[Federal Register Volume 74, Number 70 (Tuesday, April 14, 2009)]
[Notices]
[Pages 17203-17205]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-8477]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


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

ACTION: Notice.

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SUMMARY: For many decades, the pediatric medical community, the public 
health community, and government agencies have recognized a range of 
questions regarding the use of therapeutics in children, including the 
shortage of clinical studies of drugs in children resulting in 
inadequate labeling for pediatric use. The lack of appropriate labeling 
results in off-label use of prescription drugs in many children and for 
many conditions. Contributing factors to this frequent off-label use of 
drugs in pediatrics include the rarity of some conditions in children 
with limited patient availability, the ethical concerns regarding the 
conduct of clinical trials in children, the lack of accurate 
information about which drugs are used by children, and the lack of 
long-term data on the medications that are frequently used.
    Several steps have been taken in response to the growing awareness 
of the knowledge gaps that exist in pediatric therapeutics. The BPCA 
was originally enacted in January 2002 and reauthorized in September 
2007, with the overall purpose of improving the level of information 
about pharmaceuticals used to treat children (http://www.fda.gov/opacom/laws/pharmkids/contents.html). The BPCA outlines a number of 
goals, including the identification and prioritization of therapeutic 
needs in pediatrics, especially drugs, biologics, or indications that 
require study. The legislation also calls for the conduct of pediatric 
research to learn more about the efficacy and safety of drugs in 
children as well as the training of experts needed to address the 
knowledge gaps in pediatric pharmacology. To identify drugs in need of 
further study, the BPCA mandates that the National Institutes of Health 
(NIH), in consultation with the U.S. Food and Drug Administration (FDA) 
and experts in pediatrics, develop

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a process for prioritizing needs in pediatric therapeutics and publish 
a priority list at least every 3 years, starting in September 2008. In 
this notice, we will summarize past efforts to prioritize off-patent 
drugs that need further study as mandated by the BPCA 2002 and describe 
the plans for identifying needs in pediatric therapeutics as authorized 
by the BPCA 2007.

DATES: The list is effective upon publication.

FOR FURTHER INFORMATION CONTACT: Dr. Perdita Taylor-Zapata, Eunice 
Kennedy Shriver National Institute of Child Health and Human 
Development (NICHD), 6100 Executive Boulevard, Suite 4A-01, Bethesda, 
MD 20892-7510, e-mail [email protected] or 
[email protected], telephone 301-496-9584 (not a toll-
free number).

SUPPLEMENTARY INFORMATION: In the Federal Register Notice of January 
21, 2003 (Vol. 68, No. 13), the NICHD announced the first list of off-
patent drugs to be considered for study and described the process used 
in developing this list. Prioritization of drugs on the list was based 
in general on three major factors: (1) Frequency of use in the 
pediatric population, (2) severity of the condition being treated, and 
(3) potential for providing a health benefit in the pediatric 
population. These factors follow from the original BPCA legislation, 
which required NIH to consider (among other criteria) for each drug 
``whether new pediatric studies concerning the drug may produce health 
benefits in the pediatric population.''
    During the initial years of the BPCA prioritization process (2003-
2005), the NICHD identified many individual drugs and indications that 
required further dosing, efficacy, and safety information. In 2005, 
based on the input of pediatric experts, an alternative approach was 
proposed that included identifying and prioritizing pediatric 
conditions and therapeutic approaches for those conditions. This 
proposed condition-based approach would allow us to identify gaps in 
scientific knowledge, determine key research agendas in pediatric 
medicine, evaluate the treatments of these conditions, and compare the 
use of drugs within a therapeutic class (both on- and off-patent). This 
approach would also allow us to obtain focused expertise in specific 
therapeutic areas that would help elucidate the scientific gaps within 
the prioritized area.

