尹先钧-早期研发阶段的化学制造与控制(CMC).pdf

鏃╂湡鐮斿彂鐨勫寲瀛?鍒堕€?涓庢帶鍒讹紙CMC 锛 灏瑰厛閽 Introduction 飦禞oint Guidance Document Created by CDER, CBER and ORA with FDA 飦禩wo major Guidances: 鈥 Guidance for Industry: CGMP for Phase 1 Investigational Drugs, July 2008. 鈥 Guidance for Industry: INDs for Phase 2 and Phase 3 Studies Chemistry, Manufacturing, and Controls Information, May 2003. The New Drug Development Process Steps from Test Tube to New Drug Application Review CMC Submission Differences between INDs and NDAs 鈥 ICH Quality Guidelines 鈥 Do not apply to INDs submissions 鈥 Pharmaceutical Development Information 鈥 Not needed for all phases of IND 鈥 DS Characterization 鈥 Some data to support the proposed structure in early IND Phases versus full characterization for NDA 鈥 Specifications for Drug Substance and Drug Product 鈥 Tentative acceptance criteria (e.g., safety levels of solvents) from a few small IND batches, vs. those based on multiple pilot- or full- scale batches, and statistical analysis for NDA 鈥 Validation of Analytical Procedures 鈥 Scientifically sound analytical procedures without full validation, vs. full validation for NDA Objectives and CMC Requirements of the IND IND Phases 飦 Phase 1: Initial introduction of a new drug into humans 飩 Closely monitored, typically 20-80 patients or normal subjects 飩 Metabolism and pharmacological actions of drug in humans 飩 Side effects associated with increasing doses 飩 Early evidence of effectiveness 飦 Phase 2: Limited, controlled clinical studies 飩 Closely monitored, usually several hundred subjects 飩 To obtain preliminary data on effectiveness of the drug 飩 To determine common short-term side effects and risks 飦 Phase 3: Expanded, controlled and uncontrolled trials 飩