Pediatric Study Plans:   
Content of and Process for 
Submitting Initial Pediatric 
Study Plans and Amended 
Initial Pediatric Study Plans 
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)  
 
July 2020 
Procedural 
 
   
Pediatric Study Plans:   
Content of and Process for 
Submitting Initial Pediatric 
Study Plans and Amended 
Initial Pediatric Study Plans  
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  
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https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs 
 
and/or 
 
Office of Communication, Outreach, and Development  
Center for Biologics Evaluation and Research 
Food and Drug Administration 
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Phone: 800-835-4709 or 240-402-8010; Email: ocod@fda.hhs.gov 
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances 
 
 
 
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)  
 
July 2020 
Procedural
  Contains Nonbinding Recommendations 
TABLE OF CONTENTS 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  APPLICATIONS THAT REQUIRE SUBMISSION OF AN INITIAL PSP .............. 4 
IV.  TIMELINES FOR AN INITIAL PSP SUBMISSION ................................................... 5 
V.  CONTENT OF THE INITIAL PSP ................................................................................ 6 
A.  Materially Incomplete iPSPs ......................................................................................................... 7 
B.  Recommendations for the Contents of Each Section of the iPSP .............................................. 7 
VI.  RELATIONSHIP OF AGREED INITIAL PSP TO THE REQUIREMENT TO  
  SUBMIT A PEDIATRIC STUDY PLAN WITH AN APPLICATION ..................... 19 
VII.  CONTENT AND TIMING OF REQUESTED AMENDMENT TO AN  
  INITIAL PSP ................................................................................................................... 19 
VIII.  NON-AGREED INITIAL PSPs ..................................................................................... 21 
IX.  REACHING AGREEMENT ON THE NON-AGREED INITIAL PSP .................... 21 
APPENDIX:  INITIAL PEDIATRIC STUDY PLAN TEMPLATE ..................................... 22 
  Contains Nonbinding Recommendations 
Pediatric Study Plans:  Content of and Process for  
Submitting Initial Pediatric Study Plans and  
Amended Initial Pediatric Study Plans 
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 
 
The purpose of this guidance is to provide recommendations to sponsors regarding the 
submission of an initial pediatric study plan (iPSP) and any amendments to the iPSP.  
Specifically, this guidance provides the current thinking of the Food and Drug Administration 
(FDA) regarding implementation of the requirement for sponsors to submit an iPSP, described in 
section 505B(e) of the Federal Food, Drug, and Cosmetic Act (FD&C Act).   
 
This guidance addresses the following: 
 
  Applications for which an iPSP is required  
  Timing of an iPSP submission 
  Content of an iPSP 
  Content and timing of a requested amendment to an agreed iPSP 
  A template that is recommend to be used for an iPSP submission2 
                                                 
1 This guidance has been prepared by the Pediatric Study Plan Working Group, composed of members from the 
Center for Drug Evaluation and Research (CDER), the Center for Biologics Evaluation and Research (CBER), and 
the Office of the Commissioner (OC) at the Food and Drug Administration.  
 
2 In addition to consulting guidance, a sponsor is encouraged to contact the specific CDER/CBER review division to 
discuss specific issues that arise during preparation of the iPSP.   
 
1  Contains Nonbinding Recommendations 
This guidance does not contain a discussion of general requirements for development of drugs 
for pediatric use under the Pediatric Research Equity Act (PREA) or the Best Pharmaceuticals 
for Children Act (BPCA).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.  BACKGROUND 
 
Over the last 2 decades, the FDA has worked to address the problem of inadequate testing of 
drugs in pediatric populations and inadequate pediatric use information in drug labeling.  In 
1994, the FDA published a final rule that required manufacturers of marketed drugs to survey 
existing data and determine whether those data were sufficient to support adding pediatric use 
information to the drugs labeling.4  However, the 1994 rule did not impose a general 
requirement that manufacturers carry out studies when existing information was not sufficient to 
support adding pediatric use information.  This initial attempt to encourage sponsors to submit 
pediatric studies and plans to sufficiently inform use of drugs in pediatric patients was not 
successful in achieving adequate labeling for most drugs regarding use in the pediatric 
subpopulation, and product labeling frequently failed to provide directions for safe and effective 
use in pediatric patients.   
 
To address this continuing problem, the Food and Drug Administration Modernization Act of 
19975 was signed into law and contained provisions that established incentives for conducting 
pediatric studies on drugs for which exclusivity or patent protection exists.  Also, on December 
2, 1998, the FDA published a regulation known as the pediatric rule.6  This rule partially 
addressed the lack of pediatric use information by requiring manufacturers of certain new and 
marketed drugs to conduct studies to provide sufficient data and information to support 
directions for pediatric use for the claimed indications.  This pediatric rule also stated that the 
FDA would provide sponsors with its best judgment on whether pediatric studies would be 
required and whether their submission would be deferred until after approval.  This input was 
                                                 
3 For purposes of this guidance, references to drugs and drug products include drugs approved under section 505 of 
the FD&C Act (21 U.S.C. 355) and biological products licensed under section 351 of the Public Health Service Act 
(42 U.S.C. 262). 
 
4 See Specific Requirements on Content and Format of Labeling for Human Prescription Drugs; Revision of 
Pediatric Use Subsection in the Labeling (59 FR 64240, December 13, 1994). 
 
5 Public Law 105-115, 111 Stat. 2296 (Nov. 21, 1997).   
 
6 See Regulations Requiring Manufacturers to Assess the Safety and Effectiveness of New Drugs and Biological 
Products in Pediatric Patients (63 FR 66632, December 2, 1998).  
2  Contains Nonbinding Recommendations 
given by the FDA at the end-of-phase 1 meeting, for drugs for life-threatening diseases,7 and at 
the end-of-phase 2 meeting, for other drugs.8   
 
The pediatric rule also stated that sponsors should submit, at least 1 month in advance of the end-
of-phase 2 meeting, certain background information, including a proposed timeline for protocol 
finalization, enrollment, completion, and data analysis, or, in the alternative, information to 
support a planned request for waiver or deferral.  However, on October 17, 2002, the U.S. 
District Court for the District of Columbia held that the FDA had exceeded its statutory authority 
when issuing the pediatric rule and the court enjoined the rules enforcement.9 
 
Congress subsequently passed PREA, which was signed into law on December 3, 2003.10  Many 
of the provisions described under the pediatric rule were adopted under PREA.  Under PREA as 
originally enacted and under its reauthorization under the Food and Drug Administration 
Amendments Act of 2007,11 a sponsor was not required to submit a proposed timeline and plan 
for the submission of pediatric studies during the investigational new drug application (IND) 
phase of drug development.  Under the Food and Drug Administration Safety and Innovation Act 
(FDASIA), signed into law on July 9, 2012, for the first time PREA12 includes a provision that 
requires a sponsor planning to submit an application for a drug subject to PREA to submit an 
iPSP early in the development process.13  The intent of the iPSP is for a sponsor to identify 
needed pediatric studies early in development and begin planning for these studies.  Early 
dialogue with the FDA on a comprehensive pediatric development plan, including both required 
pediatric studies under PREA and potential pediatric uses under the BPCA, is intended to result 
in a more efficient pediatric drug development program.  The timing and content of the 
submission of an iPSP are described below.  The FD&C Act, as amended by FDASIA, requires 
the FDA to issue regulations and guidance to implement these and other provisions.14   
 
The FDA Reauthorization Act of 2017 (FDARA), further updated PREA with respect to certain 
drugs intended for the treatment of an adult cancer and directed at a molecular target determined 
                                                 
7 See 21 CFR 312.81(a). 
 
8 For additional information on end-of-phase 1 meetings and end-of-phase 2 meetings, see 21 CFR 312.47(b) and 
312.82(b).   
 
