**Guidance for Industry**

**Labeling OTC Human Drug Products**

**Questions and Answers**

***DRAFT GUIDANCE***

**This guidance document is being distributed for comment purposes
only.**

Comments and suggestions regarding this draft document should be
submitted within 60 days of publication in the *Federal Register* of the
notice announcing the availability of the draft guidance. Submit
comments to the Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All
comments should be identified with the docket number listed in the
notice of availability that publishes in the *Federal Register*.

For questions on the content of the draft document, contact Cazemiro R.
Martin or Gerald M. Rachanow at 301-827-2222.

**U.S. Department of Health and Human Services**

**Food and Drug Administration**

**Center for Drug Evaluation and Research (CDER)**

**OTC**

**January 2005**

**Guidance for Industry**

**Labeling OTC Human Drug Products**

**Questions and Answers**

*Additional copies of this Guidance are available from:*

*Office of Training and Communications*

*Division of Drug Information, HFD-240*

*Center for Drug Evaluation and Research*

*Food and Drug Administration*

*5600 Fishers Lane,*

*Rockville, MD 20857*

*(Tel) 301-827-4573*

*(Internet) http://www.fda.gov/cder/guidance/index.htm*

**U.S. Department of Health and Human Services**

**Food and Drug Administration**

**Center for Drug Evaluation and Research (CDER)**

**OTC**

**January 2005**

**TABLE OF CONTENTS**

#  {#section .TOC-1 .unnumbered}

# I. INTRODUCTION [1](#introduction)II. BACKGROUND [1](#ii.-background) {#i.-introduction-1ii.-background-1 .TOC-1}

# III. CONTENT Labeling REQUIREMENTS [2](#content-labeling-requirements) {#iii.-content-labeling-requirements-2 .TOC-1}

# IV. FORMAT LABELING REQUIREMENTS [8](#iv.-format-labeling-requirements) {#iv.-format-labeling-requirements-8 .TOC-1}

# V. Exemption AND DEFERRALS [13](#v.-exemption-and-deferrals) {#v.-exemption-and-deferrals-13 .TOC-1}

# Appendix A: Summary [14](#appendix-a-summary) {#appendix-a-summary-14 .TOC-1}

**Guidance for Industry**[^1]

**Labeling OTC Human Drug Products ---**

**Questions and Answers**

This draft guidance, when finalized, will represent the Food and Drug
Administration\'s (FDA\'s) current thinking on this topic. It does not
create or confer any rights for or on any person and does not operate to
bind FDA or the public. An alternative approach may be used if such
approach satisfies the requirements of the applicable statutes and
regulations.

# 

# INTRODUCTION

# 

This guidance is intended to assist manufacturers, packers, and
distributors of over-the-counter (OTC) drug products who have questions
about the standardized labeling content and format requirements in §
201.66 (21 CFR 201.66). The examples in this guidance illustrate various
format and content features of the labeling requirements and show how
OTC drug monograph labeling information can be converted to the OTC
\"Drug Facts\" format. This is one of a series of guidances intended to
facilitate compliance with the labeling requirements in § 201.66.

# II. BACKGROUND

In the *Federal Register* of March 17, 1999 (64 FR 13254), the Food and
Drug Administration (FDA) published a final rule (21 CFR 201.66)
establishing standardized content and format for the labeling of OTC
drug products (Drug Facts labeling). The Drug Facts labeling for OTC
drug products is intended to make it easier for consumers to read and
understand OTC drug product labeling and use OTC drug products safely
and effectively. The Drug Facts labeling regulation in

§ 201.66 covers all OTC drug and drug-cosmetic products, whether
marketed under a new drug marketing application (NDA), abbreviated new
drug application (ANDA), or OTC drug monograph (or product not yet the
subject of a final OTC drug monograph).[^2]

The regulation is divided into two main parts: (1) Content requirements
(i.e., headings, subheadings, and the order in which certain information
must be listed) and (2) format requirements (i.e., graphic
specifications). This guidance primarily discusses questions received
from manufacturers, packers, and distributors relating to these
requirements, which are set forth in § 201.66 (c) and (d), respectively.

# 

# CONTENT Labeling REQUIREMENTS 

The following questions and answers address the OTC labeling
requirements in § 201.66. Tables in Appendix A of this draft guidance
list the specific section-by-section requirements in § 201.66(c) and (d)
as well as the expectations for implementing the requirements in the
regulation. Please refer to these tables for details on specific
requirements.

***Question 1: What labeling information do the regulations require for
all OTC drug products?***

***Answer 1:*** Section 201.66 requires that all OTC drug product
labeling contain the following information about the product. This
information must be organized according to the following headings and
must be presented in the following order:

> 1\. Title (\"Drug Facts\" or \"Drug Facts (continued)\")
>
> 2\. Active ingredients
>
> 3\. Purpose
>
> 4\. Use(s)
>
> 5\. Warnings
>
> 6\. Directions
>
> 7\. Other information
>
> 8\. Inactive ingredients
>
> 9\. Questions (optional) (\"Questions?\" or \"Questions or
> comments?\")
>
> This information must appear on the outside container or wrapper of
> the retail package, or the immediate container label if there is no
> outside container or wrapper. (If the Drug Facts information appears
> on the outside container or wrapper of the retail package, its use on
> the immediate container is optional. See Appendix A.)

***Question 2: Why must the title \"Drug Facts (continued)\" appear on
each subsequent panel in which the Drug Facts appear?***

***Answer 2:*** The title \"Drug Facts\" must appear on the first panel
and the title \"Drug Facts (continued)\" must appear on each subsequent
panel to ensure that the person reading the labeling can follow through
to the end of the labeling (§ 201.66(c)(1)).

