Innovative Approaches 
for Nonprescription Drug 
Products 
  
Guidance for Industry 
 
 
 
DRAFT GUIDANCE
 
 
  This guidance document is being distributed for comment purposes only. 
 
Comments and suggestions regarding this draft document should be submitted within 60 days of 
publication in the Federal Register of the notice announcing the availability of the draft 
guidance.  Submit electronic comments to https://www.regulations.gov.  Submit written 
comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, Rm. 1061, Rockville, MD  20852.  All comments should be identified with the 
docket number listed in the notice of availability that publishes in the Federal Register. 
 
For questions regarding this draft document, contact (CDER) Chris Wheeler at 301-796-0151.  
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
 
July 2018 
OTC 
 
17765437dft 
07-13-18   
Innovative Approaches 
for Nonprescription Drug 
Products 
  
Guidance for Industry 
 
 
 
Additional copies are available from: 
 
Office of Communications, Division of Drug Information  
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD 20993-0002  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 
Email: druginfo@fda.hhs.gov  
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
 July 2018 
OTC 
 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  INNOVATIVE APPROACHES FOR NONPRESCRIPTION DRUG PRODUCTS . 3 
A.  Labeling in Addition to the DFL for Nonprescription Drug Products ..................................... 3 
B.  Nonprescription Drug Products With Additional Conditions for Safe and Effective Use ...... 3 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
 
Innovative Approaches for Nonprescription Drug Products 
1 
Guidance for Industry1 
2 
3   
4   
5  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
6  Administration (FDA or Agency) on this topic.  It does not establish any rights for any person and is not 
7  binding on FDA or the public.  You can use an alternative approach if it satisfies the requirements of the 
8  applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff responsible 
9  for this guidance as listed on the title page.   
10   
11   
12   
13   
14  I.  INTRODUCTION  
15   
16  This guidance describes two innovative approaches that may be useful to consider for 
17  demonstrating safety and effectiveness for a nonprescription drug product in cases where the 
18  drug facts labeling (DFL) alone is not sufficient to ensure that the drug product can be used 
19  safely and effectively in a nonprescription setting:  (1) the development of labeling in addition to 
20  the DFL, and (2) the implementation of additional conditions so that consumers appropriately 
21  self-select and use the product.   
22   
23  The appropriateness and specific details of either of these approaches will depend on the 
24  circumstances that apply to a particular drug product.   
25   
26  These innovative approaches may be useful for applicants intending to develop and seek 
27  approval of certain nonprescription drug products through the submission of a new drug 
28  application (NDA), including an application submitted pursuant to section 505(b)(2) of the 
29  Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355).2  
30   
31  In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
32  Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
33  as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
34  the word should in Agency guidances means that something is suggested or recommended, but 
35  not required.  
36   
37   
                                                 
1 This guidance has been prepared by the Office of Medical Policy in the Center for Drug Evaluation and Research 
at the Food and Drug Administration at the Food and Drug Administration.  
 
2 The recommendations on the innovative approaches presented in this guidance may also be appropriate for 
combination products (as defined at 21 CFR 3.2(e)) subject to review under a new drug application (NDA). 
 
