EMA于2024年2月發(fā)布了“證明用于哮喘和慢性阻塞性肺疾?。–OPD）的經(jīng)口吸入制劑（OIP）治療等效性（TE）要求指導(dǎo)原則”。TE是指受試制劑和參比制劑的療效和安全性非常相似，從而可以可靠地排除產(chǎn)品之間的臨床相關(guān)差異。該指導(dǎo)原則提出這類藥物的TE研究，應(yīng)采用循序漸進(jìn)的方法。如果能滿足所有體外要求，則可在體外證明TE。如果盡管存在一些體外差異，但能證明全身暴露（作為安全性的替代指標(biāo)）和肺吸收/沉積（作為療效的替代指標(biāo)）等效，則可通過藥動學(xué)證明TE。通常不建議使用藥效學(xué)或臨床終點(diǎn)證明TE，因?yàn)檫@些終點(diǎn)不敏感。該指導(dǎo)原則還用大量篇幅對這類藥物治療等效性研究的許多具體問題提出了建議。詳細(xì)介紹該指導(dǎo)原則，期望對我國這類藥物的治療等效性研究和審評有啟示。

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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