ANDA开发的准备及常见法规考虑.pdf

ANDA开发的准备及常见法规考虑 1 ANDA的研发步骤 • Pre-formulation preparation • Formulation development • Process development • BE study • ANDA submission • Process validation • Pre-approval inspection 2 研发前的准备 • Literature search • Active sourcing • Active evaluation, purchasing, and testing • RLD purchasing • RLD testing • Excipients and package enclosure systems • Regulation preparation 3 Literature preparation • RLD的标签和说明书; • FDA/EMA的审评报告; • FDA Orange book所列专利; • FDA IIG/GRAS database: 辅料用量必须确认; • For excipients and packaging materials with DMFs： 准备 Letter of Authorization; • FDA product-specific guidance：主要是BE要求，特殊产品也 有其它研究要求 • USP/EP：质量标准 • FDA dissolution database • Others: PDR （ Formula）, International PDRs(Italian, French, Swiss），Martindale, Merck Index • .uk/emc/ 4 Active sourcing,evaluation and purchasing • DMF availability • Request samples and COA and Specifications • Evaluate at least two to three potential active suppliers; • Compliance with USP monograph • Impurity profile and stability • Potential Polymorphic forms • Commitment for physical specifications, e.g. Bulk density, particle size, thermal stability • Statement of non-patent infringement • Approval by QA • TSE （海绵状脑病）/BSE （牛海绵状脑病）：动物来源的原料药出具无 疯牛病或口蹄疫的证明 • 植物来源的要提供非濒危物种证明 5 Active testing：超过Spec的详细检验 1. 全面的物理性质： • Optical rotation 比旋度 • 熔点 • Polymorphism (DTA/DSC) • B.E.T 比表面积 • IR/X-ray diffraction • Particle size distribution • Bulk/tap density • Microscopic observation • Solubility (at 25°C, different pH) 6 Active testing (2) 2、Full chemical characterization of bulk batch: • 全检 • Assay （HPLC，UV和滴定法的比较）