Over-the-Counter Monograph 
Order Requests (OMORs): 
Format and Content 
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DRAFT GUIDANCE 
 
  This guidance document is being distributed for comment purposes only.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publication in the Federal Register of the notice announcing the availability of the draft 
guidance.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) Trang Tran at 301-402-7945 or 
Trang.Tran@fda.hhs.gov.  
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
April 2023 
Over-the-Counter 
39539123dft.docx 
4/10/2023   
Over-the-Counter Monograph 
Order Requests (OMORs): 
Format and Content 
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/guidance-compliance-regulatory-information/guidances-drugs  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
April 2023 
Over-the-Counter
 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
TABLE OF CONTENTS 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  THE COMMON TECHNICAL DOCUMENT FORMAT AND CONTENT FOR 
AN OMOR ......................................................................................................................... 2 
A.  MODULE 1: ADMINISTRATIVE INFORMATION ................................................................ 3 
1. Format ............................................................................................................................................. 3 
2. Content ............................................................................................................................................. 4 
a.  Table of contents ....................................................................................................................... 4 
b.  Cover letter................................................................................................................................ 4 
c.  Administrative information ....................................................................................................... 5 
d.  References ................................................................................................................................. 6 
e.  Meetings .................................................................................................................................... 7 
f.  Labeling ..................................................................................................................................... 7 
B.  MODULE 2: SUMMARIES ......................................................................................................... 7 
1. Format ............................................................................................................................................. 7 
2. Content ............................................................................................................................................. 7 
a.  Table of contents ....................................................................................................................... 7 
b.  Introduction to the summary documents ................................................................................... 7 
c.  Quality overall summary ........................................................................................................... 8 
d.  Nonclinical overview ................................................................................................................ 8 
e.  Clinical overview ...................................................................................................................... 8 
f.  Nonclinical written and tabulated summaries ............................................................................ 9 
g.  Clinical summary .................................................................................................................... 10 
C.  MODULE 3: QUALITY DATA ................................................................................................. 10 
1. Format ........................................................................................................................................... 10 
2. Content ........................................................................................................................................... 10 
D.  MODULE 4: NONCLINICAL STUDY REPORTS ................................................................. 11 
1. Format ........................................................................................................................................... 11 
2. Content ........................................................................................................................................... 11 
a.  Nonclinical studies .................................................................................................................. 11 
b.  Individual study reports .......................................................................................................... 11 
E.  MODULE 5: CLINICAL STUDY REPORTS .......................................................................... 12 
1. Format ........................................................................................................................................... 12 
2. Content ........................................................................................................................................... 12 
a.  Clinical studies and related information .................................................................................. 12 
b.  Reports of postmarketing experience ...................................................................................... 14 
c.  Individual study reports ........................................................................................................... 14 
IV.  GENERAL CONSIDERATIONS FOR AN OMOR ................................................... 15 
A.  Language ....................................................................................................................................... 15 
B.  Fonts .............................................................................................................................................. 15 
C.  Paper size ...................................................................................................................................... 15 
D.  Pagination ..................................................................................................................................... 16 
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E.  OMOR Searchability ................................................................................................................... 16 
F.  Hyperlinks to References ............................................................................................................ 16 
V.  ENVIRONMENTAL ASSESSMENT ........................................................................... 16 
VI.  CONFIDENTIAL INFORMATION ............................................................................. 17 
 
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1  Over-the-Counter Monograph Order Requests (OMORs):  
2  Format and Content 
3  Guidance for Industry1 
4   
5   
6   
7  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
8  Administration (FDA or Agency) on this topic.  It does not establish any rights for any person and is not 
9  binding on FDA or the public.  You can use an alternative approach if it satisfies the requirements of the 
10  applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff responsible 
11  for this guidance as listed on the title page. 
12   
13   
14   
15  I.  INTRODUCTION 
16   
17  This guidance is intended to assist requestors2 in preparing over-the-counter (OTC) monograph 
18  order requests (OMORs)3 for submission to FDA under section 505G of the Federal Food, Drug, 
19  and Cosmetic Act (FD&C Act) (21 U.S.C. 355h). This guidance provides FDAs 
20  recommendations on the format and content of the information that requestors should provide in 
21  an OMOR and identifies relevant guidance documents to assist requestors in preparing their 
22  OMORs. 
23   
24  This guidance provides an overview of the information that FDA may recommend for a 
25  sufficiently complete OMOR. This guidance is not intended to indicate the studies and related 
26  information that a requestor must submit in a specific OMOR.   
27   
28  Requestors can request a formal meeting with FDA to discuss specific data, studies, and related 
29  information to be submitted in the OMORs.4  
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 
 
1 This guidance has been prepared by the Office of Nonprescription Drugs in the Center for Drug Evaluation and 
Research at the Food and Drug Administration.  
 
2 Under section 505G(q)(3) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), the term requestor refers to 
any person or group of persons marketing, manufacturing, processing, or developing an OTC monograph drug. 
 
3 An OMOR is a request for an order submitted under section 505G(b)(5) of the FD&C Act.  See also section 
744L(7) of the FD&C Act. 
 
