[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]]
_______________________________________________________________________
Part II
Department of Health and Human Services
_______________________________________________________________________
Food and Drug Administration
_______________________________________________________________________
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.
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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.
BILLING CODE 4160-01-F
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Appendix A.--Examples of Prototype OTC Drug Poducts Labeling
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[FR Doc. 97-4596 Filed 2-26-97; 8:45 am]
BILLING CODE 4160-01-C
