【正文】 tency Dosage Form Route of Administration Date Finalized Almotriptan Malate mg Tablet Oral 5/16/2023 Alosetron 1 mg Tablet Oral 5/31/2023 Atazanavir 200 mg Capsule Oral 3/18/2023 Atomoxetine 60 mg Capsule Oral 6/13/2023 Cefditoren Pivoxil 200 mg Tablet Oral 3/18/2023 Dutasteride mg Capsule Oral 7/5/2023 Eplerenone 50 mg Tablet Oral 3/18/2023 Fosamprenavir Calcium 700 mg Tablet Oral 3/18/2023 Memantine 10 mg Tablet Oral 7/8/2023 Rosuvastatin 40 mg Tablet Oral 3/18/2023 Tadalafil 20 mg Tablet Oral 3/18/2023 Vardenafil HCl 20 mg Tablet Oral 4/11/2023 QbR: 從提出到完善 ? 1/2023 – 2/2023: Questionbased Review Drafted ? 3/2023 – 4/2023: Division Directors Discussion ? 5/2023 – 6/2023: Team Leaders Discussion ? 7/2023 – 8/2023: Reviewers Discussion ? 9/2023 – 1/2023: Model Pharmaceutical Development Report and Quality Overall Summary ? 2/2023 – 12/2023: Discussions with Stakeholders and Upper Management ? 1/2023 – 12/2023: Gradual Implementation ? 1/2023: Full Implementation QbR的內(nèi)涵 ?Questionbased Review is a general framework for a science and riskbased assessment of product quality ?Questionbased Review contains the important scientific and regulatory review questions to ? 關(guān) 鍵 制 備 工 藝 及其 質(zhì) 控 ? 產(chǎn) 品的工 藝 、處 方是否有 設(shè)計 缺陷 ? 強(qiáng)調(diào) QbD ANDAs Under QbR (Continued) ? Future Generic Applications ? generic sponsors submit generic applications based on the format of ICH CTD, preferably, electronically ? Module 1: Administrative Information ? Module 2: Quality Overall Summary and Clinical Summary ? Module 3: Quality –Pharmaceutical Development。中美仿制藥研發(fā)和申報流程 涂家生， Ph. D. 中國藥科大學(xué)藥劑學(xué)教授 Tel: 02583271305 Email: 鄭州 我國仿制藥申報、審評和研發(fā)對策 主要內(nèi)容 中美關(guān)于原研藥和仿制藥的背景 美國仿制藥：申報、基于問題的審評和研發(fā)對策 展望 1 2 3 4 藥物經(jīng)濟(jì)學(xué)催生美國仿制藥制度 美國社會安全制度導(dǎo)致政府赤字嚴(yán)重 SSA已經(jīng)破產(chǎn)：如何破局？ 降低醫(yī)療費(fèi)用成為必然 HatchWaxman法案出臺 美國 FDA藥品注冊申請：新藥（兩類）、仿制藥和非處方藥申請 1984年后 New Drug Applications (NDAs) Abbreviated New Drug Applications (ANDAs) ? “ Full Reports” of Safety and Efficacy Investigations ? Applicant has right of reference to essential investigations? ? Duplicate of an already approved product ? No safety/efficacy data permitted (only bioequivalence) YES NO 505(b)(1) 505(b)(2) 505(j) NDA的研發(fā)和申報 505(b)(1) 新藥申報資料內(nèi)容 1. Index 2. Summary 3. Chemistry, Manufacturing and Control 4. Samples, Methods Validation Package and Labeling 5. Nonclinical Pharmacology and Toxicology 6. Human Pharmacokiics and Bioavailability 7. Microbiology ( for antimicrobial 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): 歷史過程 ?Hatch Waxman法案： 1984 ?Parkman Letter ? Phantom ANDA ?FDA Draft Guidance for Industry (1999) ?FDA Response to Citizen’s Petition (2023) ?可以降低研發(fā)的費(fèi)用和審評力量的浪費(fèi) 505(b)(2)的關(guān)鍵 : 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)的意義 ?介于全創(chuàng)新藥物和仿制藥之間 ?具有專利保護(hù)，且不存在產(chǎn)權(quán)糾紛 ?和仿制藥不同，無替換的要求 ?應(yīng)有突破 505(b)(2)范圍 ?New Chemical Entity (rarely)：我國 ?New dosage form：我國 5類 ?New dosing regimen：我國補(bǔ)充申請 ?New strength：我國補(bǔ)充申請 ?New route of administration：我國 2類 ?New indication：我國 505(b)(2)情形 ?New active ingredient (different salt, ester, plex, 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