1 / 44

The Best Pharmaceuticals for Children Act

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. Best Pharmaceuticals for Children Act. Enacted January 2002, will sunset October 2007

alta
Download Presentation

The Best Pharmaceuticals for Children Act

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. 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

  2. Best Pharmaceuticals for Children Act • Enacted January 2002, will sunset October 2007 • Continues exclusivity provision of FDAMA • Purpose: pediatric labeling

  3. 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

  4. 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

  5. Master List of all Off-Patent Drugs which lack adequate pediatric labeling N=169 • 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 N=15-20

  6. Prioritization Process • FDA provides list of off-patent drugs lacking pediatric labeling to NICHD • NICHD requests input from ICs, other federal agencies, experts, advocacy groups • NICHD convenes annual prioritization meeting of experts in specific disease areas and pediatric clinical pharmacology • NICHD publishes an annual list of drugs in the FR which have been prioritized for study

  7. 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

  8. Input for Pediatric Oncology • Children’s Oncology Group • Pediatric Subcommittee of the Oncologic Drug Advisory Committee

  9. Azithromycin Baclofen Bumetanide Dobutamine Dopamine Furosemide Heparin Lithium Lorazepam Rifampin Sodium nitroprusside Spironolactone Drugs on the Priority List: January 2003FR 68: 13; Jan 21, 2003

  10. Ampicillin/sulbactam Diazoxide Isoflurane Lindane Meropenem Metoclopramide Piperacillin/ tazobactam Promethazine Drugs on the Priority List: August 2003FR 68: 156; Aug 13, 2003

  11. Drugs on the Priority List: February 2004FR 69:30; February 13, 2004 • Ampicillin • Ketamine • Vincristine • Actinomycin-D • Metolazone

  12. Drugs on the Priority List: January 2005FR 70:3937; January 27, 2005 • Ivermectin • Hydrocortisone valerate • Hydrochlorothiazide • Ethambutol • Griseofulvin • Methadone • Hydroxychloroquine

  13. FDA Issues a Written Request Accept WR sent to Holders of NDA/ aNDA From Priority List FDA issues Written Request (WR) Referred to NIH for contract Decline

  14. Methods of Funding • Grant • Cooperative Agreement- partnership • Contract-legally binding agreement between contract awardee and NICHD

  15. Contracting Process WR referred to NIH RFC* FedBizOpps RFP* Proposals peer-reviewed *RFC=request for contract *RFP=request for proposal Contract(s) awarded

  16. NIH: Process for Contracts • NIH publishes the Request for Proposal (RFP) in Federal Business Opportunities www.FedBizOpps.gov

  17. Post-Award • Study performed (NIH holds IND) • Data analyzed • Results submitted to NIH, data published on the BPCA web site • Results submitted to the FDA, placed on public docket, for labeling

  18. Results So Far…

  19. Written Requests Issued by FDA • Lorazepam • Sedation • Status epilepticus • Nitroprusside • Azithromycin • Ureaplasma pneumonia • Chlamydia • Baclofen • Lithium

  20. Written Requests Issued by FDA • Lindane • Rifampin • MRSA endocarditis • CNS shunt infections • Meropenem • Vincristine • Actinomycin-D

  21. Written Requests Declined by Industry • Off-patent: • Lorazepam (2) • Nitroprusside • Azithromycin (2) • Lithium • Baclofen* • Rifampin (2)

  22. Written Requests Declined by Industry • Off-patent • Meropenem • Vincristine • Actinomycin-D

  23. Written Requests Declined by Industry • On-patent: • Morphine • Baclofen* • Bupropion • Sevelamer • Zonisamide • Hydroxyurea • Dexrazoxane • Eletriptan

  24. Contracts • Contracts awarded • Lorazepam: sedation in ventilated patients • Lorazepam: status epilepticus • Nitroprusside (2): controlled hypotension • Lithium: acute mania in bipolar disease

  25. Inter-Agency Agreements • Ketamine: pre-clinical toxicology studies in non-human primates • Vincristine: pediatric malignancies • Actinomycin-D: pediatric malignancies • Hydroxyurea: sickle-cell disease