Update on BPCA Conditions/Therapeutic Areas

    In 2006, the NICHD and the FDA, in collaboration with pediatric 
experts, considered an alternative approach for prioritization--from a 
drug/indication approach to a condition-based approach. Please refer to 
the Federal Register Notice of April 25, 2006 (Volume 71, No. 79), and 
the Federal Register Notice of March 28, 2007 (Volume 72, No. 59), for 
a complete review of the previous prioritization process and 
therapeutic categories considered under the 2002 BPCA legislation. In 
addition, an update on the status of all drugs previously listed under 
BPCA 2002 is provided at http://bpca.nichd.nih.gov. The following 
conditions have been listed to date, with brief updates on progress 
and/or current NICHD commitments.

     2006

--Oncology: Four clinical trials are under way in collaboration with 
the National Cancer Institute (NCI) and the Children's Oncology Group 
(COG) to evaluate the pharmacokinetics (PK)/pharmacodynamics (PD), 
safety, and efficacy of chemotherapeutic agents used in children with 
cancer. The drugs under study are methotrexate, vincristine, 
daunomycin, and actinomycin-D.
--Sickle Cell Disease (SCD): A clinical trial of PK, efficacy, and 
safety of hydroxyurea to treat infants and young children with SCD is 
under way, with a planned safety follow-up.
--Attention Deficit Hyperactivity Disorder: The NICHD is funding basic 
and clinical research to evaluate the potential toxicity of 
methylphenidate.
--Organophosphate poisonings: Existing data on the use of pralidoxime 
for this indication is under review.

     2007

--Oncology: The NICHD consulted with experts in pediatric oncology to 
discuss the use of 13-cis-retinoic acid for the indication of 
neuroblastoma and to develop a pediatric formulation for this 
indication.
--Methicillin-resistant Staphylococcus aureus (MRSA) infections: The 
NICHD consulted with experts in infectious disease to discuss the need 
for PK, safety, and efficacy studies of clindamycin, doxycycline, 
tetracycline, and trimethoprim-sulfamethoxazole for the treatment of 
MRSA infections.
--Asthma: The NICHD has pursued potential collaborations with research 
networks within the NIH that are conducting clinical trials and other 
research in pediatric asthma, specifically networks supported by the 
National Heart, Lung, and Blood Institute and the National Institute of 
Allergy and Infectious Diseases.
--Hypertension: A written request for the study of hydrochlorothiazide 
in hypertension has been received by the NICHD. The NICHD has conducted 
a third working group meeting with experts in the field of pediatric 
hypertension to discuss studies needed in this area. Future clinical 
trials are being considered.

     Other areas of continued or future consideration for study 
under the BPCA discussed in previous Federal Register Notices and/or 
BPCA scientific meetings include:

--Obesity: The NICHD is consulting with experts in the field on the 
treatment of the metabolic syndrome and obesity-related Type-2 diabetes 
and hypertension.
--Counterterrorism research: The NICHD has developed a working group to 
discuss the needs in pediatric therapeutics for the treatment of 
chemical, biologic, radiologic, nuclear, and explosive (CBRNE) 
exposure. The NICHD is collaborating with the National Institute of 
Neurological Disorders and Stroke on its Counter-Act initiative to 
develop new and improved medical counter-measures against chemical 
threats in children and adults.
--Influenza and parasitic diseases: The NICHD held preliminary 
discussions with international experts on global pediatric pharmacology 
issues. Influenza and parasitic diseases are potential prototypes for 
future collaborations.
--Fragile X syndrome: The NICHD continues to consult with experts in 
the field, including the National Institute of Mental Health, to 
consider selected drugs and clinical outcome measures for evaluation 
and/or study.
--Depression: The NICHD has consulted with experts in the field to 
consider the approaches and design of safety studies of psychotropic 
medications in children, including antidepressants and other 
psychotropic medications.

