[Federal Register Volume 62, Number 39 (Thursday, February 27, 1997)]
[Proposed Rules]
[Pages 9024-9062]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-4596]



[[Page 9023]]

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Part II





Department of Health and Human Services





_______________________________________________________________________



Food and Drug Administration



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21 CFR Parts 201, 330, and 358



Over-the-Counter Human Drugs; Proposed Labeling Requirements; Proposed 
Rule

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

[[Page 9024]]



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 self-medication. 
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 (Sec. 330.1(i) (21 CFR 
330.1(i))), to facilitate the use of more concise, easier to understand

[[Page 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 (Secs. 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 (Sec. 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 (Sec. 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 (Sec. 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 (Sec. 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 (Sec. 201.61(b)). Under Sec. 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 (Sec. 201.61(b)), but may be prominently placed on the 
back or side panel in accordance with section 502(e) of the act and 
Secs. 201.10 and 201.15. Under Sec. 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 Sec. 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,

[[Page 9026]]

statement, or information appears, insufficient background contrast, 
obscuring designs or vignettes, or crowding with other written, 
printed, or graphic matter'' (Sec. 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 (Sec. 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 Sec. 201.314(h) and the 
warnings for water-soluble gums and related ingredients in 
Sec. 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., 
Secs. 201.64, 201.302, 201.303, 201.308, 201.309, 201.314, 201.315, and 
201.319.) For example, Sec. 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 Sec. 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 (Sec. 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 
(Sec. 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

[[Page 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 self-medication 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 
self-medication 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

[[Page 9028]]

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 anti-inflammatory 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 self-medicate with an OTC analgesic who are also taking a 
prescription NSAID place themselves at risk for NSAID-induced 
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.

[[Page 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

[[Page 9030]]

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

[[Page 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 Sec. 201.66, then the 
format and content requirements in Sec. 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 Sec. 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

[[Page 9032]]

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 Sec. 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 Sec. 210.3(b)(7) for the CGMP regulations.
    As set forth in section 502(e)(3) of the act, proposed 
Sec. 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 Sec. 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 Sec. 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 
Sec. 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 Sec. 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 Sec. 314.70.
    Proposed Sec. 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 (Sec. 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 Sec. 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

[[Page 9033]]

information be presented immediately adjacent and to the left of the 
``Purpose'' heading and information (proposed Sec. 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 Sec. 201.66(d)(5)).
    An example of how labeling requirements proposed in 
Sec. 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 Sec. 201.64. FDA intends to include 
dietary information on the various formats that will be tested during 
the comment period.
    Proposed Sec. 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'' (Sec. 355.50(b)). Another example would be:

                                                                                                                
           ------------------------------------------------------------------------------------------           
  ........  Uses: For the temporary relief of these cold symptoms                                               
  ........    * sneezing          * nasal congestion, stuffiness                                                
  ........    * runny nose        * cough                                                                       
           ------------------------------------------------------------------------------------------           

    Proposed Sec. 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 
Sec. 201.66(c)(4)(i) through (c)(4)(viii)), if applicable.
    Proposed Sec. 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'' (Sec. 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 Sec. 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 (Sec. 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. * * * '' 
(Sec. 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'' 
(Sec. 349.78(c)(2)).
    Proposed Sec. 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 Sec. 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

[[Page 9034]]

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 Sec. 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 Sec. 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'' (Sec. 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 Sec. 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 Sec. 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 Sec. 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 Sec. 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.                                          
           ------------------------------------------------------------------------------------------           


[[Page 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 Sec. 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 
Sec. 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 Sec. 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 Sec. 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 Sec. 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 Sec. 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 Secs. 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 Sec. 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 Sec. 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 
Secs. 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 Secs. 369.20 and 369.21 to 
conform to these revised warning statements at or before the time that 
this proposed rule is finalized.
    Proposed Sec. 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 Sec. 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 
Sec. 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 Sec. 358.650(e) that describes different 
types of lice. Another example of such optional labeling is in the 
monograph for anticaries fluoride treatment rinses (Sec. 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 Sec. 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 Sec. 701.3 (21 CFR 
701.3). Current Sec. 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

[[Page 9036]]

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 Sec. 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 Secs. 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 
Sec. 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 Sec. 201.66(d)(2) would require that the letter height or 
type size for headings and subheadings in proposed Sec. 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 
Secs. 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 Sec. 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