9 Association of Am. Physicians & Surgeons, Inc. v. FDA, 226 F. Supp. 2d 204, 222 (D.D.C. 2002).   
 
10 Public Law 108-155, 117 Stat. 1936 (Dec. 3, 2003). 
 
11 Public Law 110-85, 121 Stat. 823 (Sept. 27, 2007).  
 
12 By convention, section 505B is often referred to as PREA, after the act that added that section to the FD&C Act.  
We follow that naming convention in this guidance. 
 
13 Public Law 112-144, 126 Stat. 993 (July 9, 2012). 
 
14 See section 505B(e)(7) of the FD&C Act; 21 U.S.C. 355c(e)(7). 
 
3  Contains Nonbinding Recommendations 
to be substantially relevant to the growth or progression of a pediatric cancer, and for which an 
original marketing application is submitted on or after August 18, 2020.15   
 
 
III.  APPLICATIONS THAT REQUIRE SUBMISSION OF AN INITIAL PSP 
 
A sponsor who is planning to submit a marketing application (or supplement to an application) 
for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route 
of administration is required to submit an iPSP16 unless the drug is for an indication for which 
orphan designation has been granted.17  In addition, a sponsor who is planning to submit, on or 
after August 18, 2020, an original application for a new active ingredient that is subject to the 
molecularly targeted cancer drug provision of PREA (i.e., the drug that is the subject of the 
application is intended for the treatment of an adult cancer and is directed at a molecular target 
that the FDA determines to be substantially relevant to the growth or progression of a pediatric 
cancer) is also required to submit an iPSP,18 regardless of whether the drug is for an indication 
for which orphan designation has been granted.19  By statute, a biosimilar product that has not 
been determined to be interchangeable with the reference product is considered to have a new 
active ingredient for purposes of PREA.20   
 
The sponsor must submit an iPSP for any new application or supplement that is subject to PREA, 
regardless of whether the FDA has previously granted waivers or deferrals under PREA for the 
same drug.21  Additionally, for drugs that are being developed specifically for use in pediatric 
populations, the sponsor should submit an iPSP.   
 
 
                                                 
15 Public Law 115-52, 131 Stat. 1005 (Aug. 18, 2017).  For additional information on FDAs implementation of 
these amendments to PREA and on the submission of iPSPs for oncology drugs in light of the amendments, see the 
draft guidances for industry FDARA Implementation Guidance for Pediatric Studies of Molecularly Targeted 
Oncology Drugs: Amendments to Sec. 505B of the FD&C Act (December 2019) and Pediatric Study Plans for 
Oncology Drugs:  Transitional Information Until Full Implementation of FDARA Section 504:  Questions and 
Answers (January 2020).  When finalized, these guidances will represent FDAs current thinking on these topics.  
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. 
  
16 See section 505B(e)(1) of the FD&C Act; 21 U.S.C. 355c(e)(1); and section 505B(a)(1)(A) of the FD&C Act; 21 
U.S.C. 355c(a)(1)(A).  
 
17 See section 505B(k)(1) of the FD&C Act; 21 U.S.C. 355c(k)(1). 
 
18 See section 505B(e)(1) of the FD&C Act; 21 U.S.C. 355c(e)(1); and section 505B(a)(1)(B) of the FD&C Act; 21 
U.S.C. 355c(a)(1)(B).  
 
19 See section 505B(k)(2) of the FD&C Act; 21 U.S.C. 355c(k)(2). 
 
20 See section 505B(l) of the FD&C Act; 21 U.S.C. 355c(l). 
 
21 See section 505B(e)(1) of the FD&C Act; 21 U.S.C. 355c(e)(1). 
4  Contains Nonbinding Recommendations 
IV.  TIMELINES FOR AN INITIAL PSP SUBMISSION 
 
A sponsor must submit an iPSP, if required under PREA, before the date on which the sponsor 
submits the required assessments or investigation and no later than either 60 calendar days after 
the date of the end-of-phase 2 meeting or such other time as agreed upon between FDA and the 
sponsor.22  The FDA expects to agree to time frames other than those described in this guidance 
only if there are exceptional circumstances.  In the absence of an end-of-phase 2 meeting, the 
sponsor should submit the iPSP as early as practicable but before the initiation of any phase 3 
studies, or any combined phase 2 and phase 3 studies, of the drug that is the subject of the iPSP.  
If a phase 3 study, or a combined phase 2 and phase 3 study, will not be conducted or will be 
conducted but not under IND, the sponsor should submit the iPSP no later than 210 calendar 
days before it submits a marketing application or supplement.  Sponsors should contact the 
appropriate component of the Center for Drug Evaluation and Research or the Center for 
Biologics Evaluation and Research if they believe exceptional circumstances exist. 
 
The sponsor should submit the iPSP to the relevant drugs IND for review by the Center for 
Drug Evaluation and Research or the Center for Biologics Evaluation and Research as 
appropriate.  In cases where the sponsor has no active IND for the drug but the sponsor expects 
to open the IND with an initial phase 3 study, the sponsor should submit the iPSP as a pre-IND 
submission.  In this situation, the FDA encourages the sponsor to schedule a pre-IND meeting 
before submission of the iPSP, and such submission should precede initiation of any phase 3 
studies or combined phase 2 and phase 3 studies.  In cases where the drug development program 
includes the possibility of using expedited programs,23 the FDA encourages the sponsor to have 
discussions about the pediatric development plans with the review division as early as possible. 
 
After the sponsor submits an iPSP, the FDA has 90 days to review the iPSP and provide a 
written response to the iPSP, or meet with the sponsor to discuss the iPSP, as appropriate.24  This 
review process includes consultation with FDAs internal Pediatric Review Committee 
(PeRC).25  The sponsor then has a second 90-day period during which it may review FDA 
comments and initiate any needed negotiations to discuss the iPSP.  By the end of this second 
90-day review period, the sponsor must submit an agreed iPSP.26  The FDA then has 30 days 
after receipt of the agreed iPSP to review and issue correspondence confirming agreement or 
issue correspondence stating disagreement.27  If the FDA does not agree, the iPSP is considered 
a non-agreed iPSP (see section VIII., Non-Agreed Initial PSPs).  The total length of time for 
                                                 
22 See section 505B(e)(2)(A) of the FD&C Act; 21 U.S.C. 355c(e)(2)(A). 
 
23 For further information on expedited programs, see the guidance for industry Expedited Programs for Serious 
ConditionsDrugs and Biologics (May 2014). 
 
24 See section 505B(e)(2)(C)(i)(II) and (e)(2)(C)(ii) of the FD&C Act; 21 U.S.C. 355c(e)(2)(C)(i)(II) and 
(e)(2)(C)(ii).  
 
25 See section 505B(e)(6) of the FD&C Act; 21 U.S.C. 355c(e)(6). 
 
26 See section 505B(e)(3) of the FD&C Act; 21 U.S.C. 355c(e)(3).   
 
27 See section 505B(e)(3) of the FD&C Act; 21 U.S.C. 355c(e)(3). 
5  Contains Nonbinding Recommendations 
review of an iPSP should not exceed 210 days.  A sponsor should not submit a marketing 
application or supplement until the FDA confirms agreement on the iPSP.   
 
