

of the act, authorize FDA to issue

regulations to ensure that the

information necessary to the safe and

effective use of an OTC drug product is

presented to consumers, and that this

information is easily readable, readily

understandable, and is not confusing or

misleading.

VIII. The Paperwork Reduction Act of

1995

This proposed rule contains

information collection provisions that

are subject to review by the Office of

Management and Budget (OMB) under

the Paperwork Reduction Act of 1995

(44 U.S.C. 3501–3520). Therefore, in

accordance with 44 U.S.C. 3506(c)(2)(B)

and 5 CFR part 1320, FDA is providing

below the title, description, and

respondent description of the

information collection contained in this

proposal, along with an estimate of the

resulting annual collection of

information burden. This estimate

includes the time needed for reviewing

instructions, gathering and maintaining

the data needed, and completing and

reviewing the collection of information.

With respect to the following

collection of information, FDA invites

comments on: (1) Whether the proposed

collection of information is necessary

for proper performance of FDA’s
9044 Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules

functions, including whether the

information will have practical utility;

(2) the accuracy of FDA’s estimate of the

burden of the proposed collection of

information, including the validity of

the methodology and assumptions used;

(3) ways to enhance the quality, utility,

and clarity of the information to be

collected; and (4) ways to minimize the

burden of the collection of information

on respondents, including through the

use of automated collection techniques,

when appropriate, and other forms of

information technology.

Title: Over-the-Counter Human Drugs;

Proposed Labeling Requirements.

Description: FDA’s legal authority to

modify and simplify the manner in

which certain information is presented

in OTC drug product labeling derives

from sections 201, 502, 505, 507, and

701 of the act. Regulating the order,

appearance, and format of OTC drug

product labeling is consistent with

FDA’s authority to ensure that drug

labeling convey all material information

to the consumer (21 U.S.C. 321(n) and

352(a)), and that labeling communicate

this information in a manner that is

‘‘likely to be read and understood by the

ordinary individual under customary

conditions of purchase and use’’ (21

U.S.C. 352(c)).

FDA is proposing to amend its

regulations governing labeling

requirements for human drug products

to establish a standardized, more

readable format for the labeling of all

marketed OTC drug products. The

proposed regulation merely

standardizes the format for presenting

information that is already required to

be on the labeling.

The proposed format labeling changes

present a one-time burden for

manufacturers of OTC drug products

marketed under new drug applications.

Those manufacturers would have to

submit a supplement detailing the

labeling changes to be made by the

manufacturer to comply with the format

requirements. This burden is reflected

in the chart below.

Other proposed labeling changes do

not constitute collections of information

because they provide for disclosure of

information supplied by FDA. To

enhance readability, proposed

§§ 201.63, 201.314, 201.319, and

358.650 modify specific warnings or

directions, proposed § 330.1(i) and (k)

provide terms that may be used

interchangeably in the labeling of OTC

drug products and terms that may be

deleted from the labeling, and proposed

§ 201.66(c) specifies words to be used in

headings and subheadings on the

labeling of the drug products. The

proposed regulation specifies the

wordings of the required disclosures.

These labeling requirements provide for

‘‘public disclosure of information

originally supplied by the Federal

Government to the recipient for the

purpose of disclosure to the public’’ and

are, therefore, exempt from OMB review

under 5 CFR 1320.3(c)(2).

Proposed § 201.66(d), which requires

that the information be displayed in a

certain format, is not included in the

burden estimate because it is not a

collection of information within the

meaning of 5 CFR 1320.3.

To avoid double-counting, certain

provisions in this proposal have not

been included in the burden estimate

because they merely cross-reference

information collection requirements

contained in other regulations. For

example, proposed §§ 201.66(f) and (i)

do not appear in the burden estimate

table. Provisions that merely continue

existing labeling requirements, such as

proposed § 201.66(c), also have not been

included in the burden estimate for this

proposal.

Description of Respondents: Persons

and businesses, including small

businesses and manufacturers.

TABLE 1.—ESTIMATED ANNUAL REPORTING BURDEN1

21 CFR Section No. of

Respondents

Annual

Frequency per

Response

Total Annual

Responses

Hours per

Response Total Hours

314.70 350 1 1,050 2 2,100

314.60(a) 350 1 30 2 60

314.97 20 1 102 2 204

314.96(a) 20 1 70 2 140

Total 2,504

1There are no capital costs or operating and maintenance costs associated with this collection.

The agency has submitted a copy of

the proposed rule to OMB for its review

and approval of this information

collection. Interested persons are

requested to send comments regarding

this information collection to the Office

of Information and Regulatory Affairs,

OMB (address above).

IX. Environmental Impact

The agency has determined under 21

CFR 25.24(a)(8) that this action is of a

type that does not individually or

cumulatively have a significant effect on

the human environment. Therefore,

neither an environmental assessment

nor an environmental impact statement

is required.

X. Executive Order 12612: Federalism

FDA has examined the effects of this

proposal on the relationship between

the Federal Government and the States,

as required by Executive Order 12612

on ‘‘Federalism.’’ The agency concludes

that preemption of State or local rules

that establish requirements for OTC

drug labeling format and content that

would be in addition to, or would differ

from, Federal law is consistent with this

Executive Order.

Section 3(b) of Executive Order 12612

recognizes that Federal action limiting

the discretion of State and local

governments is appropriate ‘‘where

constitutional authority for the action is

clear and certain and the national

activity is necessitated by the presence

of a problem of national scope.’’ The

constitutional basis for FDA’s authority

to regulate the safety and effectiveness

of OTC drugs is well established.

Congress’ decisions to vest in FDA the

responsibility to establish a regulatory

scheme over these products

demonstrates Congress’ view that the

safety and effectiveness of these

products is an issue of national scope.

Executive Order 12612 expressly

contemplates preemption when there is

a conflict between the exercise of State

and Federal authority under Federal

statute (section 4(a)). Moreover, section

4(b) of the Executive Order authorizes

preemption of State law in the Federal

rulemaking context when there is ‘‘firm

and palpable evidence compelling the

conclusion that the Congress intended

to delegate to the * * * agency the

authority to issue regulations

preempting State law.’’ State and local
Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules 9045

laws and regulations that would impose

different or additional requirements for

OTC drug labeling format or content

would undermine the agency’s goal of

ensuring that OTC drug labeling is easy

to read and understand. The agency

believes that a consistent format will

enable consumers to find the

information on OTC drug labeling and

will ensure that it meets minimal

standards to ensure legibility.

Additionally, national consistency in

OTC labeling information will ensure

that labeling uses language that most

consumers can understand, and will

facilitate comparisons among like

products. A fundamental purpose of the

proposed rule is to help ensure the safe

and effective use of OTC drug products.

The agency believes that the readability

and understandability of OTC drug

labeling is directly related to the safe

and effective use of these products.

Executive Order 12612 requires that

Federal preemption be restricted to the

minimum level necessary to achieve the

objectives of the statute under which the

regulations are issued (section 4(c)). The

proposed regulation is narrowly drawn

and focuses on OTC drug labeling

format and content. The proposed

regulations set forth a procedure for

States and local governments to petition

the agency for an exemption from

preemption.

