Guidance for Industry 
Labeling OTC Human Drug 
Products 
 
(Small Entity Compliance Guide) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
May 2009 
OTC 
 
 
   
Guidance for Industry
 
Labeling OTC Human Drug 
Products  
 
(Small Entity Compliance Guide) 
 
 
 
 
Additional copies are available from: 
 
Office of Communications 
Division of Drug Information 
Center for Drug Evaluation and Research 
Food and Drug Administration 
10903 New Hampshire Ave., Bldg. 51, rm. 2201 
Silver Spring, MD  20993-0002 
(Tel) 301-796-3400 
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) 
 
May 2009 
OTC
   
TABLE OF CONTENTS 
 
I.  INTRODUCTION.............................................................................................................1 
II.  BACKGROUND...............................................................................................................1 
III.  SCOPE (21 CFR 201.66(a))...............................................................................................2 
IV.  DEFINITIONS (21 CFR 201.66(b)).................................................................................2 
V.  CONTENT REQUIREMENTS (21 CFR 201.66(c))......................................................2 
VI.  FORMAT LABELING REQUIREMENTS (21 CFR 201.66(d))................................10 
VII.  STANDARD AND MODIFIED LABELING FORMATS..........................................15 
VIII.  TOPIC-SPECIFIC GUIDANCES.................................................................................16 
IX.  OTHER FDA LABELING REQUIREMENTS...........................................................16 
X.  IMPLEMENTATION OF THE OTC LABELING REQUIREMENTS...................17 
APPENDIX A:  SUMMARY OF LABELING REQUIREMENTS AND RELEVANT  
  CONTACTS....................................................................................................................18 
  Contains Nonbinding Recommendations 
1
Guidance for Industry
 
Labeling OTC Human Drug Products 
 
(Small Entity Compliance Guide) 
 
 
 
 
This guidance represents the Food and Drug Administrations (FDAs) 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.  
You can use an alternative approach if the approach satisfies the requirements of the applicable statutes 
and regulations.  If you want to discuss an alternative approach, contact the FDA staff responsible for 
implementing this guidance.  If you cannot identify the appropriate FDA staff, call the appropriate 
number listed on the title page of this guidance.  
 
 
 
 
I.  INTRODUCTION 
 
The Food and Drug Administration (FDA) has prepared this guidance in accordance with section 
212 of the Small Business Regulatory Enforcement Fairness Act.  It is intended to help small 
businesses better understand the new over-the-counter (OTC) labeling requirements set forth in 
21 CFR 201.66 and prepare new labeling.  Additional information is available in the guidance 
for industry Labeling OTC Human Drug Products Questions and Answers.2   
 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the Agencys current thinking on a topic and should 
be viewed only as recommendations, unless specific regulatory or statutory requirements are 
cited.  The use of the word should in Agency guidances means that something is suggested or 
recommended, but not required. 
 
 
II.  BACKGROUND 
 
In the Federal Register of March 17, 1999 (64 FR 13254), the FDA published a final regulation 
( 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. 
                                                 
1 This guidance has been prepared by the Office of Nonprescription Products in the Center for Drug Evaluation and 
Research (CDER) at the Food and Drug Administration. 
 
2 We update guidances periodically.  To make sure you have the most recent version of a guidance, check the CDER 
guidance Web page at http://www.fda.gov/cder/guidance/index.htm. 
1  Contains Nonbinding Recommendations 
 
The Drug Facts labeling regulation in  201.66 covers all OTC drug and drug-cosmetic 
products,3 whether marketed under a new drug application (NDA), abbreviated new drug 
application (ANDA), or OTC drug monograph (or drug product not yet the subject of a final 
OTC drug monograph).  A copy of  201.66 can be found at the Division of Dockets 
Management Web site.4  The regulation in  201.66 provides for standardized content and 
format requirements for the labeling of OTC drug and drug-cosmetic products.  The regulation is 
divided into two main parts: 1) content requirements in paragraph (c) (i.e., headings, 
subheadings, and the order in which certain information must be listed); and 2) format 
requirements in paragraph (d) (i.e., graphic specifications).  This guidance primarily discusses 
the requirements in paragraphs (c) and (d).  The sections of the guidance track the sections of the 
regulation and explain the regulations provisions. 
 
 
III.  SCOPE (21 CFR 201.66(a)) 
 
This section explains that the content and format requirements apply to the labeling of all OTC 
drug products.  This scope includes drug products marketed under a final OTC drug monograph, 
an approved NDA or ANDA, and OTC drug products for which there is no final OTC drug 
monograph or approved drug application. 
 
 
IV.  DEFINITIONS (21 CFR 201.66(b)) 
 
This section contains definitions of terms, including an explanation of certain printing, 
typesetting, and graphics terms, applicable to this section of the regulation. 
 
 
V.  CONTENT REQUIREMENTS (21 CFR 201.66(c))5 
 
This section requires that all OTC drug product labeling contain the following information about 
the drug product.  The information must be organized according to the following headings and 
must be presented in the following order, as described in  201.66(c)(1) through (c)(9): 
 
 
 
 
                                                 
3 The term drug-cosmetic products refers to drug products with both drug and cosmetic attributes; for example, a 
sunscreen drug product intended for sunscreen (i.e., drug) uses and for moisturizing (i.e., cosmetic) uses. 
 