 
V.  CONTENT OF THE INITIAL PSP 
 
The FD&C Act requires that an iPSP include (i) an outline of the pediatric study or studies that 
the sponsor plans to conduct (including, to the extent practicable, study objectives and design, 
age groups, relevant endpoints, and statistical approach); (ii) any request for a deferral, partial 
waiver, or waiver . . . if applicable, along with any supporting information; and (iii) other 
information specified in the regulations issued by the FDA.28  This section of the guidance 
describes information that is required or recommended to be included in the iPSP submission.  In 
certain situations, it may be premature to include a detailed outline of a planned pediatric study 
(or studies) because additional data are needed (e.g., efficacy, safety, potential endpoints).  In 
such cases, the outline of the pediatric studies should include a brief explanation for the lack of 
more detailed information.  The sponsor receives feedback at the time of the review of the iPSP 
on the planned request for waivers and/or deferrals.  For example, the FDA feedback may 
indicate concurrence with the planned deferral and/or waiver or, if FDA does not concur, include 
recommendations for the sponsor on the timing of pediatric drug development and on whether to 
include pediatric data in the initial marketing application instead of obtaining a deferral.  
However, FDA does not make a formal decision about granting a waiver and/or deferral of 
required pediatric assessments, or reports on the molecularly targeted pediatric cancer 
investigation, until the time of the approval of the marketing application.   
 
Appendix:  Initial Pediatric Study Plan Template provides a template that we recommend 
sponsors complete for the iPSP submission.29  The FDA acknowledges that the development 
program for a drug, including the design of the pediatric studies, may change as the sponsor 
collects new data from nonclinical studies, clinical trials, and/or other clinical development 
programs (e.g., data from drugs in the same or similar class).  The iPSP should include a well-
constructed pediatric plan based upon current knowledge of the drug and disease epidemiology; 
sponsors can submit amendments to an agreed iPSP at any time,30 including changes to the 
pediatric plan that need to be considered based on additional data described above (see also 
section VII., Content and Timing of Requested Amendment to an Initial PSP).  
 
In addition, sponsors can include information in the iPSP (see section 2 in section V.B., 
Recommendations for the Content of Each Section of the iPSP) about plans for submission of a 
concurrent or future proposed pediatric study request (PPSR), as appropriate.  However, the 
sponsor should submit the iPSP and PPSR as separate documents to facilitate the FDAs 
appropriate review and comment. 
 
                                                 
28 See section 505B(e)(2)(B) of the FD&C Act; 21 U.S.C. 355c(e)(2)(B).   
 
29 The template also is available at https://www.fda.gov/media/84944/download.  
 
30 See section 505B(e)(5) of the FD&C Act; 21 U.S.C. 355c(e)(5). 
6  Contains Nonbinding Recommendations 
Although, as stated above, the FDA does not make a formal decision about granting a waiver 
and/or deferral of required pediatric assessments or reports on the molecularly targeted pediatric 
cancer investigation until approval of the marketing application, the FDA considers the 
information contained in an agreed iPSP when considering any requests for waiver and/or 
deferral at the time of the marketing application review.   
 
A.  Materially Incomplete iPSPs 
 
Failure to include required information may result in an iPSP that the FDA considers materially 
incomplete.  For example, if a sponsor fails to address all pediatric age groups and all indications 
for which the drug is being developed that are subject to PREA, the FDA generally considers the 
iPSP to be materially incomplete.31  Additionally, if a sponsor fails to provide justification for 
any planned waivers or deferrals, the FDA may consider the iPSP to be materially incomplete.  If 
the iPSP is considered materially incomplete, the FDA intends to contact the sponsor, and the 
sponsor should submit a complete iPSP within 30 days to address the identified deficiencies.  A 
new 210-day review period will start when the sponsor submits a complete iPSP.32   
 
However, if the sponsor includes sufficient information for the FDA to evaluate the plan, even if 
the FDA disagrees with the proposed plan, the FDA in general considers the iPSP to be sufficient 
for initial review.  For example, if a sponsor includes a plan to request a full waiver with a 
justification and the FDA disagrees with this plan, the FDA does not intend to consider such 
disagreement as grounds for a determination that the iPSP is materially incomplete.   
 
B.  Recommendations for the Contents of Each Section of the iPSP 
 
This section provides specific recommendations for the content of each section of the iPSP. 
 
TITLE PAGE 
 
Sponsors should include relevant administrative information on the title page (e.g., drug name, 
IND number, indication or indications that apply) (see Appendix:  Initial Pediatric Study Plan 
Template). 
 
                                                 
31 The FDA anticipates that there will be additional considerations for applications described in section 
505B(a)(1)(B) of the FD&C Act that require submission of reports on the molecularly targeted pediatric cancer 
investigation described in section 505B(a)(3) of the FD&C Act.  For additional information, see the draft guidances 
for industry FDARA Implementation Guidance for Pediatric Studies of Molecularly Targeted Oncology Drugs: 
Amendments to Sec. 505B of the FD&C Act and Pediatric Study Plans for Oncology Drugs:  Transitional 
Information Until Full Implementation of FDARA Section 504:  Questions and Answers.  When finalized, these 
guidances will represent FDAs current thinking on these topics. 
 
32 See sections 505B(e)(2)(C) and 505B(e)(3) of the FD&C Act; 21 U.S.C. 355c(e)(2)(C) and 355c(e)(3). 
7  Contains Nonbinding Recommendations 
1.  Overview of the Disease/Condition in the Pediatric Population 
 
This section should briefly summarize (1 to 3 pages)33 available information on the 
pathophysiology of the disease, methods of diagnosis, and currently available treatments and/or 
prevention strategies in the pediatric population, including neonates.  The sponsor should also 
include available information on the incidence and prevalence of the disease in both the overall 
population and the pediatric population, including in specific age subgroups when appropriate.  
Additionally, the sponsor should discuss current understanding of and available evidence 
supporting any similarities and differences between the disease in adults and in the pediatric 
population. 
 
2.  Overview of the Drug or Biological Product 
 
This section should briefly summarize (1 to 3 pages) the proposed mechanism of action of the 
drug, the intended pediatric population that will be studied, and the indications that the sponsor is 
seeking.  In considering the indications to include in an iPSP, the sponsor should consider any 
possible therapeutic uses of the drug in children beyond the disease or indication being sought in 
adults that may serve as the basis for a Written Request under section 505A of the FD&C Act 
(21 U.S.C. 355a).  The FDA encourages sponsors to discuss the potential therapeutic benefits 
and/or fulfillment of therapeutic needs in the pediatric population, including neonates, beyond 
any indication(s) for which pediatric assessments will be required under PREA.  Any changes to 
this discussion of the use of the drug, including any clinical studies that the sponsor may propose 
other than those required under PREA, will not require an amendment to an agreed iPSP.  If a 
sponsor plans to submit a PPSR asking the FDA to issue a Written Request in the future, the 
sponsor should include that information in this section of the iPSP as appropriate.34  Sponsors 
should submit a separate PPSR when seeking FDA review and comments on proposed pediatric 
studies that could be conducted under a pediatric Written Request, in addition to those required 
under PREA and included in the iPSP. 
 
3.  Overview of Planned Extrapolation to Specific Pediatric Populations  
 
The iPSP should address whether extrapolation of effectiveness to pediatric populations is 
planned for the proposed product (1 to 3 pages).  Extrapolation of effectiveness from adult 
populations to pediatric populations may be appropriate if the course of the disease and the 
effects of the drug are sufficiently similar in adult and pediatric patients.35  Extrapolation of 
effectiveness assumes that an appropriate pediatric dose can be established either through 
achieving a similar exposure in children as in adults or by using an appropriate 
                                                 
33 The recommended page count for each section of the iPSP applies to the overall iPSP and not to the individual 
active ingredients in the case of a fixed-dose combination product. 
 
34 For additional information regarding Written Requests, see section 505A of the FD&C Act; 21 U.S.C. 355a. 
 
35 See section 505B(a)(2)(B)(i) of the FD&C Act; 21 U.S.C. 355c(a)(2)(B)(i) and section 505B(a)(3)(B) of the 
FD&C Act; 21 U.S.C. 355c(a)(3)(B). 
 