As required by the Executive Order,

States and local governments will be

given, through this notice and proposed

rulemaking, an opportunity to

participate in the proceedings to

preempt State and local laws (section

4(e)). In addition, under the Order, the

appropriate officials and organizations

representing the States will be consulted

before this proposed action is

implemented (section 3(a)).

The agency concludes that the policy

proposed in this document has been

assessed in light of the principles,

criteria, and requirements in Executive

Order 12612; that this policy is not

inconsistent with that Order; that this

policy will not impose additional costs

or burdens on the States; and that this

policy will not affect the ability of States

to discharge traditional State

governmental functions.

XI. Analysis of Impacts

A. Background and Purpose

FDA has examined the impacts of the

proposed rule under Executive Order

12866 and the Regulatory Flexibility Act

(5 U.S.C. 601–612). Executive Order

12866 directs agencies to assess all costs

and benefits of available regulatory

alternatives and, when regulation is

necessary, to select regulatory

approaches that maximize net benefits

(including potential economic,

environmental, public health and safety,

and other advantages; distributive

impacts; and equity). Under the

Regulatory Flexibility Act, if a rule has

a significant impact on a substantial

number of small entities, an agency

must analyze regulatory options that

would minimize any significant impact

of the rule on small entities.

Title II of the Unfunded Mandates

Reform Act (Pub. L. 104–4) requires that

agencies prepare a written statement

and economic analysis before proposing

any rule that may result in an annual

expenditure by State, local, and tribal

governments, in the aggregate, or by the

private sector, of $100,000,000 (adjusted

annually for inflation).

The agency believes that this

proposed rule is consistent with the

principles set out in the Executive Order

and in these two statutes. The purpose

of this proposed rule is to establish a

standardized format for the labeling of

all OTC drug products so that the

labeling will be easier to read and

understand, and will provide consistent

information in like situations. The

proposed rule is intended to help ensure

the safe and effective use of OTC drug

products.

B. Qualitative Description of Benefits

Variability and numerous weaknesses

in the presentation of critical safety and

effectiveness information in OTC drug

product labeling make it difficult for

consumers to select the most

appropriate product and to use the

product safely and effectively. For

consumers to benefit from such

information, this information must be

easy to find, readable, readily

understood, noted, and acted upon. Yet,

despite the critical role of this

information, OTC drug product labeling

is often presented in small print using

a crowded layout with minimal white

space. The proposed rule sets forth a

minimum standard for type size,

leading, and kerning, and standards for

type style, and other graphical features.

The proposed rule also sets forth

standardized headings and subheadings,

and a standardized order for

information.

At least two implicit benefits will

flow from this proposed labeling format.

First, an easy to read, standardized

labeling format will help ensure that

consumers select the right product to

meet their needs. The lack of uniform

presentation of information currently

found on OTC drug product labeling

makes product comparisons difficult.

Consumers are faced with a number of

choices for purchase decisions and can

find it difficult to determine which

product is right for them, based on their

symptoms and their personal health

situation. With this new format

consumers can more readily and easily

determine whether a product contains

ingredients that they need or should

take. Facilitating product comparisons

will reduce market inefficiencies that

can result from suboptimal purchases,

inappropriate price-quality

relationships, and competitive

inefficiencies. It can also reduce

consumer search and transaction costs

and, concomitantly, increase the ability

to select products consistent with

individual needs.

Because health care costs are

increasing and increasing numbers of

products are switching from

prescription to OTC products, more

patients are relying on self-diagnosis

and self-treatment. Consequently, the

proposed rule will benefit consumers by

allowing them to make more

appropriate choices for self-treatment,

and reduce the trial-and-error approach

to self-medication. This can lead to

decreased overall health care costs

resulting from reduced visits to the

doctor or hospital for treatment.

Second, the easy to read, standardized

format will directly benefit consumers

by helping ensure the safe and effective

use of the product. Using the product as

labeled can reduce the frequency of the

adverse drug experiences associated

with OTC drug products. Although the

frequency of such events have not been

quantified, it can be presumed that

enabling consumers to make better

choices and more easily understand the

information will lead to fewer OTC

adverse drug experiences.

The agency is not aware of any

definitive studies that could be used to

quantify such benefits. In the Federal

Register of August 16, 1995 (60 FR

42578), the agency sought written

comments addressing quantitative

measures of benefits, to aid in the

assessment of the costs and benefits of

enhanced OTC drug product labeling.

Little useful data was submitted in

response to this request. The agency,

again, requests submission of this data

to help evaluate the overall benefits to

the public health of having OTC drug

labeling that is easy to read and easy to

understand.

C. Nature of the Economic Impact

This rule will require the redesign of

OTC drug labels in accordance with a

predetermined schedule of effective

dates. FDA acknowledges the

substantial cost of preparing label

revisions for thousands of products, as

the procedures for each change involve
9046 Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules

numerous levels of review and

verification, in addition to needed

technical production supplies and

activities. This analysis, however, finds

that, while substantial, a large part of

these costs cannot be attributed to the

proposed rule, because standard

business procedures compel a periodic

redesign of most OTC labels. The cost

impact of the rule therefore is largely

dictated by the agency’s required

implementation dates. For example,

many firms already redesign labels

within a 2-year period. These firms

would incur little added cost from a rule

that allowed a 2-year implementation

period. Even if a firm typically

redesigned its labeling only every 4

years, half of its labeling would, on

average, be replaced within a 2-year

period. Thus, this firm would need to

accelerate redesign for only one-half of

its products. Moreover, even those

products whose redesign would have to

be accelerated would, on average, lose

only one-half of their expected lifetimes.

Accordingly, to calculate the

incremental cost of this rule, FDA

counted only the value that would be

lost due to the attenuation of the

labeling’s useful life, after accounting

for those design changes that would

have resulted from standard business

practice. FDA calculated this cost as the

product of the estimated number of

products affected, the estimated number

of years of lost labeling life, and the

estimated lost value of a year of labeling

life. Derivations for these variables are

discussed below.

1. Number of Products Affected

Once the rule has become fully

effective, a new OTC drug product

labeling design would be required for

each stock keeping unit (individual

products, packages and sizes),

commonly termed SKU’s. Although the

agency is unaware of any fully

comprehensive data base that provides

reliable counts of the number of SKU’s

that are regulated OTC drugs, A. C.

Nielsen (Nielsen), a recognized provider

of market research business information

and analysis, maintains product data

from a sample of 4,000 retail outlets

selected to represent the geographical

and retail characteristics of the U.S.

OTC market. FDA used this data base as

a primary source for estimating the size

of the affected OTC drug market.

According to this source, in 1995 OTC

drug products accounted for $18.7

billion in sales in grocery stores, drug

stores, and mass merchandise outlets.

These sales figures exclude categories of

OTC items not ordinarily regulated as

OTC drug products such as vitamins,

facial make-up, and nutritional

supplements, but include product

categories that may or may not be

regulated as OTC drug products

depending on the ingredients and/or

product claims, such as some lotions,

shampoos, and deodorants. To estimate

and refine the count of items covered,

FDA allocated the products in Nielsen’s

inventory into review categories based

on their monograph review status.

Because there are so few products

subject to marketing applications

relative to monograph review, it was

believed this approach would not

significantly bias the allocation. This

categorization indicated that OTC drug

products that are regulated under the

monograph review process accounted

for almost 30,000 brand name SKU’s.