***Question 3: What indications can be included in the* Use(s*) section
if the product is a drug and cosmetic product?***

***Answer 3:*** For drug-cosmetic products, only the drug-related
indications can be included in the *Use(s)* section.

***Question 4:*** ***Is there a required order for listing subject
specific warnings?***

***Answer 4:*** Section 201.66(c) requires that warnings in paragraph
(c)(5) appear in the order listed.

***Question 5: What information must appear under the* Warnings
*subheading \"Do not use\"? Can I convert the text of existing warnings
in final OTC monographs or approved applications to the bulleted
statement format under this subheading? ***

***Answer 5:*** The \"Do not use\" subheading (§ 201.66(c)(5)(iii)) is
reserved for (1) products that should not be used unless a previous
diagnosis has been made by a doctor or (2) products that should not be
used under any circumstances by certain consumers, regardless of whether
a doctor or health professional is consulted.

> Manufacturers can convert existing formats to the Drug Facts labeling
> format. For example, the current warning "Do not use this product
> unless a diagnosis of asthma has been made by a doctor" can be placed
> under the subheading \"Do not use\" and shortened to read "unless a
> diagnosis of asthma has been made by a doctor." (i.e., \"**Do not
> use** unless a diagnosis of asthma has been made by a doctor\")

***Question 6: How could I convert a lengthy warning under the
subheading \"Ask a doctor before use if you have\" into the bulleted
text format?***

***Answer 6:*** Here is an example: The warning for oral and topical
antitussives states: "Do not take this product for persistent or chronic
cough such as occurs with smoking, asthma, or emphysema, or if cough is
accompanied by excessive phlegm (mucus) unless directed by a doctor."
Under this subheading, this warning can be converted into bulleted
statements as follows:

> ● cough that occurs with too much phlegm (mucus)
>
> ● chronic cough that lasts as occurs with smoking, asthma, chronic
> bronchitis, or emphysema

***Question 7: How could I convert the OTC antihistamine drug product
warning \"Do not take this product if you are taking sedatives or
tranquilizers without first consulting your doctor\" into bulleted text
?***

***Answer 7:*** This warning could appear as follows:

> \"**Ask a doctor or pharmacist before use if you are** taking
> sedatives or tranquilizers,\" or
>
> \"**Ask a doctor or pharmacist before use if you are** taking ●
> sedatives
>
> ● tranquilizers\"

***Question 8: What information must appear under the subheading \"When
using this product\"? How could I convert text of existing required
warnings to bulleted text format under this subheading?***

***Answer 8:*** This subheading must be used for all side effects that
consumers may experience. It identifies substances (e.g., alcohol) or
activities (e.g., operating machinery, driving a car) that should be
avoided while using the product. This subheading must also include
warnings for drugs in dispensers pressurized by gaseous propellants.
Such information whould appear in bulleted text format as follows:

> ● may cause drowsiness \[or may appear as: ● drowsiness may occur\]
>
> ● alcohol, sedatives, and tranquilizers may increase the drowsiness
> effect
>
> \[or may appear as: ● alcohol, sedatives, and tranquilizers may
> increase drowsiness\]
>
> ● do not puncture or incinerate; contents under pressure.

***Question 9: What information must appear under the subheading \"Stop
use and ask a doctor if"?***

***Answer 9:*** You must include under the \"Stop use...\" subheading
any signs of toxicity or other reactions that would require a consumer
to immediately stop using the product. For example, the bulleted
statement "you get nervous, dizzy, or sleepless" would appear in this
section.

***Question 10: Where must I put warnings required in an applicable OTC
drug monograph, in other OTC drug regulations, or in an approved drug
application that do not otherwise fit under the* Warning *heading or
subheadings?***

***Answer 10:*** Such warnings must be placed in the Drug Facts
*Warning* section. For example, chlorofluorocarbons (CFC) warnings,
required in certain approved drug applications, must be put in the
*Warnings* section. The warning would appear as follows: "Contains
CFC-\[insert number\] and CFC-\[insert number\], substances that harm
public health and the environment by destroying ozone in the upper
atmosphere"

(§ 201.320).

***Question 11: Where must pregnancy information and related warnings be
placed?***

***Answer 11:*** When applicable, these types of warnings must also be
placed in the second to last subsection of the *Warnings* section.
Warnings may include one or more of the following:

> ● The pregnancy/breast-feeding warning
>
> ● The third trimester warning for products containing aspirin or
> carbaspirin calcium.
>
> ● The third trimester warning in approved drug applications for
> products containing ketoprofen, naproxen sodium, or ibuprofen (if not
> intended exclusively for use in children).

***Question 12: Should all OTC drug product labeling include the "Keep
out of reach of children" and the accidental overdose/ingestion
warnings?***

***Answer 12:*** In most cases, these warnings are required for OTC drug
products and therefore must be included in the Drug Facts box. In a few
very special instances, the "Keep out of reach of children" warning may
be omitted. (See lipstick with a sunscreen in § 352.52(f)(1)(vi).) The
accidental overdose/ingestion warning may also be omitted in some
instances, as specified in an applicable OTC drug monograph or approved
new drug application.

***Question 13: Do I have to present information under* Directions *in a
table format? ***

***Answer 13:*** Depending on the product, the directions can appear
completely in a table, as a number of bulleted statements, or as a
combination of a table and bulleted statements. For example, a table
format must be used when dosage directions are provided for three or
more age groups or populations (§ 201.66(d)(9)). Dosage directions
provided for one or two age groups or populations can be presented using
bulleted statements. However, a table format can be used for two age
groups or populations if it helps make the presentation of the
information clearer and easier to read.

