Guidance for Industry 
Labeling OTC Human Drug 
Products  Questions and 
Answers 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
December 2008 
OTC 
 
 
   
Guidance for Industry
 
Labeling OTC Human Drug 
Products  Questions and 
Answers 
 
 
 
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 
E-mail: druginfo@fda.hhs.gov 
Fax: 301-847-8714 
(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) 
 
December 2008 
OTC 
 
   
TABLE OF CONTENTS 
 
I.  INTRODUCTION.............................................................................................................1 
II.  BACKGROUND...............................................................................................................1 
III.  CONTENT LABELING REQUIREMENTS.................................................................2 
IV.  FORMAT LABELING REQUIREMENTS...................................................................8 
V.  EXEMPTIONS AND DEFERRALS.............................................................................13 
APPENDIX A:  SUMMARY OF LABELING REQUIREMENTS.......................................15 
 
  Contains Nonbinding Recommendations 
1
Guidance for Industry
 
Labeling OTC Human Drug Products 
 
Questions and Answers 
 
 
 
 
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 
 
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 set forth in 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 labeling format.  This guidance is one in a 
series of Food and Drug Administration (FDA) guidances intended to facilitate compliance with the 
labeling requirements in  201.66. 
 
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.  The Drug Facts labeling regulation in  201.66 covers all OTC drug and drug-
                                                 
1This 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.  
1  Contains Nonbinding Recommendations 
cosmetic products, 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).2  
 
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 
questions received from manufacturers, packers, and distributors relating to these requirements, 
which are set forth in  201.66(c) and (d), respectively. 
 
 
III.  CONTENT LABELING REQUIREMENTS  
 
The following questions and answers address the OTC Drug Facts labeling requirements in  
 201.66.  Tables A and B in Appendix A 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.  These tables should be referred to 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 drug 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 ingredient(s) 
3.  Purpose(s) 
4.  Use(s) 
5.  Warning(s) 
6.  Directions 
7.  Other information  
8.  Inactive ingredients  
9.  Questions? or Questions or comments? (optional) 
 
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.)  
 
                                                 
2 The text of  201.66 can be found at the Division of Dockets Management Web site located at 
http://www.fda.gov/cder/otc/label/label-fr-reg.htm. 
2  Contains Nonbinding Recommendations 
Question 2:  Why must the title Drug Facts (continued) appear on each subsequent panel in 
which the Drug Facts labeling appears? 
 
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-
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 drug 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) drug products 
that should not be used unless a previous diagnosis has been made by a doctor; or 2) 
drug products that should not be used under any circumstances by certain consumers, 
regardless of whether a doctor or health care 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 can 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: 
 
3  Contains Nonbinding Recommendations 
Ask a doctor before use if you have 
 cough that occurs with too much phlegm (mucus)  
 chronic cough that lasts as occurs with smoking, asthma, chronic bronchitis, or 
emphysema  
 
Question 7:  How can 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 can I convert text of existing required warnings to bulleted text format under 
this subheading? 
 
Answer 8:  This subheading must be used for side effects that consumers may experience  
( 201.66(c)(5)(vi)).  It identifies substances (e.g., alcohol) or activities (e.g.,  
operating machinery, driving a car) that should be avoided while using the drug product.   
This subheading also must include warnings for drugs in dispensers pressurized by 
gaseous propellants.  Such information would 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 drug product 
( 201.66(c)(5)(vii)).  For example, the bulleted statement you get nervous, dizzy, 
or sleepless would appear in this section. 
 
4  Contains Nonbinding Recommendations 
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 Warnings heading or subheadings? 
 
Answer 10:  Such warnings must be placed in the Drug Facts Warnings 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 also must 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 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) 
 
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 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 also may be omitted 
in some instances, as specified in an applicable OTC drug monograph or approved 
drug application.   
 
Question 13:  Do I have to present information under Directions in a table format?  
 
Answer 13:  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 ( 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.   
 
5  Contains Nonbinding Recommendations 
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  2 tablets every 6 hours  
older 
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, approved drug application, statute, or OTC drug 
guidance.  
 
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, and 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, K, or Na 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 drug product 
labeling? 
 
Answer 15:  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 
6  Contains Nonbinding Recommendations 
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.   
 
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 
7  Contains Nonbinding Recommendations 
 
For an OTC drug product that is a drug-cosmetic product, the inactive ingredients 
must be listed in descending order of predominance in the drug 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 are not required, we 
encourage all manufacturers, packers, and distributors to include in this section a 
telephone number of a source to answer questions about the drug product or to 
receive reports of adverse events associated with the use of the drug product.  
 
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, if used.  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. 
 
 
IV.  FORMAT LABELING REQUIREMENTS3 
 
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 
Table B in Appendix A (see also  201.66(c) and (d)). 
 
Question 19:  Can I use bold type for any information I consider needs greater prominence? 
 
Answer 19:  We recommend 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 
                                                 
3 See Table B in Appendix A for specific format labeling requirements in  201.66(d).  
8  Contains Nonbinding Recommendations 
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:  We recommend that additional text be formatted as indented sub-bulleted 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 
Warnings 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 Warnings 
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: 
 
9  Contains Nonbinding Recommendations 
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 
drug labeling requirements? 
 
Answer 25:  The guidance for industry Labeling OTC Human Drug Products Using a Column 
Format is available on the CDER Web site.4  A written request for a copy can be 
sent to the Division of Drug Information, Center for Drug Evaluation and Research, 
FDA, 10903 New Hampshire Avenue, Bldg. 51, rm. 2201, Silver Spring, MD  
20993-0002. 
 
Question 26:  How can I obtain copies of other FDA labeling guidances relating to the new OTC 
drug labeling requirements? 
 
Answer 26:  Copies of related guidances are available on the Internet,5 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 ingredient(s)?  
 
