Sandoz Inc., Princeton, NJ, USA.
Fresenius Kabi, Eysins, Switzerland.
BioDrugs. 2023 Sep;37(5):583-593. doi: 10.1007/s40259-023-00619-0. Epub 2023 Aug 5.
Biosimilars have been available in the USA for over a decade, and in Europe for almost two decades. In that time, biosimilars have become established in the treatment landscape for a wide range of diseases, facilitating patient access and affordability of healthcare. However, patients can still struggle to access biological therapies in some markets. There is a need to streamline the process of developing biosimilars without compromising their quality, safety, or efficacy. This opinion piece considers the efficiencies that could be achieved within the biosimilar approval process. In clinical trials for biosimilars, clinical efficacy endpoints have been shown to be less sensitive measures of biosimilarity than biochemical, biophysical, and biological functional assays. Additional clinical efficacy studies comparing potential biosimilars and reference products do not add information that is useful for regulatory purposes. Large clinical studies of biosimilars with immunogenicity endpoints are of limited value, given the quality control processes in place for all biologics, including biosimilars. The expectation for multiple-switch studies for US interchangeability designation should be reconsidered immediately, and the category should be eliminated in the future. As biosimilars are typically approved globally based on a single set of clinical trials, and all subsequent manufacturing changes are already carefully monitored by regulatory authorities, comparative pharmacokinetic testing of EU and US reference products is unnecessary. Manufacturers and regulators could take greater advantage of existing real-world evidence. Streamlining biosimilar development would enable biosimilar development of more and a wider variety of biological drugs, accelerating biosimilar development without impacting patient safety or effectiveness.
生物类似药在美国已经使用了十余年，在欧洲也已经使用了近二十年。在这段时间里，生物类似药已经在广泛的疾病治疗领域中得到了确立，为患者提供了更多的治疗选择，也降低了医疗保健的成本。然而，在一些市场，患者仍然难以获得生物疗法。因此，有必要在不影响其质量、安全性或疗效的前提下，简化生物类似药的开发流程。本文探讨了在生物类似药审批过程中可以实现的效率提升。在生物类似药的临床试验中，与生物化学、生物物理和生物学功能测定相比，临床疗效终点是生物类似性的敏感度较低的衡量标准。比较潜在生物类似药和参比产品的额外临床疗效研究并不能为监管目的提供有用的信息。考虑到所有生物制品（包括生物类似药）都有质量控制流程，因此具有免疫原性终点的大型生物类似药临床研究的价值有限。对于美国可互换性指定的多次转换研究的期望应立即重新考虑，并且该类别应在未来予以消除。由于生物类似药通常基于一组临床试验在全球范围内获得批准，并且所有后续的生产变更都已经由监管机构进行了仔细监测，因此比较欧盟和美国参比产品的药代动力学测试是不必要的。制造商和监管机构可以更好地利用现有的真实世界证据。简化生物类似药的开发流程将使更多和更广泛种类的生物药物能够进行生物类似药开发，从而在不影响患者安全性或疗效的情况下加速生物类似药的开发。