> Under this heading, information other than age groups should appear as
> bulleted statements. For example:
>
> ● shake well
>
> ● drink a full glass (8 oz) of liquid with each dose
>
> ● do not use more than directed

  ------------------------------------------- ---------------------------
  adults and children 12 years and older      2 tablets every 6 hours

  children 6 -12 years                        1 tablet every 6 hours

  children under 6 years                      ask a doctor
  ------------------------------------------- ---------------------------

***Question 14: What information must be included under the heading*
Other information*?***

***Answer 14:*** This section must include information that is not
included under the other headings or subheadings, but is required or is
made optional under an OTC drug monograph, other OTC drug regulation, or
approved drug application.

> If applicable, the first bulleted statement under this heading must
> include calcium, magnesium, potassium, and sodium to read as follows:
> "each (insert appropriate dosage unit) contains: \[in bold type\]
> (insert name(s) of ingredient(s) and quantity of each ingredient)\"
> (§§ 201.70, 201.71, 201.72, 201.64, respectively. See also
>
> § 201.66(c)(7)(i)).
>
> If applicable, phenylalanine/aspartame content shall appear as the
> next item as follows: "Phenylketonurics: Contains Phenylalanine
> (insert quantity) mg per (insert appropriate dosage unit)." This
> statement must be listed as the first bulleted statement under this
> heading or the second bulleted statement if Ca, Mg, Na, or K is (are)
> present. For example:
>
> ***Other information***
>
> ● **each tablet contains:** calcium 10 mg, magnesium 10 mg, and sodium
> 15 mg
>
> ● Phenylketonurics: Contains Phenylalanine 10 mg per tablet
>
> ● \[insert storage conditions\] if applicable

● \[insert tamper-evident statement\]

***Question 15: Where must the tamper-evident statement appear in my OTC
product labeling?***

***Answer 15:*** The tamper-evident statement must be prominently placed
on the drug product package to alert consumers about the product's
tamper-evident features (21 CFR 211.132). The tamper-evident statement
describes the tamper-evident feature of the product package and advises
consumers that, if the feature is breached or missing when the product
is purchased, tampering may have occurred. Tamper-evident packaging with
an appropriate labeling statement will be more likely to protect
consumers because the consumer will be in a better position to detect
tampering when he or she has knowledge that a tamper-evident feature has
been incorporated into the product design. The Agency allows flexibility
in the placement of this statement on the package and does not require
that it be included within the Drug Facts section. However, if included
in this section, the statement must appear under the heading \"**Other
information**\" (see 21 CFR 201.66(c)(7)).

> The Agency also noted in the final rule preamble for the Drug Facts
> regulation that many products are now marketed with \"peel back\" or
> \"fold out\" labels affixed to the product package and that these
> labels could be used to accommodate all of the FDA required
> information in the Drug Facts section (64 FR 13254 at 13268; March 17,
> 1999). These types of labels were not in use at the time the
> tamper-evident requirements became effective. Recently, interested
> parties have inquired whether the tamper-evident statement may be
> included in a Drug Facts section that appears in such \"peel back\" or
> \"fold out\" labels. We believe that the goals of the tamper evident
> statement would likely not be achieved if the statement only appears
> in a \"peel back\" or \"fold out\" label and is not clearly visible
> without peeling back or folding out the label.
>
> It is important that the consumer view the tamper-evident statement
> before purchase and use of the product so that he or she will be
> better aware of the tamper-evident features and any signs of
> tampering. Once the consumer opens the tamper-evident package, the
> tamper-evident features have been breached. If the consumer has failed
> to examine these features before opening, then the consumer will
> likely not know if there were any signs of tampering. A tamper-evident
> statement inside a \"peel back\" or \"fold out\" label that is not
> visible on the outside of the package is unlikely to be viewed before
> breach of the tamper evident feature. The consumer may not be aware to
> peel back or unfold this label to view the tamper-evident statement
> before opening the package. Thus, we recommend that the statement not
> appear within the Drug Facts box in a \"peel back\" or \"fold out\"
> label if the statement would not be clearly visible without peeling
> back or folding out the label. We recommend instead in these
> circumstances that the tamper evident statement be outside the Drug
> Facts box in another part of the label where the statement is clearly
> visible without further manipulation of that label.

***Question 16: Do I have to list the inactive ingredients in my OTC
drug product labeling in alphabetical order?***

***Answer 16:*** It depends.

> For OTC drug products that are not also cosmetic products, the
> established name of each inactive ingredient must be listed in
> alphabetical order (§ 201.66(c)(8)). For example, the *Inactive
> ingredients* section would appear as follows:
>
> **Inactive ingredients** colloidal silicon dioxide, FD&C blue #1 lake,
> hydroxypropyl methylcellulose, lactose, magnesium stearate,
> polyethylene glycol, povidone, propylene glycol, titanium dioxide
>
> For an OTC product that is a drug-cosmetic product, the inactive
> ingredients must be listed in descending order of predominance in the
> product formulation
>
> (§§ 201.66(c)(8) and 701.3(a)). For example, the *Inactive
> ingredients* section would appear as follows:
>
> **Inactive ingredients** water, sorbitan isostearate, sorbitol,
> triethanolamine, stearic acid, barium sulfate, benzyl alcohol,
> dimethicone, methylparaben, aloe extract, carbomer, disodium EDTA

***Question 17: Do I have to include a* Questions *section in the Drug
Facts box or similar enclosure?***

***Answer 17:*** No. Although this heading and subsequent information is
not required, the Agency encourages all manufacturers, distributors, and
repackers to include a telephone number in this section. The telephone
number of a source to answer questions about the product would be
included in this section.

> Although not permitted to appear in or otherwise interrupt the
> required Drug Facts labeling information, brand names or product
> attributes can appear in the telephone number and/or in the Web site
> address, if used. However, if the telephone number appears as letters
> of the brand name or product attribute, FDA recommends that the
> manufacturer should also include the numerical representation of the
> telephone number in this section.