Answer 27:  The ingredients must be listed in alphabetical order ( 201.66(d)(6)).   
 
Question 28:  How should I list under the heading Purpose(s) 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 
drug product? 
 
Answer 29:  These ingredients should be listed in alphabetical order along with those ingredients 
that are contained in your drug product.  We recommend that you place an asterisk 
next to those ingredients that, depending on the source, may or may not be contained 
                                                 
4 See http://www.fda.gov/cder/guidance/index.htm. 
 
5 Ibid. 
10  Contains Nonbinding Recommendations 
in the drug 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 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 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 drug 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.6   
 
Listing too many alternative ingredients could be misleading and may 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 the 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. 
 
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 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. 
 
 
                                                 
6 Two square ems are two squares of the size of the letter M.  (See  201.66(d)(4).) 
11  Contains Nonbinding Recommendations 
Illustration 1.         Illustration 2. (showing second panel)  
 
         
Drug        DF 
Facts         
Labeling    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 ( 201.66(d)(10)).  
 
Question 32:  What is the difference between the standard and modified labeling formats? 
 
Answer 32:  Table 1 illustrates the differences between the two labeling formats. 
 
Table 1.  Standard Versus Modified Labeling Format 
Labeling  Standard Format  Modified Format 
Element 
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  Larger than largest type size used in the 
size used in Drug Facts box  Drug Facts box or similar enclosure 
or similar enclosure 
Drug Facts  No smaller than 8-point  No smaller than 7-point type 
(continued)  type  
Headings  >8-point type, or 2-point  >7-point type, or 1-point type > point size 
type > point size of text  of text 
Subheadings   No smaller than 6-point  No smaller than 6-point type 
type 
Bulleted text  No smaller than 6-point  No smaller than 6-point type 
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 
 
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 21 CFR parts 201 and 211 that may be 
applicable are summarized in Table 2 as follows: 
12  Contains Nonbinding Recommendations 
 
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 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 
 201.20  Declaration of the presence of FD&C Yellow No. 5 and/or 
FD&C Yellow No. 6 
 211.132(c)  Tamper-evident labeling  
 
Question 34:  When must my product comply with the new OTC drug labeling requirements? 
 
Answer 34:  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 products.  This stay also applies to OTC sunscreen drug-cosmetic 
products.  
 
 
V.  EXEMPTIONS AND DEFERRALS 
 
Question 35:  Are there any exemptions or deferrals to the Drug Facts labeling requirements? 
 
Answer 35:  Section 201.66(e) provides that the 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.  The 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; 
13  Contains Nonbinding Recommendations 
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 drug product.  The FDA reviews each exemption and deferral request 
submitted and, based on the data submitted, makes a determination whether to grant 
or deny such requests. 
 
Manufacturers, packers, and distributors should contact the following relevant offices for questions 
on whether a particular FDA requirement applies to their drug or drug-cosmetic product: 
 
  Office of Compliance (CDER) at 
http://www.fda.gov/cder/Offices/Compliance/default.htm 
 
  Office of Nonprescription Products (CDER) at 
http://www.fda.gov/cder/Offices/OTC/default.htm 
 
  Office of Cosmetics and Colors (CFSAN) at  
http://vm.cfsan.fda.gov/%7Edms/cos-toc.html 
 
 
14  Contains Nonbinding Recommendations 
APPENDIX A:  SUMMARY OF LABELING REQUIREMENTS 
 
Table A.  Labeling Content:   201.66(c)(1) through (c)(9) 
Paragraph  Description of Paragraph  Comments 
(c)(1)  Drug Facts, Drug Facts  The title to be used is Drug Facts (on subsequent 
(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 
strength/concentration)  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/vaginal  Appears in bold type.  In some instances, the 
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 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 section. 
(c)(5)(ii)(B)  Allergic reaction warnings   The subheading Allergy alert is used. 
(c)(5)(ii)(C)  Flammability warning, with  The appropriate flammability signal word in an 
appropriate signal word  approved drug application or OTC drug monograph 
is used. 
(c)(5)(ii)(D)  Water soluble gum warning,  The subheading Choking is used. 
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. 
continued 
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Table A, continued 
Paragraph  Description of Paragraph  Comments 
(c)(5)(iii)  Do not use followed by all  The subheading used for all absolute 
contraindications  contraindications and involves different types of 
situations. 
(c)(5)(iv)  Ask a doctor before use if  The subheading used for certain preexisting 
you have  conditions or when experiencing certain symptoms.  
(c)(5)(v)  Ask a doctor or pharmacist  The subheading used for all drug-drug and drug-food 
before use if you are  interactions. 
(c)(5)(vi)  When using this product  The subheading used for all side effects that the 
consumer may experience; identifies substances or 
activities that should be avoided while using the drug 
product. 
(c)(5)(vii)  Stop use and ask a doctor if  The subheading used for any signs of toxicity or 
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 not  is not included under the other subheadings, but 
included in (c)(2)  (c)(6),  which is required or is made optional under an OTC 
(c)(8), and (c)(9) of this  drug monograph(s), other OTC drug regulation(s), 
section (e.g., storage  approved drug application, statute, or OTC drug 
conditions)  guidance. 
(c)(7)(i)  certain ingredients (e.g., Na)  See  201.64(b), 201.70(b), 201.71(b), and 
201.72(b). 
(c)(7)(ii)  Phenylalanine  See  201.21(b). 
(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 Questions or  Optional heading used to provide a telephone number 
Comments?)  of a source to answer questions about the drug 
product or to receive reports of adverse events 
associated with the use of the drug product. 
 
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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) 
  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 precedes heading immediately after the title Drug Facts   
  Horizontal hairline immediately follows the title Drug Facts (continued) 
  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 
 
 
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