4 See http://www.fda.gov/cder/otc/label/label-fr-reg.htm.  
 
5See Table A in Appendix A for a general summary of content labeling requirements set forth in  201.66(c). 
2  Contains Nonbinding Recommendations 
  (c)(1)  Title6 (Drug Facts or Drug Facts (continued)) 
  (c)(2)  Active ingredient(s) 
  (c)(3)  Purpose(s) 
  (c)(4)  Use(s) 
  (c)(5)  Warning(s) 
  (c)(6)  Directions 
  (c)(7)  Other information 
  (c)(8)  Inactive ingredients 
  (c)(9)  Questions? or Questions or comments? (optional) 
 
This information must appear on the outside container or wrapper of the retail package, or on the 
immediate container label if there is no outside container or wrapper. 
 
Drug product trade names and company names cannot appear within the Drug Facts box or 
similar enclosure ( 201.66(d)(7)). 
 
The following specific information for each heading must appear in the Drug Facts section. 
 
A.  Title ( 201.66(c)(1)) 
 
If the Drug Facts labeling appears on more than one panel or side of the labeling, the title Drug 
Facts (continued)7 must appear at the top of each subsequent panel containing such information. 
See also the guidance for industry Labeling OTC Human Drug Products Using a Column 
Format for guidance on the title when a column format is used in the drug products labeling.  
 
B.  Active ingredient(s) ( 201.66(c)(2)) 
 
An active ingredient is any component that is intended to furnish pharmacological activity or 
other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to 
affect the structure or any function of the body.  The term includes those components that may 
undergo chemical change in the manufacture of the drug product and be present in the drug 
product in a modified form intended to furnish the specified activity or effect ( 201.66(b)(2)). 
 
Depending on the type of drug product (oral or topical), the active ingredients can be stated in 
one of two ways.  As the amount in each: 
 
  [for oral dosage forms] use the dosage unit stated in the directions for use (e.g., tablet, 5 
mL teaspoonful) 
 
or 
 
                                                 
6 The term Title refers to the heading listed at the top of the required OTC drug product labeling, as set forth in  
 201.66(c)(1). 
 
7 The word (continued) appears in regular type. 
3  Contains Nonbinding Recommendations 
  [for topical dosage forms marketed with discrete dosage units] use gram, as stated in  
333.110 and 333.120, where the first aid antibiotic active ingredients are stated as an 
amount in each gram of the drug product 
 
Drug products marketed without discrete dosage units (e.g., topicals) must state the proportion 
(rather than the quantity) of each active ingredient (e.g., 1%), unless otherwise provided in an 
applicable OTC drug monograph or approved drug application.  For example, the OTC anticaries 
final monograph (21 CFR part 355) lists fluoride active ingredients as a percent fluoride with an 
available fluoride ion concentration of a certain number of parts per million (ppm).  Because the 
concentration expressed in ppm may be confusing to consumers, the available ion concentration 
must be expressed on the label in fluoride ion percent (i.e., ppm converted to a percent weight to 
volume notation of available fluoride ion).  These anticaries products must list under this 
heading the ingredient percent, followed by fluoride ion concentration in percent notation (e.g., 
Sodium fluoride 0.24% (0.14% W/V fluoride ion)).   
 
For OTC drug products that contain both drug and cosmetic ingredients, the drug ingredients are 
considered the active ingredients, and the cosmetic ingredients are considered the inactive 
ingredients.  (See  201.66(b)(2) and 201.66(b)(8).) 
 
C.  Purpose(s) ( 201.66(c)(3)) 
 
Each active ingredient in the drug product is to be followed by a description of the ingredients 
purpose, unless this information is specifically exempted in an OTC drug monograph.  The 
statement of identity that appears in an applicable OTC drug monograph shall be stated as the 
purpose of the active ingredient.  If there is no statement of identity or no applicable OTC drug 
monograph, then we recommend that one of the following factors be used in stating the 
ingredients purpose: 
 
  Its general pharmacological category(ies) 
 
  The principal intended action(s) of the drug 
 
If two active ingredients in a drug product have the same purpose (e.g., two sunscreen or skin 
protectant ingredients are present in the drug product), then the purpose can be stated only once 
as long as the purpose is clearly associated with both active ingredients.  (See the example in 
section VI., Format Labeling Requirements.) 
 
D.  Use(s) ( 201.66(c)(4)) 
 
The uses are the specific indications or approved uses for the drug product.  For drug-cosmetic 
products, only the drug-related indications can be included in the Use(s) section.    
 
E.  Warning(s) ( 201.66(c)(5)) 
 
With regard to subject-specific warnings described in  201.66(c)(5)(ii)(A) through (5)(ii)(G), 
except for the Reyes syndrome warning, which must appear first when required, there is no 
4  Contains Nonbinding Recommendations 
required order in which these specific warning statements must appear.  We suggest that 
manufacturers list the specific warning statements in the order of importance or impact.  
 
