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: 
 
Office of Communications, Division of Drug Information 
Center for Drug Evaluation and Research 
Food and Drug Administration 
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https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
 
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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 
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 FDAs 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 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/RegulatoryInformation/Guidances/default.htm.   
  1  Contains Nonbinding Recommendations 
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, FDAs guidance documents do not establish legally enforceable responsibilities.  
Instead, guidances describe the Agencys 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 FDAs current thinking on 
this topic.   
  2  Contains Nonbinding Recommendations 
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):327349. 
  3