4 See the draft guidance for industry Formal Meetings Between FDA and Sponsors or Requestors of Over-the-
Counter Monograph Drugs (February 2022). When final, this guidance will represent the FDAs current thinking on 
this topic. For the most recent version of a guidance, check the FDA guidance web page at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents.  
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34  the word should in Agency guidances means that something is suggested or recommended, but 
35  not required.  
36   
37   
38  II.  BACKGROUND 
39   
40  On March 27, 2020, the President signed into law the Coronavirus Aid, Relief, and Economic 
41  Security Act (CARES Act). The CARES Act added section 505G to the FD&C Act. Section 
42  505G reforms and modernizes the framework for the regulation of OTC monograph drugs. OTC 
43  monograph drugs may be marketed without an approved drug application under section 505 of 
44  the FD&C Act if they meet the requirements of section 505G of the FD&C Act, as well as other 
45  applicable requirements.5  
46   
47  Under the process set forth in section 505G(b) of the FD&C Act, FDA has the authority to issue 
48  a final order that adds, removes, or changes generally recognized as safe and effective (GRASE) 
49  conditions for an OTC monograph drug. Either FDA or a requestor can initiate the order process. 
50  A requestor can initiate the order process by submitting an OMOR with respect to certain drugs, 
51  classes of drugs, or combinations of drugs.6 The OMOR may request issuance of an order 
52  determining the following: (1) whether a drug is GRASE or (2) whether a change to a condition 
53  of use of a drug is GRASE.7  
54   
55  The OMOR must be submitted to FDA in the form and manner specified by the Agency.8 FDA 
56  will file the OMOR if FDA determines that the OMOR is sufficiently complete and formatted to 
57  permit FDA to conduct a substantive review.9 
58   
59   
60  III.  THE COMMON TECHNICAL DOCUMENT FORMAT AND CONTENT FOR 
61  AN OMOR 
62   
63  OMORs must be submitted in electronic format.10 OMORs should follow the organizational 
64  structure and format outlined in the Common Technical Document for the Registration of 
65  Pharmaceuticals for Human Use (CTD). The CTD format was developed by the International 
66  Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use 
67  (ICH) to streamline the submission requirements for Japan, the European Union, and the United 
 
5 The CARES Act also added section 744M to the FD&C Act authorizing FDA to assess and collect user fees 
dedicated to OTC monograph drug activities. 
 
6 See section 505G(b)(5) of the FD&C Act. 
 
7 See section 505G(b)(5)(B) of the FD&C Act. 
 
8 See section 505G(b)(5)(B)(i) of the FD&C Act. 
 
9 See section 505G(b)(5)(A) of the FD&C Act. 
 
10 See section 505G(j) of the FD&C Act. See also the draft guidance for industry Providing Over-the-Counter 
Monograph Submissions in Electronic Format (September 2022). When final, this guidance will represent the 
FDAs current thinking on this topic. 
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68  States. The CTD organizes quality, safety, and efficacy information into a common format that 
69  has been adopted by ICH regulatory authorities. The CTD format is sufficiently flexible to 
70  accommodate a variety of types and sources of information that may be included in OMORs.  
71   
72  FDA has issued guidance documents specific to CTD11 for organizing certain applications that 
73  will be submitted to FDA. The recommendations provided in these guidance documents are also 
74  applicable to OMORs. Although, in general, requestors should follow the recommendations 
75  provided in previously issued CTD guidance documents, this guidance highlights additional 
76  format and content recommendations specific to an OMOR. 
77   
78  An OMOR should be organized into five modules as follows: 
79   
80    Module 1: Administrative Information 
81    Module 2: Summaries  
82    Module 3: Quality  
83    Module 4: Nonclinical Study Reports  
84    Module 5: Clinical Study Reports  
85   
86  CTD is designed to accommodate multiple types of regulatory applications; it contains section 
87  headings and section subheadings that may not be pertinent to all OMORs. Therefore, an OMOR 
88  may not include all the information identified for an applicable module, section, or subsection 
89  described in this guidance or other CTD guidance documents. In those circumstances, a 
90  requestor should indicate that no information is being submitted for a given module or a section 
91  or subsection of a module.  
92   
93  A.  MODULE 1: ADMINISTRATIVE INFORMATION 
94   
95  1.  Format 
96   
97  Module 1: Administrative Information should contain six sections in the following order: 
98   
99    Table of Contents 
100    Cover Letter 
101    Administrative Information 
102    References 
103    Meetings 
104    Labeling 
105   
 
11 For guidances for industry that address CTD, see the FDA guidance web page at 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm. At this time, 
submission of OMORs should not be done through the electronic CTD (eCTD), which is the standard format for 
electronic regulatory submissions for new drug applications (NDAs), abbreviated new drug applications (ANDAs), 
certain biologics license applications (BLAs), and certain investigational new drug applications. See the guidances 
for industry Providing Regulatory Submissions in Electronic Format  Certain Human Pharmaceutical Product 
Applications and Related Submissions Using the eCTD Specifications (February 2020) and Providing Regulatory 
Submissions in Electronic Format  Submissions Under Section 745A(a) of the Federal Food, Drug, and Cosmetic 
Act (December 2014). See also section 745A(a) of the FD&C Act (21 U.S.C. 379k-1(a)). 
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106  2.  Content 
107   
108  a.  Table of contents 
109   
110  An OMOR should have a comprehensive table of contents (TOC) for the entire submission. The 
111  comprehensive TOC significantly enhances the usefulness of the document. It should include a 
112  complete list of all documents provided in the submission by module. 
113   
114  b.  Cover letter 
115   
116  In general, the cover letter should contain pertinent information that aids communication 
117  regarding the review of the OMOR. At minimum, the cover letter should address the following: 
118   
119    Indicate the applicable OTC monograph or request and rationale for creation of a new 
120  OTC monograph. 
121   
122    Describe the change(s) to the OTC monograph condition(s) being proposed in the 
123  OMOR. 
124   
125    Indicate the proposed classification of the OMOR as a Tier 1 or Tier 2 OMOR.12   
126   
127    Provide the name and the full contact information of the requestor(s). 
128   
129    Indicate the OMOR submission date. 
130   
131    Provide information about the proposed OTC monograph condition of use including 
132  active ingredient(s), pharmacological class, intended use, strength, specific dosage form, 
133  route of administration, directions for use, and any other pertinent information. 
134   
135    Describe the data and information included in the OMOR to support the proposed change 
136  to the OTC monograph condition of use. 
137   
 