# IV. FORMAT LABELING REQUIREMENTS[^3]

***Question 18: How must the content labeling requirements be presented
within the Drug Facts box or similar enclosure?***

***Answer 18:*** All features of the Drug Facts box or similar enclosure
and the required content information must be presented according to
graphic specifications, which are listed in Appendix A (Table 2) of this
draft guidance document (see also §§ 201.66(c) and (d)).

***Question 19: Can I use bold type for any information I consider needs
greater prominence?***

***Answer 19:*** FDA recommends that you avoid using bold type in the
immediate area where existing regulations require specific text be in
bold type.

***Question 20: How should fractions be expressed within the Drug Facts
box?***

***Answer 20:*** Fractions (e.g., 1/2) can be expressed in mathematical
notation or text format (i.e., one-half). The text must be in the same
single, clear, easy-to-read type style and type size used for the other
text included in the Drug Facts box. If expressed in mathematical
notation, each component of the numerical notation must be no smaller
than 6-point type.

***Question 21: How should I arrange additional text related to a single
bulleted statement?***

***Answer 21:*** FDA recommends that additional text be formatted as
indented subbulleted statements. For example:

> ***Uses***
>
> ● temporarily relieves pain and itching due to:
>
> ● insect bites ● minor skin irritations
>
> ● dries the oozing and weeping of:
>
> ● poison ivy ● poison oak ● poison sumac

***Question 22: Can I begin a bulleted statement on the same line as a
heading or subheading?***

***Answer 22:*** Yes. However, no bulleted statement or text can appear
on the same line as the *Warning* heading.

***Question 23: Should bulleted statements be left justified when using
the standard labeling format?***

***Answer 23:*** Yes. The first bulleted statement on each horizontal
line of text must be left justified, except if the bulleted statement
appears on the same line of an appropriate heading or subheading (§
201.66(d)(4)). Any bulleted statements that do not fit entirely on a
multi-bulleted line should begin left justified on the following line.
(Note: no bulleted statement or text can appear on the same line as the
*Warning* heading.)

> For example:
>
> **Ask a doctor before use if you have**
>
> ● heart disease ● glaucoma ● high blood pressure
>
> ● thyroid disease ● diabetes
>
> ● trouble urinating due to an enlarged prostate gland
>
> ● a breathing problem such as emphysema or chronic bronchitis

***Question 24: Should bulleted statements be aligned with the bulleted
statements on the previous line when using the modified labeling
format?***

***Answer 24:*** No. Using this format, bulleted statements do not need
to be aligned and can continue to the next line of text (§
201.66(d)(10)(iv)). For example:

> **Ask a doctor before use if you have** ● heart disease ● glaucoma
>
> ● high blood pressure ● thyroid disease ● diabetes ● trouble urinating
> due to an enlarged prostate gland ● a breathing problem such as
> emphysema or chronic bronchitis

***Question 25: Where can I find guidance on the use of a column format
as part of the new OTC labeling requirements?***

***Answer 25:*** A guidance document entitled *Labeling OTC Human Drug
Products Using a Column Format* is available on the CDER Internet site
at http://www.fda.gov/cder/guidance/index.htm. A written request for a
copy can be submitted to the Division of Drug Information (HFD-240),
Center for Drug Evaluation and Research, FDA, 5600 Fishers Lane,
Rockville, MD 20857.

***Question 26: How can I obtain copies of other FDA labeling guidance
relating to the new OTC labeling requirements?***

***Answer 26:*** Copies of the guidances are available on the Internet
at [http://www.fda.gov/cder/
guidance/index.htm](http://www.fda.gov/cder/guidance/index.htm), or send
a written request for single copies to the Division of Drug Information
(see address above).

***Question 27: How must I list ingredients under the heading* Active
ingredients*? ***

***Answer 27:*** The ingredients must be listed in alphabetical order.

***Question 28:*** ***How should I list under the heading* Purpose
*ingredients with the same pharmacological action?***

***Answer 28:*** When more than one active ingredient has the same
purpose, the information can be presented in a manner that readily
associates each active ingredient with its purpose (by using brackets,
dot leaders, or other graphical features). For example:

> **Active ingredients** **Purpose**
>
> Homosalate 6% }
>
> Oxybenzone 3% } Sunscreen
>
> Padimate O 2% }

***Question 29: How should I list inactive ingredients that may or may
not be contained in my product?***

***Answer 29:*** These ingredients should be listed in alphabetical
order along with those ingredients that are contained in your product.
FDA recommends that you place an asterisk next to those ingredients
that, depending on the source, may or may not be contained in the
product (e.g., acacia\*, dextrose\*, sucrose, xanthum gum\*). The
asterisk should be referenced at the bottom or end of the inactive
ingredient section in the Drug Facts box, with the notation "\* contains
one or more of these ingredients" (if more than one ingredient may or
may not be in the product), or "\* may contain this ingredient" (if only
one ingredient may or may not be in the product), whichever is
appropriate.

> FDA recommends that for product labeling using the standard labeling
> format as described in §§ 201.66(d)(1) through (d)(9), the statement
> ("\* contains one or more of these ingredients," or "\* may contain
> this ingredient," whichever is appropriate) should be left justified
> at the end of the inactive ingredient section. The type size of these
> statements must be at least 6-point type. For product labeling that
> uses the modified format as described in § 201.66(d)(10), the asterisk
> statement could appear on the same line as the last listed inactive
> ingredient if separated from the last listed ingredient by at least
> two square \"ems\"[^4].
>
> Listing too many alternative ingredients could be misleading and may
> cause consumer confusion. To avoid such confusion, sponsors may wish
> to consider using a second set of labels for products with a lengthy
> list of different inactive ingredients.
>
> Additionally, to provide consumers with the opportunity to learn if an
> ingredient is in the lot number of the product, the Agency recommends
> that the optional information in § 201.66(c)(9) (*Questions?* or
> *Questions or comments?* followed by the telephone number of a source
> to answer questions about the product) be included in labeling.
>
> Sponsors are also reminded to follow all applicable current good
> manufacturing practice regulations Part 211 for finished
> pharmaceuticals so that manufacturers maintain appropriate records
> showing which lot numbers of the product contain which inactive
> ingredients.