When applicable, the following information must appear under the respective subheadings in the 
Warnings section. 
 
1.  Do not use ( 201.66(c)(5)(iii)) 
 
Information appearing under this subheading includes situations in which consumers should not 
use the drug product unless a prior diagnosis has been established by a doctor, or for situations in 
which consumers should not use the drug product under any circumstances regardless of whether 
a doctor or health care professional is consulted.   
 
In some instances, manufacturers need to convert existing warnings to the new Drug Facts 
labeling format (see  201.66(a)).  For example, the current warning Do not use this product on 
irritated skin, on any area that is infected or reddened, if you are a diabetic, or if you have poor 
blood circulation would be formatted to appear after the Do not use subheading as follows:   
 
  on irritated skin 
  on any area that is infected or reddened 
  if you are a diabetic 
  if you have poor blood circulation 
 
2.  Ask a doctor before use if you have ( 201.66(c)(5)(iv)) 
 
Information under this subheading includes all warnings for persons with certain preexisting 
conditions (excluding pregnancy) and all warnings for persons experiencing certain symptoms.  
The warnings under this subheading are intended only for situations when consumers should not 
use the drug product until a doctor is consulted.  Examples of such situations include: 1) high 
blood pressure, heart disease, thyroid disease, glaucoma, diabetes, and other conditions listed in 
various OTC drug monographs or approved drug applications; and 2) certain types of cough (i.e., 
persistent or chronic cough such as occurs with smoking, asthma, or emphysema, or if cough is 
accompanied by excessive phlegm).  For example, in the new Drug Facts labeling format, these 
warnings would appear as follows: 
 
Ask a doctor before use if you have 
  heart disease 
  cough that occurs with too much phlegm (mucus)  
  chronic cough that lasts as occurs with smoking, asthma, chronic bronchitis, or 
emphysema  
 
5  Contains Nonbinding Recommendations 
3.  Ask a doctor or pharmacist before use if you are ( 201.66(c)(5)(v)) 
 
Information under this subheading includes all drug-drug and drug-food interaction warnings.  
Examples include: sedatives or tranquilizers with antihistamines and a prescription drug for 
asthma with an OTC bronchodilator.  
 
4.  When using this product ( 201.66(c)(5)(vi)) 
 
Information under this subheading includes all side effects that consumers may experience and 
identifies the substances (e.g., alcohol) that could cause a side effect and any activity (e.g., 
operating machinery, driving a car) that should be avoided while using the drug product.  This 
subheading also includes warnings for drug products in dispensers pressurized by gaseous 
propellants.  We recommend that such information appear in bulleted text format as follows: 
 
  May cause drowsiness [or can appear as: drowsiness may occur] 
  Alcohol, sedatives, and tranquilizers may increase the drowsiness effect [or can 
appear as: alcohol, sedatives, and tranquilizers may increase drowsiness] 
  Do not puncture or incinerate.  Contents under pressure.   
 
5.  Stop use and ask a doctor if ( 201.66(c)(5)(vii)) 
 
Information under this subheading includes any signs of toxicity or other reactions that would 
require a patient to immediately stop using the drug product.  For example, the bulleted 
statement you get nervous, dizzy, or sleepless would appear in this section. 
 
6.  Any [other] required warnings ( 201.66(c)(5)(viii)) 
 
This location in the warnings section includes any required warnings in an applicable OTC drug 
monograph, other OTC drug regulations, or approved drug application that do not fit within one 
of the other categories.  There are a limited number of such warnings.  One such warning is the 
chlorofluorocarbon (CFC) warning required in certain approved drug applications, which states: 
Contains CFC-[insert number] and CFC-[insert number], substances which harm public health 
and environment by destroying ozone in the upper atmosphere.8 
 
7.  Pregnancy and related warnings ( 201.66(c)(5)(ix)) 
 
When applicable, these types of warnings also must be placed in the Warnings section.  
Warnings may include one or more of the following: 
 
                                                 
8 The CFC warning is a warning statement for drug products containing or manufactured with chlorofluorocarbons 
or other ozone-depleting substances (see  201.320). 
6  Contains Nonbinding Recommendations 
  The pregnancy/breast-feeding warning in  201.63(a) 
  The third trimester warning in  201.63(e) for drug products containing aspirin or 
carbaspirin calcium 
  The third trimester warning in approved drug applications for drug products containing 
ketoprofen, naproxen sodium, or ibuprofen (if not intended exclusively for use in 
children) 
 
8.  Keep out of reach of children and the accidental overdose/ingestion warnings in  
 330.1(g) ( 201.66(c)(5)(x))   
 
In a few special instances, the Keep out of reach of children warning can be omitted (see 
lipstick with a sunscreen in  352.52(f)(1)(vi)).  The accidental overdose/ingestion warning also 
can be omitted in some instances (see  331.30(f), 332.30(c), 341.74(f)).  
 
F.  Directions ( 201.66(c)(6)) 
 
Depending on the drug 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.  Dosage directions provided for one or two age groups or populations can be 
presented using bulleted statements.  (See  201.66(d)(4) and 201.66(d)(9).)  
 
