Jun 11 2013

U.S. Pediatric Product Development

In the United States, there are two regulations in place regarding pediatric trials and related incentives: the Pediatric Research Equity Act (PREA) and the Best Pharmaceuticals for Children Act (BPCA).  The PREA requires pediatric assessments for applications submitted for changes in active ingredient, indication, dosage form, dosing regimen, or route of administration unless a waiver or deferment of the requirement is obtained.  The BPCA codifies the processes for obtaining pediatric exclusivity for PREA studies or for other, nonrequired pediatric studies.  Successful completion of pediatric studies in the U.S. can lead to a 6-month extension of marketing exclusivity or patent protection.  In the U.S., pediatric exclusivity can only be added on to current marketing exclusivity or patent protection; the exclusivity cannot stand on its own.

To qualify for pediatric exclusivity in the U.S., “a sponsor must file complete reports of the study(ies) prior to the expiration of patent or exclusivity protection they wish to extend” (Guidance: Qualifying for Pediatric Exclusivity).  Additionally, the Food and Drug Amendments Act of 2007 added the provision that the FDA’s review of studies submitted for pediatric exclusivity must be completed at least 9 months before any other patent protection or exclusivity runs out.

There are slight exceptions to the requirement that a drug still be covered by exclusivity or a patent to get U.S. pediatric exclusivity.  If a product does not retain exclusivity or patent protection but the pediatric exclusivity application has new clinical studies of safety and efficacy that are required for approval, then the product can gain 3 years of marketing exclusivity under the Hatch-Waxman Amendments.  Six months of pediatric exclusivity can then be added to the 3 years.  Additionally, if a dosage form (e.g., oral solution) of an active moiety does not have any exclusivity or patent protection, but another dosage form (e.g., solid tablet) of the same active moiety does have exclusivity, then 6 month pediatric exclusivity can be granted to all formulations.

Pediatric exclusivity is granted in the U.S. only after the following:

  1. Receiving a Written Request (WR) from the FDA;
  2. Submitting study reports after receipt of the WR; and
  3. Meeting the conditions of the WR.

A WR is a document from the FDA to a sponsor that addresses the information required for pediatric exclusivity including indications, types of studies, objectives and endpoints, number of subjects, route of administration, proposed labeling, and timeframe for submission.  The NIH maintains a priority list of “Needs in Pediatric Therapeutics”, from which the FDA often issues WRs.  Additionally, the FDA issues WRs if the agency feels studies are needed in the pediatric population or upon receipt from a sponsor of a proposed pediatric study request (PPSR).    A PPSR describes the elements of the studies needed to amend pediatric labeling.  When reviewing the PPSR, the FDA will consider “all approved indications, pending indications, and unapproved uses” of the drug in question before issuing a written request.  The review time for PPSRs is estimated to be approximately 120 days.  If the drug is approved, the WR will be submitted to the holder of the approved application.  As of 28 February 2013, the FDA had received 782 PPSRs and had issued 431 WRs.  In the Division of Metabolism and Endocrinology, 101 PPSRs have been received and 39 WR shave been issued.

Of note, “FDA generally will not accept studies submitted to an NDA before issuance of a Written Request as responsive to a Written Request.  Sponsors should obtain a Written Request before submitting pediatric studies to an NDA.” (bolding and italics from FDA).  (Guidance: Qualifying for Pediatric Exclusivity).  To gain the 6-month exclusivity period, the studies do not have to be successful in adding a pediatric indication to the label; they only have to successfully complete the WR.

In conclusion, products are eligible for 6 months of marketing exclusivity in the U.S. if they complete all studies associated with a WR.  This is the only exclusivity or data protection in place in the U.S. for developing pediatric products.

Helpful References:

Frequently Asked Questions about Qualifying for Pediatric Exclusivity

Pediatric Product Development (including links for PREA and BPCA)

Guidance for Industry: Qualifying for Pediatric Exclusivity Under Section 505A of the Federal Food, Drug, and Cosmetic Act

List of Determinations Including Written Request