1.) 2.) 3.) At Least 130 Products Have Been Studied in Numerous Therapeutic Areas under PREA and BPCA, but FDA Does Not Know If Additional Products Have Been Studied

At least 130 products—80 products under PREA and 50 under BPCA— have been studied for use in children since the 2007 reauthorization. In addition, few drugs have been studied when  sponsors have declined written requests. FDA does not track and aggregate data about  applications submitted under PREA until the PeRC has completed its  review of information from the application. Therefore, FDA was unable to  provide information about some applications that had been submitted to  the agency that were subject to PREA. This lack of data during the  review process about applications subject to PREA, hampers FDA’s ability  to manage the review process, including whether FDA is meeting statutory  requirements and whether the sponsor has complied with PREA’s  requirements for pediatric studies. FDA officials said that they could not  provide any details about these applications without locating each  application individually within the agency and reviewing it to determine  whether it included pediatric studies or requests for waivers or deferrals,  but stated that it is likely that most of the approximately 381 applications  are for products that sponsors plan to market in adult indications and,  therefore, would include a request for a deferral of the pediatric studies  rather than completed pediatric studies. 50 Products Have Been Studied under BPCA since Its 2007 Reauthorization

Fifty products have been studied under BPCA from the 2007  reauthorization through June 30, 2010; FDA has reviewed applications for  50 of these products, none of which were biological products. According to FDA officials, FDA granted pediatric exclusivity to the  sponsors of 44 of the 50 drugs. All Products with Completed Pediatric Studies Had Labeling Changes, and FDA’s Goals Often Differ from the PREA Requirement for Reaching Agreement on Labeling Changes

All of the drug and biological products with pediatric studies completed  and applications reviewed since the 2007 reauthorization had labeling  changes that included important pediatric information. Since  the 2007 reauthorization, the most commonly implemented labeling  change expanded the pediatric age groups for which a product was  indicated. Therefore, the drug’s labeling was changed to describe the study  conducted and indicate that safety and effectiveness were not established  in pediatric populations. One challenge stakeholders, including  sponsors, identified was confusion about how to comply with PREA and  BPCA due to a lack of current guidance from FDA. FDA  has not provided guidance for changes to the laws from the 2007  reauthorization for PREA or BPCA. FDA explained that officials can  discuss study timelines and questions or concerns sponsors may have  regarding their study submissions throughout the process. Another challenge identified by stakeholders is complying simultaneously  with the U.S. laws, PREA and BPCA, and the European Union’s (EU)  Paediatric Regulation. III for a description of the Paediatric  Regulation.) Because of the timing of this review, FDA staff  managing the review process cannot be certain how many applications  that have been submitted to the agency are subject to PREA, how many of  those applications include pediatric studies, or how many applications  include requests for waivers or deferrals, until FDA has almost completed  its review of the entire application. However, our recommendation is not based on FDA’s ability to determine  the status of individual applications, but rather its lack of aggregate data  on applications that are subject to PREA during its review of the  applications so as to be able to better manage its review process. HHS states  that the improvement will allow FDA to better track future applications  that are subject to PREA. We also describe the  number of products with completed and ongoing studies in neonates since  the 2007 reauthorization of the Pediatric Research Equity Act (PREA) and  the Best Pharmaceuticals for Children Act (BPCA). FDA and NIH officials  described how they maintained data on pediatric studies, and the resulting  labeling changes conducted under PREA and BPCA. BPCA authorizes  FDA to provide an incentive of an additional 6 months of market  exclusivity, known as pediatric exclusivity, to product sponsors that  conduct pediatric studies requested by FDA.
Why GAO Did This Study

In 2007, Congress reauthorized two laws, the Pediatric Research Equity Act (PREA) and the Best Pharmaceuticals for Children Act (BPCA). PREA requires that sponsors conduct pediatric studies for certain products unless the Department of Health and Human Services' (HHS) Food and Drug Administration (FDA) grants a waiver or deferral. Sponsors submit studies to FDA in applications for review. BPCA is voluntary for sponsors. The FDA Amendments Act of 2007 required that GAO describe the effect of these laws since the 2007 reauthorization. GAO (1) examined how many and what types of products have been studied; (2) described the number and type of labeling changes and FDA's review periods; and (3) described challenges identified by stakeholders to conducting studies. GAO examined data on the studies from the 2007 reauthorization through June 2010, reviewed statutory requirements, and interviewed stakeholders and agency officials.

What GAO Found

At least 130 products--80 products under PREA and 50 under BPCA--have been studied for use in children since the 2007 reauthorization. However, FDA cannot be certain how many additional products may have been studied because FDA does not track and aggregate data about applications submitted under PREA that would allow it to manage the review process. FDA was unable to provide information about some applications that had been submitted to the agency that were subject to PREA. Recent improvements to FDA's data system might assist the agency in tracking future applications. Under PREA, FDA has granted most of the study waivers and deferrals requested by sponsors since the 2007 reauthorization. Under BPCA, FDA granted pediatric exclusivity--an additional 6 months of market exclusivity, which generally delays marketing of generic forms of the product--to the sponsors of 44 of the 50 drugs in exchange for conducting pediatric studies. Because BPCA is voluntary, sponsors may decline FDA's request for pediatric studies. Although BPCA includes provisions to encourage the study of drugs when sponsors have declined FDA's request, few drugs have been studied under these provisions. Since the 2007 reauthorization, all of the 130 products with pediatric studies completed and applications reviewed under PREA and BPCA had labeling changes that included important pediatric information. The most commonly implemented labeling change expanded the pediatric age groups for which a product was indicated. The next most common type of labeling change indicated that safety and effectiveness had not been established in pediatric populations and provided a description of the study conducted. Additional labeling changes were recommended for products as a result of FDA's monitoring of adverse events associated with products after they had been approved for marketing. FDA officials said they need to complete their review of the application, including all studies, before they can reach agreement with the sponsor on labeling changes. Stakeholders, including sponsors, pediatricians, and health advocacy organizations, described challenges faced by sponsors that could limit the success of PREA and BPCA. Those challenges included confusion about how to comply with PREA and BPCA due to a lack of guidance from FDA for changes to the laws from the 2007 reauthorization of PREA or BPCA. FDA officials explained that they mitigate this lack of guidance by discussing questions or concerns that sponsors have regarding their pediatric studies with sponsors throughout the process. An additional challenge sponsors described was a lack of economic incentives to study products with no remaining market exclusivity.

What GAO Recommends

GAO recommends that the Commissioner of FDA track applications during its review process and maintain aggregate data on applications subject to PREA. HHS agreed that better tracking of information is needed but disagreed with GAO's finding that it does not track applications. While FDA is able to identify the status of individual applications during its review, it has not maintained data that would allow it to better manage its review process.