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.   
 
We recommend that when a combination of a table and bulleted statements is used, the bulleted 
statements (e.g., do not use more than directed) appear before or after the table.  We also 
recommend that statements such as shake well appear as a separate bulleted statement within 
the directions.  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  2 tablets every 6 
and older  hours  
children 6  12 years  1 tablet every 6 
hours  
children under 6 years  ask a doctor 
 
G.  Other information ( 201.66(c)(7)) 
 
Information under this heading must contain information 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.   
7  Contains Nonbinding Recommendations 
 
If present and required by the OTC drug regulation to be included in the OTC drug labeling, 
certain ingredients in OTC drug products (e.g., sodium in  201.64(c)) must appear as follows: 
each (insert appropriate dosage unit) contains: [in bold type] (insert name(s) of ingredient(s) 
and quantity of each ingredient).  This statement must be the first statement under this heading. 
 
Under this heading, phenylalanine/aspartame content required by  201.21(b), if applicable, must 
appear as the next bulleted statement as follows: Phenylketonurics: Contains Phenylalanine 
(insert quantity) mg per (insert appropriate dosage unit).    
 
The tamper-evident statement must be prominently placed on the drug product package to alert 
consumers about the drug products tamper-evident features (21 CFR 211.132).  The tamper-
evident statement describes the tamper-evident feature of the drug product package and advises 
consumers that, if the feature is breached or missing when the drug 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 drug product design.  We allow flexibility in the placement of this 
statement on the package and do 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  201.66(c)(7)).   
 
We also noted in the final rule preamble for the Drug Facts regulation that many drug products 
are now marketed with peel back or fold out labels affixed to the drug 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 drug 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.   
 
8  Contains Nonbinding Recommendations 
For example, the above-mentioned statements would appear under this heading as follows: 
 
Other information 
  each tablet contains: calcium 10 mg,  magnesium 10 mg,  and sodium 15 mg 
  Phenylketonurics: Contains phenylalanine 10 mg per tablet 
  [insert storage information]  
  [if applicable, insert tamper-evident statement] 
 
H.  Inactive ingredients ( 201.66(c)(8)) 
 
This section contains a list of inactive ingredients, using their established names.  For OTC drug 
products (that are not also cosmetic products), the established names of inactive ingredients must 
be listed in alphabetical order ( 201.66(c)(8)).  For example: 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 drug 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: Inactive ingredients water, sorbitan isostearate, sorbitol, triethanolamine, stearic 
acid, barium sulfate, benzyl alcohol, dimethicone, methylparaben, aloe extract, carbomer, 
disodium EDTA. 
 
Note: For ingredients that may be contained in the drug product, see section VI.E., Inactive 
ingredients. 
 
I.  Questions? or Questions or comments? ( 201.66(c)(9)) 
 
If this heading is included in the Drug Facts box (see  201.66(c)(9)), the telephone number or a 
source to answer questions about the drug product must be included in this section.  It is 
acceptable for drug products to be labeled with two telephone numbers  one number to speak 
with someone in English and the other number to speak with someone in Spanish.  We 
recommend that the days of the week and times of the day when a person is available to respond 
to questions also be included.  Although this heading and subsequent information are not 
required, we recommend all manufacturers, distributors, and packers include this heading and 
subsequent information within the Drug Facts box. 
 
Although not permitted to appear in or otherwise interrupt the required Drug Facts labeling 
information, brand names or drug product attributes can appear in the telephone number and/or 
in the Web site address.  However, if the telephone number appears as letters of the brand name 
or drug product attribute, we recommend that the manufacturer also include the numerical 
representation of the telephone number in this section.  
 
 
9  Contains Nonbinding Recommendations 
VI.  FORMAT LABELING REQUIREMENTS (21 CFR 201.66(d))9 
 
This section addresses the manner in which the title, headings, subheadings, and other 
information set forth in  201.66(c) must be presented in the labeling of OTC drug products.  
Sample annotated graphics appear in Appendix A of 21 CFR part 201. 
 
A.  Use of bold type and mathematical notation 
 
Where FDA regulations require bold print for specific information, we recommend that 
manufacturers not use bold print for other information in that immediate area (unless required by 
regulation to do so) because this practice might reduce the emphasis on the FDA bold print 
information.  
 
For easier understanding, fractions (e.g., 1/2) may be expressed in text format (i.e., one-half) 
when used within the Drug Facts box or similar enclosure.  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. 
However, if fractions are expressed in mathematical notation, each component of the numerical 
notation must be no smaller than 6-point type.  
 
B.  Bulleted statements 
 
Bullets are a visual cue adopted by the FDA to aid in the presentation of OTC drug or drug-
cosmetic product labeling information.  Bullets are a solid square or solid circle in a 5-point type 
size, presented in the same shape and color throughout the labeling.  Under  201.66(d)(4), 
bullets are required to be used in the following ways: 
 
  When there is more than one statement listed under the headings Use(s), Warnings, 
Directions, or Other information, or any subheadings under these headings, each 
individual statement is preceded by a bullet (see all examples below). 
 
