18228 Federal Register / Vol. 76, No. 63 / Friday, April 1, 2011 / Notices 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

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 list. 

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 longterm 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/DevelopmentApproval

Process/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 

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Federal Register / Vol. 76, No. 63 / Friday, April 1, 2011 / Notices 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 process. 

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 review. 

• 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 evaluators. 

• 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 list. 

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 areas. 

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 

taylorpe@mail.nih.gov 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] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

Center for Scientific Review; Notice of 

Closed Meeting 

Pursuant to section 10(d) of the 

Federal Advisory Committee Act, as 

amended (5 U.S.C. App.), notice is 

hereby given of the following meeting. 

The meeting will be closed to the 

public in accordance with the 

provisions set forth in sections 

552b(c)(4) and 552b(c)(6), Title 5 U.S.C., 

as amended. The grant applications and 

the discussions could disclose 

confidential trade secrets or commercial 

property such as patentable material, 

and personal information concerning 

individuals associated with the grant 

applications, the disclosure of which 

would constitute a clearly unwarranted 

invasion of personal privacy. 

Name of Committee: Center for Scientific 

Review Special Emphasis Panel; Cell 

Signaling and Guidance. 

Date: April 7–11, 2011. 

Time: 10 a.m. to 11 a.m. 

Agenda: To review and evaluate grant 

applications. 

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