12 This information is relevant to the requirements under sections 505G(b)(5)(A)(i) and 505G(b)(5)(C)(iv)(II) of the 
FD&C Act. Section 744L of the FD&C Act defines Tier 1 and Tier 2 OMORs. A Tier 1 OMOR is any OMOR not 
determined to be a Tier 2 OMOR. See section 744L(8) of the FD&C Act. A Tier 2 OMOR is a request for the 
following: (1) reordering of existing information in the Drug Facts label of an OTC monograph drug; (2) addition of 
information to the Other Information section of the Drug Facts label of an OTC monograph drug (subject to 
certain limitations); (3) modification to the Directions section of the Drug Facts label of an OTC monograph drug, 
consistent with changes made pursuant to section 505G(c)(3)(A) of the FD&C Act; (4) standardization of the 
concentration or dose of a specific finalized ingredient within a particular finalized monograph; (5) change to 
ingredient nomenclature to align with nomenclature of a standards-setting organization; or (6) addition of an 
interchangeable term in accordance with 21 CFR 330.1 (or any successor regulations). See section 744L(9) of the 
FD&C Act. 
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138    Provide a certification that the requestor has submitted all evidence, both positive and 
139  negative, related to whether the ingredient or other condition of use is GRASE.13 
140   
141    Indicate whether the requestor is seeking market exclusivity under section 
142  505(G)(b)(5)(C) of the FD&C Act for a change subject to a final order, and provide the 
143  rationale. 
144   
145    Indicate whether FDA reviewed any protocols or held formal meetings with the requestor 
146  during the development of the OMOR, and if so, indicate the date(s).  
147   
148    Provide a statement listing the approximate size of the electronic submission (e.g., 2 
149  gigabytes) and a statement that the submission is virus-free with a description of the 
150  software (name, version, and company) that was used to check the files for viruses. 
151   
152    Provide the name, title, address, phone, fax, and email of the individual the Agency 
153  should contact about issues related to the submission. If there are separate regulatory and 
154  technical points of contact, include this information for both individuals.  
155   
156    Provide the signatorys name and contact information 
157   
158  c.  Administrative information 
159   
160  The requestor should provide the appropriate administrative documents and information in the 
161  OMOR. Examples of administrative documents and information include the following: 
162   
163    U.S. agent letter of appointment, if applicable.14  
164   
165    A statement that all information considered by the requestor to be confidential has been 
166  identified in the OMOR, including a description of the method used to identify the 
167  information as confidential. See section VI., Confidential Information, of this guidance 
168  for details on limitations associated with confidential information submitted under the 
169  OTC monograph order process.15  
170   
 
13 See the Over-the-Counter Monograph User Fee Program Performance Goals and Procedures  Fiscal Years 
20182022 document, which discusses content and format of monograph submissions, available at 
https://www.fda.gov/media/106407/download. 
 
14 If the requestor does not reside or have a place of business in the United States, an agent that resides or maintains 
a place of business in the United States should countersign the OMOR. 
 
15 Pursuant to section 505G(d) of the FD&C Act, FDA must make all information in an OMOR, with certain 
exceptions, public at the time of a proposed order. See section VI., Confidential Information. 
 
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171    An environmental assessment16 or the claim of categorical exclusion17 and the 
172  justification for the exclusion. A claim of categorical exclusion must (1) include a 
173  statement of compliance with the categorical exclusion criteria and (2) state that to the 
174  applicant's knowledge, no extraordinary circumstances exist.18 See section V., 
175  Environmental Assessment, of this guidance.  
176   
177    Statement of claimed exclusivity. 
178   
179  d.  References 
180   
181  The References section should include the following information, as applicable: 
182   
183    Letter of authorization. If providing reference to a third partys new drug application 
184  (NDA), abbreviated new drug application (ANDA), biologics license application (BLA), 
185  or drug master file (DMF), include letter(s) of authorization by the owner(s) of 
186  information giving authorization for the information to be used by the requestor in 
187  connection with the OMOR.19 If authorization to an NDA, ANDA, BLA, or DMF is not 
188  available, justify why the reference is still relevant.  
189   
190    Statement of right of reference. If providing reference to a third partys NDA, ANDA, 
191  BLA, or DMF, the requestor should include a statement indicating the NDA, ANDA, 
192  BLA, or DMF to which the requestor has a right of reference and identify the section(s) 
193  of the OMOR for which the letter(s) of authorization is relevant.  
194   
195    Previously submitted information to FDA, including the following:  
196   
197   Indicate whether the OMOR references data or information from any approved NDA 
198  or ANDA, licensed BLA, or DMF. 
199   
200   Identify data or information previously provided to FDA (such as data submitted to 
201  another OMOR, public comment(s) submitted to an order, or a citizen petition) for 
202  FDA to consider when reviewing the OMOR, including the submission date and file 
203  number.20  
204   
 
16 See 21 CFR 25.20. 
 
17 21 CFR 25.31. 
 