  The first bulleted statement on each horizontal line of text is either left justified or 
separated from an appropriate heading or subheading by at least 2 square ems (i.e., 2 
squares the size of the capital letter M in the font being used). 
 
  If more than one bulleted statement is placed on the same horizontal line, the end of one 
bulleted statement is separated from the beginning of the next bulleted statement by at 
least 2 square ems and the complete additional bulleted statements do not continue to the 
next line of text.  
 
Note: If the modified format is used, additional bulleted statements can continue to the 
next line of text. 
 
  Additional bulleted statements on each subsequent horizontal line of text under a heading 
or subheading are vertically aligned with the bulleted statements appearing on the 
                                                 
9 See Table B in Appendix A for a general summary of content labeling requirements set forth in  201.66(c). 
10  Contains Nonbinding Recommendations 
previous line (see the example in B.2.).  This requirement does not apply when the 
modified labeling format (as described in section VII., Standard and Modified Labeling 
Formats) in  201.66(d)(10) is used (see the example in B.3.). 
 
  If necessary, because of space constraints when using the standard labeling format, we 
allow a single bulleted statement to appear on the same line as a heading (except the 
heading Warnings) or a subheading (see the example in B.5.).  If a bulleted statement is 
placed on the same line as a heading or subheading, additional bulleted statements that 
appear under the heading or subheading can be either left justified (see the example in 
B.5.) or aligned with the first bulleted statement.  
 
  If the text size is greater than 6-point type, we will allow in our discretion that bullets be 
greater than 5-point type.  
 
The following examples show various arrangements of bulleted statements. 
 
1.  Uses 
 temporarily relieves pain and itching due to: 
 insect bites   minor skin irritations 
 rashes due to poison ivy, oak, and sumac 
 dries the oozing and weeping of: 
 poison ivy   poison oak   poison sumac 
 
Note: Align major bulleted statements and sub-bulleted statements. 
 
2.  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 
 
Note: Multi-bulleted statements on the same line are aligned with the previous line of 
bulleted statements.  Any bulleted statements not able to fit entirely on a multi-bulleted 
line must be left justified. 
 
3.  [Modified format] 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  
 
Note: No bullet alignment is required in the modified format; bulleted statements can 
continue to the next line of text. 
 
4.  Ask a doctor or pharmacist before use if you are taking a prescription drug for: 
 anticoagulation (blood thinning)   gout   diabetes   arthritis 
 
11  Contains Nonbinding Recommendations 
Note: Multi-bulleted statements are not required to appear on the same line as the 
subheading. 
 
5.  Directions   shake well 
 adults and children 2 years and over: apply to affected area not more than 3 to 4 times  
daily 
 children under 2 years: ask a doctor 
 
Note: Bullets can appear on the same line as headings and subheadings.  However, no 
bulleted statements or text can appear on the same line as the Warnings heading. 
 
C.  Number of label panels/Column format/Graphic 
 
See the guidance for industry Labeling OTC Human Drug Products Using a Column Format. 
 
D.  Active ingredient(s) and Purpose(s) 
 
When there is more than one active ingredient, they are listed in alphabetical order.  
Furthermore, when more than one active ingredient has the same purpose, the purpose does not 
need to be repeated for each ingredient if the information is presented in a manner that readily 
associates each active ingredient with its purpose (by using brackets, dot leaders, or other 
graphical features).  Examples include: 
 
Active ingredients (in each tablet)                                                                              Purpose 
Acetaminophen 500 mg ...................................................................Pain reliever/fever reducer 
Pseudoephedrine HCl 30 mg ...........................................................................Nasal decongestant 
Triprolidine HCl 1.25 mg......................................................................................Antihistamine 
 
Active ingredients                                                                                                        Purpose 
Homosalate 6%  } 
Oxybenzone 3% }....................................................................................................Sunscreen 
Padimate O 2%  } 
 
Note: Active ingredients with the same pharmacological activity can be bracketed together to 
avoid repetitive listing of purpose. 
 
E.  Inactive ingredients: contains one or more of these ingredients labeling 
 
There may be circumstances when manufacturers, packers, and distributors who market OTC 
drug products use multiple suppliers for some drug products to maintain an uninterrupted supply 
of the drug product to their customers.  In such cases, the specific inactive ingredients in the drug 
products may vary slightly from supplier to supplier: some inactive ingredients may be present in 
drug products coming from all suppliers while other inactive ingredients may not be present.  To 
have one label for all drug products, we recommend that the ingredients that may (or may not) be 
contained in each individual drug product be listed on the labeling in the following manner.  
 
12  Contains Nonbinding Recommendations 
 
  We believe that this type of inactive ingredient labeling can be accomplished best by 
placing those ingredients that may (or may not) be contained in an OTC drug product in 
the inactive ingredient listing, as set forth in  201.66(c)(8), with an asterisk placed next 
to those ingredients (e.g., acacia*, dextrose*, sucrose, xanthum gum*).  The asterisk 
would then be reprinted 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 drug product), or * may contain this 
ingredient (if only one ingredient may (or may not) be in the drug product), whichever is 
appropriate.   
 