The breakdown of these branded SKU’s

by monograph review status is as

follows: 10,910 are under a final

monograph, 8,241 are scheduled to

become final within the next 2 years,

and the remaining 8,488 after 3 years.

(There is some uncertainty with the

number ‘‘8,488’’ because the Neilsen

coverage of products that have

sunscreens is incomplete.)

FDA’s estimate of the number of

SKU’s for private label store brands is

much less certain, because the Nielsen

data base did not provide adequate

information for this purpose. Instead,

FDA based its estimate on the number

of private label store brands likely to be

carried by individual retail outlets,

multiplied by the number of such

outlets in the United States. FDA

assumed that only larger retail firms

have the resources necessary to compete

in the OTC drug product market with

their own store label. As shown in Table

2, nearly 400 firms were found likely to

market private label brands, including

those that operate supermarkets, drug

stores, and proprietary stores, with more

than 9 establishments, and the very

largest mass merchandising firms.

According to the Nielsen data, firms that

relabel generic OTC drug products carry

from 55 to 280 different SKU’s, with an

average of 135 SKU’s per firm. Since

large retail stores would compete across

more product categories than individual

generic relabelers, FDA assumed that

such retailers would carry from 100 to

400 SKU’s, depending on their size, as

displayed in the third column of Table

2. Multiplying the average number of

private label store brand SKU’s per firm

type by the number of retailers adds

71,000 private label SKU’s to the

branded count. Assuming the same

regulatory status distribution as for

branded SKU’s, FDA estimated that 40

percent of the 71,000 private label

SKU’s, or 28,400, are currently covered

under final OTC drug monographs,

21,300 are scheduled to become final

within the next 2 years, and the

remainder after 3 years.

TABLE 2.—ESTIMATE OF PRIVATE LABEL SKU’S

Kind of Business No. of Firms1 No. of SKU’s2 Total SKU’s Average Sales/Firm

($Mil.)1

Supermarket

10–24 establishments 148 100 14,800 133

25–49 establishments 45 150 6,750 380

50–99 establishments 35 200 7,000 750

100 establishments or more 37 350 12,950 4,187

Drug Store

10–24 establishments 54 150 8,100 48

25–49 establishments 16 200 3,200 121

50–99 establishments 11 350 3,850 144
Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules 9047

TABLE 2.—ESTIMATE OF PRIVATE LABEL SKU’S—Continued

Kind of Business No. of Firms1 No. of SKU’s2 Total SKU’s Average Sales/Firm

($Mil.)1

100 establishments or more 23 400 9,200 1,851

Proprietary Store

10–24 establishments 5 100 500 12

25–49 establishments 4 150 600 (*)

50–99 establishments 1 200 200 (*)

100 establishments or more 1 350 350 (*)

Discount or Mass Merchandising

10–24 establishments 8 122

25–49 establishments 3 299

50–99 establishments 5 2,160

100 establishments or more 10 350 3,500 8,661

Total affected 390 71,000

1Source: U.S. Department of Commerce, 1992 Census of Retail Trade, Establishment and Firm Size, Table 3.

(*) Withheld to avoid disclosing data for individual companies.

2Estimate.

While the proposed rule would affect

all OTC drug products covered under

monographs, the implementation dates

for labeling changes will vary according

to regulatory status. Those products

currently covered by a final drug

monograph or marketing application, or

about 39,400 SKU’s, would be affected

within 2 years of publication of this

final rule. A second group of up to

29,550 SKU’s could be affected by the

final rule, depending on the timing of

the publication of their final OTC drug

monographs. Monographs for the

remaining 29,788 SKU’s are assumed to

become final only after publication of

this rule. Since products marketed

under these OTC drug monographs

would require labeling changes

regardless of this rule, no costs were

assigned to this latter group of products.

Table 3 presents FDA’s estimates of the

number of SKU’s for each respective

regulatory status.

TABLE 3.—NUMBER OF ESTIMATED SKU’S BY REGULATORY STATUS

Brand name Private Total

Final 10,910 28,400 39,310

Final by 1998 8,241 21,300 29,541

Remaining 8,488 21,300 29,788

Total 27,639 71,000 98,639

2. Cost of a Labeling Redesign

In the August 16, 1995, Federal

Register notice announcing the

September 29, 1995, public hearing,

FDA requested economic data on the

cost to design OTC drug product

labeling, but received only one written

comment with quantitative data. The

agency obtained other estimates of

labeling costs, but they vary widely and

generally include the cost of redesigning

the principal display panel (PDP) as

well as the labeling affected by this

proposal. Estimates of the average cost

to redesign, including the cost of

redesigning the PDP, ranged from

$2,700 to $10,000 per SKU for branded

products, and from $500 to $1,500 per

SKU for private label products. (These

costs included the drafting of language,

art work, review, and implementation.)

If the PDP accounts for 50 percent of the

cost to redesign branded products, the

average cost to redesign the labeling of

the branded products affected by this

proposal would be $1,350 to $5,000 per

SKU. These high volume, nationally

marketed, brand name OTC drug

products, make up a small portion of the

total number of OTC drug products, but

the majority of the sales. For this

analysis, FDA assumed that 20 percent

of the SKU’s affected by this proposal

will be branded products, with

incremental redesign costs of $1,350 to

$5,000, and the remainder of the SKU’s

will have incremental costs ranging

from $500 to $1,500 per SKU. Using the

midpoints of the incremental redesign

cost ranges, the average incremental cost

to redesign OTC drug product labeling,

weighted for type of product, is $1,500

per SKU.

Several industry comments indicated

that most companies redesign OTC drug

product labeling periodically, as part of

standard business practice. Some

companies redesign OTC drug product

labeling more than once a year, while

others redesign every 3 to 6 years. With

the proposed 2-year implementation

period, firms that normally redesign

labeling every 2 years or less should

incur no incremental costs as a result of

this proposed rule.
9048 Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules

3. Methodology

To calculate the economic impact on

industry, FDA made the following

assumptions:

Frequent labeling redesigns and the

cost of printing labeling are part of the

cost of doing business in the OTC drug

product industry. As standard business

practice, the labeling for 20 percent of

the SKU’s affected by the proposal are

redesigned at least every 2 years; for the

remainder of the SKU’s, 50 percent are

redesigned every 3 years and 50 percent

are redesigned every 6 years.

In any given year, the number of OTC

drug products requiring redesign are

evenly distributed over the labeling life.

For example, if the average life of a

labeling design is 3 years, one-third of

the products are redesigned in year one,

one-third in year two, and one-third in

year three. Moreover, in any given year,

the expected return from the labeling

design is constant (straight line

depreciation of the labeling’s value).

As a result, the economic impact of

requiring OTC drug product labeling

redesign can be measured as the lost

value of the existing labeling designs.

FDA estimated this loss as the

amortized cost, using a discount rate of

7 percent, of the number of years of

labeling use lost.

The above assumptions imply that 20

percent of the SKU’s will incur no

incremental costs, because their labeling

would normally be redesigned within

the proposed rule’s 2-year

implementation period. For the

remaining SKU’s, the loss will range

from 1 to 4 years of the remaining

usefulness of the design. The

calculation of the economic impact (EI)

was prepared in two steps and summed:

First, for labeling designs with a 3-year

expected life and second, for labeling

designs with a 6-year expected life.

