Contact Dermatitis from 
Topical Drug Products for 
Cutaneous Application:  
Human Safety Assessment 
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DRAFT GUIDANCE
 
 
  This guidance document is being distributed for comment purposes only.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 30 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publication in the Federal Register of the notice announcing the availability of the draft 
guidance.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) Jennifer Harmon at 240-402-4880. 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
March 2020 
Clinical/Medical
03/05/20   
Contact Dermatitis from 
Topical Drug Products for 
Cutaneous Application:  
Human Safety Assessment 
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) 
 
March 2020 
Clinical/Medical 
   
TABLE OF CONTENTS 
 
I.  INTRODUCTION..................................................................................................1 
II.  BACKGROUND ....................................................................................................2 
III.  RECOMMENDATIONS .......................................................................................2 
 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
1  Contact Dermatitis from Topical Drug Products 
2  for Cutaneous Application:  Human Safety Assessment 
3  Guidance for Industry1 
4   
5   
6   
7   
8  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
9  Administration (FDA or Agency) on this topic.  It does not establish any rights for any person and is not 
10  binding on FDA or the public.  You can use an alternative approach if it satisfies the requirements of the 
11  applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff responsible 
12  for this guidance as listed on the title page. 
13   
14   
15   
16   
17  I.  INTRODUCTION 
18   
19  The purpose of this guidance is to provide FDAs current thinking about local safety assessment 
20  for the risk of contact dermatitis (irritant, allergic, and photoallergic) during development of new 
21  drug products2 intended for topical application to the skin.  The recommendations in this 
22  guidance are informed in part by the public workshop entitled Human Dermal (Skin) Safety 
23  Testing for Topical Drug Products, which FDA hosted on September 10, 2018.3 
24   
25  This guidance does not address local safety assessment for other cutaneous adverse reactions 
26  (e.g., hyperpigmentation, atrophy) for topical drug products, local safety assessment for 
27  transdermal systems, evaluation of nonprescription drug ingredients to determine whether they 
28  are generally recognized as safe, or development of generic drug products.  It also does not 
29  address phototoxicity (photoirritation), as this topic has been addressed in the ICH guidance for 
30  industry S10 Photosafety Evaluation of Pharmaceuticals (January 2015).4 
31   
32  In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
33  Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
34  as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
                                                 
1 This guidance has been prepared by the Division of Dermatology and Dental Products in the Center for Drug 
Evaluation and Research at the Food and Drug Administration. 
 
2 For the purposes of this guidance, all references to drugs include both human drugs and therapeutic biological 
products unless otherwise specified. 
 
3 Check the workshop web page at https://www.fda.gov/drugs/news-events-human-drugs/human-dermal-skin-safety-
testing-topical-drug-products-regulatory-utility-and-evaluation-public. 
 
4 We update guidances periodically.  To make sure you have  the most recent version of a guidance, check the FDA 
guidance web page at https://www.fda.gov/regulatory-information/search-fda-guidance-documents. 
1  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
35  the word should in Agency guidances means that something is suggested or recommended, but 
36  not required. 
37   
38  II.  BACKGROUND 
39   
40  Topical drug products have the potential to induce contact dermatitis because of their route of 
41  administration.  Information about contact dermatitis, including the etiology (e.g., irritant, 
42  allergic, photoallergic), incidence, and severity, is incorporated into labeling to inform treatment 
43  decisions and is most clinically relevant when derived from clinical trials that replicate labeled 
44  conditions of use. 
45   
46   
47  III.  RECOMMENDATIONS  
48   
49  We recommend assessing local skin reactions in clinical studies conducted during topical drug 
50  product development: 
51   
52    Use static (e.g., current state, noncomparative) scales to evaluate cutaneous signs such as 
53  erythema, edema, and erosion. 
54   
55    Use patient-reported outcome measures to assess symptoms such as pruritus or burning. 
56   
57    Plan the timing and frequency of assessments to identify anticipated reactions.  
58  
59    Characterize suspected adverse reactions of allergic or photoallergic contact dermatitis 
60  using diagnostic patch testing or photopatch testing with the individual ingredients 
61  (active and excipient) as well as the product. 
62   
63  We encourage sponsors to obtain information about contact dermatitis from study conditions that 
64  reflect proposed labeled use and to meet with FDA to discuss planned safety assessments.  
65  Separate studies designed solely to elicit contact dermatitis are not generally needed. 
66   
67  We also recommend that applicants submit information from existing databases regarding known 
68  associations of individual ingredients with allergic or photoallergic contact reactions. 
2