  We recommend that for drug product labeling using the standard labeling format set forth 
in  201.66, 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.  For drug product labeling that uses the modified format 
set forth in  201.66(d)(10), the appropriate statement should appear at the end of the 
inactive ingredient section with 2 square ems between the last inactive ingredient and the 
statement.  The type size of these statements must be at least 6-point type (see  
 201.66(d)(2)). 
 
Listing too many alternative ingredients could be misleading and could cause consumer 
confusion.  To avoid such confusion, manufacturers, packers, and distributors may wish to 
consider using a second set of labels for drug 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 drug product, we recommend 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 drug product) be included in labeling. 
 
Manufacturers, packers, and distributors are also reminded to follow all applicable current good 
manufacturing practice regulations in 21 CFR part 211 for finished pharmaceuticals so that 
manufacturers maintain appropriate records showing which lot numbers of the drug product 
contain which inactive ingredients. 
 
F.  HEADINGS: Use(s), Warnings, Directions, Other information, Inactive ingredients, 
and Questions  Information on same line as heading 
 
  The information under any of these headings, except Warnings, may start on the same 
line as the heading. 
 
  None of the information under the heading Warnings can appear on the same line as this 
heading ( 201.66(d)(6)).  However, information under any of the subheadings that 
appear under the heading Warnings can start on the same line as the subheading. 
 
13  Contains Nonbinding Recommendations 
G.  Graphical images/Pictograms 
 
Graphical images (e.g., the American Dental Association seal, Good Housekeeping seal, 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)).  Below are examples of the 
possible placement of the UPC graphic image: 
 
Illustration 1                 Illustration 2 
         
Drug        DF 
Facts         
Labeling    DF     
     
          (DF) 
    UPC 
         
  UPC       
 
A pictogram is a pictorial representation of some object used to symbolize information.  The use 
of pictograms is voluntary in drug product labeling.  If used, pictograms must not appear within 
the Drug Facts labeling (see  201.66(d)(7)).  The only allowed exception is the use of a 
telephone or telephone receiver before the Questions? heading (see 201.66(c)(9)).  A 
pictogram that directs attention away from required information, that is ambiguous, or that can 
be misunderstood by consumers may render a drug product misbranded.  
 
Note: The drug product trade name and company name cannot appear in, or in any way interrupt, 
the information required in the Drug Facts labeling. 
 
H.  Barlines/Hairlines10 
 
  All of the Drug Facts information must be set off in a box or similar enclosure by the use 
of a barline ( 201.66(d)(8)).  We recommend size 2.5-point type. 
 
  A distinctive horizontal barline (recommended size 2.5-point type) extending to each end 
of the Drug Facts box or similar enclosure must separate each of the headings in the Drug 
Facts labeling ( 201.66(d)(8)).  
 
  A horizontal hairline (recommended size 0.5-point type) extending within two spaces on 
either side of the Drug Facts box or similar enclosure must immediately follow the title 
Drug Facts ( 201.66(d)(8)). 
 
                                                 
10 A barline is a distinctive horizontal line that extends to each end of the Drug Facts box or similar enclosure and 
provides separation between each of the headings listed in  201.66(c)(2) through (c)(9) ( 201.66(d)(8)).  A hairline 
is a distinctive horizontal line that extends within two spaces on either side of the Drug Facts box or similar 
enclosure ( 201.66(d)(8)).  This line immediately follows the title Drug Facts and the title Drug Facts (continued) 
on subsequent panels and immediately precedes each of the subheadings set forth in  201.66(c)(5), except the 
subheadings in  201.66(c)(5)(ii)(A) through (c)(5)(ii)(G). 
14  Contains Nonbinding Recommendations 
  When a heading appears on a subsequent panel after the Drug Facts (continued) title, a 
horizontal hairline (recommended size 0.5-point type), rather than a barline, must follow 
the title and immediately precede the heading ( 201.66(d)(8)). 
 
  A horizontal hairline (recommended size 0.5-point type) extending within two spaces on 
either side of the Drug Facts box or similar enclosure must immediately precede each of 
the subheadings in the Warnings section except for the subheadings in paragraphs 
(c)(5)(ii)(A) through (c)(5)(ii)(G).  The specific subheadings in these paragraphs are not 
preceded by any horizontal hairlines.  
 
  When a table is used as the last item of information in the Directions section, the last line 
of the table may be the horizontal barline that immediately precedes the heading of the 
next section of the labeling ( 201.66(d)(9)). 
 
Examples of the use of barlines and hairlines appear in Appendix A of 21 CFR part 201.  See 
also the guidance for industry Labeling OTC Human Drug Products Using a Column Format for 
additional information when a column format is used in the labeling. 
 
 
VII.  STANDARD AND MODIFIED LABELING FORMATS  
 
The regulation contains a formula that allows use of a modified labeling format, which is 
described in  201.66(d)(10).  When the required Drug Facts content information in paragraph 
(c) printed as specified in paragraph (d), 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, the Drug 
Facts labeling must appear in the modified labeling format.  When determining whether more 
than 60 percent available labeling space is required, the indications for use listed under the 
Use(s) heading must be limited to the minimum required uses reflected in the applicable 
monograph (see  330.1(c)(2)).  Table 1 describes selected format requirements used in the 
standard and modified labeling formats. 
 
