Biosimilars – biological medicines highly similar to a licensed reference product (RP) – can mitigate the risk of drug shortages by providing treatment alternatives and, with their lower costs, increase patient access to medication and reduce health care expenditure. However, limited knowledge of biosimilar approval processes and lack of confidence in their quality and efficacy can limit their uptake. Importantly, biosimilars are approved based on tightly controlled regulatory pathways to demonstrate that the physical, chemical, and biological properties of the proposed biosimilar are highly similar to the RP, with no clinically meaningful differences. Initially, a battery of highly sensitive in vitro studies are performed, comparing critical quality attributes between the proposed biosimilar and RP. Subsequently, in vivo pharmacodynamic studies compare the activity and physiologic effects of the biosimilar and RP. Finally, clinical studies are conducted, including a pharmacokinetic equivalence study and a confirmatory comparative clinical trial. The latter is performed in the most sensitive patient population for which the RP is licensed, to provide the greatest possibility of identifying any clinically meaningful differences between the proposed biosimilar and RP. When equivalent safety and efficacy have been demonstrated in one setting, the totality of evidence, together with scientific justification that there are no anticipated differences between the RP and proposed biosimilar in mechanism of action, pharmacokinetics, immunogenicity or toxicity, allows extrapolation into indications where clinical studies were not performed with the proposed biosimilar. Here, we review the approval process for biosimilars, focusing on the licensing of bevacizumab biosimilars and their extrapolation to metastatic colorectal cancer.

生物仿制药——与获得许可的参考产品 (RP) 高度相似的生物药物——可以通过提供治疗替代方案来减轻药物短缺的风险，并以较低的成本增加患者获得药物的机会并减少医疗保健支出。然而，对生物仿制药审批流程的了解有限以及对其质量和功效缺乏信心可能会限制其采用。重要的是，生物仿制药的批准基于严格控制的监管途径，以证明所提议的生物仿制药的物理、化学和生物学特性与 RP 高度相似，没有临床意义的差异。最初，进行了一系列高度敏感的体外研究，比较了提议的生物仿制药和 RP 之间的关键质量属性。随后，体内药效学研究比较了生物仿制药和 RP 的活性和生理作用。最后，进行临床研究，包括药代动力学等效性研究和验证性比较临床试验。后者是在获得 RP 许可的最敏感的患者群体中进行的，以提供最大的可能性来识别提议的生物仿制药和 RP 之间的任何临床意义差异。当在一种情况下证明了等效的安全性和有效性时，所有证据以及科学依据表明 RP 和提议的生物仿制药之间在作用机制、药代动力学、免疫原性或毒性方面没有预期差异，允许外推到未使用提议的生物仿制药进行临床研究的适应症。在这里，我们回顾了生物仿制药的审批流程，重点关注贝伐单抗生物仿制药的许可及其对转移性结直肠癌的外推。