18 21 CFR 25.15(a). 
 
19 The owner of the information should be aware that in general the OTC monograph order process is a public 
process. Under this order process, section 505G(d) of the FD&C Act limits the information that can remain 
confidential after submission to FDA in connection with proceedings on an order, including an OMOR. See section 
VI., Confidential Information. 
 
20 The requestor should provide a complete copy of the previously submitted information in the appropriate module. 
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205  e.  Meetings 
206   
207  The Meetings section should contain a listing of all meetings with FDA, including complete 
208  copies of meeting background materials and meeting correspondence, pertaining to the specific 
209  OMOR. The requestor should identify all meetings that pertain to the specific OMOR and 
210  identify any information that it considers to be confidential, if applicable. 
211   
212  f.  Labeling 
213   
214  The Labeling section should include the following: 
215   
216    An example of proposed labeling that reflects the OTC monograph condition(s) of use 
217  proposed in the OMOR 
218   
219    The proposed OTC monograph that reflects the OTC monograph condition(s) of use 
220  proposed in the OMOR 
221   
222  B.  MODULE 2: SUMMARIES 
223   
224  1.  Format 
225   
226  Module 2: Summaries should contain seven sections in the following order: 
227   
228  2.1 Table of Contents 
229  2.2 Introduction to the Summary Documents 
230  2.3 Quality Overall Summary 
231  2.4 Nonclinical Overview 
232  2.5 Clinical Overview 
233  2.6 Nonclinical Written and Tabulated Summaries 
234  2.7 Clinical Summary 
235   
236  2.  Content 
237   
238  a.  Table of contents  
239   
240  The comprehensive TOC should list all the documents provided in the OMOR for Modules 2 
241  through 5.  
242   
243  b.  Introduction to the summary documents 
244   
245  The Introduction section to the summary documents should provide a concise narrative summary 
246  of (1) the positive safety and effectiveness data supporting a determination that a specific drug, 
247  class of drugs, or combination of drugs with the proposed active ingredient or other condition of 
248  use is GRASE for the intended nonprescription use, and (2) the negative safety and effectiveness 
249  data that are not supportive of a determination that the specific drug, class of drugs, or 
250  combination of drugs or other condition of use is GRASE. The introduction should clearly 
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251  identify and address each of the major topics addressed in the submission. The introduction 
252  should include a summary table listing all studies included in the submission with their 
253  corresponding titles (as they appear in the study reports), study numbers, and location in the 
254  submission (with hyperlinks to each study). There should be one clearly identified study number 
255  for each study submitted.  
256   
257  c.  Quality overall summary 
258   
259  The Quality Overall Summary section should provide a summary of all chemistry and 
260  manufacturing data included in the submission. It should not include information, data, or 
261  justification that was not included in Module 3 (the quality module). It should include a 
262  discussion of key issues that integrates information from sections in Module 3 and supporting 
263  information from other modules, including cross-referencing to volume and page number in 
264  other modules. Most of the information in this section, including tables, figures, or other items, 
265  can be imported directly from Module 3. 
266   
267  For content and format recommendations for the Quality Overall Summary section for an 
268  OMOR, requestors should refer to the ICH guidance for industry M4Q: The CTD  Quality 
269  (August 2001).  
270   
271  d.  Nonclinical overview 
272   
273  The Nonclinical Overview section should present an integrated and critical assessment of the 
274  pharmacologic, pharmacokinetic, and toxicologic evaluation of the active ingredient or other 
275  conditions of use. Where relevant guidances on the conduct of studies exist, requestors should 
276  take these guidances into consideration and discuss any deviation from the recommendations in 
277  these guidances. The nonclinical testing strategy should be discussed and justified. There should 
278  be comments on the good laboratory practice status of the studies submitted, taking into 
279  consideration which studies are pivotal to support the safety of the ingredient. Requestors should 
280  indicate any association between nonclinical findings and the quality assessment, the results of 
281  clinical studies, or the effects seen with related drug products or ingredients, as appropriate.  
282   
283  For content and structural format recommendations for the Nonclinical Overview section for an 
284  OMOR, requestors should refer to the ICH guidance for industry M4S: The CTD  Safety 
285  (August 2001). 
286   
287  e.  Clinical overview 
288   
289  The Clinical Overview section should present an integrated and critical assessment of all the 
290  clinical data included in the OMOR (e.g., clinical effectiveness studies, biopharmaceutics, 
291  clinical pharmacology data, safety studies, consumer behavior studies, postmarketing safety 
292  data). The Clinical Overview section should provide the rationale for the OTC monograph drug 
293  development program and a succinct discussion and interpretation of the clinical findings 
294  together with any other relevant information (e.g., pertinent animal data or drug product quality 
295  issues that may have clinical implications) necessary to present the conclusions and implications 
296  of the data. The Clinical Overview section should (1) present the strengths and limitations of the 
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297  OTC monograph drug development program and study results, (2) analyze the benefits and risks 
298  of the conditions of use proposed in the OMOR for the OTC monograph drug for its intended 
299  use, and (3) describe how the study results support critical parts of the labeling. 
300   
301  For content and format recommendations for the Clinical Overview section for an OMOR, 
302  requestors should refer to the ICH guidance for industry M4E(R2): The CTD  Efficacy (July 
303  2017). 
304   
305  f.  Nonclinical written and tabulated summaries 
306   
307  The Nonclinical Written and Tabulated Summaries section should provide data summaries, not a 
308  complete exposition. Only in unusual cases should the narrative parts of the Nonclinical 