***Question 30: Can I use a pictogram or graphical image such as the
Universal Product Code (UPC) symbol within the Drug Facts box?***

***Answer 30:*** No. The only pictogram that may be included within the
Drug Facts information is a telephone or telephone receiver before the
Questions heading. Pictograms and graphical images such as the Universal
Product Code (UPC) symbol cannot appear in, or in any way interrupt, the
information required in the Drug Facts labeling (§ 201.66(d)(7)). They
can appear outside the Drug Facts box. The following examples illustrate
how the UPC code can be placed in relation to the Drug Facts Box.

> **Illustration 1. Illustration 2.** (showing second panel)

+---+------+-----------------------------------+---------+----+-------+
| D |      |                                   | DF      |    | DF    |
| r |      |                                   |         |    |       |
| u |      |                                   |         |    |       |
| g |      |                                   |         |    |       |
|   |      |                                   |         |    |       |
| F |      |                                   |         |    |       |
| a |      |                                   |         |    |       |
| c |      |                                   |         |    |       |
| t |      |                                   |         |    |       |
| s |      |                                   |         |    |       |
|   |      |                                   |         |    |       |
| L |      |                                   |         |    |       |
| a |      |                                   |         |    |       |
| b |      |                                   |         |    |       |
| e |      |                                   |         |    |       |
| l |      |                                   |         |    |       |
| i |      |                                   |         |    |       |
| n |      |                                   |         |    |       |
| g |      |                                   |         |    |       |
|   |      |                                   |         |    |       |
| ( |      |                                   |         |    |       |
| D |      |                                   |         |    |       |
| F |      |                                   |         |    |       |
| ) |      |                                   |         |    |       |
+---+------+-----------------------------------+---------+----+-------+
|   |      |                                   |         |    |       |
+---+------+-----------------------------------+---------+----+-------+
|   |      |                                   |         |    | UPC   |
+---+------+-----------------------------------+---------+----+-------+
|   | UPC  |                                   |         |    |       |
+---+------+-----------------------------------+---------+----+-------+

***Question 31: When can I use the modified labeling format?***

***Answer 31:*** When the required Drug Facts content information
printed in the standardized format plus any other FDA required
information for drug or drug-cosmetic products, other than information
required to appear on the principle display panel, requires more than 60
percent of the total surface area available to bear labeling.

***Question 32: What is the difference between the standard and modified
labeling formats?***

***Answer 32:*** The following table illustrates the differences between
the two labeling formats.

**Table 1. Standard Versus Modified Labeling Format**

> Labeling Element Standard Format Modified Format

+--------------+---------------------+---------------------------------+
| Drug Facts   | Set off by barline  | Barline may be omitted if color |
| Box          |                     | contrast used to set off from   |
|              |                     | the rest of the labeling        |
+--------------+---------------------+---------------------------------+
| Drug Facts   | Larger than largest | Larger than largest type size   |
|              | type size used in   | used in Drug Facts box or       |
|              | Drug Facts box or   | similar enclosure               |
|              | similar enclosure   |                                 |
+--------------+---------------------+---------------------------------+
| Drug Facts   | No smaller than     | No smaller than 7-point type    |
| (continued)  | 8-point type        |                                 |
+--------------+---------------------+---------------------------------+
| Headings     | [\>]                | [\>]{.underline}7-point or      |
|              | {.underline}8-point | greater type, or 1-point type   |
|              | or greater type, or | greater than point size of text |
|              | 2-point type        |                                 |
|              | greater than point  |                                 |
|              | size of text        |                                 |
+--------------+---------------------+---------------------------------+
| Subheadings  | No smaller than     | No smaller than 6-point type    |
|              | 6-point type        |                                 |
+--------------+---------------------+---------------------------------+
| Bulleted     | No smaller than     | No smaller than 6-point type    |
| text         | 6-point type        |                                 |
+--------------+---------------------+---------------------------------+
| Leading      | Minimum 0.5 point   | Less than 0.5 point may be      |
|              |                     | used, provided the ascenders    |
|              |                     | and descenders do not touch     |
+--------------+---------------------+---------------------------------+
| Bullets      | Minimum 5-point     | Minimum 5-point type            |
|              | type                |                                 |
|              |                     | No alignment required           |
|              | Vertical alignment  |                                 |
+--------------+---------------------+---------------------------------+

***Question 33: What other labeling requirements may be applicable in
addition to the standardized content and format requirements in §
201.66?***

***Answer 33:*** Additional labeling requirements in Part 201 that may
be applicable are summarized as follows:

**Table 2. Additional Labeling Requirements**

+----------------+-----------------------------------------------------+
| **Paragraph**  | ######### **Description of Paragraph**              |
+----------------+-----------------------------------------------------+
| § 201.1        | Name and place of business of manufacturer, packer, |
|                | or distributor                                      |
+----------------+-----------------------------------------------------+
| § 201.17       | Location of expiration dates                        |
+----------------+-----------------------------------------------------+
| § 201.18       | Control numbers                                     |
+----------------+-----------------------------------------------------+
| § 201.60       | Principle display panel                             |
+----------------+-----------------------------------------------------+
| § 201.61       | Statement of identity                               |
|                |                                                     |
|                | -   Established name of drug                        |
|                |                                                     |
|                | -   Statement of general pharmacological            |
|                |     category(ies) or the principal intended actions |
|                |                                                     |
|                | -   Bold type                                       |
|                |                                                     |
|                | -   Size related to the most prominent printed      |
|                |     matter                                          |
+----------------+-----------------------------------------------------+
| § 201.62       | Declaration of net quantity of contents             |
+----------------+-----------------------------------------------------+
| § 201.20       | Declaration of the presence of FD&C Yellow No. 5    |
|                | and/or FD&C Yellow No. 6                            |
+----------------+-----------------------------------------------------+
| § 201.132(c)   | Tamper-evident labeling                             |
+----------------+-----------------------------------------------------+