4. Total Incremental Cost

Table 4 presents estimates of the

incremental costs of this rule under

alternative implementation periods. The

estimates are shown for products

currently covered under a final OTC

drug monograph and for OTC drug

products expected to be covered under

a final OTC drug monograph as of the

time the final rule is published. The cost

to industry would range from $1.4

million for a 5-year implementation

period to $43.2 million for the 1-year

period. The shorter implementation

periods are associated with higher costs

because firms lose a greater part of a

label’s useful life. With a 2-year

implementation period, the cost to

industry would be $11.3 million for

final OTC drug monographs and $8.5

million for OTC drug monographs under

review, for a total cost of $19.8 million.

Actual costs for the set of OTC drug

monographs under review will depend

on the number of SKU’s affected by each

monograph and the timing of the

respective publication dates.

TABLE 4.—TOTAL INCREMENTAL COSTS OF LABELING CHANGE FOR AFFECTED SKU’S ($ MILLION)

Years to Implement Final Monographs Monographs Under Review (final

by 1998) Total Cost

1 24.7 18.5 43.2

2 11.3 8.5 19.8

3 5.0 3.7 8.7

4 2.5 1.9 4.4

5 0.8 0.6 1.4

To reduce the economic impact on

small entities, the proposed rule would

allow an additional year for individual

OTC drug products having sales of less

than $25,000 per year. According to the

Nielsen data, this extension applies to

about 40 percent of the OTC drug

products, but accounts for only about 1

percent of retail sales. (To calculate

costs for the 40 percent, it was assumed

that the labeling design for half of the

SKU’s had a 3-year expected life, and

the other half, a 6-year life.) With this

extension and a 2-year implementation

period, the cost to industry would be

about $14.2 million, almost a 30 percent

reduction in the economic burden

(Table 5).

TABLE 5.—SMALL BUSINESS ALTERNATIVES ($ MILLION)

Years to Implement

Small Business Extension

Total Costs 1 Year 2 Year

1 43.2 28.6 23.1

2 19.7 14.2 12.0

3 8.7 6.5 5.1

4 4.3 2.9 2.2

5 1.4 0.7 0.7

D. Small Business Impact

1. Need For, and Objectives of the Rule

Variability in the design, format, and

placement of required labeling

information may cause difficulties for

consumers in both finding and reading

information on OTC drug product

labeling regarding safe and effective use.

For consumers to benefit from having

information, they must not only have

ready access to the information, but it

must also be readable and readily

understandable. If information is not

processed or is ignored because of

factors affecting readability, such as

small print size or crowded format, it

cannot provide the expected benefits

that would result from safe and effective

use.

The purpose of this proposed rule is

to establish a standardized format for

the labeling of all OTC drug products so

that the labeling will be easier to read,

have uniform presentation of

information, and consistent information

in like situations. The proposed rule is

intended to help ensure the safe and

effective use of OTC drug products.

2. Types of Small Entities Affected

OTC drug product manufacturers and

those entities that engage in the
Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules 9049

relabeling of OTC drug products would

be required to revise product labeling.

Census data provide aggregate industry

statistics on the number of

manufacturers for Standardized

Industrial Classification Code 2834

Pharmaceutical Preparations by

establishment size, but do not

distinguish between manufacturers of

prescription and OTC products.

According to the U.S. Small Business

Administration (SBA) designations for

this industry, however, over 92 percent

of the roughly 700 establishments and

over 87 percent of the 650 firms are

small. (Because census size categories

do not correspond to the SBA

designation of 750 employees, these

figures are based on 500 employees.)

IMS data on manufacturers of OTC

drug products were also analyzed as an

alternative method for estimating the

number of small entities affected.

Roughly 400 firms were identified as

manufacturers of OTC products covered

by IMS. Using the SBA size designation

of 750 employees, 31 percent of the

firms are large, 46 percent are small, and

size data were not available for another

23 percent. Therefore, from 184 to 276

of the affected manufacturing firms

would be considered small.

The agency is uncertain of the number

of entities that relabel OTC products

under private label store brands, but

estimates that about 400 retail firms will

need to relabel. (See Table 2.) These

large retail stores offering private labels

have average sales well above the SBA

designations for small businesses.

3. Projected Reporting, Recordkeeping,

and Other Compliance Requirements

This regulation would affect the

information content and format

associated with OTC drug product

labeling. Firms that manufacture or

relabel OTC drug products will need to

change the information panel for each

affected product. Since the agency has

coordinated these requirements with

labeling changes conducted in the

normal course of business, many of

these costs will be mitigated. Those

OTC drug products that are marketed

under a marketing application would

need to submit revised labeling to the

agency in accordance with § 314.70.

This is a standard procedure that

companies routinely follow for OTC

drug product labeling changes. The

proposed rule would not require new

reporting and recordkeeping activities.

Therefore, no additional professional

skills are necessary.

4. Alternatives and Steps to Minimize

the Impact on Small Entities

The proposed rule would require

affected entities to change the

information panel for affected OTC drug

products. Among the steps the agency is

taking to minimize the impact on small

entities are: (1) To provide enough time

for implementation to enable entities to

use up existing labeling stock, (2) to

provide sufficient time to coordinate a

substantial proportion of the labeling

changes with routine industry-initiated

labeling changes, (3) to provide a

mechanism for applying for an

exemption or a deferral (when the

requirements are judged inapplicable or

impracticable), and (4) to provide an

additional year to comply for individual

OTC drug products having sales of less

than $25,000 per year. Allowing 1

additional year for OTC drug products

with sales of less than $25,000 per year

reduces total industry costs by $5.5

million. While this last provision to

extend the compliance time is targeted

primarily at small entities, it provides

flexibility for a substantial number of

individual OTC drug products (about 40

percent), and the impact on overall

retail sales would be negligible (less

than 1 percent). The agency believes

that the above actions provide

substantial flexibility and reductions in

cost for small entities.

The agency considered but rejected a

voluntary labeling scheme, as previous

industry efforts have been unsuccessful

in achieving both a uniform format and

an acceptable minimum print size for a

majority of products in a timely manner.

Further, a voluntary program would not

provide relief to industry for conflicting

labeling requirements at the State level.

The agency considered alternative

implementation periods as options for

all affected entities and for small

entities. Industry costs for these

implementation options are presented

above in Tables 4 and 5, respectively.

The agency selected a 2-year

implementation period for all affected

products. This reduces costs from $43

million (for a 1-year period) to $20

million. In order to further reduce the

economic burden for small entities, the

agency provided one additional year for

low volume products. This alternative

reduces total industry costs to $14

million. The agency believes that its

approach provides significant reduction

in cost while meeting the agency

objective of achieving a standardized

labeling format for a majority of

products in a timely manner.

The agency considered but rejected

revising all monographs on an

individual basis because this approach

would not achieve a standardized

labeling format for a majority of

products in a timely manner.

This analysis shows that this rule is

not economically significant under

Executive Order 12866 and that the

agency has undertaken important steps

to reduce the burden to small entities.

