The Best Pharmaceuticals for Children Act

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The Best Pharmaceuticals for Children Act

• Anne Zajicek, M.D., Pharm.D.
• Pediatric Medical Officer
• National Institute of Child Health and Human
  Development
• National Institutes of Health

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Best Pharmaceuticals for Children Act

• Enacted January 2002, exclusivity provision will
  sunset October 2007
• Continues exclusivity provision of FDAMA
• Purpose pediatric labeling

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Pediatric Labeling

• Pre-approval Pediatric Research Equity Act
• On-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

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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

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Master List of all Off-Patent Drugs which lack
adequate pediatric labeling N200

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

Consultation with experts in pediatric practice
and research
Develop, prioritize, publish an Annual
List N5-15
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Priority List

• Developed by NIH
• In 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

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Drugs on the Priority List January 2003FR 68
13 Jan 21, 2003

• Azithromycin
• Baclofen
• Bumetanide
• Dobutamine
• Dopamine
• Furosemide
• Heparin

• Lithium
• Lorazepam
• Rifampin
• Sodium nitroprusside
• Spironolactone

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

• Ampicillin/sulbactam
• Diazoxide
• Isoflurane
• Lindane
• Meropenem

• Metoclopramide
• Piperacillin/ tazobactam
• Promethazine

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Drugs on the Priority List February 2004FR
6930 February 13, 2004

• Ampicillin
• Ketamine
• Vincristine
• Actinomycin-D
• Metolazone

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Drugs on the Priority List January 2005FR
7017 January 27, 2005

• Ivermectin
• Hydrocortisone valerate
• Hydrochlorothiazide
• Ethambutol
• Griseofulvin
• Methadone
• Hydroxychloroquine
• Sevelamer
• Morphine

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Drugs on the Priority List April 2006FR 7079
April 25, 2006

• ADHD methylphenidate
• Hypertension diuretics
• Parasitic Diseases albendazole, mebendazole
• Influenza amantidine, rimantidine
• Cancer methotrexate, daunomycin
• Poisonings pralidoxime
• Sickle Cell Anemia hydroxyurea

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Drugs on the Priority ListMarch 2007FR 72
14588 March 28, 2007

• Infectious Diseases Methicillin-resistant Staph
  aureus infection
• Clindamycin, tetracyclines, trimethoprim-sulfameth
  oxazole
• Hypertension clinical trial designs
• Neonatal Research clinical trial designs
• Cancer Neuroblastoma
• 13-cis retinoic acid
• Asthma clinical trial designs in young children

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FDA Issues a Written RequestOn-Patent
Accept
WR sent to Holder of NDA
From Priority List FDA issues Written Request
(WR)
Referred to FNIH for funding
Decline
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FDA Issues a Written Request Off-Patent
Accept
WR sent to Holders of NDA/ aNDA
From Priority List FDA issues Written Request
(WR)
Referred to NIH for contract
Decline
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Contracting Process
WR referred to NIH
RFC
FedBizOpps
RFP
Proposals peer-reviewed
RFCrequest for contract RFPrequest for
proposal
Contract(s) awarded
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Results So Far
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Studies On-Going under BPCA

• Lorazepam Clinical studies for treatment of
  status epilepticus
• Study 1 PK
• Study 2 Efficacy, safety study comparing
  lorazepam to diazepam
• Lorazepam Clinical studies of sedation of
  children on ventilators in an intensive care unit
• Nitroprusside 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

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Studies On-Going

• Ketamine - Preclinical studies to evaluate the
  scientific and safety concerns about the use as
  an anesthetic in children
• Hydroxyurea- 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

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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)

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Vincristine and Actinomycin-D

• Retrospective chart review of
• Demographics
• Treatment history
• Toxicity
• Neurotoxicity
• Veno-occlusive disease
• Line-clearing method
• Pharmacokinetic modeling
• Prospective PK study

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Summary

• Partnership with FDA
• NIH responsible for
• prioritizing list of drugs for study
• sponsoring clinical studies in children that will
  improve pediatric therapeutics