美国和欧洲生物类似药的发展

生物类似药(biosimilars)是与已批准上市的生物制品高度相似的药物,与小分子仿制药物(generics)不同,生物类似药并不是他们参比制品的精确复制品。尽管高度相似,生物类似药在某些方面仍然可能与参比制品不同,生物类似药间也会互不相同。生物制品不仅由于其复杂的性质和生产过程,还由于存在独特的免疫原性和活性的安全隐患,给研发和监管带来了相当大的挑战。欧洲药品管理局和美国食品药品管理局的指导原则建议采用"证据链完备性"(totality-of-evidence)的方法全面覆盖生物类似药物开发的各个步骤,包括分析表征化、结构相似性和功能等效性等的证据。这种"证据链完备性"是生物类似药整个研发过程中其余工作的基石,包括必须的动物试验研究、人体药代动力学/药效学研究,以及至少1个临床研究,以证实生物类似药功效等效,并且免疫原性或安全性风险没有增加。临床研究应选择敏感人群来进行试验,以便发现任何有临床意义的差异。工艺稳定质量恒定的生物类似药的研发需要丰富的经验和专业技能,只有这样才能够确保患者得到良好治疗。

Biosimilars are highly similar versions of approved branded biologics;unlike generics, they are not exact replicas of their reference molecules.Despite being highly similar, biosimilars are expected to be potentially different in some aspects from the reference, suggesting that biosimilar products will also differ from each other.The development and regulation of recombinant biologics presents considerable challenges due not only to their complex nature and production process but also to specific safety concerns linked to immunogenicity and activity.Both the European Medicines Agency and United States Food and Drug Administration guidelines recommend a totality-of-evidence approach focused on stepwise development of biosimilars that involves analytical characterization and demonstration of structural similarity and functional equivalence.This forms the cornerstone of the rest of the development program, including the need for animal studies, human pharmacokinetics/pharmacodynamics studies, and finally at least one clinical study to confirm equivalent efficacy and the absence of increased immunogenicity or safety risk.The clinical study(ies)should be performed in sensitive populations to allow detection of any clinically meaningful differences.Considerable experience and expertise is required for the development of a robust biosimilar that can be reproduced with predefined and established quality characteristics to ensure that patients receive high-quality therapies.