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Regulatory Focus™ > News Articles > 2020 > 8 > FDA provides guidance on preparation and submission of pediatric study plans

FDA provides guidance on preparation and submission of pediatric study plans

Posted 05 August 2020 | By Kari Oakes 

FDA provides guidance on preparation and submission of pediatric study plans

In a final guidance document, the US Food and Drug Administration provides sponsors with a detailed framework for how to prepare and submit pediatric study plans. The final guidance supplants a draft guidance published in 2016.
The new pediatric study plan guidance follows on from regulations and laws promulgated in the late 1990s and early 2000s that addressed the dearth of pediatric data in drug development. These rules aimed to increase pediatric studies for exclusive or patent-protected drugs, and to address a prior lack of data supporting pediatric use and dosing of drugs for claimed indications.
The Pediatric Research Equity Act (PREA), passed in 2003 and reauthorized in 2012, requires sponsors making applications for drugs or biologics subject to the act to submit an initial pediatric study plan (iPSP) early in the course of drug development. This early dialog, according to the guidance, “is intended to result in a more efficient pediatric drug development program.”
Sponsors must submit iPSPs if they plan to submit a marketing application of supplement for a new active ingredient, new indication, new dosage form or regimen, or a new route of administration; an exception is made for indications that have received orphan designations.
Starting 18 August 2020, sponsors planning applications for new active ingredients subject to the molecularly targeted cancer drug provision of PREA must also submit iPSPs, whether or not the indication has orphan status. Biosimilars not determined to be interchangeable with their referents are considered new active ingredients for this purpose.
Required iPSPs must be submitted no later than 60 calendar days after the end-of-Phase-2 meeting, or at a time agreed on between FDA and sponsor. However, cautions the guidance, “The FDA expects to agree to time frames other than those described in this guidance only if there are exceptional circumstances.” The guidance outlines submission timelines for other circumstances, such as when a combined Phase 2-3 study is conducted.
After iPSP submission, the agency has 90 days to review and respond in writing or request a meeting; the sponsor, in turn, has 90 days to review and respond to FDA comments. The sponsor submits an agreed iPSP at the end of its review period, with FDA having a final 30 days to review this submission and issue a confirmation (or note disagreement) in written correspondence.
If the iPSP doesn’t address such required information as all pediatric age groups and indications for which the drug is being developed, FDA will judge the iPSP as materially incomplete. In this case, the sponsor will have 30 days after notification to correct deficiencies, and the 210-day cycle of FDA and sponsor review will recommence when the corrected iPSP is filed.
FDA provides direction in the guidance about how to handle non-agreed iPSPs and the mechanism for reaching agreement. “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,” notes the agency.
The guidance also provides detail about what should be included in iPSPs and includes narrative instructions and a sample template for preparing the iPSP. In addition to providing an overview of the condition in the pediatric population and summarizing the mechanism of action, intended pediatric population, and indications sought, the iPSP should speak to whether effectiveness will be extrapolated to the pediatric population.
Detailed criteria for when extrapolation from adult data may be appropriate, and which data should be used in support of an extrapolation strategy, are laid out in the guidance.
The iPSP should include a tabular summary of what is planned for both planned nonclinical and clinical development; the guidance provides a sample scenario and table. The iPSP should also address age-appropriate formulation issues and provides a summary of nonclinical and clinical studies supporting pediatric use of the drug or biologic.
The guidance provides information about what sponsors should include in their outline of the proposed pediatric clinical studies of the drug or biologic. Sponsors also need to provide a general timeline for all planned studies.
If submissions are planned to other global regulatory authorities, those pediatric investigation planned should also be included with the iPSP, and the sponsor should note differences between the plan submitted to FDA and those submitted to other authorities. “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,” notes the guidance.
In some cases, sponsors may request to waive pediatric assessments under PREA at the time of new drug or biologics license, or supplement, applications. PREA allows FDA to waiver required pediatric assessments or reports on molecularly targeted pediatric cancer investigations in certain cases. Waivers can be considered if necessary studies are either impossible or “highly impracticable,” as can be the case when very small numbers of patients are involved; when evidence strongly suggests that the drug would not be effective or would be unsafe for all pediatric age groups; or if the drug is not likely to be used in a “substantial number” of pediatric patients because it does not offer a meaningful therapeutic advantage over existing therapies.
Sponsors can also request deferral of pediatric assessments for molecularly targeted pediatric cancer investigations as well. The process for requesting a waiver or deferral, including how to adjust the iPSP template for these requests, is reviewed in detail in the guidance.
The guidance does not address other general topics covered under PREA or the Best Pharmaceuticals for Children Act, notes the agency.

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