Nevertheless, some small entities may

incur significant impacts. Thus, this

economic analysis, together with other

relevant sections of this document,

serves as the agency’s initial regulatory

flexibility analysis, as required under

the Regulatory Flexibility Act. Finally,

this analysis shows that the Unfunded

Mandate Reform Act does not apply to

the proposed rule because it would not

result in an annual expenditure by

State, local, and tribal governments, in

the aggregate, or by the private sector, of

$100 million.

XII. Request for Comments

Interested persons may, on or before

June 27, 1997, submit to the Dockets

Management Branch (HFA–305), Food

and Drug Administration, 12420

Parklawn Dr., rm. 1–23, Rockville, MD

20857, written comments regarding this

proposal. Two copies of any comments

are to be submitted, except that

individuals may submit one copy.

Comments are to be identified with the

docket number found in brackets in the

heading of this document. Received

comments may be seen in the office

above between 9 a.m. and 4 p.m.,

Monday through Friday.

XIII. References

The following references have been

placed on display in the Dockets

Management Branch (address above)

and may be seen by interested persons

between 9 a.m. and 4 p.m., Monday

through Friday.

(1) Holt, G. A., and E. Hall, ‘‘The Self-Care

Movement,’’ in ‘‘Handbook of

Nonprescription Drugs,’’ 9th ed., American

Pharmaceutical Association, Washington,

1990.

(2) Holt, G. A., et al., ‘‘OTC Labels: Can

Consumers Read and Understand Them?’’

American Pharmacy, NS30:51–54, 1989.

(3) Watanabe, R. K., ‘‘The Ability of the

Geriatric Population to Read Labels on Overthe-Counter Medication Containers,’’ Journal

of the American Optometric Association,

65:32–37, 1994.

(4) Wilkins, A. J., and M. I. Nimmo-Smith,

‘‘The Clarity and Comfort of Printed Text,’’

Ergonomics, 30:1705–2020, 1987.

(5) Kalsher, M. J., et al., ‘‘Enhancing the

Perceived Readability of Pharmaceutical

Container Labels and Warnings: The Use of

Alternative Designs and Pictorials,’’

Proceedings of the Human Factors and

Ergonomics Society 38th Annual Meeting,

1994.

(6) Landress, H. J., and M. A. Morck,

‘‘Prevalence and Risk of Medication
9050 Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules

Mismanagement by the Elderly,’’ Journal of

Florida Medical Association, 71:261–266,

1984.

(7) Desaulniers, D. R., ‘‘Layout,

Organization, and the Effectiveness of

Consumer Product Warnings,’’ Human

Factors Prospectives on Warnings, Kenneth

R. Laughery, Michael S. Wogalter, and

Stephen L. Young (editors), the Human

Factors and Ergonomics Society, pages 26–

30, 1994.

(8) Manasse, H. R., ‘‘Medication Use in an

Imperfect World,’’ ASHP Research and

Education Foundation, 1989.

(9) Caranasos, G. J., R. B. Stewart, and L.

E. Cluff, ‘‘Drug-Induced Illness Leading to

Hospitalization,’’ Journal of the American

Medical Association, 228:713–717, 1974.

Quoted in J. E. Fincham, ‘‘Over-the-Counter

Drug Use and Misuse by the Ambulatory

Elderly: A Review of the Literature,’’ Journal

of Geriatric Drug Therapy, 1:3–21, 1987.

(10) Fincham, J. E., ‘‘Over-the-Counter

Drug Use and Misuse by the Ambulatory

Elderly: A Review of the Literature,’’ Journal

of Geriatric Drug Therapy, 1:3–21, 1987.

(11) Lumpkin, J. R., et al., ‘‘A Shopping

Orientation Based Prescription for the

Treatment of OTC Medication Misuse Among

the Elderly,’’ Health Marketing Quarterly,

8:95–118, 1990.

(12) Meckstroth, S., M. Scheartz, and N.

Arawal, ‘‘NSAIDs—Safety Implications of

Over-the-Counter Availability,’’ Drug Safety,

7:221–244, 1992.

(13) Macro International Inc., ‘‘Women’s

Health Study Focus Groups Report,’’

presented to the U.S. Food and Drug

Administration on March 26, 1996.

List of Subjects

21 CFR Part 201

Drugs, Labeling, Reporting and

recordkeeping requirements.

21 CFR Part 330

Over-the-counter drugs.

21 CFR Part 358

Labeling, Over-the-counter drugs.

Therefore, under the Federal Food,

Drug, and Cosmetic Act, the Public

Health Service Act, and under authority

delegated to the Commissioner of Food

and Drugs, the proposed rule to amend

21 CFR 330.1 (61 FR 8450, March 4,

1996) is withdrawn, and it is proposed

that 21 CFR parts 201, 330, and 358 be

amended to read as follows:

PART 201—LABELING

1. The authority citation for 21 CFR

part 201 continues to read as follows:

Authority: Secs. 201, 301, 501, 502, 503,

505, 506, 507, 508, 510, 512, 530–542, 701,

704, 721 of the Federal Food, Drug, and

Cosmetic Act (21 U.S.C. 321, 331, 351, 352,

353, 355, 356, 357, 358, 360, 360b, 360gg–

360ss, 371, 374, 379e); secs. 215, 301, 351,

361 of the Public Health Service Act (42

U.S.C. 216, 241, 262, 264).

2. Section 201.63 is amended by

revising the section heading, the first

sentence in paragraph (a), and the

warning statement in paragraph (e) to

read as follows:

§ 201.63 Pregnancy breast-feeding

warning.

(a) The labeling for all over-thecounter (OTC) drugs that are intended

for systemic absorption, unless

specifically exempted, shall contain a

general warning under the heading

‘‘Warning’’ (or ‘‘Warnings’’ if it appears

with additional warning statements) as

follows: ‘‘If pregnant or breast-feeding,

ask a health professional before use.’’

* * *

* * * * *

(e) * * *

‘‘IT IS ESPECIALLY IMPORTANT

NOT TO USE’’ (SELECT ‘‘ASPIRIN’’ OR

‘‘CARBASPIRIN CALCIUM,’’ AS

APPROPRIATE) ‘‘DURING THE LAST 3

MONTHS OF PREGNANCY UNLESS

SPECIFICALLY DIRECTED TO DO SO

BY A DOCTOR BECAUSE IT MAY

CAUSE PROBLEMS IN THE UNBORN

CHILD OR COMPLICATIONS DURING

DELIVERY.’’

3. New § 201.66 is added to subpart C

to read as follows:

§ 201.66 Format and content requirements

for over-the-counter (OTC) drug product

labeling.

(a) Scope. This section sets forth the

format and content requirements for the

labeling of OTC drug products. Where

an OTC drug product is the subject of

an applicable final monograph or

regulation that contains content and

format requirements that conflict with

this section, then the content and format

requirements in this section must be

followed.

(b) Definitions. The following

definitions of terms apply to this

section:

(1) Act means the Federal Food, Drug,

and Cosmetic Act (secs. 201 et seq. (21

U.S.C. 321 et seq.)).

(2) Active ingredient means any

component that is intended to furnish

pharmacological activity or other direct

effect in the diagnosis, cure, mitigation,

treatment, or prevention of disease, or to

affect the structure or any function of

the body of humans or other animals.

The term includes those components

that may undergo chemical change in

the manufacture of the drug product and

be present in the drug product in a

modified form intended to furnish the

specified activity or effect.