8  Contains Nonbinding Recommendations 
pharmacodynamic or clinical endpoint to achieve the targeted effect.36  Extrapolation of 
effectiveness from one pediatric age group to another pediatric age group also may be 
appropriate.37  The sponsor should consider all age ranges of pediatric patients, including 
neonates, when applicable.  The sponsor should provide justification for the extrapolation, 
including any available supporting data for all age groups for which the sponsor intends to 
extrapolate effectiveness.  This justification should include supportive data from all available 
sources (e.g., sponsor data, published literature, expert panels, workshops).  Extrapolation of 
effectiveness for other drugs in the same class, if previously accepted by the FDA, also may be 
considered supportive information. 
 
In some cases, sponsors may include in the iPSP plans for studies to assess pediatric 
effectiveness because the ability to extrapolate effectiveness from adults to children is not known 
at the time of the iPSP submission.  Subsequently, if information becomes available to support 
extrapolation to a pediatric population, the sponsor can then submit a proposed amendment to the 
agreed iPSP to address plans for extrapolation in the marketing application or supplement.   
 
When determining whether the data are sufficient to support extrapolation of effectiveness, 
sponsors should include information in the iPSP on the similarities (and differences) between, for 
example, adults and children (or between one pediatric age group and another) in disease 
pathogenesis; criteria for disease definition; clinical classification; and measures of disease 
progression as well as pathophysiologic, histopathologic, and pathobiological characteristics of 
the disease.  In addition, if appropriate, the sponsor should include discussion on similarity in 
exposure-response relationship for effectiveness between adults and pediatrics based on 
experience with drugs in the same class or other drugs approved for use in the same 
disease/disorder.  Extrapolation of effectiveness from one pediatric age group to another, often 
from older to younger patients, and from one formulation to another should be discussed when 
applicable.  The sponsor also should discuss use of modeling and simulation to optimize studies 
to support extrapolation, when applicable.   
 
In certain circumstances, one may be able to leverage existing safety and dosing information in 
adults or other pediatric populations to draw inferences about the safety of the drug in one or 
more pediatric populations.  For example, for a drug that is approved for another pediatric 
indication that has similar dosing as the new indication, it may be possible to use the existing 
safety data to support safety for the new indication (e.g., if the different disease populations 
likely have similar susceptibility to any potential adverse effects of the drug).  For drugs that 
may have disparate pediatric and adult safety profiles, such as drugs that act in the central 
nervous system, the adult safety data may not be sufficient to support safety in the pediatric 
population.   
 
                                                 
36 For further discussion, see the draft guidance for industry General Clinical Pharmacology Considerations for 
Pediatric Studies for Drugs and Biological Products (December 2014) and the Pediatric Study Planning & 
Extrapolation Algorithm in its Appendix.  When final, this guidance will represent the FDAs current thinking on 
this topic. 
 
37 See section 505B(a)(2)(B)(ii) of the FD&C Act; 21 U.S.C. 355c(a)(2)(B)(ii) and section 505B(a)(3)(B) of the 
FD&C Act; 21 U.S.C. 355c(a)(3)(B). 
9  Contains Nonbinding Recommendations 
4.  Planned Request for Drug-Specific Waiver(s)  
 
Under PREA, sponsors may request a waiver of pediatric assessments, or reports on the 
molecularly targeted pediatric cancer investigation, at the time of the submission of the new drug 
application (NDA), biologics license application (BLA), or supplement.38  FDA does not 
formally grant or deny a request for a waiver in response to the iPSP.  The FDA formally grants 
a waiver(s) when it issues an approval letter for an NDA, BLA, or supplement. PREA authorizes 
the FDA to grant a full waiver of required pediatric assessments or reports on the molecularly 
targeted pediatric cancer investigation if it finds that:  (1) necessary studies are impossible or 
highly impracticable (because, for example, the number of patients is so small or the patients are 
geographically dispersed); (2) there is evidence strongly suggesting that the drug would be 
ineffective or unsafe in all pediatric age groups; or (3) the drug does not represent a meaningful 
therapeutic benefit over existing therapies for pediatric patients and is not likely to be used in a 
substantial number of pediatric patients.39   
 
In addition, PREA authorizes the FDA to grant a partial (i.e., with respect to a specific pediatric 
age group) waiver of required pediatric assessments or reports on the molecularly targeted 
pediatric cancer investigation if it finds that:  (1) necessary studies are impossible or highly 
impracticable (because, for example, the number of patients in that age group is so small or 
patients in that age group are geographically dispersed); (2) there is evidence strongly suggesting 
that the drug would be ineffective or unsafe in that age group; (3) the drug does not represent a 
meaningful therapeutic benefit over existing therapies for pediatric patients in that age group and 
is not likely to be used by a substantial number of pediatric patients in that age group; or (4) the 
applicant can demonstrate that reasonable attempts to produce a pediatric formulation necessary 
for that age group have failed.40   
 
This section should discuss the plans to request a waiver (either full or partial) of the requirement 
to provide data from pediatric studies (1 to 3 pages).  Because the information in this section will 
be relevant to formal requests for a full or partial waiver when the sponsor submits the 
NDA/BLA, the information in this section should be as complete as possible and updated as 
needed.  The sponsor should provide justification with a summary of supporting data, for all age 
groups for which the waiver will be sought.  This justification should include supportive data 
from all available sources (e.g., sponsor data, published literature, expert panels, workshops).  
                                                 
38 Under PREA, a pediatric assessment shall contain data, gathered using appropriate formulations for each age 
group for which the assessment is required, that are adequate (i) to assess the safety and effectiveness of the drug or 
the biological product for the claimed indications in all relevant pediatric subpopulations; and (ii) to support dosing 
and administration for each pediatric subpopulation for which the drug or the biological product is safe and 
effective.  Section 505B(a)(2)(A) of the FD&C Act; 21 U.S.C. 355c(a)(2)(A).  A molecularly targeted pediatric 
cancer investigation shall be designed to yield clinically meaningful pediatric study data, gathered using 
appropriate formulations for each age group for which the study is required, regarding dosing, safety, and 
preliminary efficacy to inform potential pediatric labeling.  Section 505B(a)(3)(A) of the FD&C Act; 21 U.S.C. 
355c(a)(3)(A).  For waiver requirements, see section 505B(a)(5) of the FD&C Act; 21 U.S.C. 355c(a)(5). 
 
39 See section 505B(a)(5)(A) of the FD&C Act; 21 U.S.C. 355c(a)(5)(A). 
 
40 See section 505B(a)(5)(B) of the FD&C Act; 21 U.S.C. 355c(a)(5)(B); see also section 505B(a)(5)(C) of the 
FD&C Act; 21 U.S.C. 355c(a)(5)(C). 
10  Contains Nonbinding Recommendations 
Full or partial waivers previously granted for other drugs in the same class can be considered 
supportive information.   
 
For indications that have extremely limited applicability to the pediatric population because the 
pathophysiology of the relevant disease occurs for the most part only in adults, the FDA 
generally does not intend to require sponsors to provide additional evidence that studies are 
impossible or highly impracticable.41  The FDA anticipates that the partial waiver provision 
based on failure to produce a pediatric formulation may, for example, apply to situations where 
the sponsor can demonstrate that unusually difficult technological problems prevented the 
development of a pediatric formulation for a particular pediatric age group. 
 
