中美仿制药研发申报流程.ppt

药物经济学催生美国仿制药制度 美国社会安全制度导致政府赤字严重 SSA已经破产：如何破局？ 降低医疗费用成为必然 Hatch-Waxman法案出台 美国FDA药品注册申请：新药（两类）、仿制药和非处方药申请 1984年后 NDA的研发和申报 505(b)(1) 新药申报资料内容 Index Summary Chemistry, Manufacturing and Control Samples, Methods Validation Package and Labeling Nonclinical Pharmacology and Toxicology 6. Human Pharmacokinetics and Bioavailability 7. Microbiology ( for anti-microbial drugs only) 8. Clinical Data 9. Safety Update report ( typically submitted 120 days after the NDA’s submission ) 10. Statistical 11. Case Report Tabulations 12. Case Report Forms 13. Patent Information 14. Patent Certification 505(b)(2): 历史过程 Hatch Waxman法案：1984 Parkman Letter Phantom ANDA FDA Draft Guidance for Industry (1999) FDA Response to Citizen’s Petition (2003) 可以降低研发的费用和审评力量的浪费 505(b)(2)的关键: 可靠性 What is “Reliance” By whom? On what? Reliance and Exclusivity Market vs. Data Exclusivity Safety/Efficacy Data vs. CMC data FDA Process for Determining Reliance Who, when and how? 505(b)(2)的意义 介于全创新药物和仿制药之间 具有专利保护，且不存在产权纠纷 和仿制药不同，无替换的要求 应有突破 505(b)(2)范围 New Chemical Entity (rarely)：我国1.1-1.3 New dosage form：我国5类 New dosing regimen：我国补充申请 New strength：我国补充申请 New route of administration：我国2类 New indication：我国1.6 505(b)(2)情形 New active ingredient (different salt, ester, complex, chelate, clathrate, racemate, or enantiomer of active moiety) New inactive ingredient that requires more than limited confirmatory studies Rx ? OTC switch New Combination Products “Generic biologics” 505(b)(2)排他性 Exclusivities available for 505(b)(2) products NCE Exclusivity (5 years) New Product Exclusivity (3 years) Orphan Drug Exclusivity (7 years) Pediatric exclusivity extensions (6 months) Patent Issues 505(b)(2) drugs can have Orange Book-listed patents, and enjoy 30-month stay protection against generic competitors But, 505(b)(2) NDAs may also be blocked by patents on Reference Drugs 505(b)(2)新药的成功例子 NCE Thalomid? (thalidomide) (1998) Marketed unapproved drugs Levothyroxine (2000) Guaifenesin extended release (20