15  Contains Nonbinding Recommendations 
Table 1.  Comparison of Standard and Modified Labeling Formats 
Labeling Element  Standard Format  Modified Format 
Drug Facts box  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  Larger than largest type size used in the 
used in Drug Facts box or  Drug Facts box or similar enclosure 
similar enclosure 
Drug Facts  No smaller than 8-point type   No smaller than 7-point type 
(continued) 
Headings   8-point type, or 2-point type >   7-point type, or 1-point type > point 
point size of text  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 type   Smaller than 0.5-point type can be used, 
provided the ascenders and descenders 
do not touch 
Bullets  Minimum 5-point type  Minimum 5-point type 
Vertical alignment  No alignment required 
 
For assistance in making content or format conversions of existing labeling to the new required 
labeling, manufacturers should contact the Office of Nonprescription Products for guidance. 
 
 
VIII.  TOPIC-SPECIFIC GUIDANCES 
 
The following guidances are available to help manufacturers, packers, and distributors 
implement the Drug Facts regulation establishing standardized content and format requirements 
for the labeling of all OTC drug products:11   
 
  Guidance for industry Labeling OTC Human Drug Products Using a Column Format 
(column format) 
 
  Guidance for industry Labeling OTC Human Drug Products Questions and Answers 
 
 
IX.  OTHER FDA LABELING REQUIREMENTS 
 
In addition to the standardized content and format regulations, there are other labeling 
requirements that may be applicable to the drug product and that manufacturers, packers, and 
distributors are required to follow.  The general labeling requirements in 21 CFR part 201 and 
part 211 specify what information must be included on a drug products labeling and how the 
information should be presented, among other things.  The Federal Food, Drug, and Cosmetic 
                                                 
11 The draft guidances for industry Labeling OTC Human Drug Products  Submitting Requests for Exemptions and 
Deferrals ( 201.66(e)) and Labeling OTC Human Drug Products Updating Labeling in ANDAs (ANDA labeling) 
are also available on the CDER guidance Web page (http://www.fda.gov/cder/guidance/index.htm).  
16  Contains Nonbinding Recommendations 
Act (the Act) defines labeling in broad terms, such that labeling means all labels and other 
written, printed, or graphic matter (1) upon any article or any of its containers or wrappers, or (2) 
accompanying such article (see section 201(m) of the Act (21 U.S.C. 321(m)).  This definition 
does not require labeling to be physically attached to a drug product.  For example, an outer 
carton, a brochure about the drug product, or a package insert is considered labeling.  Table 2 
summarizes some of the other labeling requirements that may be applicable in addition to the 
standardized content and format requirements in  201.66. 
 
Table 2.  General Labeling Requirements in 21 CFR Parts 201 and 211 
Paragraph  Description of Paragraph 
201.1   Name and place of business of manufacturer, packer, or distributor 
201.5  Adequate directions for use 
  201.17  Location of expiration date 
  201.18  Control numbers 
  201.60  Principal display panel 
  201.61  Statement of identity 
  Established name of drug product 
  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 
  201.63  Pregnancy/breast-feeding warnings 
   211.132(c)   Tamper-evident labeling  
 
 
X.  IMPLEMENTATION OF THE OTC LABELING REQUIREMENTS 
 
All OTC drug products must be in compliance with  201.66 at this time, except for the 
following: 
 
  The FDA has granted a stay of compliance for implementation of the Drug Facts 
regulation until further notice (67 FR 16304; April 5, 2002) for OTC drug products that 
contain no more than two doses of an OTC drug product and, because of their limited 
surface area available to bear labeling, qualify for the labeling modifications set forth in  
 201.66(d)(10). 
 
  The FDA has granted a stay of compliance for implementation of the Drug Facts 
regulation until further notice (69 FR 53801; September 3, 2004) for OTC sunscreen drug 
and drug-cosmetic products.  
 
Appendix A provides a quick reference to certain content and format requirements associated 
with key labeling elements.  Manufacturers should contact the relevant office listed in Appendix 
A for questions on whether a particular FDA requirement applies to their drug or drug-cosmetic 
product. 
17  Contains Nonbinding Recommendations 
APPENDIX A:  SUMMARY OF LABELING  
REQUIREMENTS AND RELEVANT CONTACTS 
 