***Question 34: When must my product comply with the new OTC labeling
requirements?***

***Answer 34:*** The date by which your product must comply with the new
labeling requirements depends on its current marketing status. See
Appendix A (Table 3) of this guidance to determine the date of
implementation of the \"Drug Facts\" requirements.

# V. Exemption AND DEFERRALS

***Question 35: Are there any exemptions or deferrals to the Drug Facts
labeling requirements?***

***Answer 35:*** Section 201.66(e) provides that FDA on its own
initiative or in response to written request from any manufacturer,
packer, or distributor, may exempt or defer, based on the particular
circumstances presented, one or more specific requirements set forth in
§ 201.66(a) through (d), on the basis that the requirement is
inapplicable, impracticable, or contrary to public health or safety. FDA
points out that exemption and deferral requests shall: (1) Document why
a particular requirement is inapplicable, impracticable, or is contrary
to public health or safety; and (2) include a representation of the
proposed labeling, including any outserts, panel extensions, or other
graphical or packaging techniques intended to be used with the product.
FDA reviews each exemption and deferral request submitted and, based on
the data submitted, makes a determination whether to grant or deny such
requests.

If you have questions on whether a particular FDA requirement applies to
your drug or drug-cosmetic product, please contact:

Office of Compliance (HFD-310)

Center for Drug Evaluation and Research

Food and Drug Administration

5600 Fishers Lane

Rockville, MD 20857

301-827-8958 or 301-827-8959

Division of OTC Drug Products (HFD-560)

Center for Drug Evaluation and Research

Food and Drug Administration

5600 Fishers Lane

Rockville, MD 20857

301-827-2222

Office of Cosmetics and Colors (HFS-105)

