[Federal Register Volume 76, Number 63 (Friday, April 1, 2011)]
[Pages 18228-18229]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-7673]

[[Page 18228]]



National Institutes of Health

Best Pharmaceuticals for Children Act (BPCA) Priority List of 
Needs in Pediatric Therapeutics

AGENCY: National Institutes of Health, the Eunice Kennedy Shriver 
National Institute of Child Health and Human Development (NICHD).

ACTION: Notice.


SUMMARY: The National Institutes of Health (NIH) hereby announces the 
Best Pharmaceuticals for Children Act (BPCA) Priority List of Needs in 
Pediatric Therapeutics for 2011. The BPCA seeks to improve the level of 
information--in scientific publications and on the label--about 
pharmaceuticals used to treat children. The BPCA requires that the NIH 
identify the drugs of highest priority for study in pediatric 
populations and publish a list of drugs/needs in pediatric 
therapeutics. This notice fulfills the requirement to publish that 

SUPPLEMENTARY INFORMATION: For many decades, the pediatric medical 
community, the public health community, and government agencies have 
recognized multiple gaps in knowledge regarding the use of therapeutics 
in children, including the correct dose, the indication, the side 
effects, and the safety profile of pharmaceuticals in the long term. 
These gaps have frequently resulted in inadequate labeling for 
pediatric use and in widespread off-label use of prescription drugs in 
children. Off-label use of a drug results in a limited gain in 
scientific knowledge in dosing of a drug, changes in drug metabolism 
and response during growth and development, and ultimately the long-
term effects. Contributing factors to the extensive off-label product 
use include limited access to patient populations for study, lack of 
knowledge related to the ethical conduct of clinical trials in 
children, the absence of sufficient evidence-based information about 
medication use in children, and a general lack of long-term safety data 
on the medications that are used. This limitation in information can 
increase a child's risk for adverse reactions.
    The Eunice Kennedy Shriver National Institute of Child Health and 
Human Development (NICHD), the Food and Drug Administration (FDA), 
other Federal agencies, and various non-profit and commercial 
organizations have taken steps to address the knowledge gaps that exist 
in pediatric therapeutics. The BPCA seeks to improve the level of 
information in scientific publications and in the FDA-approved product 
label about pharmaceuticals used to treat children.

The 2002 BPCA Legislation

    In November 1997, Congress enacted the Food and Drug Administration 
Modernization Act (FDAMA), which contains the provision establishing 
economic incentives in the form of exclusivity for conducting pediatric 
studies. Patents are granted by the U.S. Patent and Trademark Office 
and provide exclusive rights, such as intellectual property rights. 
Exclusivity, as it relates to manufacturers of drugs, is defined as 
exclusive marketing rights granted by the FDA upon approval of a drug 
(refer to the following FDA Web site for more details: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/default.htm). The initial 
BPCA legislation reauthorized an incentive program for on-patent drugs 
that meet certain criteria first authorized in the FDAMA. The BPCA also 
contains provisions for off-patent drugs and general support for 
pediatric product development. The legislation, as it applies to the 
NIH, authorizes a research program through the Department of Health and 
Human Services (HHS), with implementation through the NIH, specifically 
the NICHD. The NICHD is responsible for the development of (1) a 
priority list of needs in pediatric therapeutics, in consultation with 
the FDA and experts in pediatrics; (2) sponsorship of relevant 
pediatric clinical trials; and (3) submission of resulting data to FDA 
for pediatric labeling changes.
    Since 2002, the NICHD has sought public comment and collaborated 
with other NIH Institutes and Centers and experts in pediatrics to 
identify drugs in need of further study and to prioritize needs in 
pediatric therapeutics. Under the 2002 BPCA legislation, prioritization 
was based on three major factors:
     Availability of information concerning the safe and 
effective use of a drug in the pediatric population and the need for 
additional information;
     Potential health benefits in the pediatric population 
resulting from new studies; and
     Possible need for reformulation of existing products.

The Updated BPCA Legislation of 2007

    Title V of Public Law 110-85, the Best Pharmaceuticals for Children 
Act of 2007, was enacted on September 27, 2007, as part of the Food and 
Drug Administration Amendments Act of 2007. This legislation, which 
reauthorizes the BPCA (Section 409I of the Public Health Service Act), 
extends the 6-month patent exclusivity provision for currently on-
patent drugs being studied for pediatric use, and also extends and 
expands the research program that the NIH established by the earlier 
law. The priority list procedure was revised to emphasize knowledge 
gaps in therapeutic areas in contrast to knowledge gaps about specific 
drug products. Specifically, the legislation authorizes that:
     The NIH, in consultation with the Commissioner of Food and 
Drugs and experts in pediatric research, develop and publish a priority 
list of needs in pediatric therapeutics, including drugs or indications 
that require study. This list is to be revised every three years.
     In developing and prioritizing the list, the Secretary is 
to consider the following available information:
    (A) Therapeutic gaps in pediatrics that may include developmental 
pharmacology, pharmacogenetic determinants of drug response, metabolism 
of drugs and biologics in children, and pediatric clinical trials;
    (B) Particular pediatric diseases, disorders, or conditions where 
more complete knowledge and testing of therapeutics, including drugs 
and biologics, may be beneficial in pediatric populations; and
    (C) The adequacy of necessary infrastructure to conduct pediatric 
pharmacological research, including research networks and trained 
pediatric investigators.

