多规格口服固体制剂仿制药规格之间生物豁免的药学考虑

CMC considerations for additional strength biowaiver of oral solid generic drugs

对于多规格口服固体制剂,不同规格之间的生物豁免在实际研发及审评工作中较为常见,虽然国内外相关指导原则中都有所提及,但具体要求不细化,甚至相互之间存在差异,给研发及审评工作带来挑战。本文基于对国内外技术指南的比较分析,重点从药学角度(处方和体外溶出度要求)对多规格固体口服制剂规格间生物豁免的要求(包括常释和调释制剂)进行梳理讨论,希望对仿制药及已上市化学药品仿制药的一致性评价工作提供借鉴。

For oral solid generic products with multiple strengths,the in vivo bioequivalence(BE)requirement for one or more strength(s)can be waived if some requirements can be fulfilled.This is a realistic and challenging topic for both pharmaceuticals and regulatory bodies.Although there have been some guidelines published by different regulatory agencies,there are still some unclear points and even differences in the technical requirements of additional strength biowaiver.Based on comparative analysis of the requirements from FDA,EMA and NMPA,this article addressed and discussed the requirement differences for additional strength biowaiver of oral solid products from the CMC perspective,such as formulation and dissolution studies.We hope this article can provide useful suggestions for consistency evaluation of generic drugs under development and post-approval generic drugs.