2013.10.30尹先钧—美国临床试验用药品的CMC变更及技术审评重点.pdf

美国临床试验用药品的CMC变 更及技术审评重点 尹先钧 1 Discovery and Development Viewpoints Discovery View Development View (Preclinical Experiment) (Candidate Selection Experiment) • Get it into solution anyway • Solubilization options are you can to enable the constrained. Unrealistically experiment. solubilized systems can be misleading. • Metastable systems are • Equilibrium (thermodynamic) okay. solubility is all that matters. • Isn’t DMSO a marvelous • Never use DMSO. solvent? • First add cosolvent. • First adjust pH (if there is an ionizable group). • Reasonably pure is • Methods in place to separate sufficient. impurities and assess purity a must. • Stability requirement is • Stability is measured in months or measured in hours or days. years. 2 Basic CMC Strategy for IND • Develop pre-clinical data or cite research to answer these two questions: – Does the chemistry of either the drug substance or the drug product present any signals of potential human risk? – Does the manufacturing of either the drug substance or the drug product present any signals of potential human risk? 3 The IND Application Must Contain …. “Manufacturing Information – • Information pertaining to the composition, manufacturer, stability, and controls used for manufacturing the drug substance and th