Wang Yow-Ming C, Chow Andrew T
Department of Pharmacokinetics and Drug Metabolism, Amgen, Inc., Thousand Oaks, California 91320, USA.
J Biopharm Stat. 2010 Jan;20(1):46-61. doi: 10.1080/10543400903280357.
The European Medicines Agency (EMEA) leads in providing regulatory guidelines to this emerging industry. While biosimilars are not yet available in the United States, as the legal and regulatory pathway is being developed there, biosimilars and other such products are marketed in other regions of the world. We reviewed the European assessment reports of biosimilars to gain insights into the current practices pertaining to the pharmacokinetic (PK) and pharmacodynamic (PD) similarity evaluations because we believe that they might help to shape the future global regulatory landscape. This paper illustrates the molecular complexity of therapeutic proteins, challenges associated with PK and PD evaluations, limitations of similarity assessment using PK and PD endpoints, and design considerations for PK and PD studies. The scope of biotechnology-derived products will be limited to therapeutic protein products, including recombinant human proteins, fusion proteins, and monoclonal antibodies. The challenges to demonstrate similarity are complex and appear to be unique to each therapeutic agent; therefore, the requirements for regulatory approval will most likely continue to be handled at a product-specific level as stipulated in current EMEA guidelines.
欧洲药品管理局（EMEA）在为这个新兴行业提供监管指南方面处于领先地位。虽然生物类似药在美国尚未上市，因为其法律和监管途径正在美国制定中，但生物类似药和其他此类产品在世界其他地区已上市。我们审查了欧洲生物类似药的评估报告，以深入了解当前与药代动力学（PK）和药效动力学（PD）相似性评估相关的做法，因为我们认为这些报告可能有助于塑造未来的全球监管格局。本文阐述了治疗性蛋白质的分子复杂性以及与PK和PD评估相关的挑战、使用PK和PD终点进行相似性评估的局限性，以及PK和PD研究的设计考量。生物技术衍生产品的范围将限于治疗性蛋白质产品，包括重组人蛋白、融合蛋白和单克隆抗体。证明相似性面临的挑战很复杂，而且似乎每种治疗药物都有其独特之处；因此，监管批准要求很可能继续按照欧洲药品管理局当前指南的规定，在产品特定层面进行处理。
