April 1, 2019
Division of Dockets Management (HFA-305)
Food and Drug Administration
5630 Fishers Lane, Rm. 1061
Rockville, MD 20852
Re: Docket No. FDA-2018-D-4524: S11 Nonclinical Safety Testing in Support of Development of Pediatric Medicines
The Biotechnology Innovation Organization (BIO) thanks the Food and Drug Administration (FDA or Agency) for the opportunity to submit comments on “S11 Nonclinical Safety Testing in Support of Development of Pediatric Medicines” (Draft Guideline or Guideline).
BIO is the world’s largest trade association representing biotechnology companies, academic institutions, state biotechnology centers, and related organizations across the United States and in more than 30 other nations. BIO members are involved in the research and development of innovative healthcare, agricultural, industrial and environmental biotechnology products.
One area where the guideline is of particular relevance to BIO, and is thus appreciated, is in establishing both clarity and flexibility around the need and value of studies conducted in nonhuman primates. The language in Section 3.3 that acknowledges the limited value of dedicated studies in postweaning juvenile NHP is supported, as is the final paragraph in Section 4 which specifically addresses the situation of “pediatric first” clinical development in neonates.
Some of the suggested datasets (i.e., clinical data, ePPND) that inform the nonclinical pediatric plan would not generally be available or well-characterized at the expected time of pediatric submission. As such, the guidance should be clear as to whether these data need to be completed earlier than otherwise expected (e.g., in parallel with phase 3 per S6).
There are several references to in vitro nonclinical investigations BIO looks forward to using in vitro methods wherever possible if they help to support the program.
BIO believes that commentary to address the necessity of repeating juvenile toxicity studies on a prodrug of an approved drug when there may or may not be existing adult toxicity data for the prodrug would be helpful. It is currently unclear whether there any particular concerns or strategies to be considered in those cases...