Biosimilars are biotherapeutic products with similar efficacy, safety, and quality to a licensed bio-originator. Biosimilars include monoclonal antibodies, soluble receptors, growth factors, and hormones. The manufacture of biosimilars is a sophisticated multi-step process; factors at each stage, such as production cell line, culture conditions, and formulation, may each alter the final product through post-translational modifications. A vial of a therapeutic antibody contains multiple species with distinct glycosylation profiles (microheterogeneity), which are responsible, for example, for complement activation, pharmacokinetics, and structural stability. Whereas the focus for the manufacturer of the bio-originator is to show safety and efficacy in clinical trials, biosimilar development focuses predominantly on in-depth analyses to confirm that the product is identical to the originator in terms of structure, composition, and in vitro activity. Therefore, the critical quality attributes of a biological drug that influences clinical safety and efficacy should be carefully assessed. At least one clinical study is required to compare pharmacokinetics of bio-originator and biosimilar, and at least one sufficiently large randomised controlled trial to demonstrate clinical equivalence. Once biosimilarity is confirmed, regulators may allow extrapolation to other licensed bio-originator indications, provided efficacy relies on a similar mechanism of action in each one. Consequently, a biosimilar may be approved in all indications for which the bio-originator has been approved, without multiple clinical trials.

中文翻译：

---

生物仿制药审批流程：有何不同？

生物仿制药是与获得许可的生物原研药具有相似功效、安全性和质量的生物治疗产品。生物仿制药包括单克隆抗体、可溶性受体、生长因子和激素。生物仿制药的制造是一个复杂的多步骤过程；每个阶段的因素，如生产细胞系、培养条件和配方，都可能通过翻译后修饰改变最终产品。一小瓶治疗性抗体含有多种具有不同糖基化特征（微异质性）的物质，这些物质负责例如补体激活、药代动力学和结构稳定性。鉴于生物源制造商的重点是在临床试验中显示安全性和有效性，生物仿制药开发主要侧重于深入分析，以确认产品在结构、组成和体外活性方面与原研药相同。因此，应仔细评估影响临床安全性和有效性的生物药物的关键质量属性。至少需要一项临床研究来比较生物原研药和生物仿制药的药代动力学，并且至少需要一项足够大的随机对照试验来证明临床等效性。一旦生物相似性得到确认，监管机构可能允许外推至其他许可的生物起源适应症，前提是疗效依赖于每种适应症的相似作用机制。因此，无需多次临床试验，生物仿制药就可以在生物原研药已获批准的所有适应症中获得批准。