Update on BPCA Prioritization

    The BPCA requires that the NIH identify drugs of highest priority 
for study in pediatric populations. The first priority list consisting 
of off-patent drugs needing further study under the 2002 BPCA 
legislation was published in January 2003 in the Federal Register (FR 
Vol. 68, No. 13; Tuesday, January 21, 2003: 2789-2790). After the BPCA 
reauthorization in 2007, a revised priority list of needs in pediatric 
therapeutics was published in April 2009 (FR Vol. 74, No. 70; Tuesday, 
April 14, 2009: 17203-17205) and revised in September 2009. The latest 
version of the list from the September 2009 revision can be found at 
this Web site: http://bpca.nichd.nih.gov/about/process/upload/2009-Summary-091509-1-rev.pdf. NIH is required by the BPCA to update the 
priority list every 3 years. This notice serves as an update to the 
BPCA priority list of needs in pediatric therapeutics.
    In the transition from prioritizing drugs to prioritizing 
therapeutic needs, several changes have been implemented

[[Page 18229]]

over the last year in refining the prioritization process. These 
include the need for more preliminary information on candidate drugs 
(for example, information on frequency of use and frequency of 
condition) as well as expert input, a better approach for mass 
outreach, enhancement of NIH interagency collaborations, and 
improvement in the overall prioritization process.
    The revised process includes:
     A Well-defined process, using a systematic approach with 
clear objectives and outcomes;
     Well-defined objective criteria that are mutually 
exclusive and of a manageable number;
     A dynamic process, including transparency, stakeholder 
input, and leadership; and
     Expert involvement to inform and contribute to the 
    For 2010, NIH solicited nominations for the BPCA Priority List of 
Needs in Pediatric Therapeutics through a ``Request for Information'' 
(RFI) announcement as part of NIH's authority and responsibility to 
establish the program for pediatric drug testing and development 
outlined in the BPCA legislation. The BPCA Priority List consists of 
key therapeutic needs in the medical treatment of children and 
adolescents. The list is organized by Therapeutic Area, which can be a 
group of conditions, a subgroup of the population, or a setting of 
care. Each calendar year, a few Therapeutic Areas are selected for 
discussion and further prioritization. Below is a summary of the 
revised BPCA prioritization process:
     In early 2010, the RFI was issued to solicit nominations 
for future studies of pediatric therapeutics under the BPCA.
     The Obstetric and Pediatric Pharmacology Branch of the 
NICHD received 107 nominations, 67 of which met the criteria for 
     All nominations were reviewed and evaluated on six key 
criteria, as follows:
     Relevance to BPCA Mission and Goals
     No disqualifying ethical concerns
     Evidence: consideration of the level of evidence available 
and current gaps
     Impact: potential effect on children, society, and 
delivery of care
     Population: consideration of the different populations 
that may benefit from the research
     Feasibility: consideration of the resources available to 
conduct the study
     Twenty-two volunteer health professional evaluators scored 
the 67 nominations according to evidence, impact, and the pediatric 
population affected. Each nomination was reviewed by a panel of three 
     Therapeutic Area working groups (several Therapeutic Areas 
are determined annually) were developed and met through the 2010 year 
to discuss the gaps in knowledge in the therapeutic approaches to 
diseases in gastroenterology, endocrinology, and neurology.
     Minutes of all working group meetings conducted under the 
BPCA can be found on the BPCA Web site, http://bpca.nichd.nih.gov.
     As a final step in the process, the NICHD, with input from 
the FDA, ranked the nominations based on the evaluators' scores, 
quality and quantity of existing studies, and feasibility of the 
proposed study. The result was a tiered list of nominations considered 
for listing. Tier One represents the highest percentage of scores: 
nominations of interest to the NICHD for prioritization. Tier Two 
represents the average percentage of scores: nominations of possible 
interest to the NICHD at a later time. Tier Three represents the lowest 
percentage of scores: Nominations of least interest to the NICHD at 
this time for prioritization.
    The NICHD sponsored the annual BPCA prioritization meeting, held 
November 9-10, 2010, with stakeholders from the NIH, the FDA, the 
American Academy of Pediatrics, other pediatric organizations and 
societies, and patient advocates. The meeting allowed the NICHD to 
review the present progress from ongoing research and to discuss the 
proposed Therapeutic Areas from the 2010 nominations to be prioritized 
for future study under the BPCA and added to the existing BPCA priority 
    Below is an updated list of Therapeutic Areas and drugs that have 
been prioritized for study since the inception of the BPCA. It includes 
new areas of prioritization from Tier One nominations of the 2010 
outreach and a summary of the NICHD's plans and progress in all these 

Priority List of Needs in Pediatric Therapeutics 2011

    In accordance with the BPCA legislation, the list outlines priority 
needs in pediatric therapeutics for multiple Therapeutic Areas listed 
below. The priority list can be found on the BPCA Web site at the 
following address: http://bpca.nichd.nih.gov
     Table 1: Infectious Disease Priorities
     Table 2: Cardiovascular Disease Priorities
     Table 3: Respiratory Disease Priorities
     Table 4: Intensive Care Priorities
     Table 5: Bio-defense Research Priorities
     Table 6: Pediatric Cancer Priorities
     Table 7: Psychiatric Disorder Priorities
     Table 8: Neurological Disease Priorities
     Table 9: Neonatal Research Priorities
     Table 10: Adolescent Research Priorities
     Table 11: Hematologic Disease Priorities
     Table 12: Endocrine Disease Priorities and Diseases with 
Limited Alternative Therapies
     Table 13: Dermatologic Disease Priorities
     Table 14: Gastrointestinal Disease Priorities
     Table 15: Renal Disease Priorities
     Table 16: Rheumatologic Disease Priorities
     Table 17: Special Considerations

FOR FURTHER INFORMATION CONTACT: Dr. Perdita Taylor-Zapata via e-mail 
at [email protected] or by telephone at 301-496-9584 (not a toll-
free number).

    Dated: March 24, 2011.
Francis S. Collins,
Director, National Institutes of Health.
[FR Doc. 2011-7673 Filed 3-31-11; 8:45 am]