GAO Report Finds BPCA and PREA to be Ongoing Successes, But Says that FDA Needs to Improve Tracking of Products Studied for Pediatric Uses

June 6, 2011

By Nisha P. Shah & Kurt R. Karst

The U.S. Government Accountability Office (“GAO”) recently issued a report required by the FDA Amendments Act of 2007 (“FDAAA”) concerning the effects of the Pediatric Research Equity Act (“PREA”) (FDC Act § 505B) and the Best Pharmaceuticals for Children Act (“BPCA”) (FDC Act § 505A) on the study and labeling of drug and biological products for pediatric use.   The GAO found that at least 130 products (80 products under PREA and 50 under the BPCA) have been studied for use in children since FDAAA’s enactment on September 27, 2007.  Despite this success, the GAO says in its report that “FDA lacks an important internal control that would allow it to manage its review process to ensure that the agency and sponsors are meeting the law’s requirements and that FDA is meeting its own mission, goals, and objectives during the period of its review of the application.”

The BPCA and PREA are sometimes referred to as the “carrot and stick” approach to obtaining pediatric labeling.  PREA (the stick) requires sponsors to conduct pediatric studies in various pediatric age groups for certain drug and biological products, and to submit the results and proposed labeling changes to FDA with a marketing application.  FDA may waive (partially or fully) the PREA requirement or defer the submission pediatric study results until after product approval.  Under the BPCA (the carrot), FDA issues a written request to a sponsor to conduct pediatric studies for products that may have important health benefits in children.  A sponsor can decline FDA’s request; however, if the sponsor completed the requested studies, FDA grants six months of marketing exclusivity for the drug or biological product.  Additionally, a sponsor can request that a product that must be studied under PREA to be studied also under the BPCA to allow the sponsor to be eligible for six-months of  pediatric exclusivity. 

For drugs approved under the FDC Act, pediatric exclusivity attaches to any unexpired patent and non-patent marketing exclusivities listed in the Orange Book for any of the sponsor’s approved drug products (including certain combination products) that contain the active moiety for which pediatric exclusivity was granted.  For biological products licensed under the PHS Act, pediatric exclusivity extends by six months the 12- and 4-year reference product exclusivity periods described at PHS Act § 351(k)(7).  Pediatric exclusivity also extends by six months the 7-year period of orphan drug exclusivity applicable to a biological product.  For both drug and biological products, the law contains a similar exception with respect to the applicability of pediatric exclusivity.  Specifically, for post-September 2007 written requests, pediatric exclusivity will not apply to a particular period of patent or non-patent exclusivity if FDA grants pediatric exclusivity “later than 9 months prior to the expiration of such period.” 

According to the GAO report, FDA claimed that about 830 applications subject to PREA were submitted to FDA from September 27, 2007 to June 30, 2010, but FDA could not provide an exact number.  The Pediatric Review Committee (“PeRC”), a FDA committee responsible for assisting in the review of pediatric study results, completed reviews for 449 applications, 80 of which contained the results of pediatric studies (59 were drug applications and 21 were biological product applications).  The GAO claims that FDA could not provide information on the remaining 381 applications.  The GAO also found that FDA granted a full or partial waiver or deferral to more than half of the applications it received under PREA (237 waivers and 131 deferrals).  Under the BPCA, 50 products have been studied between the 2007 reauthorization through June 30, 2010, all of which were for drug products.  According to FDA officials, FDA granted pediatric exclusivity to 44 of the 50 drugs.  The report indicated that sponsors for five of the six drugs that did not receive exclusivity submitted only partial responses to FDA’s requests. 

Since the 2007 reauthorization of PREA and the BPCA, all of the 130 drug and biological products with studies completed and applications reviewed by FDA had labeling changes.  In comparison, in the prior nine years, 256 products had pediatric study-related labeling changes agreed upon by FDA and the sponsor.  According to the report, the top three categories of labeling changes are: (1) expansion of pediatric age groups approved in the label, (2) safety and effectiveness were not established in pediatric populations and a description of the study conducted was added, and (3) new and enhanced pediatric safety information was included. 

The GAO interviewed stakeholders, including drug and biological product sponsors, concerning challenges to conducting pediatric studies, which include:

  • “confusion about how to comply with PREA and BPCA due to a lack of current guidance from FDA … [since] the most recent PREA guidance is draft guidance from 2005 and that the most recent BPCA guidance was revised in 1999;”
  • “since PREA and BPCA are subject to reauthorization every 5 years, some of the statutory requirements for studies could change while studies are under way or as they are being planned; therefore, there is uncertainty as to the requirements that will apply when they conduct the studies;”
  • “complying simultaneously with … PREA and BPCA, and the [EU] Paediatric Regulation;” and
  • “the lack of economic incentives presents a challenge to sponsors’ willingness to conduct pediatric studies voluntarily, as under BPCA,” particularly for products that are nearing the end of their market exclusivity or are off-patent because of the lack of economic benefit associated with conducting pediatric studies.  This is because once a drug or biological product is off-patent, the sponsor cannot receive pediatric exclusivity for conducting such studies. 

The GAO recommended that FDA implement a system “to track applications upon their submission and throughout its review process and maintain aggregate data, including the total number of applications that are subject to PREA and whether those applications include pediatric studies.”  HHS officials stated that an update to a tracking system, which was completed in May 2011, will allow FDA to track applications subject to PREA.  Although the GAO acknowledged the benefits of an improved tracking system, the GAO also responded that it was unclear whether the data system would allow FDA to track and aggregate data about applications that are currently under review.

Separate from the GAO report, the Institute of Medicine (“IOM”) has convened an ad hoc committee to examine pediatric studies conducted under the BPCA and PREA.  Among other things, the committee is reviewing and assessing a representative sample of PREA and BPCA studies and related labeling changes, and is supposed to issue a report offering “recommendations for ensuring pediatric testing of biological products.”