Center for Food Safety and Applied Nutrition

> Food and Drug Administration

200 C St., SW.

Washington, DC 20204

202-205-4061

# 

# Appendix A: Summary 

**Table 1. Labeling Content: § 201.66(c)(1) Through (c)(9)**

+----------------+-------------------+---------------------------------+
| **Paragraph**  | **Description of  | **Comments**                    |
|                | Paragraph**       |                                 |
+================+===================+=================================+
| (c)(1)         | **Drug Facts,     | Title to be used is **Drug      |
|                | Drug Facts**      | Facts** (on subsequent panels   |
|                | **(continued)**   | use "**Drug Facts**             |
|                |                   | (continued)")                   |
+----------------+-------------------+---------------------------------+
| (c)(2)         | **Active          | For drug-cosmetic products, the |
|                | ingredient**      | drug ingredients are considered |
|                |                   | the active ingredients, and the |
|                | (established      | cosmetic ingredients are        |
|                | name,             | considered the inactive         |
|                | streng            | ingredients.                    |
|                | th/concentration) |                                 |
+----------------+-------------------+---------------------------------+
| (c)(3)         | **Purpose(s)**    | If there is no statement of     |
|                |                   | identity or no applicable OTC   |
|                |                   | drug monograph, the ingredient  |
|                |                   | purpose is stated based on its  |
|                |                   | general pharmacological         |
|                |                   | category(ies), or the principal |
|                |                   | intended action(s) of the drug. |
|                |                   | See 21 CFR 201.66(b)(2),        |
|                |                   | (b)(8), (c)(8); and 21 CFR      |
|                |                   | 701.3(a) and (f).               |
+----------------+-------------------+---------------------------------+
| (c)(4)         | **Use(s)**        | The use(s) is/are the specific  |
|                |                   | indication(s) or approved       |
|                |                   | use(s) for the drug product.    |
|                |                   | For drug-cosmetic products, the |
|                |                   | use in the **Drug Facts**       |
|                |                   | labeling is attributed only to  |
|                |                   | the drug component.             |
+----------------+-------------------+---------------------------------+
| (c)(5)         | **Warning(s)**    | Warning(s) information appears  |
|                |                   | in a specific order, under the  |
|                |                   | heading **Warnings**, as        |
|                |                   | applicable. Most warnings       |
|                |                   | follow specific subheadings, as |
|                |                   | described below in (c)(5)(i)    |
|                |                   | through (c)(5)(x).              |
+----------------+-------------------+---------------------------------+
| (c)(5)(i)      | **For             | Appears in bold type. In some   |
|                | external/rectal/  | instances (e.g., lip protectant |
|                | vaginal use       | drug products), the             |
|                | only**            | **external** **use only**       |
|                |                   | warning may be omitted.         |
+----------------+-------------------+---------------------------------+
| (c)(5)(ii)     | All applicable    | Appear with subheadings         |
|                | warnings          | highlighted in bold type.       |
+----------------+-------------------+---------------------------------+
| (c)(5)(ii)(A)  | **Reye's syndrome | When this warning is required,  |
|                | warning**         | it is the first warning of the  |
|                |                   | warnings listed in paragraphs   |
|                |                   | (c)(5)(ii)(A) through           |
|                |                   | (c)(5)(ii)(G) to appear in this |
|                |                   | location in the **Warnings**    |
|                |                   | labeling.                       |
+----------------+-------------------+---------------------------------+
| (c)(5)(ii)(B)  | Allergic reaction | Subheading **Allergy alert** is |
|                | warnings          | used.                           |
+----------------+-------------------+---------------------------------+
| (c)(5)(ii)(C)  | **Flammability    | The appropriate flammability    |
|                | warning**, with   | signal word in an approved drug |
|                | appropriate       | application or OTC drug         |
|                | signal word       | monograph is used.              |
+----------------+-------------------+---------------------------------+
| (c)(5)(ii)(D)  | Water soluble gum | The subheading **Choking** is   |
|                | warning,          | used.                           |
|                | **Choking**       |                                 |
+----------------+-------------------+---------------------------------+
| (c)(5)(ii)(E)  | **Alcohol         | Subheading **Alcohol warning**  |
|                | warning**         | is used.                        |
+----------------+-------------------+---------------------------------+
| (c)(5)(ii)(F)  | **Sore throat     | Subheading **Sore throat        |
|                | warning**         | warning** is used.              |
+----------------+-------------------+---------------------------------+
| (c)(5)(ii)(G)  | **Dosage          | The warnings in 21 CFR          |
|                | warning**         | 201.307(b)(2)(i) or (b)(2)(ii)  |
|                |                   | for drug products containing    |
|                |                   | sodium phosphates. The          |
|                |                   | subheading **Dosage warning**   |
|                |                   | is used to introduce this       |
|                |                   | information.                    |
+----------------+-------------------+---------------------------------+
| (c)(5)(iii)    | **Do not use**    | Subheading used for all         |
|                |                   | absolute contraindications and  |
|                |                   | involve several different types |
|                |                   | of situations.                  |
+----------------+-------------------+---------------------------------+
| (c)(5)(iv)     | **Ask a doctor    | Subheading is used for certain  |
|                | before use if you | preexisting conditions.         |
|                | have**            |                                 |
+----------------+-------------------+---------------------------------+
| (c)(5)(v)      | **Ask a doctor or | Subheading used for all         |
|                | pharmacist before | drug-drug and drug-food         |
|                | use if you are**  | interactions.                   |
+----------------+-------------------+---------------------------------+
| (c)(5)(vi)     | **When using this | Subheading used for all side    |
|                | product**         | effects that the consumer may   |
|                |                   | experience; identifies          |
|                |                   | substances or activities that   |
|                |                   | should be avoided while using   |
|                |                   | the product.                    |
+----------------+-------------------+---------------------------------+
| (c)(5)(vii)    | **Stop use and    | Subheading used for any signs   |
|                | ask a doctor if** | of toxicity or other adverse    |
|                |                   | reactions that would            |
|                |                   | necessitate immediately         |
|                |                   | discontinuing use of product.   |
+----------------+-------------------+---------------------------------+
| (c)(5)(viii)   | Any required      | Location used to include any    |
|                | warnings          | other required warnings that do |
|                |                   | not fit within sections         |
|                |                   | 201.66(c)(5)(i) through         |
|                |                   | (c)(5)(vii), (c)(5)(ix), and    |
|                |                   | (c)(5)(x).                      |
+----------------+-------------------+---------------------------------+
| (c)(5)(ix)     | **The             | General warning and other       |
|                | pregnancy/breast  | related warnings.               |
|                | feeding warning** |                                 |
+----------------+-------------------+---------------------------------+
| (c)(5)(x)      | **Keep out of     | General warning and accidental  |
|                | reach of**        | **overdose/ingestion** warning  |
|                |                   | in 21 CFR 330.1(g).             |
|                | **children**      |                                 |
+----------------+-------------------+---------------------------------+
| (c)(6)         | **Directions**    | Described in an applicable OTC  |
|                |                   | drug monograph or approved drug |
|                |                   | application.                    |
+----------------+-------------------+---------------------------------+
| (c)(7)         | **Other           | Subheading used for additional  |
|                | information** and | information that is not         |
|                | additional        | included under the other        |
|                | information not   | subheadings, but which is       |
|                | included in       | required or is made optional    |
|                | (c)(2) -- (c)(6), | under an OTC drug monograph(s), |
|                | (c)(8), (c)(9) of | other OTC drug regulation(s),   |
|                | this section,     | or approved drug application.   |
|                | e.g., storage     |                                 |
|                | conditions.       |                                 |
+----------------+-------------------+---------------------------------+
| (c)(7)(i)      | certain           | See 21 CFR 201.64(b),           |
|                | ingredients (e.g. | 201.70(b), 201.71(b), and       |
|                | Na)               | 201.72(b)                       |
+----------------+-------------------+---------------------------------+
| (c)(7)(ii)     | Phenylalanine     | See 21 CFR 201.21(b)            |
+----------------+-------------------+---------------------------------+
| (c)(7)(iii)    | additional        | For example: storage            |
|                | information       | conditions, tamper-evident      |
|                |                   | statement                       |
+----------------+-------------------+---------------------------------+
| (c)(8)         | **Inactive        | List of each inactive           |
|                | ingredients**     | ingredient, using its           |
|                |                   | established name                |
+----------------+-------------------+---------------------------------+
| (c)(9)         | **Questions?**    | Optional heading used to        |
|                | (or **Questions   | provide a telephone number of a |
|                | or Comments?**)   | source to answer questions      |
|                |                   | about the product.              |
+----------------+-------------------+---------------------------------+

**Table 2 Labeling Format: 21 CFR 201.66(d)(1) through (d)(9)**

  -----------------------------------------------------------------------
  **Paragraph**    **Description of Paragraph**
  ---------------- ------------------------------------------------------
  (d)(1)           Drug Facts: first letter of words uppercase