(3) Established name of a drug or

active ingredient means the applicable

official name designated under section

508 of the act, or, if there is no

designated official name and the drug or

active ingredient is recognized in an

official compendium, the official title of

the drug or active ingredient in such

compendium, or, if there is no

designated official name and the drug or

active ingredient is not recognized in an

official compendium, the common or

usual name of the drug or active

ingredient.

(4) FDA means the Food and Drug

Administration.

(5) Ingredient means any substance in

the drug product, whether added to the

formulation as a single substance or in

admixture with other substances.

(c) Content requirements. The outside

container or wrapper of the retail

package, or the immediate container

label if there is no outside container or

wrapper, of all marketed OTC drug

products shall contain the labeling

information required in the applicable

final OTC drug monograph or in the

labeling of an approved marketing

application of an OTC drug product, in

the order listed in paragraphs (c)(1)

through (c)(7) of this section, under the

appropriate headings and subheadings

listed therein. The headings and

subheadings shall be highlighted by

bold type.

(1) ‘‘Active Ingredient (In Each [insert

type of dosage unit]):’’ or ‘‘Active

Ingredients (In Each [insert type of

dosage unit]):’’, followed by the

established name of the active

ingredient(s) and, if contained in or if

required to appear in the labeling, the

quantity or proportion of each active

ingredient per dosage unit. For products

marketed without discrete dosage units

(e.g., most topicals), the section heading

shall read ‘‘Active Ingredient:’’ or

‘‘Active Ingredients:’’, followed by the

established name of the active

ingredient(s) and, if contained in or if

required to appear in the labeling, the

quantity or proportion of each active

ingredient;

(2) ‘‘Purpose:’’ or ‘‘Purposes:’’,

followed by an accurate statement of the

general pharmacological category(ies) or

the principal intended action(s) of the

drug or, where the drug consists of more

than one ingredient, the general

pharmacological categor(ies) or the

principal intended action(s) of each

active ingredient;

(3) ‘‘Use:’’ or ‘‘Uses:’’, followed by the

indication(s) for the specific drug

product;

(4) ‘‘Warning:’’ or ‘‘Warnings:’’,

followed by one or more of the

following specific warning subheadings,

if applicable:

(i) ‘‘Warning:’’, followed by any

specific warnings that are required for

certain products (such as Reye’s

syndrome for drug products containing
Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules 9051

salicylates (§ 201.314(h)(1))). Where

appropriate, the subject of the warning

must be specified in the heading before

the word ‘‘Warning’’ (such as ‘‘Allergy

Warning:’’ or ‘‘Alcohol Warning:’’); (ii) ‘‘Do Not Use:’’, followed by any

contraindications for use with the

product. These contraindications are

‘‘absolute’’ and are intended specifically

for situations where consumers should

not use the product unless a prior

diagnosis has been established by a

physician or where consumers should

not use the product under any

circumstances regardless of whether a

doctor or health professional is

consulted; or

(iii) ‘‘Ask a Doctor Before Use’’,

immediately followed by one or more of

the following specific warning

subheadings, as appropriate. These

specific warnings are intended only for

situations where consumers should not

use the product until a doctor is

consulted:

(A) ‘‘If You Have:’’, followed by any

warnings for persons with certain

preexisting conditions (excluding

pregnancy) and warnings for persons

experiencing certain symptoms;

(B) ‘‘If You Are:’’, followed by any

drug/drug interaction warnings and

drug/food interaction warnings; or (C) ‘‘If You:’’, followed by a

combination of the warnings listed in

paragraphs (c)(4)(iii)(A) and (c)(4)(iii)(B)

of this section;

(iv) ‘‘When Using This Product:’’,

followed by the side effects that the

consumer may experience, and the

substances or activities to avoid while

using the product;

(v) ‘‘Stop Using This Product If:’’,

followed by any signs of toxicity and

other serious reactions that would

necessitate immediately discontinuing

use of the product, followed by the

words: ‘‘Ask a doctor. These may be

signs of a serious condition’’

(highlighted by bold type) or ‘‘Ask a

doctor. This may be a sign of a serious

condition.’’ (highlighted by bold type));

(vi) Any required warnings that do

not fit within one of the categories of

warnings listed in paragraphs (c)(4)(i)

through (c)(4)(v), (c)(4)(vii), and

(c)(4)(viii) of this section;

(vii) The pregnancy-breast feeding

warning set forth in § 201.63 of this part;

or

(viii) The ‘‘Keep out of reach of

children’’ warning and the overdose/

accidental ingestion warning, as set

forth in § 330.1(g) of this chapter;

(5) ‘‘Directions:’’, followed by the

directions for use;

(6) ‘‘Other Information:’’, followed by

additional information that is not

included under paragraphs (c)(1)

through (c)(5) of this section, but is

required by or is optional under an

applicable OTC drug monograph or is

included in the labeling of an approved

marketing application for an OTC drug

product, where appropriate. If included,

this information must immediately

follow the ‘‘Directions’’ for use section;

(7) ‘‘Other Ingredients:’’ or ‘‘Inactive

Ingredients:’’, followed by the cosmetic

and/or inactive ingredients, as

appropriate. (d) Format requirements. All required

labeling information for OTC drug

products, except for the labeling on the

principal display panel, shall be printed

in accordance with the following

specifications: (1) All headings and subheadings set

forth in paragraphs (c)(1) through (c)(7)

of this section shall use only upper and

lower case letters and shall be

highlighted by bold type that

prominently distinguishes the headings

and subheadings from other

information. In addition, shading or

color contrast may be used to highlight

headings and subheadings. Reverse type

is not permitted as a form of

highlighting. A horizontal line shall

separate each section of information

under the major headings listed in

paragraphs (c)(1) through (c)(7) of this

section;

(2) The letter height or type size for

headings and subheadings set forth in

paragraphs (c)(1) through (c)(7) of this

section and all other required OTC drug

product labeling shall be no smaller

than 6 point type, except for the

manufacturer’s name and address;

(3) All headings, subheadings, and

information set forth in or required

under paragraphs (c)(1) through (c)(7) of

this section shall be legible and clearly

presented. The headings, subheadings,

and information shall be presented only

in the Helvetica type style. At least 1

point leading (i.e., space between two

lines of text) shall be used for the

headings, subheadings, and information

set forth in or required under

paragraphs (c)(1) through (c)(7) of this

section, and letters shall not touch.

Shading or color contrasts may be used

to increase the prominence and

conspicuousness of the text, but shall

not be used to highlight or emphasize

specific text or portions of text unless

otherwise provided in an approved

marketing application, final monograph,

or an applicable regulation (e.g., current

requirements for bold print in §§ 341.76,

341.80 of this chapter, and requirement

for box and red letters in

§ 201.318(c)(1));

(4) Each unique labeling requirement

for OTC drug product information listed

under the headings and subheadings in

paragraphs (c)(1) through (c)(6) of this

section shall be preceded by a bullet

point. If more than one bulleted phrase

is placed on the same horizontal line,

the end of one bulleted phrase shall be

separated from the beginning of the next

bulleted phrase by at least two square

em’s (i.e., two squares of the size of the

letter ‘‘M’’);

(5) The heading and information

required under paragraph (c)(1) of this

section shall appear immediately

adjacent and to the left of the heading

and information required under

paragraph (c)(2) of this section. Where

there is more than one active ingredient,

the active ingredients shall be listed in

alphabetical order; and

(6) All information required under the

general heading ‘‘Warnings’’ shall be

presented in one continuous space and

shall not be separated in any way on the

labeling.

