AAP Chimes in on Pediatric Exclusivity and Whether a Written Request is a Condition Precedent to FDA Awarding Exclusivity

October 14, 2014

By Kurt R. Karst –      

In recent comments submitted to FDA, the American Academy of Pediatrics (“AAP”) is taking a stand against the relief requested in a June 2014 Citizen Petition (Docket No. FDA-2014-P-0830) submitted on behalf of Merz North America.  The petition calls into question the long-held belief that FDA’s issuance of a Pediatric Written Request (“PWR”) is a condition precedent to the Agency awarding a period of 6-month pediatric exclusivity pursuant to the Best Pharmaceuticals for Children Act (“BPCA”) (FDC Act § 505A).  According to the AAP, Congress never intended for certain provisions of the BPCA “to be an end-run around the requirement for exclusivity to be granted on the basis of a written request.”

As we previoulsy reported, FDA approved the Merz (formerly Shionogi) drug CUVPOSA (glycopyrrolate) Oral Solution on July 28, 2010 under NDA No. 022571 for a pediatric-only indication: to reduce chronic severe drooling in pediatric patients (aged 3-16) with neurologic conditions associated with problem drooling (e.g., cerebral palsy).  FDA awarded periods of 3-year new clinical investigation exclusivity and 7-year orphan drug exclusivity, but not 6-month pediatric exclusivity.  That’s because the NDA sponsor never obtained a PWR from FDA.  But a PWR should not have been necessary says Merz, because the company’s “predecessor fulfilled the requirements for six-month pediatric exclusivity pursuant to FFDCA § 505A(h) as it existed at the time [FDA] approved Cuvposa in 2010.  The pediatric studies were performed as required under a provision of law and regulations (i.e., for NDA approval), and thus satisfied the requirements for pediatric exclusivity under § 505A(h) without a formal written request from FDA.”

In 2010, FDC Act § 505A(h), which concerns the relationship between the BPCA and the Pediatric Research Equity Act (“PREA”) (FDC Act § 505B) under which FDA can require sponsors to conduct pediatric testing for on-label uses, stated:

Notwithstanding any other provision of law, if any pediatric study is required by a provision of law (including a regulation) other than this section and such study meets the completeness, timeliness, and other requirements of this section, such study shall be deemed to satisfy the requirement for market exclusivity pursuant to this section.

That provision, originally added to the statute in 1997 at FDC Act § 505A(i) with the enactment of the FDA Modernization Act (“FDAMA”), and moved to FDC Act § 505A(i) with the enactment of the 2007 FDA Amendments Act (“FDAAA”), was changed in 2012 with the enactment of the FDA Safety and Innovation Act (“FDASIA”) to state:

Exclusivity under this section shall only be granted for the completion of a study or studies that are the subject of a written request and for which reports are submitted and accepted in accordance with subsection (d)(3).  Written requests under this section may consist of a study or studies required under section 355c of this title [FDC Act § 505B].

Merz says that the difference between the 2007 and 2012 versions of FDC Act § 505A(h) is significant for two reasons: “First, it includes language referencing written requests which was not present in that particular subsection when Cuvposa was approved,” and “[s]econd, it facially narrows the relationship between studies conducted for pediatric exclusivity and for other required purposes.”  Continuing on with the second point, the petition says that the 2010 version of FDC Act § 505A(h) “broadly referenced pediatric studies conducted as required by another provision of law or regulation,” but that the 2012 version of FDC Act § 505A(h) “only references PREA studies by name as being eligible for pediatric exclusivity.” 

The upshot of the differences in the statutory text, says Merz, is that for CUVPOSA to have been eligible for pediatric exclusivity under FDC Act § 505A(h) as it existed in 2010, two requirements must have been met: (1) the pediatric studies performed must have been “required by a provision of law (including a regulation);” and (2) the studies must have met the pediatric exclusivity requirements, including completeness and timeliness.  And both of these elements were met, argues the company:

Cuvposa met the first hurdle for receiving pediatric exclusivity under § 505A(h) because the sponsor was required to complete pediatric studies for NDA approval under both the FFDCA and the regulations. . . . Cuvposa also cleared the second hurdle for pediatric exclusivity under § 505A(h) — that the studies meet the “completeness, timeliness, and other requirements” for exclusivity.  The completeness requirement was certainly met because, if not, then the NDA would not have been approved.  The timeliness factor is not relevant here, because the studies were completed as required for NDA approval.  As far as any of the “other requirements” — a written request, internal review of the request, and internal review of the completed studies — none of these were required for Cuvposa to be eligible for exclusivity under § 505A(h).

In its comments to FDA, the AAP says there is no reason to believe that Congress ever intended to award pediatric exclusivity under the circumstances in which a company was seeking approval for pediatric-only use of a drug: 

To argue that Congress intended to allow for the awarding of pediatric exclusivity under §505A(i)/§505A(h) for studies submitted in accordance with a pediatric-only new drug application under §505(b)(1), requires one to also argue that Congress also intended pediatric exclusivity to be an incentive for the development of new pediatric-only therapies.  There is no factual basis to make this claim and no record to indicate this is what Congress intended.  While improving incentives for the development of first-in-pediatrics therapies is a worthy goal, the goals of the Pediatric Rule, BPCA, and PREA is and always has been to ensure that drugs developed for adults are studied in children and to provide incentives for completing additional FDA-requested studies in children.

Indeed, says the AAP, if that was the case, then Congress would not have pursued legislation to expand the existing Tropical Disease Priority Review Voucher program set forth at FDC Act § 524 (as added by FDAAA) to create the Rare Pediatric Disease Priority Review Voucher under FDC Act § 529 (as added by FDASIA) (see our previous post here).  Morover, says the AAP, removing the PWR element as a condition to obtaining pediatric exclusivity could be dangerous:

The written request is and always has been an essential element of the pediatric exclusivity program.  Six months of exclusivity is a powerful incentive for manufacturers but it does not come without a cost to society.  Tying this incentive to the fulfillment of a written request allows the FDA to ensure that the data generated by trials involving children are maximized, that product sponsors are meeting the objectives and timeframes agreed to in the written request, and that data and labeling generated by such trials are available to the public.  It would be a dangerous precedent to allow the awarding of exclusivity without a written request.  The written request is in essence a contract between the FDA and the sponsor to conduct specific pediatric studies in return for a generous incentive. Allowing the awarding of exclusivity without a written request would not appropriately serve the interests of child health.