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Pediatric Applicability or Not–This Revised Guidance Is for You

Since 1994, the statutory and regulatory requirements for drug product labeling for pediatric populations have been evolving. The FDA Modernization Act of 1997 (FDAMA) contained incentives for conducting pediatric studies on drugs that had exclusivity or patent protection. In 2003, the Pediatric Research Equity Act (PREA) was signed into law requiring, for certain drugs, sponsors to conduct studies on pediatric populations for the claimed indications; however, it did not include a proposed timeline and plan for the submission of pediatric studies to the IND. The FDA Safety and Innovation Act of 2012 (FDASIA) required sponsors planning to submit an application for a drug subject to PREA, to submit an Initial Pediatric Study Plan, or iPSP, early in the drug development process.

Currently, a sponsor who plans to submit a marketing application for a drug that includes a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration (i.e., that is subject to PREA) is required (under FDASIA) to submit an iPSP, unless the drug was granted orphan designation for the proposed indication at the time the iPSP is required. Thus, unless you are developing an orphan drug, ALL NDAs must have a pediatric plan, even if your drug is not targeted at this population. If you fail to adhere to the timings presented below, your NDA may be refused.

Pediatric Study Plans: FDA Revised Draft Guidance

On March 8, 2016, the Federal Register (FR DOC# 2016-05223) announced availability of a revised draft guidance, Pediatric Study Plans: Content of and Process for Submitting Initial Pediatric Study Plans and Amended Initial Pediatric Study Plans, (CDER/CBER, 2016) replacing the July 2013 draft guidance for industry of the same title.

This Procedural Revision 1 is currently distributed for comment purposes only; however, it addresses the FDA’s current thinking regarding implementation of the requirement for sponsors to submit an iPSP to an application. The guidance includes additional clarifications to existing sections, an updated Appendix 1 iPSP template, and the addition of new sections. Highlights are as follows:


  • A sponsor must submit the iPSP before the date on which the sponsor submits the required assessments and not later than 60 calendar days after the date of the end-of-phase 2 meeting. 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.
  • If a phase 3 study or a combined phase 2 and phase 3 study will not be conducted, the sponsor should submit the iPSP no later than 210 calendar days before it submits a marketing application or supplement.
  • A sponsor should submit the iPSP to its IND for the drug.
  • In cases when there is no active IND for the drug, but the sponsor expects upon submission of the IND that the initial studies would include a phase 3 study, the iPSP should be submitted as a pre-IND submission. In this situation, the FDA encourages sponsors to schedule a pre-IND meeting before submission of the iPSP, and, as stated above, the sponsor should submit the iPSP before the initiation of any phase 3 studies or combined phase 2 and phase 3 studies.
  • FDA has 90 days to review and comment on an iPSP. The sponsor then has 90 days to submit an agreed iPSP. FDA has 30 days to issue correspondence confirming agreement or to issue a non-agreed iPSP letter. [total review time = 210 days].
  • Do not submit a marketing application until an agreed-iPSP is reached.

The following sections are added in the revised guidance:

Section V.A. Materially Incomplete iPSPs.

If all pediatric age groups and all indications are not addressed, a sponsor will be contacted and a complete iPSP should be submitted within 30 days. A new 210-day clock starts.

Section VI. Relationship of Agreed iPSP to the Requirement to Submit a Pediatric Plan with an Application.

The sponsor must submit the agreed iPSP in the NDA. Any waivers/deferrals in the agreed iPSP serve as the official requests and a decision is made during review of the application.

Section VII. Contents and Timing of Requested Amendment to an iPSP.

An agreed iPSP may be amended and can include changes that would significantly delay the start and/or completion of pediatric studies, or from changing the plans for deferrals, waivers, or partial waivers arising from safety data generated from nonclinical studies and/or clinical trials. A request for an amendment should include:

  • specifications of the changes with justification,
  • a redline of the agreed-iPSP showing the changes
  • a clean copy of the amended iPSP.

The amendment is not agreed until FDA sends an acceptable letter. If the amendment is submitted within 210 days of the planned NDA submission, include the previously agreed iPSP as part of the application. Changes will be considered during application review. However, if studies were expected to be completed before NDA submission as part of the agreed iPSP, this may result in a refusal-to-file. If that is the case, submit a justification for the delay in completing the studies in the request for an amendment to the agreed iPSP.

Section VIII. Non-Agreed iPSP.

If the sponsor and the FDA are unable to reach an agreed iPSP within the 210 day review period, FDA issues a non-agreed letter. There is no timeline for review and agreement of a non-agreed iPSP. If no agreement is reached for an amended iPSP, a non-agreed amended iPSP letter is issued. The agreed iPSP is considered in force until the amended iPSP agreement is reached. If agreement is not reached before NDA submission when a deferral is requested, submit the agreed iPSP and all correspondence regarding non-agreed amendments.

Section IX. Reaching Agreement on the Non-Agreed iPSP.

There is no statutory timeline to resolve the non-agreement; however, FDA will work to resolve it as quickly as possible. The sponsor can request a meeting with FDA to discuss any disagreement. After resolution, submit the proposed agreed iPSP or amendment for FDA review.

Premier Consulting can provide expert guidance through the process of developing an initial pediatric study plan. For more information about services Premier Consulting can provide, visit our Services page or Contact Us for more information.


Annette Arlinghaus
Associate Director of Submissions