309  Overview section be the same as the summaries found in the nonclinical study reports in Module 
310  4. In general, the narrative parts of the Nonclinical Written and Tabulated Summaries section 
311  should be different from those in the Nonclinical Overview section. 
312   
313  For recommendations on general presentation of this section such as the order of presentation of 
314  information within each section, use of tables and figures, length of written nonclinical 
315  summaries, and sequence of written summaries and tabulated summaries, requestors should refer 
316  to the ICH guidance for industry M4S: The CTD  Safety. 
317   
318  Nonclinical written summaries 
319   
320  The nonclinical written summaries should include a narrative summary of all the nonclinical data 
321  included in the submission. This includes nonclinical pharmacology, pharmacokinetics, and 
322  toxicology.  
323   
324  For recommendations on the content for each nonclinical written summary, requestors should 
325  refer to the ICH guidance for industry M4S: The CTD  Safety. Requestors should modify the 
326  format, if needed, to provide the best possible presentation of the information and to facilitate the 
327  understanding and evaluation of the results.  
328   
329  Nonclinical tabulated summaries 
330   
331  Requestors should follow the order of presentation given for the nonclinical written summaries 
332  for the preparation of the tables for the nonclinical tabulated summaries. 
333   
334  The summary tables for the nonclinical information submitted in an OMOR should be provided 
335  in the format outlined in the ICH guidance for industry M4S: The CTD  Safety.  
336   
337  For the recommended formats for the tables in the nonclinical tabulated summaries, requestors 
338  should refer to Appendices B and C in the ICH guidance for industry M4S: The CTD  Safety 
339  Appendices (August 2001). However, requestors should modify the format, if warranted, to 
340  provide the best possible presentation of the information and to facilitate the understanding and 
341  evaluation of the results.  
342   
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343  g.  Clinical summary 
344   
345  The Clinical Summary section should provide a detailed, factual summary of all of the clinical 
346  information in the OMOR. This includes information provided in clinical study reports; 
347  information provided in consumer behavior study reports; information obtained from any meta-
348  analyses or other cross-study analyses for which full reports have been included in Module 5; 
349  and postmarketing data for drugs that have been marketed in the United States or in other regions 
350  including data from both the prescription and nonprescription settings. When summarizing 
351  postmarketing data for drugs that have been marketed in the nonprescription setting in other 
352  regions, the requestor should provide the regulatory status of the drug for each region including 
353  information about whether there are limitations or restrictions on access (e.g., pharmacy only, 
354  pharmacist only, general sales).  
355   
356  For recommendations on the content and format for each subsection in the Clinical Summary 
357  section, requestors should refer to the ICH guidance for industry M4E(R2): The CTD  Efficacy. 
358   
359  C.  MODULE 3: QUALITY DATA 
360   
361  1.  Format 
362   
363  Module 3: Quality Data should be organized according to the following general section outline: 
364   
365  3.1 Module 3 Table of Contents  
366  3.2 Body of Data  
367  3.3 Literature References 
368   
369  For recommendations on the format of information in Module 3 and its organizational placement 
370  within the module, requestors should refer to the ICH guidances for industry M4Q: The CTD  
371  Quality and M4: The CTD  Quality Questions and Answers/Location Issues (June 2004).  
372   
373  2.  Content 
374   
375  Module 3 should discuss the chemistry, manufacturing, and controls reports for both drug 
376  substance and drug product. 
377   
378  For recommendations on content to include in Module 3 of the OMOR, requestors should refer 
379  to the ICH guidance for industry M4Q: The CTD  Quality. 
380   
381  In addition, for the drug substance, Module 3 should also include the compendial status of the 
382  active ingredients in the United States Pharmacopeia (USP) National Formulary (NF). If there is 
383  no USP monograph for the active ingredient(s), then the requestor should provide a proposed 
384  USP monograph including a complete validation of the methods. 
385   
386   
387   
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388  D.  MODULE 4: NONCLINICAL STUDY REPORTS 
389   
390  1.  Format 
391   
392  Module 4: Nonclinical Study Reports should be organized according to the following general 
393  section outline: 
394   
395  4.1 Module 4 Table of Contents  
396  4.2 Study Reports  
397  4.3 Literature References 
398   
399  For recommendations on the structural format and organization of nonclinical study reports in an 
400  OMOR, requestors should refer to the ICH guidance for industry M4S: The CTD  Safety. 
401   
402  2.  Content 
403   
404  Module 4 should include data and reports from the nonclinical studies.  
405   
406  a.  Nonclinical studies  
407   
408  The nonclinical studies that may be necessary to support an OMOR include the following: (1) 
409  pharmacology studies, (2) general toxicity studies, (3) toxicokinetic and nonclinical 
410  pharmacokinetic studies, (4) reproduction toxicity studies, (5) genotoxicity studies, and (6) an 
411  assessment of carcinogenic potential. Requestors should conduct other nonclinical studies to 
412  assess phototoxicity, immunotoxicity, juvenile animal toxicity, and abuse liability on a case-by-
413  case basis.  
414   
415  For recommendations on the types of nonclinical safety studies that should be conducted to 
416  support an OMOR and their relation to the conduct of human clinical studies, requestors should 
417  refer to the ICH guidance for industry M3(R2): Nonclinical Safety Studies for the Conduct of 
418  Human Clinical Trials and Marketing Authorization for Pharmaceuticals (January 2010). 
419   
420  b.  Individual study reports 
421   
422  Each individual nonclinical study report should include its own TOC and summary. Requestors 
423  should include complete data sets (not selected or summary data) in the submission.21 Data from 
424  studies provided only in summary form will generally not be sufficiently informative to support a 
425  determination that the condition of use is GRASE. 
426   
427   
428   
 
