EMA于2024年2月发布了“证明用于哮喘和慢性阻塞性肺疾病（COPD）的经口吸入制剂（OIP）治疗等效性（TE）要求指导原则”。TE是指受试制剂和参比制剂的疗效和安全性非常相似，从而可以可靠地排除产品之间的临床相关差异。该指导原则提出这类药物的TE研究，应采用循序渐进的方法。如果能满足所有体外要求，则可在体外证明TE。如果尽管存在一些体外差异，但能证明全身暴露（作为安全性的替代指标）和肺吸收/沉积（作为疗效的替代指标）等效，则可通过药动学证明TE。通常不建议使用药效学或临床终点证明TE，因为这些终点不敏感。该指导原则还用大量篇幅对这类药物治疗等效性研究的许多具体问题提出了建议。详细介绍该指导原则，期望对我国这类药物的治疗等效性研究和审评有启示。

EMA published the Guideline on the requirements for demonstrating therapeutic equivalence (TE) between orally inhaled products (OIP) for asthma and chronic obstructive pulmonary disease (COPD) in February 2024. TE means that the efficacy and safety profile of the test and reference products is sufficiently comparable so that a clinically relevant difference between products can be reliably excluded. The guideline proposes that TE investigation on such drugs should adopt a stepwise approach. If all in vitro requirements can be fulfilled, TE can be demonstrated in vitro. If equivalent systemic exposure (as a surrogate marker for safety) and equivalent lung absorption/deposition (as a surrogate marker for efficacy) is demonstrated in spite of some in vitro differences, then TE can be demonstrated through pharmacokinetics. It is generally not recommended to aim at demonstrating TE using pharmacodynamic or clinical endpoints as these are deemed insensitive. This guideline also provides extensive recommendations on many specific issues related to TE investigation of such drugs. This article provides a detailed introduction to the guideline, hoping to provide inspiration for the investigation and evaluation of TE of such drugs in China.

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