Table A.  Labeling Content:   201.66(c)(1) through (c)(9) 
Paragraph  Description of  Comments 
Paragraph 
(c)(1)  Drug Facts, Drug  The title to be used is Drug Facts (on subsequent 
Facts (continued)  panels use Drug Facts (continued)). 
(c)(2)  Active ingredient(s)  For drug-cosmetic products, the drug ingredients are 
(established name,  considered the active ingredients, and the cosmetic 
quantity)  ingredients are considered the inactive ingredients. 
See  201.66(b)(2), (b)(8), and (c)(8); and  
 701.3(a) and (f).   
(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 product. 
(c)(4)  Use(s)  The use(s) 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.  See  
 201.66(c)(4). 
(c)(5)  Warning(s)  Warning information appears in a specific order, 
under the heading Warnings, as applicable.  Most 
warnings follow specific subheadings, as described in 
(c)(5)(i) through (c)(5)(x). 
(c)(5)(i)  For external/rectal/  Appears in bold type.  In some instances, the 
vaginal use only  external use only warning can be omitted.  For 
example, OTC lip protectant drug products that meet 
the criteria of  201.66(d)(10) may omit this warning 
( 347.50(e)(1)(iii)).  
(c)(5)(ii)  All applicable warnings  Appear with subheadings highlighted in bold type. 
(c)(5)(ii)(A)  Reyes syndrome  When this warning is required, it is the first warning 
warning   of the warnings listed in paragraphs (c)(5)(ii)(A) 
through (c)(5)(ii)(G) to appear in this location in the 
Warnings section. 
(c)(5)(ii)(B)  Allergic reaction  The subheading Allergy alert is used. 
warnings  
(c)(5)(ii)(C)  Flammability warning,  The appropriate flammability signal word in an 
with appropriate signal  approved NDA or OTC drug monograph is used. 
word 
continued 
18  Contains Nonbinding Recommendations 
Table A, continued 
Paragraph  Description of  Comments 
Paragraph 
(c)(5)(ii)(D)  Water soluble gum  The subheading Choking is used. 
warning, Choking 
(c)(5)(ii)(E)  Alcohol warning   The subheading Alcohol warning is used. 
(c)(5)(ii)(F)  Sore throat warning  The subheading Sore throat warning is used. 
(c)(5)(ii)(G)  Dosage warning  The warnings in  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 followed by  The subheading used for all absolute 
all contraindications  contraindications and involves different types of 
situations. 
(c)(5)(iv)  Ask a doctor before  The subheading used for certain preexisting 
use if you have  conditions or when experiencing certain symptoms.   
(c)(5)(v)  Ask a doctor or  The subheading used for all drug-drug and drug-food 
pharmacist before use  interactions. 
if you are 
(c)(5)(vi)  When using this  The subheading used for all side effects that the 
product  consumer may experience; identifies substances or 
activities that should be avoided while using the drug 
product. 
(c)(5)(vii)  Stop use and ask a  The subheading used for any signs of toxicity or 
doctor if  other adverse reactions that would necessitate 
immediately discontinuing use of the drug product. 
(c)(5)(viii)  Any required warnings  The location used to include any other required 
warnings that do not fit within  201.66(c)(5)(i) 
through (c)(5)(vii), (c)(5)(ix), and (c)(5)(x). 
(c)(5)(ix)  The pregnancy/breast- General warning and other related warnings. 
feeding warning 
(c)(5)(x)  Keep out of reach of  General warning and accidental overdose/ingestion 
children  warning in  330.1(g). 
(c)(6)  Directions  Described in an applicable OTC drug monograph or 
approved drug application. 
(c)(7)  Other information and  The subheading used for additional information that 
additional information  is not included under the other subheadings, but 
not included in (c)(2)   which is required or is made optional under an OTC 
(c)(6), (c)(8), and (c)(9)  drug monograph(s), other OTC drug regulation(s), or 
of this section (e.g.,  approved NDA. 
storage conditions) 
(c)(7)(i)  certain ingredients   See  201.64(b), 201.70(b), 201.71(b), and 
(e.g., Na)  201.72(b). 
(c)(7)(ii)  Phenylalanine  See  201.21(b). 
continued 
19  Contains Nonbinding Recommendations 
Table A, continued 
Paragraph  Description of  Comments 
Paragraph 
(c)(7)(iii)  Additional information  For example: storage conditions, tamper-evident 
statement. 
(c)(8)  Inactive ingredients  A list of each inactive ingredient, using its 
established name. 
(c)(9)  Questions? (or  Optional heading used to provide a telephone number 
Questions or  of a source to answer questions about the drug 
Comments?)  product. 
 
Table B.  Labeling Format:   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 > largest type size used in Drug Facts 
labeling 
  Heading 8-pt, or 2-pt type sizes > text point size 
   6-pt type size for information in Drug Facts 
  Subheadings  6-pt type size 
  Drug Facts (continued): type size no smaller than 8-pt type 
(d)(3)  Letters do not touch 
   0.5-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) 
continued 
20  Contains Nonbinding Recommendations 
Table B, continued 
Paragraph  Description of Paragraph 
  Alphabetical order of active ingredients 
  Information required by (c)(4), (c)(6)  (c)(9) may start on same 
line as required headings 
  None of the information required in (c)(5) shall appear on the 
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 immediately follows the title Drug Facts 
(continued), and immediately precedes a heading or subsequent 
text that follows after this title 
  Horizontal hairline extending within two 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 
 
Contact the following offices for additional information: 
  CDER Office of Nonprescription Products 
(http://www.fda.gov/cder/Offices/OTC/default.htm) 
  CDER Office of Compliance (http://www.fda.gov/cder/Offices/Compliance/default.htm) 
  CFSAN Office of Cosmetics and Colors (http://vm.cfsan.fda.gov/%7Edms/cos-toc.html)  
 
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