Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 7500 Standish Place, Rockville, MD 20855, USA.
AAPS J. 2013 Jan;15(1):41-52. doi: 10.1208/s12248-012-9411-0. Epub 2012 Oct 9.
This review presents considerations which can be employed during the development of a semi-solid topical generic product. This includes a discussion on the implementation of quality by design concepts during development to ensure the generic drug product has similar desired quality attributes to the reference-listed drug (RLD) and ensure batch to batch consistency through commercial production. This encompasses the concept of reverse-engineering to copy the RLD as a strategy during product development to ensure qualitative (Q1) and quantitative (Q2) formulation similarity, as well as similarity in formulation microstructure (Q3). The concept of utilizing in vitro skin permeation studies as a tool to justify formulation differences between the test generic product and the RLD to ensure a successful pharmacodynamic or clinical endpoint bioequivalence study is discussed. The review concludes with a discussion on drug product evaluation and quality tests as well as in vivo bioequivalence studies.
本文综述了在半固体制剂仿制药开发过程中需要考虑的因素。其中包括在开发过程中实施质量源于设计理念的讨论，以确保仿制药产品具有与参比制剂（RLD）相似的所需质量属性，并通过商业化生产确保批次间的一致性。这涵盖了逆向工程的概念，即将 RLD 作为产品开发过程中的一种策略进行复制，以确保定性（Q1）和定量（Q2）配方相似，以及配方微观结构（Q3）相似。本文还讨论了利用体外皮肤渗透研究作为工具的概念，以证明测试仿制药产品与 RLD 之间的配方差异，以确保成功进行药效学或临床终点生物等效性研究。本文最后讨论了药物产品评估和质量测试以及体内生物等效性研究。