If, early in the preapproval development period (e.g., end-of-phase 1 or end-of-phase 2 meeting), 
the FDA agrees that a plan for a waiver is reasonable, such agreement would reflect the FDAs 
best judgment at that time.  However, the FDA does not formally grant a waiver until it issues an 
approval letter for an NDA, BLA, or supplement.  If, before approval of an application, the 
sponsor becomes aware of new or additional information that affects the plan for a waiver of 
pediatric assessments or reports on the molecularly targeted pediatric cancer investigation, the 
sponsor should submit at the earliest possible time an amended iPSP with an updated plan.  If the 
FDA becomes aware of new information, it intends to notify the sponsor at the earliest possible 
time and request that the sponsor amend the iPSP to reflect the new information (see section VI., 
Relationship of Agreed Initial PSP to the Requirement to Submit a Pediatric Study Plan with an 
Application).  Such a requested amendment could include a plan for deferral of pediatric studies 
if appropriate.   
 
Sponsors submitting a plan for a full waiver of pediatric studies should complete only sections 1, 
2, 4, and 12 of the iPSP template (see Appendix:  Initial Pediatric Study Plan Template).  For 
sponsors submitting a plan for a full waiver of pediatric studies, based on an indication that 
appears on the list of adult-related conditions that rarely or never occur in children,42 the iPSP 
should be limited to a one-page plan that specifies that the drug product is intended for the 
treatment of such an adult-related condition.  This one-page plan should also include a sentence 
that the sponsor plans to request a full waiver of pediatric studies.    
 
                                                 
41 The FDA anticipates that there will be additional considerations for applications described in section 
505B(a)(1)(B) of the FD&C Act that require submission of reports on the molecularly targeted pediatric cancer 
investigation described in section 505B(a)(3) of the FD&C Act.  For additional information, see the draft guidances 
for industry FDARA Implementation Guidance for Pediatric Studies of Molecularly Targeted Oncology Drugs: 
Amendments to Sec. 505B of the FD&C Act and Pediatric Study Plans for Oncology Drugs:  Transitional 
Information Until Full Implementation of FDARA Section 504:  Questions and Answers.  When finalized, these 
guidances will represent FDAs current thinking on these topics.  
 
42 See Adult-Related Conditions That Qualify for a Waiver Because They Rarely or Never Occur in Pediatrics, 
available at https://www.fda.gov/media/101440/download.  The FDA anticipates that there will be additional 
considerations for applications described in section 505B(a)(1)(B) of the FD&C Act that require submission of 
reports on the molecularly targeted pediatric cancer investigation described in section 505B(a)(3) of the FD&C Act. 
For additional information, see the draft guidances for industry FDARA Implementation Guidance for Pediatric 
Studies of Molecularly Targeted Oncology Drugs: Amendments to Sec. 505B of the FD&C Act and Pediatric Study 
Plans for Oncology Drugs:  Transitional Information Until Full Implementation of FDARA Section 504:  Questions 
and Answers.  When finalized, these guidances will represent FDAs current thinking on these topics. 
11  Contains Nonbinding Recommendations 
If pediatric studies will be waived because evidence exists that the drug would be ineffective or 
unsafe in any pediatric age group, this information must be included in the product labeling.43  
Generally, this information would be included in the Pediatric Use subsection of labeling and 
also may be included in the CONTRAINDICATIONS or WARNINGS AND PRECAUTIONS 
sections, depending on the seriousness of any safety concern that would be the grounds for 
waiver of pediatric studies. 
 
5.  Planned Request for Deferral(s) of Pediatric Studies   
 
Under PREA, sponsors may request deferral of pediatric assessments or reports on the 
molecularly targeted pediatric cancer investigation at the time of the submission of the NDA, 
BLA, or supplement.44  The FDA does not formally grant or deny a request for a deferral at the 
time of iPSP review.  Rather, the FDA formally grants a deferral when it issues an approval letter 
for an NDA, BLA, or supplement.  It is important to include in the iPSP any plan to submit a 
request for a deferral for any study required under PREA that will not be submitted as part of a 
planned application (i.e., NDA, BLA, efficacy supplement).  Because the sponsor must submit 
with the NDA/BLA an agreed iPSP when there are plans for requests for deferral of pediatric 
assessments or reports on the molecularly targeted pediatric cancer investigation,45 the 
information in this section should be as complete as possible and updated as needed.   
 
If new information, such as data from ongoing or planned studies, indicates that a criterion for a 
waiver (or partial waiver) is met, the sponsor can change planned requests for deferral of 
pediatric assessments or reports on the molecularly targeted pediatric cancer investigation in the 
iPSP to planned requests for waiver (or partial waiver).  The sponsor should submit these 
changes as an amendment to an agreed or amended iPSP.   
 
At the time of approval of an application, the FDA may grant a deferral of required pediatric 
assessments or reports on the molecularly targeted pediatric cancer investigation if it finds that:  
(1) the drug is ready for approval for use in adults before pediatric studies are complete; (2) 
pediatric studies should be delayed until additional safety or effectiveness data have been 
                                                 
43 See section 505B(a)(5)(D) of the FD&C Act; 21 U.S.C. 355c(a)(5)(D).  
 
44 See section 505B(a)(4) of the FD&C Act; 21 U.S.C. 355c(a)(4).  Under PREA, a pediatric assessment required 
under section 505B(a)(1)(A) of the FD&C Act shall contain data, gathered using appropriate formulations for each 
age group for which the assessment is required, that are adequate (i) to assess the safety and effectiveness of the 
drug or the biological product for the claimed indications in all relevant pediatric subpopulations; and (ii) to support 
dosing and administration for each pediatric subpopulation for which the drug or the biological product is safe and 
effective.  Section 505B(a)(2)(A) of the FD&C Act; 21 U.S.C. 355c(a)(2)(A).  A molecularly targeted pediatric 
cancer investigation required under section 505B(a)(1)(B) of the FD&C Act shall be designed to yield clinically 
meaningful pediatric study data, gathered using appropriate formulations for each age group for which the study is 
required, regarding dosing, safety, and preliminary efficacy to inform potential pediatric labeling.  Section 
505B(a)(3)(A) of the FD&C Act; 21 U.S.C. 355c(a)(3)(A). 
 
45 See sections 505B(a)(1), 505B(a)(4)(A)(ii)(II), and 505B(e) of the FD&C Act; 21 U.S.C. 355c(a)(1), 
355c(a)(4)(A)(ii)(II), and 355c(e).   
 
12  Contains Nonbinding Recommendations 
collected; or (3) there is another appropriate reason for deferral.46  The planned request for a 
deferral should list the proposed deferred studies in the same order as they are presented in the 
table in section 6 of the iPSP.   
 
The planned request for a deferral should include adequate justification and any currently 
available evidence supporting the justification for a deferral (1 to 2 pages).  If the FDA agrees 
that a plan for a deferral is reasonable early in the preapproval development period (e.g., end-of-
phase 1 or end-of-phase 2 meeting), such agreement would reflect the FDAs best judgment at 
that time.  
 
If the sponsor becomes aware of new or additional information that affects the decision to plan 
for any deferral of pediatric assessments or reports on the molecularly targeted pediatric cancer 
investigation, the sponsor should reconsider the agreed iPSP and should submit an amended iPSP 
at the earliest possible time.  The FDA may also request that the sponsor amend the iPSP to 
reflect any new information (see section VI., Relationship of Agreed Initial PSP to the 
Requirement to Submit a Pediatric Study Plan with an Application).   
 
6.  Tabular Summary of Planned Nonclinical and Clinical Development 
 
This section should include a summary in tabular form of all planned:  (1) nonclinical 
development to be conducted in support of the proposed pediatric clinical trials (see also section 
8); and (2) clinical pediatric development (categorized by age).  The table should include a 
column to identify whether the sponsor plans to request a deferral of the study (i.e., the sponsor 
does not plan to submit the data until after FDA approves the application).  The table should also 
include any age groups for which the sponsor plans to request waivers.  An example table is 
included below.  The table is provided as an example only.  The specific studies planned for a 
specific drug (e.g., the type of studies, the age groups studied) may differ from those studies 
listed in the example table.   
 
