Atopic Dermatitis: Timing of Pediatric Studies During Development of Systemic Drugs

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

Atopic Dermatitis: Timing
of Pediatric Studies During
Development of Systemic
Drugs
Guidance for Industry
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
October 2018
Clinical/Medical

Atopic Dermatitis: Timing
of Pediatric Studies During
Development of Systemic
Drugs
Guidance for Industry
Additional copies are available from:
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Center for Drug Evaluation and Research
Food and Drug Administration
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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
and/or
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Phone: 800-835-4709 or 240-402-8010; Email: ocod@fda.hhs.gov
https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
October 2018
Clinical/Medical

TABLE OF CONTENTS
I. 	INTRODUCTION AND BACKGROUND .................................................................... 1
II. 	TIMING OF PEDIATRIC STUDIES OF SYSTEMIC DRUGS FOR AD ................. 2

Contains Nonbinding Recommendations
1
Atopic Dermatitis: Timing of Pediatric Studies During
Development of Systemic Drugs
Guidance for Industry1
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on
this topic. It does not establish any rights for any person and is not binding on FDA or the public. You
can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.
To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the
title page.
I. 	INTRODUCTION AND BACKGROUND
This guidance addresses FDA’s current thinking about the relevant age groups to study and how
early in drug development applicants should incorporate pediatric patients for development of
systemic drugs for atopic dermatitis (AD). The recommendations in this guidance are based on
input received from the March 9, 2015, Dermatologic and Ophthalmic Drug Advisory
Committee (DODAC) meeting on this topic and review of medical literature and relevant
statutes and regulations.
This guidance does not address the technical aspects of drug development for pediatric patients
with AD, which FDA will address in a future guidance.2
AD is a chronic pruritic inflammatory skin disease that primarily affects pediatric patients but
also occurs in adults. AD is associated with substantial morbidity, including sleep disruption,
decreased neurocognitive function, and impaired quality of life for patients and their families.
AD is also associated with numerous comorbidities, including cutaneous infections,
extracutaneous infections, asthma, rhinitis, food allergies, obesity, and hypertension.
Historically, FDA recommended that applicants provide data on the use of topical drug products
in pediatric patients for treatment of AD before initial drug approval. In contrast, FDA did not
recommend initiation of pediatric studies for systemic drugs under development for treatment of
1 This guidance has been prepared by the Division of Dermatology and Dental Products in the Center for Drug
Evaluation and Research in cooperation with the Center for Biologics Evaluation and Research at the Food and Drug
Administration.
2 Currently available is the draft guidance for industry General Clinical Pharmacology Considerations for Pediatric
Studies for Drugs and Biological Products. When final, this guidance will represent the FDA’s current thinking on
this topic. For the most recent version of a guidance, check the FDA guidance web page at
https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.

Contains Nonbinding Recommendations
2
AD and instead recommended the studies after approval of the drugs for adult use. At the March
9, 2015, meeting, the DODAC recommended that, for systemic drugs for AD, pediatric studies
generally should be initiated earlier during development.3
In general, FDA’s guidance documents do not establish legally enforceable responsibilities.
Instead, guidances describe the Agency’s 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. 	TIMING OF PEDIATRIC STUDIES OF SYSTEMIC DRUGS FOR AD
Applicants for systemic drugs for AD should consider the following recommendations
concerning the timing of pediatric studies, the relevant age groups to study, and the inclusion of
pediatric use information in labeling at the time of initial approval:
• 	Applicants should provide at the time of initial approval as much information as possible
in labeling regarding use in relevant pediatric populations to facilitate an understanding
of how to use the drug safely and effectively in pediatric patients.
• 	Studies of systemic treatments in pediatric patients with AD should be initiated early in
development, typically after obtaining initial evidence of efficacy and safety from early
phase studies in adults. Applicants are encouraged to discuss the specifics of pediatric
programs as early as is feasible with the division because sponsors generally are required
to submit pediatric study plans under section 505B of the Federal Food, Drug, and
Cosmetic Act no later than 60 days after an end-of-phase 2 meeting.4
• 	A juvenile animal toxicity study that incorporates appropriate endpoints should be
considered before enrollment of pediatric patients with AD in clinical studies.
• 	Some major safety questions, such as the risk for long-latency or low-frequency adverse
reactions, may not be resolved before initiation of studies in pediatric patients with AD.
Considering the effect on the pediatric population of disease-related morbidity, the risk of
disease-related progression (e.g., atopic march), and the relative risk-benefit calculus with
3 See the 2015 DODAC meeting materials available at https://wayback.archive-
it.org/7993/20170111202321/http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Derma
tologicandOphthalmicDrugsAdvisoryCommittee/ucm431514.htm.
4 See section 505B(e)(2)(A)(ii) of the Federal Food, Drug, and Cosmetic Act (requiring the submission of the initial
pediatric plan “not later than 60 calendar days after the date of the end-of-Phase 2 meeting” or “such other time as
may be agreed upon between the Secretary and the applicant”). For further information on this subject, see the draft
guidance for industry Pediatric Study Plans: Content of and Process for Submitting Initial Pediatric Study Plans
and Amended Initial Pediatric Study Plans. When final, this guidance will represent the FDA’s current thinking on
this topic.

Contains Nonbinding Recommendations
3
off-label use of immunosuppressive therapies,5 it is not generally necessary to have an
extensive safety database in adults before initiating pediatric studies.
• 	It is important to study all relevant age groups, including children younger than 2 years of
age. A sequential approach (i.e., studying older pediatric subpopulations before younger
subpopulations) may be needed if:
‒ 	Specific information from the older subpopulation (e.g., pharmacokinetic
information) is needed to inform the study design for the younger subpopulation;
‒ 	An age-related technical issue (e.g., development of an age-appropriate dosage form
or measurement instrument) needs to be addressed before study of the younger
subpopulation; or
‒ 	A safety concern is expected to arise in a younger subpopulation (e.g., because of
immaturity of metabolic pathways), even if the safety concern was not observed in an
older subpopulation.
5 Sidbury R, Davis DM, Cohen DE, Cordoro KM, Berger TG, Bergman JN, et al., 2014, Guidelines of Care for the
Management of Atopic Dermatitis: Section 3. Management and Treatment With Phototherapy and Systemic
Agents, J Am Acad Dermatol, 71(2):327–349.