The Best Pharmaceuticals for Children Act

Anne Zajicek, M.D., Pharm.D.Pediatric Medical OfficerNational Institute of Child Health and Human DevelopmentNational Institutes of Health

Best Pharmaceuticals for Children Act

Enacted January 2002, exclusivity provision will sunset October 2007Continues exclusivity provision of FDAMAPurpose: pediatric labeling

Pediatric Labeling

Pre-approval: Pediatric Research Equity ActOn-patent: Best Pharmaceuticals for Children Act which

continues the exclusivity provisions of FDAMA Studies supported by the Foundation for the NIH

Off-patent: Best Pharmaceuticals for Children Act

Best Pharmaceuticals for Children Act

In pediatric oncology prioritize new drugs for study assure timely access to new

treatments develop pre-clinical models of

pediatric cancers

Master List of all Off-Patent Drugs which lack adequate pediatric labeling

N=200

Consultation with experts in pediatric practice and research

Develop, prioritize, publish an Annual List

N=5-15

Consider for prioritizing: Availability of S/E dataAre additional data needed?Will new studies produce health benefits?Reformulation?

Priority List

Developed by NIHIn consultation with Institutes and Centers of the National

Institutes of Health Federal Agencies

Food and Drug Administration Centers for Disease Control and Prevention

Pediatric subspecialists and subspecialty groups

Advocacy groups

Drugs on the Priority List: January 2003

FR 68: 13; Jan 21, 2003

AzithromycinBaclofen*BumetanideDobutamineDopamineFurosemideHeparin

LithiumLorazepamRifampinSodium nitroprussideSpironolactone

Drugs on the Priority List: August 2003FR 68: 156; Aug 13, 2003

Ampicillin/sulbactamDiazoxideIsofluraneLindaneMeropenem

Metoclopramide*Piperacillin/ tazobactamPromethazine

Drugs on the Priority List: February 2004

FR 69:30; February 13, 2004

AmpicillinKetamineVincristineActinomycin-DMetolazone

Drugs on the Priority List: January 2005FR 70:17; January 27, 2005

IvermectinHydrocortisone valerateHydrochlorothiazideEthambutolGriseofulvinMethadoneHydroxychloroquineSevelamer*Morphine*

Drugs on the Priority List: April 2006

FR 70:79; April 25, 2006

ADHD: methylphenidate Hypertension: diureticsParasitic Diseases: albendazole, mebendazoleInfluenza: amantidine, rimantidineCancer: methotrexate, daunomycinPoisonings: pralidoximeSickle Cell Anemia: hydroxyurea

Drugs on the Priority List:March 2007

FR 72: 14588; March 28, 2007

Infectious Diseases: Methicillin-resistant Staph aureus infection Clindamycin, tetracyclines, trimethoprim-

sulfamethoxazoleHypertension: clinical trial designsNeonatal Research: clinical trial designsCancer: Neuroblastoma 13-cis retinoic acid

Asthma: clinical trial designs in young children

FDA Issues a Written Request:On-Patent

From Priority ListFDA issues

Written Request (WR)

WR sent toHolder of

NDA

Accept

Decline

Referredto FNIH

for funding

FDA Issues a Written Request: Off-Patent

From Priority ListFDA issues

Written Request (WR)

WR sent toHolders of

NDA/aNDA

Accept

Decline

Referredto NIH

for contract

Contracting Process

WR referred to NIH

RFC* RFP* FedBizOpps

Proposals peer-reviewed

Contract(s) awarded

*RFC=request for contract*RFP=request for proposal

Results So Far…

Studies On-Going under BPCA

Lorazepam: Clinical studies for treatment of status epilepticus Study 1: PK Study 2: Efficacy, safety study comparing

lorazepam to diazepamLorazepam: Clinical studies of sedation of children on ventilators in an intensive care unitNitroprusside: Clinical studies to reduce blood pressure during surgery to reduce blood loss Lithium: Clinical studies to define treatment of mania in children with bipolar disorder Baclofen: Clinical studies of oral baclofen to treat spasticity, most commonly from cerebral palsy

Studies On-Going

Ketamine - Preclinical studies to evaluate the scientific and safety concerns about the use as an anesthetic in childrenHydroxyurea- Clinical studies to improve treatment of children with sickle cell disease (NHLBI)Methylphenidate – Preclinical and clinical evaluation of pharmacokinetics and safety to understand reports of cytogenetic toxicity (NIEHS)Morphine – preclinical basic science evaluations of the developmental expression of opioid receptors to better understand management of pain in children of different developmental stages and safety issues in treating pain in neonates

Studies On-Going under BPCA

Vincristine: Studies to evaluate neurotoxicity, PK in children (NCI-COG)Actinomycin-D: Studies to evaluate hepatotoxicity/ VOD, PK in children (NCI-COG)Methotrexate: Clinical studies to evaluate neurocognitive outcomes of pediatric patients with high risk acute lymphoblastic leukemia (NCI-COG)Daunomycin: Pharmacokinetics, safety, efficacy of daunomycin to treat childhood cancers and relationship to body weight (NCI-COG)

Vincristine and Actinomycin-D

Retrospective chart review of Demographics Treatment history Toxicity

Neurotoxicity Veno-occlusive disease

Line-clearing methodPharmacokinetic modelingProspective PK study

SummaryPartnership with FDANIH responsible for prioritizing list of drugs for study sponsoring clinical studies in children

that will improve pediatric therapeutics