21 Although Standard for Exchange of Nonclinical Data (SEND) data sets and CTD tables are not required for 
OMORs, we recommend that requestors submit both data sets and tables in their submissions to facilitate review of 
the data. See the FDA Data Standards Advisory Board web page at https://www.fda.gov/industry/fda-resources-
data-standards. 
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429  E.  MODULE 5: CLINICAL STUDY REPORTS 
430   
431  1.  Format 
432   
433  Module 5: Clinical Study Reports should be organized according to the following general section 
434  outline: 
435   
436  5.1 Module 5 Table of Contents  
437  5.2 Tabular Listing of All Clinical Studies  
438  5.3 Clinical Study Reports  
439  5.4 Literature References 
440   
441  For recommendations on the specific organization and placement of clinical study reports and 
442  related information in Module 5, requestors should refer to the ICH guidance for industry 
443  M4E(R2): The CTD  Efficacy. 
444   
445  2.  Content 
446   
447  Module 5 in the OMOR should include full reports of the following: (1) all clinical effectiveness 
448  and safety studies and other clinical data, (2) all clinical pharmacology and human toxicokinetic 
449  data, (3) all consumer behavior studies, and (4) postmarketing experience. In addition to actual 
450  study reports, the requestor should include all other types of clinical data (e.g., from literature 
451  searches, scientific articles, other published materials) in this module.22  
452   
453  a.  Clinical studies and related information 
454   
455  For recommendations on the types of clinical studies and related information that can be 
456  included in Module 5 of an OMOR, requestors should refer to the ICH guidance for industry 
457  M4E(R2): The CTD  Efficacy. 
458   
459  In addition to the clinical studies referenced in the ICH guidance for industry M4E(R2): The 
460  CTD  Efficacy, requestors may also need to include consumer behavior study reports or other 
461  information demonstrating prima facie safe nonprescription marketing and use23 in Module 5 of 
462  the OMOR. 
463   
 
22 Requestors should include a hyperlink to a full copy of the referenced article or other referenced published 
material. If the scientific article or other published material is not accessible online, the requestor should include a 
complete copy in the submission. 
 
23 See section 505G(b)(6)(C) of the FD&C Act. 
 
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464  Consumer Behavior Studies 
465   
466  While not all consumer behavior studies are clinical studies, all consumer behavior study reports 
467  should be included in Module 5. Consumer behavior studies include label comprehension 
468  studies,24 self-selection studies,25 actual use studies, and human factors studies.26  
469   
470  Safe nonprescription marketing and use 
471   
472  Some OMORs may propose that a drug is GRASE if the drug contains an active ingredient not 
473  previously incorporated in a drug specified in section 505G(a)(1), (a)(2), or (a)(3) of the FD&C 
474  Act, subject to a final order under section 505G(b) of the FD&C Act, or subject to a final 
475  sunscreen order (as defined in section 586(2)(A) of the FD&C Act).27 For such OMORs, Module 
476  5 must include information demonstrating prima facie safe nonprescription marketing and use, 
477  including the following, as applicable:28   
478   
479  1)  Information demonstrating that the drug has a history of being marketed and safely used 
480  by consumers in the United States as a nonprescription drug under comparable conditions 
481  of use must be included.29   
482   
483  2)  If the drug has not been previously marketed in the United States as a nonprescription 
484  drug, the requestor must include information sufficient for a prima facie demonstration 
485  that the drug was marketed and safely used under comparable conditions of marketing 
486  and use in a country listed in section 802(b)(1)(A) of the FD&C Act or designated by 
487  FDA in accordance with section 802(b)(1)(B) of the FD&C Act.30 The time period of 
488  marketing and use must provide reasonable assurances concerning the safe 
489  nonprescription use of the drug. Additionally, the requestor should provide evidence that 
490  during the time period of nonprescription use, the drug was subject to sufficient 
491  monitoring by a regulatory body considered acceptable by FDA for such monitoring, 
492  including for adverse events associated with nonprescription use of the drug.31  
493   
 
24 See the guidance for industry Label Comprehension Studies for Nonprescription Drug Products (August 2010).  
 
25 See the guidance for industry Self-Selection Studies for Nonprescription Drug Products (April 2013).  
 
26 See the draft guidance for industry and FDA staff Human Factors Studies and Related Clinical Study 
Considerations in Combination Product Design and Development (February 2016). When final, this guidance will 
represent the FDAs current thinking on this topic. 
 