[[Page 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 Sec. 201.66(d)(3) would require that all headings, 
subheadings, and information set forth in proposed Sec. 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 Secs. 341.76 
and 341.80, and requirement for box and red letters in 
Sec. 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 
Sec. 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 Sec. 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 Sec. 201.66(c)(7)) to be set off 
by bullet points.
    Proposed Sec. 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 pregnancy-nursing warning, 
at 47 FR 54750, December 3, 1982 (Sec. 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 Sec. 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 Sec. 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

[[Page 9038]]

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 Sec. 201.66(e) provides that the labeling information 
required under Sec. 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 Secs. 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 Sec. 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 Sec. 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 Sec. 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 Sec. 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 Sec. 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 Sec. 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 Sec. 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 
Sec. 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 Sec. 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, 
Secs. 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 Sec. 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

[[Page 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 Sec. 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 Sec. 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 Sec. 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 Sec. 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 Sec. 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 Sec. 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 Sec. 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 (Sec. 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 (Sec. 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 Sec. 330.1(c)(2) to make 
it

[[Page 9040]]

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 Sec. 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 
Sec. 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

[[Page 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.

[[Page 9042]]

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 Sec. 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 Sec. 314.70(c)(2) or (d). Under 
Sec. 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 Sec. 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 Sec. 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

[[Page 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 Sec. 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'' (Sec. 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

[[Page 9044]]

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 Secs. 201.63, 201.314, 
201.319, and 358.650 modify specific warnings or directions, proposed 
Sec. 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 Sec. 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 Sec. 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 Secs. 201.66(f) and (i) do not 
appear in the burden estimate table. Provisions that merely continue 
existing labeling requirements, such as proposed Sec. 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 Burden\1\                                 
----------------------------------------------------------------------------------------------------------------
                                                      Annual                                                    
         21 CFR Section               No. of       Frequency per   Total Annual      Hours per      Total Hours 
                                    Respondents      Response        Responses       Response                   
----------------------------------------------------------------------------------------------------------------
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       
----------------------------------------------------------------------------------------------------------------
\1\ There 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

[[Page 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

[[Page 9046]]

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                                   
----------------------------------------------------------------------------------------------------------------
                                                                                              Average Sales/Firm
        Kind of Business            No. of Firms\1\     No. of SKU's\2\       Total SKU's         ($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       
----------------------------------------------------------------------------------------------------------------

[[Page 9047]]

                                                                                                                
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                           
----------------------------------------------------------------------------------------------------------------
\1\ Source: U.S. Department of Commerce, 1992 Census of Retail Trade, Establishment and Firm Size, Table 3.     
(*) Withheld to avoid disclosing data for individual companies.                                                 
\2\ Estimate.                                                                                                   

    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.

[[Page 9048]]

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)              
----------------------------------------------------------------------------------------------------------------
                                                            Monographs Under Review                             
     Years to Implement            Final Monographs             (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)                               
----------------------------------------------------------------------------------------------------------------
                                                             Small Business Extension                           
       Years to Implement       --------------------------------------------------------------------------------
                                        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

[[Page 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 Sec. 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 Over-the-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

[[Page 9050]]

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:

Sec. 201.63  Pregnancy breast-feeding warning.

    (a) The labeling for all over-the-counter (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 Sec. 201.66 is added to subpart C to read as follows:

Sec. 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

[[Page 9051]]

salicylates (Sec. 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 Sec. 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 Sec. 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 Secs. 341.76, 341.80 of this chapter, and requirement for 
box and red letters in Sec. 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 Sec. 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 
Sec. 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 
Sec. 330.1(k) of this chapter may be deleted from the labeling of OTC 
drug products when the

[[Page 9052]]

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 Sec. 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 Sec. 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:

Sec. 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:

Sec. 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 ((B-1,4 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:

Sec. 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 Sec. 201.66 of this chapter. An OTC drug product that is not 
in compliance with chapter V and subchapter C, including Sec. 201.66, 
is liable to regulatory action. For purposes of Sec. 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., Sec. 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

[[Page 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:

Sec. 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.

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[FR Doc. 97-4596 Filed 2-26-97; 8:45 am]
BILLING CODE 4160-01-C