Case example:  Drug X is a new drug under development in adults for disease Y.  The sponsor is 
seeking a partial waiver of pediatric studies required under PREA for patients less than 2 years of 
age because necessary studies are impossible or highly impracticable.  The rarity of the diagnosis 
in children less than 2 years of age is supported by literature data.  The course of disease Y and 
the effects of drugs in this class are expected to be sufficiently similar in adults and pediatric 
patients.  However, the similarity of the exposure-response relationship between the two 
populations is not known.  Therefore, the sponsor is proposing to include adolescents 12 to less 
than 17 years of age in the adult trial and is not seeking a deferral request.  In patients 2 to less 
than 12 years of age, the sponsor plans to conduct a pharmacokinetic/pharmacodynamic (PK/PD) 
study followed by an efficacy/safety study.  The sponsor is proposing stratification by body size 
in the phase 2 PK/PD study as age is not expected to be a significant covariate for PK or PD for 
                                                 
46 See section 505B(a)(4)(A)(i) of the FD&C Act; 21 U.S.C. 355c(a)(4)(A)(i).  In addition, the sponsor must submit:  
(1) a certification of the grounds for deferring the assessments or reports on the molecularly targeted pediatric cancer 
investigation; (2) an iPSP; (3) evidence that the studies are being conducted or will be conducted with due diligence 
and at the earliest possible time; and (4) a timeline for the completion of the studies.  See section 505B(a)(4)(A)(ii) 
of the FD&C Act; 21 U.S.C. 355c(a)(4)(A)(ii). 
13  Contains Nonbinding Recommendations 
the drug.  The sponsor did not propose further stratification by age for the efficacy/safety study 
in patients 2 to less than 12 years of age.  The following is an example table based on this case:   
 
EXAMPLE TABLE:  Table of Nonclinical and Clinical Development for Drug X 
PLANNED NONCLINICAL DEVELOPMENT* 
Species  Type of Study (If  Comments  Deferral Request 
known, include  Planned for the 
duration)  Study (Y/N)** 
Rat (or appropriate animal  Toxicology study in  To support initiation of  N 
species)  juvenile animals ages x  clinical studies in 
to xx  children ages x to xx 
PLANNED PEDIATRIC CLINICAL DEVELOPMENT 
Pediatric PK or PK/PD Studies 
Age Group  Type of Study (If  Comments  Deferral Request 
known, include  Planned for the 
duration)  Study (Y/N) 
2 to <12 years  Phase 2 PK/PD study  To determine appropriate  N 
dose based on an   
established PD endpoint   
Clinical Effectiveness and Safety Evaluation 
Age Group  Type of Study (If  Comments  Deferral Request 
known, include  Planned for the 
duration)  Study (Y/N) 
0 to <1 month  Not applicable (plan to  Studies are highly   
request waiver)  impracticable 
1 month to <2 years  Not applicable (plan to  Studies are highly   
request waiver)  impracticable 
2 to <12 years  Efficacy/safety study (R,  Endpoints to be  Y 
DB, PC)  determined 
12 to <17 years  Efficacy/safety study (R,  Study to be submitted  N 
DB, PC)   with initial NDA 
* May not be applicable for all drugs. 
** See section 11 of the Initial Pediatric Study Plan Template. 
 PK = pharmacokinetic; PD = pharmacodynamic; R = randomized; DB = double-blind; PC = placebo-controlled 
 
Note:  A table generated for a specific drug may not be the same as the sample case above and 
should be based on the planned studies needed for the drug. 
 
14  Contains Nonbinding Recommendations 
7.  Age-Appropriate Formulation Development 
 
If the current formulation is not suitable for all pediatric age groups, sponsors should provide 
specific plans for the development of an age-appropriate formulation for all pediatric age groups 
that will be studied.  In this section (1 to 3 pages), sponsors should include information regarding 
planned excipients, to the extent practicable, which will be contained in any pediatric 
formulation being developed.  Sponsors also should provide details of measures taken to ensure 
appropriate design of a drug formulation, including, to the extent practicable, the design of 
delivery systems (e.g., capsules, tablets, infusions, devices) to be used in pediatric studies.47  
 
8.  Nonclinical Studies  
 
This section should provide a brief summary (1 to 3 pages) of the data from relevant nonclinical 
studies that support the use of the drug in all pediatric age groups the sponsor will study in the 
proposed clinical trials.  The sponsor should include information that supports the maximum 
dose and duration of treatment to be used in pediatric studies.  If the sponsor has determined that 
the nonclinical data are sufficient to support the proposed clinical trials and additional 
nonclinical studies are not planned, this summary should include such a statement and 
justification for this conclusion.  If a sponsor plans to conduct a juvenile animal study, we 
recommend sponsors contact the review division for feedback before initiating this study.   
 
If the existing nonclinical data are not sufficient to support the proposed clinical trials,48 
sponsors should provide a brief description for each of the nonclinical studies they will conduct, 
including, at a minimum the following:  
 
  The species to be studied  
 
  The age of animals at the start of dosing  
 
  The duration of dosing 
 
  The route of administration 
 
  The target organ systems of concern with key developmental endpoints to be evaluated, 
as appropriate   
 
                                                 
47 For more on considerations for age-appropriate formulations, see the 2014 European Medicines Agency Guideline 
on Pharmaceutical Development of Medicines for Pediatric Use, available at https://www.ema.europa.eu/en/human-
regulatory/research-development/paediatric-medicines/paediatric-investigation-plans/paediatric-formulations. 
 
48 We support the principles of the 3Rs (reduce/refine/replace) for animal use in testing when feasible.  The FDA 
encourages sponsors to consult with review divisions when considering a nonanimal testing method believed to be 
suitable, adequate, validated, and feasible.  The FDA will consider if the alternative method could be assessed for 
equivalency to an animal test method. 
15  Contains Nonbinding Recommendations 
For further information see other guidances, as appropriate.49   
 
Sponsors should also list the planned nonclinical studies in the table in section 6 and note (as 
described in section 11) the timeline for conduct of any such studies. 
 
9.  Clinical Data to Support Design and/or Initiation of Studies in Pediatric Patients  
 
This section should provide a brief summary (1 to 5 pages) of any clinical data that support the 
design or initiation of pediatric studies.  This section also should include a summary of available 
data in adult or pediatric patients who have received treatment with the drug (or related drugs) 
for the proposed indication, for other conditions, or in earlier studies.  This section is intended to 
provide an overview of information already available to support design or initiation of pediatric 
studies; therefore, a detailed review of available data is not needed in this section. 
 
10. Planned Pediatric Clinical Studies 
 
10.1  Pediatric Pharmacokinetic or Pharmacokinetic/Pharmacodynamic Studies  
 
This section (1 to 10 pages) should provide an outline of each of the pediatric PK/PD studies 
planned, if applicable.50  Sponsors should discuss the studies in the order they are presented in 
the table in section 6.  For each study, to the extent practicable, the sponsor should address the 
following: 
 
  The type of study/study design 
 
  The objectives of the study 
 
  The age group and population in which the study will be conducted 
 
  The pediatric formulation(s) to be used in the study 
 
  The dose ranges to be used in the PK studies 
 
  The endpoints and justification (PK parameters; PD biomarkers) 
 
  The existing or planned modeling and simulation to support dose selection and/or study 
design, data analysis, and interpretation for planned pediatric studies 
 
                                                 
49 See the guidance for industry Nonclinical Safety Evaluation of Pediatric Drug Products (February 2006) and the 
ICH guidances for industry M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and 
Marketing Authorization for Pharmaceuticals (January 2010) and S9 Nonclinical Evaluation for Anticancer 
Pharmaceuticals (March 2010). 
 
