Feagan Brian G, Choquette Denis, Ghosh Subrata, Gladman Dafna D, Ho Vincent, Meibohm Bernd, Zou Guangyong, Xu Zhenhua, Shankar Gopi, Sealey David C, Russell Anthony S
Robarts Clinical Trials Inc., Western University, 100 Perth Drive, London, ON, N6A 5K8, Canada.
University of Montreal, Montreal, QC, Canada.
Biologicals. 2014 Jul;42(4):177-83. doi: 10.1016/j.biologicals.2014.05.005. Epub 2014 Jun 21.
A biosimilar is intended to be highly similar to a reference biologic such that any differences in quality attributes (i.e., molecular characteristics) do not affect safety or efficacy. Achieving this benchmark for biologics, especially large glycoproteins such as monoclonal antibodies, is challenging given their complex structure and manufacturing. Regulatory guidance on biosimilars issued by the U.S. Food and Drug Administration, Health Canada and European Medicines Agency indicates that, in addition to a demonstration of a high degree of similarity in quality attributes, a reduced number of nonclinical and clinical comparative studies can be sufficient for approval. Following a tiered approach, clinical studies are required to address concerns about possible clinically significant differences that remain after laboratory and nonclinical evaluations. Consequently, a critical question arises: can clinical studies that satisfy concerns regarding safety and efficacy in one condition support "indication extrapolation" to other conditions? This question will be addressed by reviewing the case of a biosimilar to infliximab that was approved recently in South Korea, Europe, and Canada for multiple indications through extrapolation. The principles discussed should also apply to biosimilars of other monoclonal antibodies that are approved to treat multiple distinct conditions.
生物类似药旨在与参照生物制品高度相似，使得质量属性（即分子特征）的任何差异都不会影响安全性或有效性。鉴于生物制品，尤其是诸如单克隆抗体之类的大型糖蛋白结构复杂且制造过程复杂，要达到这一生物制品基准具有挑战性。美国食品药品监督管理局、加拿大卫生部和欧洲药品管理局发布的关于生物类似药的监管指南表明，除了证明质量属性高度相似外，减少数量的非临床和临床对比研究对于批准而言可能就足够了。按照分层方法，需要进行临床研究以解决在实验室和非临床评估后仍然存在的有关可能具有临床显著差异的担忧。因此，出现了一个关键问题：在一种病症中满足安全性和有效性担忧的临床研究能否支持“适应症外推”至其他病症？将通过回顾一种英夫利昔单抗生物类似药的案例来解决这个问题，该生物类似药最近在韩国、欧洲和加拿大通过外推获批用于多种适应症。所讨论的原则也应适用于被批准用于治疗多种不同病症的其他单克隆抗体的生物类似药。
