Guidance for Industry
Labeling OTC Human Drug Products
Questions and Answers
(PDF
version of this document)
DRAFT GUIDANCE
This guidance document is being distributed for comment
purposes only.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draft guidance.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
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
http://www.fda.gov/cder/guidance/index.htm
.
TABLE OF CONTENTS
I.
INTRODUCTION
II.
BACKGROUND
III.
CONTENT Labeling
REQUIREMENTS
IV.
FORMAT LABELING
REQUIREMENTS
V.
Exemption AND
DEFERRALS
Appendix A:
Summary
Guidance for Industry
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draft guidance, when finalized, will represent the Food and Drug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.
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.
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).
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.
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 6: How could I convert a lengthy warning under
the subheading "Ask a doctor before use if you have" into the
bulleted text format?
● 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 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).
● 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 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.
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
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.
Answer 26: Copies of the guidances are available
on the Internet at
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".
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)
Drug
Facts
Labeling
(DF) |
|
DF |
|
DF
|
|
|
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 principal 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
|
Set off
by barline |
Barline
may be omitted if color contrast used to set off from the rest
of the labeling |
Drug
Facts |
|
Larger
than largest type size used in Drug Facts box or similar
enclosure |
Drug
Facts (continued) |
|
No
smaller than 7-point type |
Headings |
>8-point
or greater type, or 2-point type greater than point size of
text |
>7-point
or greater type, or 1-point type greater than point size of
text |
Subheadings |
No
smaller than 6-point type |
No
smaller than 6-point type |
Bulleted
text |
No
smaller than 6-point type |
No
smaller than 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 type
Vertical
alignment |
Minimum
5-point type
No
alignment required |
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 |
Principal
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 |
§ 211.132(c)
|
Tamper-evident labeling |
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
Table 1. Labeling Content: § 201.66(c)(1) Through (c)(9)
Paragraph
|
Description of Paragraph |
Comments |
(c)(1) |
Drug
Facts, Drug Facts
(continued) |
Title to be
used is Drug Facts (on subsequent panels use “Drug
Facts (continued)”) |
(c)(2) |
Active
ingredient
(established name, strength/concentration) |
For
drug-cosmetic products, the drug ingredients are considered the
active ingredients, and the cosmetic ingredients are considered
the inactive ingredients. |
(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
external/rectal/ vaginal use only |
Appears in
bold type. In some instances (e.g., lip protectant drug
products), the external use only warning may be
omitted. |
(c)(5)(ii) |
All
applicable warnings |
Appear with
subheadings highlighted in bold type. |
(c)(5)(ii)(A) |
Reye’s
syndrome warning |
When this
warning is required, 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 warnings |
Subheading
Allergy alert is used. |
(c)(5)(ii)(C) |
Flammability warning,
with appropriate signal word |
The
appropriate flammability signal word in an approved drug
application or OTC drug monograph is used. |
(c)(5)(ii)(D) |
Water
soluble gum warning, Choking |
The
subheading Choking is used. |
(c)(5)(ii)(E) |
Alcohol
warning |
Subheading
Alcohol warning is used. |
(c)(5)(ii)(F) |
Sore
throat warning |
Subheading
Sore throat warning is used. |
(c)(5)(ii)(G) |
Dosage
warning |
The
warnings in 21 CFR 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 before use if you have |
Subheading
is used for certain preexisting conditions. |
(c)(5)(v) |
Ask a
doctor or pharmacist before use if you are |
Subheading
used for all drug-drug and drug-food interactions. |
(c)(5)(vi) |
When
using this product |
Subheading
used for all side effects that the consumer may experience;
identifies substances or activities that should be avoided while
using the product. |
(c)(5)(vii) |
Stop
use and ask a doctor if |
Subheading
used for any signs of toxicity or other adverse reactions that
would necessitate immediately discontinuing use of product. |
(c)(5)(viii) |
Any
required warnings |
Location
used to include any 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
pregnancy/breast feeding warning |
General
warning and other related warnings. |
(c)(5)(x) |
Keep
out of reach of
children |
General
warning and accidental overdose/ingestion warning in 21
CFR 330.1(g). |
(c)(6) |
Directions |
Described
in an applicable OTC drug monograph or approved drug
application. |
(c)(7) |
Other
information and
additional information not included in (c)(2) – (c)(6), (c)(8),
(c)(9) of this section, e.g., storage conditions. |
Subheading
used for additional information that is not included under the
other subheadings, but which is required or is made optional
under an OTC drug monograph(s), other OTC drug regulation(s), or
approved drug application. |
(c)(7)(i) |
certain
ingredients (e.g. Na) |
See 21 CFR
201.64(b), 201.70(b), 201.71(b), and 201.72(b) |
(c)(7)(ii) |
Phenylalanine |
See 21 CFR
201.21(b) |
(c)(7)(iii) |
additional
information |
For
example: storage conditions, tamper-evident statement |
(c)(8) |
Inactive
ingredients |
List of
each inactive ingredient, using its established name |
(c)(9) |
Questions? (or
Questions or Comments?) |
Optional
heading used to provide a telephone number of a source to answer
questions about the product. |
Table 2 Labeling Format: 21 CFR
201.66(d)(1) through (d)(9)
|
|
(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
>6 pt size for information in Drug Facts |
“ |
Subheadings
³
6 point type size |
“ |
Drug Facts
(continued) type size no smaller than 8-point type |
(d)(3) |
Letters do
not touch |
“ |
>.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
approved before May 16, 1999. |
By May 16,
2002 (or by May 16, 2003, if annual sales of the product are
less than $25,000). |
Single
entity products approved on or after May 16, 1999. |
Immediately
upon approval of the application. |
Combination products
approved before May 16, 1999. |
By May 16,
2002 (or by May 16, 2003, if annual sales of the product are
less than $25,000). |
Combination products
approved on or after May 16, 1999. |
Immediately
upon approval of the application. |
Subject
to OTC Drug Monograph(s): |
Single
entity products finalized before May 16, 1999. |
By May 16,
2002 (or by May 16, 2003, if annual sales of the product are
less than $25,000). |
Single
entity products finalized on or after May 16, 1999. |
Within the
period specified in the final monograph. However, if a
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 all applicable monographs were finalized before May 16,
1999. |
By May 16,
2002 (or by May 16, 2003, if annual sales of the product are
less than $25,000). |
Combination products
in which at least one applicable monograph was finalized before
May 16, 1999, and at least one applicable monograph is finalized
on or after May 16, 1999. |
Within the
period specified in the last applicable monograph to be
finalized, or by May 16, 2002 (or by May 16, 2003, if annual
sales of the product are less than $25,000), whichever occurs
first, unless the last applicable monograph to be finalized
specifies a later date. |
Combination products
in which all applicable monographs are finalized on or after May
16, 1999. |
Within the
period specified in the last applicable monograph to be
finalized. However, if the last monograph is not 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 combination
OTC drug products (e.g., products in the OTC drug review that
are not yet the subject of proposed OTC drug monographs). |
If a
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 by May 16, 2005, whichever occurs first. |
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).
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.
Back
to Top
Back to Guidance Page
Date created: January 11, 2005 |