27 See section 505G(b)(6)(B) of the FD&C Act.  
 
28 See section 505G(b)(6)(C) of the FD&C Act. 
 
29 See section 505G(b)(6)(C)(i) of the FD&C Act. 
 
30 See section 505G(b)(6)(C)(ii) of the FD&C Act. 
 
31 See section 505G(b)(6)(C)(ii) of the FD&C Act. 
 
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494  3)  If FDA determines that information described in (1) or (2) above is not needed to provide 
495  a prima facie demonstration that the drug can be safely marketed and used as a 
496  nonprescription drug, the requestor must submit other information FDA determines is 
497  sufficient for such purposes.32 
498   
499  If the OMOR fails to include such information, FDA will refuse to file the OMOR and require 
500  that the nonprescription marketing of the drug be pursuant to an approved application under 
501  section 505 of the FD&C Act.33   
502   
503  b.  Reports of postmarketing experience 
504   
505  For drug products or active ingredients that are currently marketed, Module 5 should include 
506  reports that summarize the marketing experience relevant to the OTC monograph condition of 
507  use proposed in the OMOR, including detailed information for relevant safety observations.  
508   
509  Module 5 should include all relevant postmarketing data available to the requestor (published 
510  and unpublished, including periodic safety update reports if available). The requestor should 
511  provide in Module 5 a tabulation of serious adverse events reported after the drug is marketed, 
512  including any potentially serious drug interactions. The requestor should describe any 
513  postmarketing findings in subgroups. The requestor should provide safety information from 
514  various safety databases such as the FDA Adverse Event Reporting System, World Health 
515  Organization VigiBase, American Association of Poison Control Centers, other countrys or 
516  regions safety database, or a requestors (or their affiliates) safety database.  
517   
518  If data are available for different combinations of active ingredients, different doses, different 
519  dosage forms, significantly different formulations, or different populations of use, the requestor 
520  should provide separate tabular summaries in Module 5.  
521   
522  The reports of postmarketing experience should include discussions and analyses of the 
523  postmarketing data along with the conclusions and implications of the data as it pertains to the 
524  OTC monograph condition of use proposed in the OMOR. The reports should also include any 
525  relevant safety discussions and analyses from the literature, if available. 
526   
527  Reports that are heavily redacted or do not provide clear drug product identification are unlikely 
528  to provide useful information.  
529   
530  c.  Individual study reports 
531   
532  Each individual clinical study report should include its own TOC and summary. The requestor 
533  should include complete subject-level data sets (not selected or summary data). Each study 
534  should have its own data sets for efficacy and safety data, and there should be integrated datasets 
535  for safety and, if applicable, integrated datasets for efficacy. In general, we expect that data from 
536  studies provided only in summary form will not be sufficiently informative to support a 
 
32 See section 505G(b)(6)(C)(iii) of the FD&C Act. 
 
33 See section 505G(b)(6)(A) of the FD&C Act.  
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537  conclusion that a drug, class of drugs, or combination of drugs is GRASE for the intended 
538  nonprescription use.  
539   
540  Each individual study should describe the statistical evaluation of clinical data (e.g., information 
541  concerning the description and analysis of each controlled clinical study and the documentation 
542  and supporting statistical analyses used in evaluating the controlled clinical studies; information 
543  concerning a summary of information about the safety of the drug, the documentation and 
544  supporting statistical analyses used in evaluating the safety information).  
545   
546  Each individual study report should include all necessary appendices including but not limited to 
547  study information (e.g., full protocols and protocol amendments, list of all independent ethics 
548  committees or institutional review boards consulted, documentation of statistical methods), 
549  patient data listings, and case report forms.  
550   
551  For additional guidance on the structure and content of clinical study reports, requestors should 
552  refer to the ICH guidance for industry E3 Structure and Content of Clinical Study Reports (July 
553  1996).  
554   
555   
556  IV.  GENERAL CONSIDERATIONS FOR AN OMOR 
557   
558  A.  Language 
559   
560  The OMOR should be in the English language. If any portion of a submission is in a foreign 
561  language, the requestor should provide a complete and accurate English translation, including 
562  English translations of any references. 
563   
564  B.  Fonts 
565   
566  Font size for text and tables should be of a style and size that is large enough to be easily legible, 
567  even after photocopying or when provided electronically. We recommend that narrative text be 
568  submitted in Times New Roman 12 point font. Generally, font sizes 9 to 10 points are considered 
569  acceptable in tables, but requestors should avoid fonts smaller than 12 points whenever possible. 
570  When choosing a font size for tables, it is important to balance the desirability of providing 
571  sufficient information on a single page to facilitate data comparisons with that of maintaining a 
572  font size that remains readable. If the font size is too large, data comparisons may be complicated 
573  because data may be presented in multiple tables. We recommend 10 point font for footnotes. 
574   
575  C.  Paper size 
576   
577  Generally, the requestor should format an OMOR to standard U.S. letter size paper (8.5 by 11 
578  inches). Occasionally, a requestor may format individual pages larger than standard paper size to 
579  present a floor plan, synthesis diagram, batch formula, or manufacturing instructions. 
580   
581   
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582  D.  Pagination 
583   
584  Page numbering should be at the document level and not at the module level. (The entire 
585  submission should never be numbered consecutively by page.) In general, all documents should 
586  have page numbers. Because the page numbering is at the document level, there should only be 
587  one set of page numbers for each document.  
588   
589  If the OMOR includes a document within a document, such as a protocol within a study report, 
590  the document to be included (in this case, the protocol) should be attached as an appendix.  
591   
592  E.  OMOR Searchability 
593   
594  The entire OMOR submission should be electronically searchable. An OMOR should not contain 
595  nonsearchable text or images. 
596   
597  F.  Hyperlinks to References 
598   
599  All items in reference lists and all in-text references citing scientific articles or other published 
600  materials should include a hyperlink to a full copy of the referenced article or other referenced 
601  published material. Requestors should place hyperlinks to scientific articles and other published 
602  materials in the relevant sections by subject.  
603   
604   
605  V.  ENVIRONMENTAL ASSESSMENT 
606   
607  The National Environmental Policy Act of 1969 (NEPA) requires all Federal agencies to assess 
608  the environmental impacts of their actions and to ensure that the interested and affected public is 
609  informed of environmental analyses. FDA complies with NEPA by evaluating environmental 
610  impacts of agency action such as decisions on applications or petitions as a part of its regulatory 
611  process.  
612   
613  FDAs regulations in 21 CFR part 25 specify that environmental assessments (EAs) must be 
614  submitted as part of applications or petitions that request FDA action, unless the action qualifies 
615  for categorical exclusion.34 Because an OMOR is a request for agency action analogous to an 
616  application or petition, the requestor must accompany such a request with either an EA or a 
617  claim of categorical exclusion.35  
618   
 