  26. RFPs published for • Azithromycin • Ureaplasma • Chlamydia • Baclofen • Meropenem

  27. Coordinating Center • Purpose: • Coordinate patient enrollment • Coordinate, monitor data collection • Report adverse events and other data (usually blinded) to Data Safety Monitoring Board (DSMB) • Analyze, organize results into a supplemental NDA for submission to FDA • Contract awarded to Premier Research, Philadelphia, Pennsylvania

  28. Written Requests for VCR, Actinomycin-D • Study 1: prospective PK study in patients 0-16 years of age • Dx: Wilms’, RMS, other • N=100 • Endpoint: relationship of PK to body size/composition, cancer type/severity, age, gender, con meds

  29. Written Requests for VCR, Actinomycin-D • Study 2: Analysis of databases and ongoing clinical trials to evaluate safety/efficacy endpoints in the same population • EFS • Toxicity • Actinomycin-D • Hepatotoxicity • thrombocytopenia • VCR • neurotoxicity

  30. Drugs Proposed by the Children’s Oncology Group • Doxorubicin (on-patent) • Daunorubicin • Relationship of obesity and efficacy/safety/PK • Methotrexate • Safety (neurotoxicity)/efficacy of two treatment regimens

  31. Off-Patent Drugs 2005

  32. Off-Patent Drugs 2005: Anti-Infectives • Meropenem • Mupirocin • Nafcillin • Piperacillin • Piperacillin/Tazobactam • Quinupristin/Dalfopristin • Ticarcillin/Clavulanate • Trimethoprim • Amantadine Amphotericin B Complex Clarithromycin Enoxacin Fluconazole Flucytosine Furazolidine Ketoconazole Norfloxacin Pentamidine Rifampin Terconazole

  33. Off-Patent Drugs 2005:Anti-Infectives • Amantadine • Amphotericin B Complex • Clarithromycin • Enoxacin • Fluconazole • Flucytosine • Furazolidine • Ketoconazole • Norfloxacin • Pentamidine • Rifampin • Terconazole

  34. Off-Patent Drugs 2005:Anti-Infectives • Metronidazole • Amoxicillin • Clindamycin • Co-trimoxazole • Ampicillin • Ampicillin/sulbactam • Amoxicillin clavulanate potassium • Azithromycin • Aztreonam

  35. Off-Patent Drugs 2005:Anti-Infectives • Cefazolin • Cefdinir • Cefepime • Cefixime • Cefprozil • Ceftizoxime • Cefuroxime • Cephalexin • Loracarbef

  36. Off-Patent Drugs 2005:Anti-Neoplastics • Dacarbazine • 6-Mercaptopurine • Bleomycin • Cisplatin • Cyclophosphamide • Actinomycin-D • Daunorubicin

  37. Off-Patent Drugs 2005:Anti-Neoplastics • Hydroxyurea • Lomustine • Methotrexate • Methylprednisolone • Mechlorethamine • Procarbazine • Thioguanine • Thiotepa • Vinblastine • Vincristine

  38. Off-Patent Drugs 2005:Sedation • Lorazepam • Oxazepam • Chloral Hydrate • Pentobarbital

  39. Off-Patent Drugs 2005: Pain Management • Hydromorphone • Ketamine • Methadone • Nalbuphine • Naltrexone • Pentazocine • Meperidine • Morphine

  40. Off-Patent Drugs 2005:Miscellaneous • Allopurinol • Aminocaproic Acid • Fludrocortisone • Cyclosporine • Dexamethasone • Prednisone/Prednisolone • Loperamide • Loperamide/simethicone • Leucovorin

  41. Questions from NIH to the Pediatric Subcommittee of the Oncologic Drug Advisory Committee • What type of prioritization process should be used for deciding which off-patent drugs should be studied? • What is the definition of health benefit? • Number of patients affected • Lack of other drugs that treat the disease • Severity of the disease

  42. Questions • Are there other drugs that should be studied? • Antineoplastics • Supportive Care • Anti-emetics • Anti-infectives • Analgesics • Other

  43. Summary • Work in Progress • Partnership with FDA • NIH responsible for • prioritizing list • providing input on the Written Request • sponsoring clinical studies in children that will produce improvement in pediatric therapeutics

More Related