(e) Location. All information required

under paragraphs (c)(1) through (c)(7) of

this section shall be the first information

that appears on the back or side panel

of the outside container or wrapper of

the retail package, or the immediate

container label if there is no outside

container or wrapper, of all marketed

OTC drug products.

(f) Exemptions and deferrals. FDA on

its own initiative or in response to a

written request from any manufacturer,

packer, distributor, or applicant, may

exempt or defer, based on the particular

circumstances presented, or on more

specific requirements set forth in this

section on the basis that the requirement

is inapplicable or impracticable.

Requests for exemptions shall be

submitted in the form of a citizen

petition under § 10.30 of this chapter,

and should be clearly identified on the

envelope as a ‘‘Request for Exemption

from 21 CFR 201.66 (OTC Labeling

Format).’’ Such requests shall include

documentation which demonstrates

why a requirement of this section is

inapplicable to or impracticable for the

labeling of the OTC drug product, and

which demonstrates that the

manufacturer, packer, distributor, or

applicant has complied with as many of

the format requirements in this section

as practicable, including the use of all

other graphical techniques to enhance

readability.

(g) Interchangeable terms and

connecting terms. The terms listed in

§ 330.1(i) of this chapter may be used

interchangeably in the labeling of OTC

drug products, provided such use does

not alter the meaning of the labeling that

has been established and identified in

an applicable monograph or by

regulation. The terms listed in § 330.1(k)

of this chapter may be deleted from the

labeling of OTC drug products when the
9052 Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules

labeling is revised to comply with this

section, provided such deletion does not

alter the meaning of the labeling that

has been established and identified in

an applicable monograph or by

regulation. The terms listed in § 330.1(i)

and (k) of this chapter shall not be used

to change in any way the specific

headings and subheadings required

under paragraph (c)(1) through (c)(7) of

this section.

(h) Preemption. No State or local

governing entity may establish or

continue in effect any law, rule,

regulation, or requirement for OTC drug

product labeling format or content that

is different from, or in addition to, that

required by FDA. This paragraph is not

intended to preempt statutory and

common law causes of action in tort.

(i) Requests for exemption from

preemption. A State or local governing

entity may request an exemption from

preemption upon petition under § 10.30

of this chapter. A petition for an

exemption shall contain a detailed

explanation of why an exemption

should be granted, and include

supporting documentation and data

justifying the need for an exemption.

(j) An OTC drug product that fails to

comply with the format and content

requirements in this section is liable to

regulatory action.

4. Section 201.314 is amended by

revising the first two sentences in

paragraph (a) and paragraph (g)(1) to

read as follows:

§ 201.314 Labeling of drug preparations

containing salicylates.

(a) The label of any oral drug

preparation intended for sale without

prescription and which contains any

salicylate ingredient (including aspirin,

salicylamide, other salicylates, and

combinations) must bear a conspicuous

warning statement in heavy block type

on clearly contrasting background, such

as: ‘‘Warning—Keep out of reach of

children’’ (highlighted in bold type). ‘‘In

case of overdose, get medical help right

away.’’ * * *

* * * * *

(g)(1) The label of any drug containing

more than 5 percent methyl salicylate

(wintergreen oil) should bear a

conspicuous warning such as:

‘‘Warning: Do not use otherwise than as

directed. ‘Keep out of reach of children’

(highlighted in bold type). The labeling

of drugs shall also state as follows: For

drugs used by oral administration, ‘‘In

case of overdose, get medical help right

away;’’ for drugs used topically and not

inteded for oral ingestion, If swallowed,

get medical help right away.’’

* * * * *

5. Section 201.319 is amended by

revising paragraph (b) to read as follows:

§ 201.319 Water-soluble gums, hydrophilic

gums, and hydrophilic mucilloids

(including, but not limited to agar, alginic

acid, calcium polycarbophil,

carboxymethylcellulose sodium,

carrageenan, chondrus, glucomannan ((B1,4 linked) polymannose acetate), guar

gum, karaya gum, kelp, methylcellulose,

plantago seed (psyllium), polycarbophil

tragacanth, and xanthan gum) as active

ingredients; required warnings and

directions.

* * * * *

(b) Any drug products for human use

containing a water-soluble gum,

hydrophilic gum, or hydrophilic

mucilloid as an active ingredient in an

oral dosage form when marketed in a

dry or incompletely hydrated form as

described in paragraph (a) of this

section are misbranded within the

meaning of section 502 of the Federal

Food, Drug, and Cosmetic Act unless

their labeling bears the following

warnings and directions:

‘‘‘Warnings’ (highlighted in bold

type): Taking this product without

adequate fluid may cause it to swell and

block your throat or esophagus and may

cause choking. Do not take this product

if you have difficulty in swallowing. If

you experience chest pain, vomiting, or

difficulty in swallowing or breathing

after taking this product, seek

immediate medical attention;’’ and

‘‘‘Directions’ (highlighted in bold

type):’’ (Select one of the following, as

appropriate: ‘‘Take’’ or ‘‘Mix’’) ‘‘this

product (child or adult dose) with at

least 8 ounces (a full glass) of water or

other fluid. Taking this product without

enough liquid may cause choking. See

warnings.’’

* * * * *

PART 330—OVER–THE–COUNTER

(OTC) HUMAN DRUGS WHICH ARE

GENERALLY RECOGNIZED AS SAFE

AND EFFECTIVE AND NOT

MISBRANDED

6. The authority citation for 21 CFR

part 330 continues to read as follows:

Authority: Secs. 201, 501, 502, 503, 505,

510, 701 of the Federal Food, Drug, and

Cosmetic Act (21 U.S.C. 321, 351, 352, 353,

355, 360, 371).

7. Section 330.1 is amended by

revising paragraphs (c)(1), (c)(2)(i), and

(c)(2)(ii), by removing the first three

sentences in paragraph (g) and adding

two sentences in their place, and by

revising, paragraph (i), and by adding

new paragraph (k) to read as follows:

§ 330.1 General conditions for general

recognition as safe, effective, and not

misbranded.

* * * * *

(c)(1) The product is labeled in

compliance with chapter V of the

Federal Food, Drug, and Cosmetic Act

(the act) and subchapter C et seq. of this

chapter, including the format and

content requirements set forth in

§ 201.66 of this chapter. An OTC drug

product that is not in compliance with

chapter V and subchapter C, including

§ 201.66, is liable to regulatory action.

For purposes of § 201.61(b) of this

chapter, the statement of identity of the

product shall be the term or phrase used

in the applicable monograph established

in this part.

(2)(i) The label and labeling of the

product contain in a prominent and

conspicuous location the labeling

describing the product information that

has been established in an applicable

final monograph. At the option of the

manufacturer, this labeling may be

designated ‘‘FDA Approved

Information.’’ If the designation ‘‘FDA

Approved Information’’ is used, the

product labeling information that has

been established in an applicable final

monograph, or by regulation, shall

appear within a boxed area and shall be

stated in the exact language of the

monograph or the regulation (i.e., stated

in the exact language that has been

established and identified by quotation

marks in an applicable monograph or by

regulation (e.g., § 201.63 of this

chapter)).