    Throughout 2007 and 2008, the NICHD continued its outreach to 
pediatric organizations and other NIH Institutes and Centers. The goal 
of these discussions was specifically to identify current gaps in 
scientific knowledge regarding research and treatment of pediatric 
conditions with the ultimate goal of determining approved drugs for 
which future pediatric studies are needed. Minutes of all working group

[[Page 17205]]

meetings conducted under the BPCA can be found on the BPCA Web site 
listed above.

The ``New'' BPCA

    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 provision of additional patent 
exclusivity for currently on-patent drugs that are being tested for 
pediatric use. This legislation also extends and expands the research 
program at the NIH established in the earlier law. The NICHD 
administers the research program through its Obstetric and Pediatric 
Pharmacology Branch, working in cooperation with the other NIH 
Institutes and Centers with significant pediatric research portfolios. 
Important changes to the 2002 BPCA legislation for the NIH include the 
following:
     Focus on condition-based approach.
     More flexible funding mechanisms.
     Development of Proposed Pediatric Study Requests (PPSR).
     Feasibility study for the development of a pediatric 
formulary.
    The NICHD will prioritize all therapeutic areas over the upcoming 
years based on the following considerations:
     Building upon the current foundation established by the 
2002 BPCA implementation;
     Evaluating all currently listed drugs and therapeutic 
areas for feasibility and identification of additional or new 
scientific and therapeutic gaps;
     Changing the listing process from an individual drug/
indication approach to listing needs in pediatric therapeutic areas;
     Determining new areas of need based on consultation with 
other NIH Institutes and Centers, as well as experts in pediatric 
therapeutics and the pediatric medical community.
    The overall goal of the NIH for implementing the provisions of the 
BPCA is to improve pediatric therapeutics through scientific 
advancements and labeling changes that will have an impact on the safe 
and effective use of drugs in children. This can be accomplished 
through the following:
     Data gathering

--Using the principles of pharmacoepidemiology research to quantify 
adverse drug reactions, drug efficacy, and patterns of drug use in 
large populations to elucidate health services utilization.
--Bringing together multidisciplinary teams to provide input on needs 
in pediatric therapeutics through outreach to experts in pediatric 
research in academic institutions; other NIH Institutes and Centers; 
and pediatric organizations, societies, advocacy groups, and industry.

     Clinical trials

--Phase 1, 2, and 3 clinical trials to increase the knowledge of PK, 
safety, and efficacy of medicines used in children.

     Basic and translational research

--To inform such areas as developmental pharmacology, pharmacogenomics, 
and pediatric clinical trial design.

    There will be an open scientific meeting annually, starting in 
2008, to review and discuss the proposed therapeutic areas, to present 
progress from ongoing research, and to provide an opportunity for the 
medical community to provide input into the future therapeutic areas to 
be studied under the BPCA. Stakeholders will include the NIH, the FDA, 
and members of the American Academy of Pediatrics, and other pediatric 
organizations and societies. There will be a report to Congress at 
least every 3 years starting in 2008. Throughout the year, there will 
also be smaller group meetings with expert panels within prioritized 
therapeutic areas under the BPCA. The goals of the working group 
meetings will be to evaluate and discuss the gaps in scientific 
knowledge (whether necessary data are available or unavailable) as well 
as to determine gaps in the treatments of these conditions; for 
example, to determine what may be needed to enhance the treatment of 
these conditions in children. These consultations will assist the NICHD 
in the development of future proposed areas of study encompassing 
multiple therapeutic categories and/or addressing multiple questions 
within a therapeutic category.
    A scientific prioritization meeting was held in Rockville, 
Maryland, from June 30 to July 1, 2008, to determine needs in pediatric 
therapeutics as mandated by the BPCA 2007 legislation. The final BPCA 
List of Needs in Pediatric Therapeutics, and information on the 
prioritization process, will be posted on the BPCA Web site http://bpca.nichd.nih.gov.

    Dated: April 7, 2009.
Raynard S. Kington,
Acting Director, National Institutes of Health.
[FR Doc. E9-8477 Filed 4-13-09; 8:45 am]
BILLING CODE 4140-01-P