FDA clarifies deferral policy on pediatric studies for new cancer drugs

Final guidance from the US Food and Drug Administration (FDA) specifies when sponsors must conduct pediatric studies for new cancer drugs as well as when those requirements can be waived or deferred.
 
Sponsors are required to evaluate these oncology drugs in pediatric populations for applications submitted on or after 18 August 2020, under changes made by the FDA Reauthorization Act of 2017 (FDARA).
 
The guidance addresses molecularly targeted oncology drugs for which an original new drug application (NDA) or biologics license application (BLA) is expected to be submitted to FDA. These include cancer drugs with new active ingredients based on molecular mechanism of action rather than clinical indication.

The document has been revised from the previous draft to provide additional information and clarification on waivers and deferrals, to describe additional safeguards for children in clinical investigations, to provide the information sources used to develop its molecular target lists and to describe information that should be included in a request for a meeting, according to a Federal Register announcement on 24 May.
 
Early pediatric evaluation of these drugs is expected to “accelerate the creation of an informed pediatric development plan and ultimately the development of promising drugs for pediatric patients,” according to the Federal Register announcement.
 
The guidance outlines factors FDA will consider in determining whether a molecular target is “substantially relevant” to the growth or progression of a pediatric cancer.
 
These include “acceptable” levels of evidence that the target has been shown to be associated with one or more types of cancer which occur in pediatric patients, and the biological function of the target may be functionally related to the etiology, growth, and therapy resistance of a cancer that occurs in pediatric patients.
 
Clarification on deferrals, waivers
 
FDA heeded industry’s pleas to provide more information on the criteria it will use in granting deferrals from these studies. The Biotechnology Innovation Organization wrote in its February 2020 comments that the deferral provision was not “clearly articulated” in draft guidance.
 
To qualify for a deferral, applicants must submit the following: certification of the grounds used to defer the assessment or reports on the investigation, a pediatric study plan, evidence that the studies are being conducted or will be conducted with due diligence at the earlier possible time and a timeline for the completion of these studies, according to the final guidance.
 
The agency also clarified its policy on waivers. A full or partial waiver may be granted if a known serious toxicity precludes its use in the pediatric population, if there are known or strongly suspected severe developmental toxicities which may present an unreasonable risk to pediatric patients, when a sponsor is not able to develop an appropriate pediatric formulation, or where there is “no convincing evidence” that the new active ingredients developed for later generation products would provide a “superior” pharmcocologic toxicity when compared to product already under investigation.
 
The draft finalizes a previous draft issued on 13 December 2019. (RELATED: When FDA requires pediatric studies for new cancer drug submissions: new draft guidance, Regulatory Focus. 12 December 2019)
 
Guidance