制药工艺研发基础(I).pptx

Pharmaceutical Process Research Development Basics制药工艺研发基础(I);工艺研发的目标-Process RD Goals; 基本的工艺操作-Basic Process Operations; 基本的工艺操作-Basic Process Operations;Route Selection and lock (工艺路线的选择和确定) Choice of reagents and solvents Optimizing the reaction (反应优化) Data collection (数据收集) and In-Process-Control (IPC,中控) Methods Reduction of organic reaction mixture before work-up (分离技巧) Use-test (试用) guideline or Front-run (前试) Design of Experiments (DOE)/Guidance for identifying critical parameters High throughput solubility including in mixed solvents and crystallization Add co-solvent to dissolve byproducts for direct drop Effect of water crystallization reaction rate enhancement No reaction (water content by Karl Fischer Titration). consider after charging to vessel ;试剂的选择-Reagents Selection for Scale Up;溶剂的选择-Solvent Selection for Scale Up; 溶剂的选择与替代-Alternative Solvent; 溶剂CH2Cl2即二氯甲烷的反应性;In-Process-Control (IPC,中控) Methods On-line monitoring (即时跟踪 via PAT (Process Analytical Technologies) Common Lab Instrumentation Validation/calibration Impurity fate and tolerance (每步杂质命运和容许量) Document template/examples SOPs (Standard Operating Procedures) and SPs Final Form (physical properties of API) Analytical methods development Development of performance indicating assays Outsourcing ;Actions taken to ensure that processing proceeds as expected May rely on in-process assays (needed for rapid, efficient process development) IPC may be used for each operation in processing IPCs are filed with FDA (part of CMC section of NDA) Without IPC there is only hope (没有中控剩下的仅有希望)! IPC ensure: Reproducible plant operations (productivity) Expected batch outputs (productivity) Consistent product quality Compliance with process filed with FDA other regulatory authorities ; IPC include: Monitoring and adjusting processing conditions to meet operational guidelines (physical assessments) Confirming process operations through in-process assays (qual