April 2012 Volume 8 Number 8

New Bipartisan Legislation Poised to Enhance Regulatory Regime for Children’s Clinical Studies

By Steven W. Postal, JD, Manager, Oncology Research, Washington Cancer Institute at MedStar Washington Hospital Center1

AuthorOn March 28, 2012, Representatives Anna Eshoo (D-CA), Edward Markey (D-MA) and Mike Rodgers (R-MI) introduced the BPCA and PREA Reauthorization Act of 2012 (H.R. 4274) (“The 2012 Bill”), which has been referred to the House Energy and Commerce Committee.2 If the 2012 Bill does not pass, BPCA (Best Pharmaceuticals for Children Act) and PREA (Pediatric Research Equity Act) will sunset on October 1, 2012, five years after their last reauthorization.3 The 2012 Bill would make both Acts permanent.4 The American Academy of Pediatrics (“AAP”), the Elizabeth Glaser Pediatric AIDS Foundation (“EGPAF”), the Pharmaceutical Research and Manufacturers of America (“PhRMA”), and the Biotechnology Industry Organization (“BIO”) have already issued public statements of support, with the latter two expressly supporting permanent reauthorization.5

The 2012 Bill would not only reauthorize the current laws, but also add enhancements incorporating findings from a February 29, 2012 Institute of Medicine (“IOM”) report evaluating BPCA, PREA, and previous laws regarding clinical studies in children.6 The 2012 Bill and underlying report findings are poised to strengthen the existing clinical legal regime surrounding pediatric studies. Permanent reauthorization would be the latest step in a burgeoning field of pediatric studies regulation.

Regulatory History Regarding Children’s Clinical Studies

Regulations surrounding children’s clinical studies kicked into high gear beginning in the 1990s, but initially contained various shortcomings. In 1994, the Food and Drug Administration (“FDA”) issued the Pediatric Rule, whereby drug companies were allowed to label drugs for pediatric use by extrapolating data from clinical trials in adults, if disease cycles and drug reactions were similar in children and adults.7 However, this extrapolation proved problematic in accurately predicting children’s responses to those drugs.8

In 1997, approximately 70 percent of medicines used in children did not have sufficient dosing information for pediatric application.9 To incentivize the pharmaceutical industry to conduct more pediatric clinical trials, in 1997, the FDA Modernization Act (“FDAMA”) granted pharmaceutical companies six more months of market exclusivity for the drugs studied and ultimately labeled for pediatric use.10 However, despite this incentive, many participating studies failed to demonstrate efficacy in children.11

While FDAMA expired on January 1, 2002, its relevant provisions were reauthorized in 2002 as part of BPCA and PREA, and in 2007 as part of the Food and Drug Administration Amendments Act (“FDAAA”).12 BPCA established a pediatric drug list and research fund for pediatric clinical studies, and authorized the IOM to examine best practices for pediatric studies.13 Reauthorized in FDAAA in 2007, BPCA also tasked the National Institutes of Health (“NIH”) to consult with the FDA and other experts to create and publish a priority list of needs for pediatric therapeutic areas at least every three years beginning in September 2008.14

PREA gave the FDA the power to require testing in children for pediatric drugs in certain instances.15 In 2010, the Biologics Price Competition and Innovation Act was signed into law as part of the Patient Protection and Affordable Care Act. It granted 12 years of exclusivity to biologics, with a six-month extension for pediatric indications.16

The Legacy of BPCA and PREA

BPCA and PREA are responsible for 180 new pediatric drug studies, and inclusion of pediatric information in over 400 drug labels.17 The FDA maintains that the six months exclusivity of FDAMA and BPCA was the most effective government initiative in getting information on pediatric drug use.18 Also, by 2008, at least in part thanks to BPCA and PREA, 50 to 60 percent of all drugs used in pediatric medicine had been tested in pediatric populations. 19 Pharmaceutical companies declined only five percent of all pediatric studies from 2007 to 2010 (following BPCA and PREA reauthorization in 2007), as compared with 19 percent between 2002 and 2005.20

Key Findings of the IOM Report

The IOM Report reviewed recent laws surrounding pediatric studies. It has provided the following discoveries regarding the effectiveness of pediatric trial regulation, and children’s clinical trials generally:

