Contact Dermatitis From Topical Drug Products for Cutaneous Application: Human Safety Assessment Guidance for Industry

Administrative draft guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

03/05/20
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DRAFT GUIDANCE
This guidance document is being distributed for comment purposes only.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publication in the Federal Register of the notice announcing the availability of the draft
guidance.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

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Draft — Not for Implementation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	1
for Cutaneous Application: Human Safety Assessment	2
Guidance for Industry1
3
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
16
I. 	INTRODUCTION	17
18
The purpose of this guidance is to provide FDA’s current thinking about local safety assessment	19
for the risk of contact dermatitis (irritant, allergic, and photoallergic) during development of new	20
drug products2 intended for topical application to the skin. The recommendations in this	21
guidance are informed in part by the public workshop entitled “Human Dermal (Skin) Safety	22
Testing for Topical Drug Products,” which FDA hosted on September 10, 2018.3	
23
24
This guidance does not address local safety assessment for other cutaneous adverse reactions	25
(e.g., hyperpigmentation, atrophy) for topical drug products, local safety assessment for	26
transdermal systems, evaluation of nonprescription drug ingredients to determine whether they	27
are “generally recognized as safe,” or development of generic drug products. It also does not	28
address phototoxicity (photoirritation), as this topic has been addressed in the ICH guidance for	29
industry S10 Photosafety Evaluation of Pharmaceuticals (January 2015).4	
30
31
In general, FDA’s guidance documents do not establish legally enforceable responsibilities.	32
Instead, guidances describe the Agency’s 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
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.

Contains Nonbinding Recommendations
Draft — Not for Implementation
2
the word should in Agency guidances means that something is suggested or recommended, but	35
not required.	36
37
II. 	BACKGROUND	38
39
Topical drug products have the potential to induce contact dermatitis because of their route of	40
administration. Information about contact dermatitis, including the etiology (e.g., irritant,	41
allergic, photoallergic), incidence, and severity, is incorporated into labeling to inform treatment	42
decisions and is most clinically relevant when derived from clinical trials that replicate labeled	43
conditions of use.	44
45
46
III. 	RECOMMENDATIONS	47
48
We recommend assessing local skin reactions in clinical studies conducted during topical drug	49
product development:	50
51
• 	Use static (e.g., current state, noncomparative) scales to evaluate cutaneous signs such as	52
erythema, edema, and erosion.	53
54
• 	Use patient-reported outcome measures to assess symptoms such as pruritus or burning.	55
56
• 	Plan the timing and frequency of assessments to identify anticipated reactions.	57
58
• 	Characterize suspected adverse reactions of allergic or photoallergic contact dermatitis	59
using diagnostic patch testing or photopatch testing with the individual ingredients	60
(active and excipient) as well as the product.	61
62
We encourage sponsors to obtain information about contact dermatitis from study conditions that	63
reflect proposed labeled use and to meet with FDA to discuss planned safety assessments.	64
Separate studies designed solely to elicit contact dermatitis are not generally needed.	65
66
We also recommend that applicants submit information from existing databases regarding known	67
associations of individual ingredients with allergic or photoallergic contact reactions.	68