50  For further discussion, see 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. 
16  Contains Nonbinding Recommendations 
  Any planned pharmacogenomic analyses 
 
  Sample size justification 
 
A sponsor must submit full protocols separately to the IND for FDA review and should obtain 
FDA agreement regarding all full protocols before initiation of pediatric studies outlined in this 
section.51  
 
A dedicated PK study is not always needed in every age group.  For example, prior experience 
with dosing in adolescent patients has demonstrated that knowledge of adult dosing and 
appropriate dose scaling may be sufficient for some drugs with adequate justification.  It may be 
appropriate for a sponsor to use confirmatory population PK studies to supplement such a 
program in which a dedicated PK study is not considered essential.52 
 
10.2  Clinical Effectiveness and Safety Studies 
 
This section should provide a brief outline of each pediatric study planned, discussed in the order 
each is presented in the table in section 6 (1 to 10 pages).  For each study, to the extent 
practicable, the sponsor should address the following: 
 
  The type of study/study design 
 
  The objectives of the study 
 
  The age group and population in which the study will be conducted 
 
  The key inclusion and exclusion criteria for the study 
 
  The endpoints (primary and key secondary) to be used 
 
  The timing of endpoint assessments 
 
  The safety assessments (including timing and length of follow-up)  
 
  The statistical approach 
 
  The modeling and simulation to be used to optimize the design of planned pediatric 
studies, when applicable   
 
This section should provide a brief outline of the planned pediatric studies.  Therefore, sponsors 
should not include a detailed protocol and/or statistical analysis plan in the iPSP.  Sponsors 
                                                 
51 See 21 CFR 312.23(a)(6) and 312.30. 
 
52 For additional information, see 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. 
17  Contains Nonbinding Recommendations 
should be aware that agreement with the outline of planned clinical studies does not constitute 
agreement with the protocol.  Sponsors must submit full protocols separately to their INDs for 
FDA review and should obtain FDA agreement regarding all full protocols before initiation of 
pediatric studies outlined in this section. 53  Sponsors should also submit statistical analysis plans 
separately to their INDs for FDA review and agreement.   
 
11. Timeline of the Pediatric Development Plan 
 
For each study listed in the table in section 6, a general timeline for completion should be 
included in this section (1 page).  A suggested template is provided below.  The sponsor should 
estimate these dates based on current projections for the drug development program.  As stated 
above, the intent of the iPSP is to identify needed pediatric studies early in drug development 
and to begin planning for these studies.  Therefore, the timeline of the pediatric development 
plan should be based on clinical, scientific, and operational considerations and should be made 
independent of an anticipated submission date of an application or approval date of a drug.  For 
example, pediatric formulation development can begin before the anticipated submission date of 
an application or approval date of a drug.  If the dates provided in the iPSP change as drug 
development proceeds, the sponsor should submit a request to amend the iPSP and include 
justification for the change.   
 
1.  Formulation development, if applicable 
 
2.  Nonclinical studies, if applicable 
  Estimated protocol submission date:    No later than ___(month/year) 
  Estimated study initiation date:     No later than ___(month/year) 
  Estimated study completion date:    No later than ___(month/year) 
  Estimated final report submission date:   No later than ___(month/year) 
 
3.  Clinical studies 
  PK or PK/PD studies, if applicable: 
  Estimated protocol submission date:    No later than ___(month/year) 
  Estimated study initiation date:     No later than ___(month/year) 
  Estimated study completion date:    No later than ___(month/year) 
  Estimated final report submission date:   No later than ___(month/year) 
 
  Efficacy/safety and/or dedicated safety studies, if applicable 
  Estimated protocol submission date:    No later than ___(month/year) 
  Estimated study initiation date:     No later than ___(month/year)  
  Estimated study completion date:    No later than ___(month/year) 
  Estimated final report submission date:   No later than ___(month/year) 
 
                                                 
53 See 21 CFR 312.23(a)(6) and 312.30. 
18  Contains Nonbinding Recommendations 
4.  Target date of application submission 
 
12. Agreements for Pediatric Studies With Other Regulatory Authorities 
 
It is recommended that sponsors include, if available, a summary (1 to 3 pages) of the most 
recent agreed pediatric investigation plan with other regulatory authorities (e.g., European 
Medicines Agency).  If negotiations with a regulatory authority are in progress or previous plans 
are under modification, a sponsor should include a summary of the most recent draft plan.  A 
sponsor should highlight and comment on any differences between the most recent plan with 
other regulatory authorities and the plan submitted to the FDA.  The purpose of including a 
summary of agreements with other regulatory authorities is to encourage global alignment in 
pediatric development plans across regulatory authorities when possible. 
 
 
VI.  RELATIONSHIP OF AGREED INITIAL PSP TO THE REQUIREMENT TO 
SUBMIT A PEDIATRIC STUDY PLAN WITH AN APPLICATION 
 
For NDAs, BLAs, or supplemental applications subject to PREA, sponsors must include an 
agreed iPSP in the application when a deferral of pediatric studies is requested.54  In such cases, 
submission of the iPSP (specifically, the agreed iPSP) fulfills the requirement of the sponsor to 
submit a pediatric study plan, which must be included in the appropriate section of the 
application.55  Failure to fulfill the requirement to submit a pediatric study plan with the 
application may be grounds for refusal to file an application.56  Any planned requests for waivers 
and/or deferrals included in the iPSP serve as the official request with the application 
submission.57  The PeRC will review any requests for waivers and/or deferrals and make 
recommendations as needed to the review division.58  A final decision about granting or denying 
such requests is made by the review division at the time of approval of the marketing application.   
 
 
VII.  CONTENT AND TIMING OF REQUESTED AMENDMENT TO AN INITIAL 
PSP 
 
Sponsors can request an amendment to an agreed iPSP at any time.  Requests can include, for 
example, changing a date listed in section 11 of the iPSP that would significantly delay the 
initiation and/or completion of pediatric studies (e.g., by more than 12 months), changing 
planned requests for a deferral to planned requests for a waiver or partial waiver, or changing a 
                                                 
54 See sections 505B(a)(4)(A)(ii)(II), 505B(a)(1) and 505B(e) of the FD&C Act; 21 U.S.C. 355c(a)(4)(A)(ii)(II), 
355c(a)(1), and 355c(e).   
 
55 See sections 505B(a)(4)(A)(ii)(II) and 505(B)(e)(3) of the FD&C Act; 21 U.S.C. 355c(a)(4)(A)(ii)(II) and 
355c(e)(3). 
 
56 See 21 CFR 314.101(d).  
 
57 See section 505B(e)(2)(B)(ii) of the FD&C Act; 21 U.S.C. 355c(e)(2)(B)(ii). 
 
58 See section 505B(f)(4) of the FD&C Act; 21 U.S.C. 355c(f)(4). 
19  Contains Nonbinding Recommendations 
planned request for a waiver or partial waiver to a planned request for a deferral.  For example, 
emerging safety data from nonclinical juvenile animal studies and/or adult human clinical trials 
may support converting a planned request for a deferral to a planned request for a waiver for 
reasons of safety.  Alternatively, the need for additional safety data from adult human clinical 
trials may support a delay in the initiation of pediatric clinical trials.  In addition, formulation 
data could necessitate a change in a development program.  The PeRC will be consulted on the 
review of significant amendments to an agreed iPSP.59 
 
A request for an amendment to an agreed iPSP should include the following: 
 
  The requested change(s) supported with a justification  
 
  A copy of the agreed iPSP with the requested change(s) tracked and clearly identified  
 
  A clean copy of the proposed amended iPSP 
 
Amendments should not be considered agreed upon until the FDA issues a letter stating that the 
amendments are acceptable.  
 
