PREA is All You Need? FDA’s Recent Draft Guidance States an Intention to Limit Pediatric Exclusivity By Issuing Fewer Written Requests Under the BPCA

In May 2023, CDER and CBER published a draft guidance titled “Pediatric Drug Development: Regulatory Considerations – Complying with the Pediatric Research Equity Act [“PREA”] and Qualifying for Pediatric Exclusivity Under the Best Pharmaceuticals for Children Act [“BPCA”]” (the “Draft Guidance”).  This Draft Guidance, in part, replaces a 2005 guidance titled “How to Comply with the Pediatric Research Equity Act.”  The Federal Register notice notes that “[c]ombining discussion of PREA and the BPCA together in regulatory guidance emphasizes the sponsor’s need to consider both laws when developing pediatric drugs and biological products.”

The Draft Guidance covers the legal requirements of PREA and the voluntary incentive  mechanisms of the BPCA in a comprehensive fashion.  However, one piece, excerpted below, stood out to us:

Historically, FDA has at times issued WRs solely for studies required under PREA, even if there were no other indications that may produce health benefits in the pediatric population.  However, over time, data on pediatric labeling changes pursuant to BPCA and/or PREA have been collected.  Between 2002 and 2019, there were 768 products with pediatric labeling changes under BPCA and/or PREA.  Sixty-three percent of these labeling changes were based on studies conducted under PREA/Pediatric Rule alone; 21 percent were based on studies conducted under BPCA alone; 16 percent were based on studies conducted under both the BPCA and PREA.  These data suggest that studies required under PREA are successfully completed, and that PREA requirements have resulted in an increase in pediatric labeling, even without the added incentive of the BPCA.

The BPCA provides FDA with discretion to determine whether to issue, and the appropriate scope of, WRs based on the information that “may produce health benefits” in the pediatric population.  In light of the data on pediatric labeling changes pursuant to the BPCA and/or PREA, FDA believes WRs should be reserved for those sponsors who conduct additional pediatric studies — beyond what is required under PREA — that may produce health benefits in children.  Thus, upon finalization of this guidance, FDA does not expect to issue WRs solely for studies or planned studies that are required under PREA.  In general, FDA expects that a WR that includes studies or planned studies required under PREA will also include additional indications or populations.  If there are no additional studies for indications or populations that may produce health benefits in the pediatric population beyond the studies or planned studies required under PREA, then FDA does not expect to issue a WR for that drug.

This represents a significant policy change from the 2005 guidance, wherein the Agency stated: “It is the Agency’s policy to offer applicants the opportunity to qualify for pediatric exclusivity under section 505A of the Act for studies required and conducted under PREA.”

It is perhaps not surprising that the statutory requirement of PREA, with accompanying enforcement tools, is responsible for such a large percentage of relevant pediatric labeling changes as compared to BPCA’s voluntary incentive.  Moreover, it is not surprising that such a small percentage of relevant pediatric labeling changes are due to the BPCA alone, as one might speculate these largely to be studies outside the scope of PREA – that is, studies for uses unapproved in adults.  However, given FDA’s prior announced policy, it is somewhat surprising that only 16% of pediatric labeling changes pursuant to BPCA and/or PREA between 2002 and 2019 were conducted under both the BPCA and PREA.

Still, however, it appears FDA has had enough of these 16%.  Instead, the Draft Guidance expresses an intention to limit pediatric exclusivity to the 21% of relevant pediatric labeling changes based on studies conducted under the BPCA alone.

It is not clear if any or all of the 16% of pediatric labeling changes based on studies conducted under both BPCA and PREA would have been conducted if BPCA exclusivity was not an option, but the Agency appears ready to test the theory that PREA is all it needs, when applicable.  BPCA exclusivity, consequently, appears likely to now be limited to studies outside the scope of PREA, such as studies in indications or populations unapproved in adults.