  1. Increased Information. BPCA and PREA-initiated pediatric studies have provided useful information to guide pediatric care. That said, this information sometimes conflicted with hypotheses regarding efficacy, pharmacokinetics, and safety of drugs in children.21
  2. Increased Transparency. Congress has greatly increased public access to BPCA and PREA-initiated studies, thereby increasing these studies’ value.22
  3. Greater Insight into Shortcomings. Some BPCA and PREA-initiated studies fall short of their potential. Possible reasons for this include: sponsors’ inability to recruit enough children, lack of sufficient dose-ranging studies, and incomplete labeling.23
  4. Limitations. Present limitations of pediatric studies include neonatal applications and long term safety and efficacy for all pediatric studies.24
  5. Importance of Expedited Planning. Children would benefit from expedited planning, initiation, and completion of studies. While European requirements reflect an overly aggressive timeline, the U.S. requirements appear to need expediting.25
  6. Reauthorization Process is a Mixed Bag. The reauthorization process for BPCA and PREA is a double-edged sword: it has improved the policies enacted under these laws, but has created uncertainties for both the FDA and the pharmaceutical industry.26
  7. Biologics is the Frontier. Enforcement of PREA has yielded valuable information on biologics, but it remains too early to tell the effect the 2010 legislation. Further, Congress should encourage more study of biologics in pediatric studies.27

New Enhancements Proposed to BPCA and PREA

The 2012 Bill proposes several new regulations for strengthening pediatric studies, incorporating the findings of the IOM Report. First, it mandates expedited planning and completion for pediatric studies, unless a delay results from an appropriate reason.28 Thanks in part to lobbying efforts by the AAP and the EGPAF, the legislation also calls for increased data collection for neonatal pediatric studies.29 Also, the law calls for permanent reauthorization, which eliminates the uncertainties that a five-year reauthorization process creates. Finally, the 2012 Bill increases transparency for the status of pediatric studies, and greater safety for infant pediatric drugs.30


Dwarfed by the public debate surrounding the constitutionality of the Patient Protection and Affordable Care Act of 2010, the smaller in scope BPCA and PREA Reauthorization Act of 2012 offers a promising example of more measured and incremental, yet more bipartisan and popular health reform. Given the success of recent laws in increasing knowledge of pediatric care, and in providing economic incentives to conduct more pediatric studies, the 2012 Bill provides a win-win situation for the industry, the public, and patients.


Opinions expressed herein are attributable to the author and are not those of the Washington Cancer Institute, MedStar Washington Hospital Center, or MedStar Health. The author would like to thank Robyn Whipple Diaz for contributing ideas to this article, and for her continual inspiration and support.

2 http://www.aap.org/en-us/about-the-aap/aap-press-room/pages/Child-Health-Groups-Praise-Introduction-of-BPCA-and-PREA-Reauthorization-Act-of-2012.aspx; http://www.bioportfolio.com/news/article/998908/Lawmakers-Seek-Reauthorization-Of-Pediatric-Drug-Laws.html.





http://www.aap.org/en-us/about-the-aap/aap-press-room/pages/Child-Health-Groups-Praise-Introduction-of-BPCA-and-PREA-Reauthorization-Act-of-2012.aspx; http://www.pharmalive.com/News/index.cfm?articleid=832694.


http://www.aap.org/en-us/about-the-aap/aap-press-room/pages/Child-Health-Groups-Praise-Introduction-of-BPCA-and-PREA-Reauthorization-Act-of-2012.aspx. The report is entitled “Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act.” For the full report, as well as a summary, and a searchable table of contents, see http://www.nap.edu/catalog.php?record_id=13311.




Id. The United States District Court for the District of Columbia struck down the Pediatric Rule on October 17, 2002, stating the FDA could not require pharmaceutical companies to test their products in children. See http://www.ahrp.org/infomail/1002/18a.php.












https://www.federalregister.gov/articles/2009/04/14/E9-8477/the-best-pharmaceuticals-for-children-act-bpca-priority-list-of-needs-in-pediatric-therapeutics; see also “the new BPCA” in same website.











20 “Testimony of Daniel A.C. Frattarelli MD FAAP, On Behalf of the American Academy of Pediatrics, Before the Energy and Commerce Committee Health Subcommittee, Feb. 1, 2012, page 4. www.aap.org.
21 “Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act (2012): Summary,” http://www.nap.edu/openbook.php?record_id=13311&page=5 s-5.  
22 Id.
23 Id.
24 Id.
25 Id.
26 Id., at s-6.
27 http://www.iom.edu/~/media/Files/Report%20Files/2012/Safe-and-Effective-Medicines-for-Children/safeeffectivemeds_RB.pdf.
28 http://www.aap.org/en-us/about-the-aap/aap-press-room/pages/Child-Health-Groups-Praise-Introduction-of-BPCA-and-PREA-Reauthorization-Act-of-2012.aspx.
29 Id.


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