The US Food and Drug Administration (FDA) on Tuesday released updated draft guidance intended to help pharmaceutical sponsors submit pediatric study plans, including what should be included in the plans and how they should be submitted.
This revision, which FDA says was based largely on public comments, includes additional clarifications on the 2013 draft guidance, such as new information on what constitutes a materially incomplete initial pediatric study plan (iPSP), the contents and timing of a requested amendment to an iPSP and how to reach an agreement on a non-agreed iPSP. FDA also updated the iPSP template in the first appendix of the guidance.
For more than 20 years, FDA has worked to address the issue of inadequate testing of drugs in pediatric populations. In 1994, FDA issued a final rule requiring drugmakers to survey existing data and determine whether sponsors could support adding pediatric use information to a drug’s labeling. However, as FDA notes, this effort “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.”
Fast forward to 2003, when Congress passed the Pediatric Research Equity Act (PREA), which has since been reauthorized under the Food and Drug Administration Safety and Innovation Act of 2012, and now requires sponsors planning to submit an application for a drug subject to PREA to submit an iPSP early in the development process.
This latest draft guidance on iPSPs, which is meant for sponsors submitting a marketing application for a drug with a new active ingredient, new dosage form, new indication, new dosing regimen or new route of administration, addresses:
- When an iPSP must be submitted
- What should be included in an iPSP
- What should be included in a requested amendment to an agreed iPSP
- The template that should be used for an iPSP submission
In terms of what should be considered a materially incomplete iPSP, FDA says that “if a sponsor fails to address all pediatric age groups and all indications, the FDA would consider the iPSP to be materially incomplete,” which means the sponsor will be contacted and a complete iPSP should be submitted within 30 days. A new 210-day review period will begin when a complete iPSP is submitted.
However, if there’s sufficient information for FDA to evaluate the plan, even if FDA disagrees with it, the agency in general will consider the iPSP to be complete.
“For example, if a sponsor has included a plan to request full waivers as part of the iPSP, and the FDA disagrees with this plan, then the FDA would not consider this iPSP materially incomplete and would proceed with the usual timeline for internal review,” according to the updated guidance.
As far as requests to amend an agreed iPSP, FDA says they can occur at any time and can include, for example, “changes to an original milestone submission date that would significantly delay the initiation and/or completion of pediatric studies (e.g., more than 12 months), changing planned requests for a deferral to planned requests for a waiver or partial waiver, or changing a 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, FDA notes.
A request for an amendment to an agreed iPSP should include:
- Specifications of the requested change(s), along with a justification for the requested change(s)
- A copy of the agreed iPSP with the requested change(s) shown in red
- A clean copy of the amended iPSP
- Amendments should not be considered agreed with FDA until a letter stating that the amendments are acceptable has been received.
And in terms of what a “non-agreed” iPSP means, the agency says that if FDA and the sponsor are unable to reach agreement on proposed amendments, FDA will issue correspondence stating this, meaning “the agreed iPSP will be considered to be in force until such time that agreement on an amended iPSP is reached. If agreement is not reached before the submission of a marketing application when a deferral of pediatric studies is requested, then the agreed iPSP and all correspondence with the FDA regarding any non-agreed amendments must be included in the appropriate section of the application.”
Pediatric Study Plans: Content of and Process for Submitting Initial Pediatric Study Plans and Amended Initial Pediatric Study Plans Guidance for Industry