  1  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
 
38  II.  BACKGROUND 
39   
40  FDA approves new drugs3 as prescription or nonprescription drug products under section 505 of 
41  the FD&C Act (21 U.S.C. 355).  A drug product must be dispensed by prescription if it is not 
42  safe to use except under the supervision of a practitioner licensed by law to administer the drug 
43  (health care practitioner) (see section 503(b)(1) of the FD&C Act (21 U.S.C. 353(b)(1)).  If a 
44  drug product does not meet the criteria for prescription-only dispensing, it may be marketed as a 
45  nonprescription drug product. 
46   
47  FDA determines whether the information submitted as part of a new drug application (NDA) for 
48  a nonprescription drug product is sufficient to ensure that the drug product is safe and effective 
49  for nonprescription use under the conditions prescribed, recommended, or suggested in its 
50  proposed labeling (see sections 505(d) and 503(b)(1) of the FD&C Act (21 U.S.C. 355(d) and 
51  353(b)(1)).  Studies regarding self-selection and actual use can help demonstrate that the drug 
52  product is safe and effective for use without the supervision of a health care practitioner.  Self-
53  selection studies test whether consumers can apply information in the drug products labeling to 
54  their personal medical situations and make correct decisions to use or not use the drug product, 
55  and actual use studies provide information on how consumers will use the drug product.4  
56   
57  Nonprescription drug products must comply with applicable labeling requirements for over-the-
58  counter (OTC) drug products under 21 CFR part 201, including, but not limited to, the format 
59  and content requirements for OTC drug product labeling under  201.66.  Labeling created to 
60  satisfy the requirements in  201.66 is commonly referred to as the DFL.  The DFL is intended to 
61  enable consumers to appropriately self-select and use the nonprescription drug product safely 
62  and effectively.  In instances where the DFL alone would not be sufficient, an applicant may 
63  consider proposing innovative approaches, in addition to the DFL, to ensure that the drug 
64  product is safe and effective for use as a nonprescription drug product.  
65   
66  FDA believes the innovative approaches described in this guidance could lead to the approval of 
67  a wider range of nonprescription drug products, including drug products that may treat chronic 
68  conditions or other conditions for which the limitations of the DFL present challenges for 
69  adequate communication of information needed for safe and effective use without the 
70  supervision of a health care practitioner.  Approval of a wider range of nonprescription drug 
71  products has the potential to improve public health by increasing the types of drug products 
72  consumers can access and use that would otherwise only be available by prescription. 
73   
74   
                                                 
3 The term new drug is defined at section 201(p) of the FD&C Act (21 U.S.C. 321(p)). 
 
4 See the guidance for industry Self-Selection Studies for Nonprescription Drug Products.  We update guidances 
periodically.  For the most recent version of a guidance, check the FDA guidance web page at  
https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.  
  2  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
 
75  III.  INNOVATIVE APPROACHES FOR NONPRESCRIPTION DRUG PRODUCTS 
76   
77  A.  Labeling in Addition to the DFL for Nonprescription Drug Products 
78   
79  In addition to labeling created to satisfy the DFL requirements,5 FDA may approve additional 
80  labeling for nonprescription drug products (see section 505(d) of the FD&C Act (21 U.S.C. 
81  355(d)).  Examples of nonprescription drug product labeling the Agency may consider approving 
82  in addition to the DFL include, but are not limited to, the following:  
83   
84    Information leaflets or other documents contained inside the carton or container for the 
85  nonprescription drug product 
86   
87    Text or images on a video display, including interactive displays for consumers to review  
88   
89    Information displayed on websites 
90   
91    Statements or questions in a mobile application 
92   
93  B.  Nonprescription Drug Products With Additional Conditions for Safe and 
94  Effective Use  
95   
96  Applicants may consider proposing one or more additional conditions that consumers must fulfill 
97  to ensure that the drug product is safe and effective for nonprescription use, when labeling alone 
98  is not sufficient for this purpose. 
99   
100  Examples of additional conditions for safe and effective use that the Agency may consider, 
101  particularly with regard to appropriate self-selection and actual use, include, but are not limited 
102  to, the following:  
103   
104    Prior to purchase, the consumer is required to respond to a set of questions on a self-
105  selection test in a mobile application, and the outcome of the self-selection test 
106  affirmatively indicates that the consumer is an appropriate candidate to use the 
107  nonprescription drug product.  
108   
109    Prior to purchase, the consumer is required to view and affirm that they viewed text or 
110  images in a video that describes how to appropriately use the nonprescription drug 
111  product.  
112   
113  As part of the development process for a nonprescription drug product for which an additional 
114  condition for nonprescription use will be proposed, applicants should consider how to ensure 
115  proper implementation of any additional condition necessary for safe and effective use.  
116   
                                                 
5 21 CFR 201.66 
  3  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
 
117  We encourage applicants to meet with FDA staff to discuss any questions that arise during the 
118  development of a nonprescription drug product for which an additional condition for safe and 
119  effective use will be proposed. 
120   
  4