  "                Headings, subheadings: first letter of first word
                   uppercase

  "                Left justification

  (d)(2)           Drug Facts type size greater than largest type size
                   used in Drug Facts labeling

  "                Heading 8 pt or 2 point sizes greater than text point
                   size

  "                Type size [\>]{.underline}6 pt size for information in
                   Drug Facts

  "                Subheadings ≥ 6 point type size

  "                Drug Facts (continued) type size no smaller than
                   8-point type

  (d)(3)           Letters do not touch

  "                [\>]{.underline}.5 pt leading (space between lines)

  "                No more than 39 characters per inch

  "                Bold Italic headings and title

  "                Bold subheading except the phrase "(continued)"

  "                Contrasting dark color for title and heading

  (d)(4)           Bullet: solid circle or square 5 pt type, same shape
                   and color, left justified or separated from heading or
                   subheading by at least two square "ems"

  "                Bullet on same lines: end of statement separated from
                   bulleted statement by two "ems"

  "                Bullet on same lines: additional bulleted statement
                   does not continue on next line

  "                Vertical alignment of bulleted statements

  (d)(5)           Appear on more than one panel

  "                Visual graphic signals continuation

  (d)(6)           Left justification of information required by (c)(2)

  "                Right justification of information required by (c)(3)

  "                Alphabetical order of active ingredients

  "                Information required by (c)(4), (c)(6) - (c)(9) may
                   start on same line as required headings

  "                None of information required in (c)(5) shall appear on
                   same line as Warnings

  (d)(7)           Graphical images should not interrupt the heading,
                   subheading and information. Hyphens should not be used
                   except to punctuate compound words.

  (d)(8)           Enclosed box using barline

  "                Horizontal barline separates headings listed in
                   (c)(2) - (c)(9)

  "                Horizontal hairline precedes heading immediately after
                   the title "Drug Facts"

  "                Horizontal hairline follows the title "Drug Facts
                   (continued)"

  "                Horizontal hairline extending within 2 spaces on
                   either side of the Drug Facts box shall immediately
                   follow the title and precede the subheadings set forth
                   in (c)(5) \[except (c)(5) (ii) A -- G\]

  (d)(9)           Directions in table format when dosage instructions
                   are provided for three or more age groups or
                   populations

  "                Horizontal barline preceding the next heading may end
                   the table
  -----------------------------------------------------------------------

####### **Table 3. Implementation Chart**

  ------------------------------- ---------------------------------------
  **Products**                    **Time periods\***

  **Subject to NDA/ANDA:**        

  *Single* entity products        By May 16, 2002 (or by May 16, 2003, if
  approved before May 16, 1999.   annual sales of the product are less
                                  than \$25,000).

  *Single* entity products        Immediately upon approval of the
  approved on or after May 16,    application.
  1999.                           

  *Combination* products approved By May 16, 2002 (or by May 16, 2003, if
  before May 16, 1999.            annual sales of the product are less
                                  than \$25,000).

  *Combination* products approved Immediately upon approval of the
  on or after May 16, 1999.       application.

  **Subject to OTC Drug           
  Monograph(s):**                 

  *Single* entity products        By May 16, 2002 (or by May 16, 2003, if
  finalized before May 16, 1999.  annual sales of the product are less
                                  than \$25,000).

  *Single* entity products        Within the period specified in the
  finalized on or after May 16,   final monograph. However, if a
  1999.                           monograph has not been finalized as of
                                  May 16, 2002, then the product must
                                  comply as of the first major labeling
                                  revision after May 16, 2002, or May 16,
                                  2005, whichever occurs first.

  *Combination* products in which By May 16, 2002 (or by May 16, 2003, if
  all applicable monographs were  annual sales of the product are less
  finalized before May 16, 1999.  than \$25,000).

  *Combination* products in which Within the period specified in the last
  at least one applicable         applicable monograph to be finalized,
  monograph was finalized before  or by May 16, 2002 (or by May 16, 2003,
  May 16, 1999, and at least one  if annual sales of the product are less
  applicable monograph is         than \$25,000), whichever occurs first,
  finalized on or after May 16,   unless the last applicable monograph to
  1999.                           be finalized specifies a later date.

  *Combination* products in which Within the period specified in the last
  all applicable monographs are   applicable monograph to be finalized.
  finalized on or after May 16,   However, if the last monograph is not
  1999.                           finalized as of May 16, 2002, then the
                                  product must comply as of the first
                                  major labeling revision after May 16,
                                  2002, or by May 16, 2005, whichever
                                  occurs first.

  *All other single entity and    If a monograph has not been finalized
  combination* OTC drug products  as of May 16, 2002, then the product
  (e.g., products in the OTC drug must comply as of the first major
  review that are not yet the     labeling revision after May 16, 2002,
  subject of proposed OTC drug    or by May 16, 2005, whichever occurs
  monographs).                    first.
  ------------------------------- ---------------------------------------

\* Time delayed until further notice for OTC drug products that contain
no more than two doses of an OTC drug product and, because of their
limited total surface area available to bear labeling, qualify for the
labeling modifications set forth in § 201.66(d)(10).

[^1]: This guidance has been prepared by the Division of
    Over-the-Counter (OTC) Drug Products in the Center for Drug
    Evaluation and Research (CDER) at the Food and Drug Administration
    (FDA).

[^2]: The text of § 201.66 can be found at the FDA Division of Dockets
    Management Internet site located at
    http://www.fda.gov/cder/otc/label/label-fr-reg.htm.

[^3]: ^4^ See Appendix A (Table 2) of this draft guidance for specific
    format labeling requirements in § 201.66(d).

[^4]: Two square \"ems\" are two squares of the size of the letter
    \"M.\" (See 21 CFR 201.66(d)(4).)