Once the FDA accepts for filing an application or supplemental application, it is not necessary to 
submit amendments to the iPSP because changes to the plan for pediatric development can be 
negotiated during the review cycle as appropriate.  For example, a sponsor submits a marketing 
application with an agreed iPSP, and the review division files the application.  The sponsor 
proposes to modify the timeline for studies after filing the application; in this case, it is not 
necessary to submit an amended iPSP, but instead the newly proposed timeline can be negotiated 
with the review division during the review cycle of the application. 
 
The timeline for submission, review, and agreement on an amended iPSP is the same as on an 
iPSP.60  (See Section IV., Timing of an Initial PSP Submission).  If the FDA does not agree to 
the amended iPSP, the original agreed iPSP remains in force.  If the sponsor submits an 
amendment to an agreed iPSP within 210 days of the planned submission of an NDA, BLA, or 
supplement, the amendment may not be considered agreed absent sufficient time for the FDA 
review.  However, the sponsor may submit the NDA, BLA, or supplement with the previously 
agreed iPSP.  FDA intends to, as appropriate, consider changes to the plan for pediatric 
development during the application review cycle (see section VIII., Non-Agreed Initial PSPs).   
 
However, if, under certain situations, the agreed iPSP included nonclinical and/or pediatric 
clinical studies that were expected to have been completed before submission of the NDA, BLA, 
or supplement, failure of the sponsor to complete these agreed studies in a timely manner may 
                                                 
59 See section 505B(e)(6) of the FD&C Act; 21 U.S.C. 355c(e)(6). 
 
60 See section 505B(e)(5) of the FD&C Act; 21 U.S.C. 355c(e)(5). 
 
20  Contains Nonbinding Recommendations 
result in a refusal to file.61  In this situation, a sponsor should submit a request for an amendment 
to the agreed iPSP that includes an updated timeline for the studies and justification for the delay 
in completing one or more of the agreed pediatric studies.  If the FDA considers the justification 
for the delay to be inadequate and does not agree with the proposed iPSP amendment, the agreed 
iPSP would remain in force until the FDA and sponsor agree on an amended iPSP (See Section 
VIII., Non-Agreed Initial PSPs), and the failure of the sponsor to complete the agreed nonclinical 
and/or pediatric clinical studies in a timely manner still may result in a refusal to file. 
 
 
VIII.  NON-AGREED INITIAL PSPs 
 
If the FDA and the sponsor are unable to reach agreement on an iPSP at the end of the 210-day 
review period, the FDA intends to issue a letter stating that the iPSP is considered a non-agreed 
iPSP.  As discussed in section IX., Reaching Agreement on the Non-Agreed Initial PSP, there is 
no established timeline for the review and agreement of a non-agreed iPSP.  Therefore, sponsors 
are encouraged to work with FDA to reach agreement during the initial 210-day review period.  
 
If the FDA and the sponsor are unable to reach agreement on the proposed amendments to an 
agreed iPSP, the FDA intends to issue a letter stating that the amended iPSP is considered a non-
agreed amended iPSP.  Under this circumstance, the agreed iPSP would be considered to be in 
force until the FDA and sponsor agree on an amended iPSP.   
 
As stated above, for NDAs, BLAs, or supplemental applications subject to PREA, sponsors must 
include an agreed iPSP in the application when a deferral of pediatric studies is requested, and 
the failure to submit an agreed iPSP when a deferral is requested may be grounds for refusal to 
file the application.62  All correspondence with the FDA regarding any non-agreed amendments 
should be included in the appropriate section of the application.  
 
 
IX.  REACHING AGREEMENT ON THE NON-AGREED INITIAL PSP 
 
When a sponsor receives a letter of nonagreement, the FDA makes every effort to work with the 
sponsor and resolve the area(s) of disagreement as quickly as possible; however, no statutory 
timeline is attached to this process.  If the sponsor disagrees with the FDAs recommendations, 
the sponsor can request a meeting with the FDA.  After the sponsor and the FDA have resolved 
any disagreements, the sponsor should submit the proposed agreed iPSP for FDA review. 
 
                                                 
61 See section 505B(a)(1) of the FD&C Act (21 U.S.C. 355c(a)(1)), which requires that the assessments or reports on 
the molecularly targeted pediatric cancer investigation be submitted with the application or supplement to which 
PREA applies.  See also 21 CFR 314.101(d). 
 
62 See sections 505B(a)(4)(A)(ii)(II), 505B(a)(1), and 505B(e) of the FD&C Act; 21 U.S.C. 355c(a)(4)(A)(ii)(II), 
355c(a)(1), and 355c(e).  See also 21 CFR 314.101(d). 
21  Contains Nonbinding Recommendations 
APPENDIX:  INITIAL PEDIATRIC STUDY PLAN TEMPLATE1 
 
When submitting an initial pediatric study plan (iPSP), sponsors should mark the submission 
INITIAL PEDIATRIC STUDY PLAN in large, bolded type at the beginning of the title 
page.  For an agreed iPSP or amended iPSP, sponsors should mark the submission PROPOSED 
AGREED PEDIATRIC STUDY PLAN or AMENDED PEDIATRIC STUDY PLAN, 
respectively, in large, bolded type at the beginning of the title page.   
 
INITIAL PEDIATRIC STUDY PLAN TITLE PAGE 
 
The proprietary name and the established name of the drug, if any, or, for biological 
products, the proper name including any appropriate descriptors 
 
Dosage form:   
 
  NDA/BLA/IND #: 
 
  Drug class: 
 
  Approved indication (if applicable):  
 
  Proposed indication (if applicable): 
 
  Proposed General Plan:  (i.e., full or partial waiver, deferral, and inclusion of a pediatric 
assessment or molecularly targeted pediatric cancer investigation in the future 
application) 
 
Cross-reference to other investigational new drug applications for which an iPSP is 
submitted for this drug development program 
 
1.  OVERVIEW OF THE DISEASE/CONDITION IN THE PEDIATRIC 
POPULATION (13 pages) 
 
 
2.  OVERVIEW OF THE DRUG OR BIOLOGICAL PRODUCT (13 pages)  
 
 
3.  OVERVIEW OF PLANNED EXTRAPOLATION TO SPECIFIC PEDIATRIC 
POPULATIONS (13 pages)  
 
 
4.  PLANNED REQUEST FOR DRUG-SPECIFIC WAIVER(S) (13 pages)  
 
 
5.  PLANNED REQUEST FOR DEFERRAL(S) OF PEDIATRIC STUDIES (12 pages)  
                                                 
1 This template is also available at https://www.fda.gov/media/84944/download. 
22  Contains Nonbinding Recommendations 
 
 
6.  TABULAR SUMMARY OF PLANNED NONCLINICAL AND CLINICAL 
DEVELOPMENT  
 
 
7.  AGE-APPROPRIATE FORMULATION DEVELOPMENT (13 pages)  
 
 
8.  NONCLINICAL STUDIES (13 pages)  
 
 
9.  CLINICAL DATA TO SUPPORT DESIGN AND/OR INITIATION OF STUDIES IN 
PEDIATRIC PATIENTS (15 pages) 
 
 
10. PLANNED PEDIATRIC CLINICAL STUDIES  
 
10.1 Pediatric Pharmacokinetic or Pharmacokinetic/Pharmacodynamic Studies (110 
pages)  
 
10.2 Clinical Effectiveness and Safety Studies (110 pages)  
 
 
11. TIMELINE OF THE PEDIATRIC DEVELOPMENT PLAN (1 page)  
 
 
12. AGREEMENTS FOR PEDIATRIC STUDIES WITH OTHER REGULATORY 
AUTHORITIES (13 pages) 
 
If there is a pending or agreed pediatric investigational plan with EMA (European Medicines 
Agency), sponsors should provide the corresponding application number (e.g., EMEA-000206-
PIP01-08). 
23