34 21 CFR 25.15(a). 
 
35 As stated in 21 CFR 25.15, all applications or petitions requesting agency action require the submission of an EA 
or a claim of categorical exclusion. Under 21 CFR 25.31, the same categorical exclusion criteria apply to actions 
on OTC monographs as apply to applications like NDAs and ANDAs.  See the final rule, National Environmental 
Policy Act; Revision of Policies and Procedures (NEPA final rule), published July 29, 1997 (62 FR 40570 at 
40578). It follows that the requirement to submit an EA, when not categorically excluded, would similarly apply to 
requests for actions on OTC monographs.  FDA will treat like actions alike, regardless of the avenue through which 
the actions are requested (NEPA final rule at 40578). 
 
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619  Regulation 21 CFR 25.31 sets forth the classes of actions related to human drugs and biologics 
620  that are subject to categorical exclusions and, therefore, ordinarily do not require the preparation 
621  of an EA. Barring extraordinary circumstances,36 the OMORs described below each have a claim 
622  of categorical exclusion: 
623   
624    The OMOR does not propose to increase the use of the active moiety.37 
625   
626    The OMOR proposes to increase the use of active moiety, but the estimated concentration 
627  of the substance at the point of entry into the aquatic environment will be below 1 part 
628  per billion.38 
629   
630    The OMOR is for a substance that occurs naturally in the environment, and the OMOR 
631  does not propose to alter significantly the concentration or distribution of the substance, 
632  its metabolites, or degradation products in the environment.39 
633   
634  If none of these categorical exclusions apply, then the requestor must prepare an EA that 
635  addresses the relevant environmental issues and include the EA in the OMOR.40 An adequate EA 
636  is one that contains sufficient information to enable FDA to determine whether the proposed 
637  action may significantly affect the quality of the human environment.41 
638   
639  Requestors must comply with the requirements as set forth in 21 CFR 25. In addition, requestors 
640  should refer to the guidances for industry Environmental Assessment of Human Drug and 
641  Biologics Applications (July 1998) and Environmental Assessment: Questions and Answers 
642  Regarding Drugs With Estrogenic, Androgenic, or Thyroid Activity (March 2016) for general 
643  recommendations on how to prepare EAs for submission. For further information see regulations 
644  promulgated by the Council of Environmental Quality at 40 CFR part 1500. 
645   
646   
647  VI.  CONFIDENTIAL INFORMATION 
648   
649  In general, the OTC monograph order process is a public process. Under this order process, 
650  section 505G(d) of the FD&C Act limits the information that can remain confidential after 
651  submission to FDA in connection with proceedings on an order, including an OMOR.  
 
36 As described in 21 CFR 25.21, an EA is required for an action that ordinarily would be excluded if certain 
extraordinary circumstances indicate that the proposed action may significantly affect the quality of the human 
environment. When extraordinary circumstances exist, then the requestor of an OMOR that otherwise would be 
categorically excluded is required to submit an EA consistent with 21 CFR 25.21. 
 
37 21 CFR 25.31(a). 
 
38 21 CFR 25.31(b). 
 
39 21 CFR 25.31(c). 
 
40 See 21 CFR 25.15(a), 21 CFR 25.21, and 21 CFR 25.31. 
 
41 21 CFR 25.15(a). 
 
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652   
653  In general, until disclosure is triggered under section 505G(d)(2) of the FD&C Act, any 
654  information, including reports of testing conducted on the drug or drugs involved, that is 
655  submitted by a requestor in connection with proceedings on an order under section 505G and is a 
656  trade secret or confidential information subject to 5 U.S.C. 552(b)(4) or 18 U.S.C. 1905 will not 
657  be disclosed to the public unless the requestor consents to that disclosure.42 However, FDA 
658  generally must make any information submitted by a requestor in support of an OMOR (e.g., the 
659  contents of the OMOR) available to the public not later than the date on which the proposed 
660  order is issued.43 Nonetheless, the information will remain confidential if (1) the information 
661  pertains to pharmaceutical quality information, unless such information is necessary to establish 
662  standards under which a drug is GRASE; (2) the information is of the type contained in raw 
663  datasets; (3) the information is submitted in a requestor-initiated request, but the requestor 
664  withdraws the request in accordance with withdrawal procedures established by FDA before 
665  FDA issues the proposed order; or (4) FDA requests and obtains the information under section 
666  505G(c) of the FD&C Act and the information is not submitted in relation to an order under 
667  section 505G(b) of the FD&C Act.44 
 
42 See section 505G(d)(1) of the FD&C Act. 
 
43 See section 505G(d)(2)(A)(i) of the FD&C Act. 
 
44 See section 505G(d)(2)(B) of the FD&C Act. 
  18