(ii) At the option of the manufacturer,

as an alternative to the requirements of

paragraph (c)(2)(i) of this section, the

label and labeling of the product may

contain in the ‘‘Uses’’ section, other

truthful and nonmisleading statements

describing only those indications for use

that have been established in an

applicable monograph, subject to the

provisions of section 502 of the act

relating to misbranding and the

prohibition in section 301(d) of the act

against the introduction or delivery for

introduction into interstate commerce of

unapproved new drugs in violation of

section 505(a) of the act. Such product

labeling information shall not be boxed

and shall not contain the statement

provided in paragraph (c)(2)(i) of this

section.

* * * * *

(g) The labeling for all drugs contains

the general warning: ‘‘Keep out of reach

of children (highlighted in bold type).’’

The labeling of drugs shall also state as

follows: For drugs used by oral

administration, ‘‘In case of overdose, get

medical help right away;’’ for drugs

used topically, rectally, or vaginally and
Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules 9053

not intended for oral ingestion, ‘‘If

swallowed, get medical help right

away;’’ for drugs used topically and

intended for oral use, ‘‘If more than

used for * * * is accidentally

swallowed, get medical help right

away.’’ * * *

* * * * *

(i) The following terms may be used

interchangeably in any of the labeling

for OTC drug products provided such

use does not alter the meaning of the

labeling that has been established and

identified in an applicable monograph

or by regulation.

(1) ‘‘Aggravate(s)’’ or ‘‘makes(s) * * *

worse’’.

(2) ‘‘Ask’’ or ‘‘consult’’ or ‘‘contact’’.

(3) ‘‘Asking’’ or ‘‘consulting’’.

(4) ‘‘Assistance’’ or ‘‘help’’ or ‘‘aid’’.

(5) ‘‘Avoid contact with eyes’’ or ‘‘do

not get into eyes’’.

(6) ‘‘Avoid inhaling’’ or ‘‘do not

inhale’’.

(7) ‘‘Before a doctor is consulted’’ or

‘‘without first consulting your doctor’’

or ‘‘consult your doctor before * * *’’

or ‘‘unless first told to do so by a

doctor’’.

(8) ‘‘Clean’’ or ‘‘cleanse’’.

(9) ‘‘Consulting’’ or ‘‘advising’’.

(10) ‘‘Continue(s)’’ or ‘‘persist(s)’’ or

‘‘do(es) not go away’’ or ‘‘last(s)’’.

(11) ‘‘Discard’’ or ‘‘throw away’’.

(12) ‘‘Discontinue * * *’’ or ‘‘stop

* * *’’ or ‘‘quit * * *’’.

(13) ‘‘Doctor’’ or ‘‘physician’’.

(14) ‘‘Exceed’’ or ‘‘use more than’’ or

‘‘go beyond’’.

(15) ‘‘Exceed recommended dosage’’

or ‘‘use more than directed’’.

(16) ‘‘Excessive’’ or ‘‘too much’’.

(17) ‘‘Give to’’ or ‘‘use in’’.

(18) ‘‘Immediately’’ or ‘‘right away’’ or

‘‘directly’’.

(19) ‘‘Immediately’’ or ‘‘as soon as’’.

(20) ‘‘Immediately following * * *’’

or ‘‘right after’’.

(21) ‘‘Improve(s)’’ or ‘‘get(s) better’’ or

‘‘make(s) better’’.

(22) ‘‘Indication(s)’’ or ‘‘Use(s)’’.

(23) ‘‘Instill’’ or ‘‘put in (quantity)

drop by drop’’.

(24) ‘‘Is (are) accompanied by’’ or

‘‘you also have’’ (in context only) or

‘‘occur(s) with’’.

(25) ‘‘Is persistent’’ or ‘‘continues’’ or

‘‘does not go away’’ or ‘‘lasts’’.

(26) ‘‘Lung’’ or ‘‘pulmonary’’.

(27) ‘‘Medication’’ or ‘‘drug’’.

(28) ‘‘Not to exceed’’ or ‘‘not more

than’’.

(29) ‘‘Obtain(s)’’ or ‘‘get(s)’’.

(30) ‘‘Perforation of’’ or ‘‘hole in’’.

(31) ‘‘Persistent’’ or ‘‘that does not go

away’’ or ‘‘that continues’’ or ‘‘that

lasts’’.

(32) ‘‘Presently’’ or ‘‘now’’.

(33) ‘‘Take’’ or ‘‘use’’.

(34) ‘‘Tend(s) to recur’’ or ‘‘come(s)

back’’.

(35) ‘‘To avoid contamination’’ or

‘‘avoid contamination’’ or ‘‘do not

contaminate’’.

(36) ‘‘Unless directed by a [the

child’s] doctor’’ or ‘‘except under the

advice of a [the child’s] doctor’’ or

‘‘unless told to do so by a [the child’s]

doctor’’.

(37) ‘‘Worsen(s)’’ or ‘‘get(s) worse’’ or

‘‘make(s) worse’’.

* * * * *

(k) The following connecting terms

may be deleted from the labeling of OTC

drug products provided such deletion

does not alter the meaning of the

labeling that has been established and

identified in an applicable monograph

or by regulation:

(1) ‘‘And’’.

(2) ‘‘As may occur with’’.

(3) ‘‘Associated with’’.

(4) ‘‘Consult a doctor’’.

(5) ‘‘Discontinue use’’.

(6) ‘‘Due to’’.

(7) ‘‘If this occurs’’.

(8) ‘‘Or’’.

(9) ‘‘Occurring with’’.

(10) ‘‘Such as’’.

(11) ‘‘While taking this product’’.

(12) ‘‘Within’’.

(13) ‘‘Unless directed by a doctor’’.

PART 358—MISCELLANEOUS

EXTERNAL DRUG PRODUCTS FOR

OVER–THE–COUNTER HUMAN USE

8. The authority citation for 21 CFR

part 358 continues to read as follows:

Authority: Secs. 201, 501, 502, 503, 505,

510, 701 of the Federal Food, Drug, and

Cosmetic Act (21 U.S.C. 321, 351, 352, 353,

355, 360, 371).

9. Section 358.650 is amended in

paragraph (d)(1) by revising the

information in the brackets to read as

follows:

§ 358.650 Labeling of pediculicide drug

products.

* * * * *

(d) * * *

(1) * * * [sentence in boldface type].

* * * * *

Dated: December 20, 1996.

David A. Kessler,

Commissioner of Food and Drugs.

Donna E. Shalala,

Secretary of Health and Human Services.

Note: The following Appendix will not

appear in the Annual Code of Federal

Regulations.

BILLING CODE 4160–01–F
9054 Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules

Appendix A.—Examples of Prototype OTC Drug Poducts Labeling
Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules 9055
9056 Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules
Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules 9057
9058 Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules
Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules 9059
9060 Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules
Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules 9061
9062 Federal Register / Vol. 62, No. 39 / Thursday, February 27, 1997 / Proposed Rules

[FR Doc. 97–4596 Filed 2–26–97; 8:45 am]

BILLING CODE 4160–01–C