GB/Z 44363-2024 致热性 医疗器械热原试验的原理和方法

ICS

11.100.20

CCS

C30

中华人民共和国国家标准化指导性技术文件

GB/Z44363—2024/ISO/TR21582:2021

致热性医疗器械热原试验的

原理和方法

Pyrogenicity—Principlesandmethodsforpyrogentestingofmedicaldevices

（ISO/TR21582:2021，IDT）

2024-08-23发布2025-09-01实施

国家市场监督管理总局发布

国家标准化管理委员会

GB/Z44363—2024/ISO/TR21582:2021

目次

前言

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Ⅲ

引言

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1

范围

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规范性引用文件

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3

术语和定义

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4

缩略语

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热原的特性

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5.1

概述

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5.2

细菌内毒素

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5.3

除内毒素以外的微生物成分

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5.4

促炎细胞因子

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5.5

化学物质和其他致热原

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5.6

发热反应的原理

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致热性评估

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6.1

概述

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6.2

细菌内毒素试验（BET）

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6.2.1概述

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6.2.2鲎试剂反应的原理

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6.2.3BET的一般步骤

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6.2.4BET的特性

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6.3

家兔热原试验

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6.3.1概述

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6.3.2家兔试验的原理

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6.3.3家兔试验的步骤

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6.3.4家兔试验的特点

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6.4

基于人体细胞的热原试验（HCPT）

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6.4.1概述

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6.4.2HCPT的原理

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6.4.3人类细胞的选择

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6.4.4细胞因子标志物的选择

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6.4.5HCPT的步骤

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6.4.6HCPT的特性

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Ⅰ

GB/Z44363—2024/ISO/TR21582:2021

6.4.7确认研究

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结论

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参考文献

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Ⅱ

GB/Z44363—2024/ISO/TR21582:2021

前言

本文件按照GB/T1.1—2020《标准化工作导则第1部分：标准化文件的结构和起草规则》的规

定起草。

本文件等同采用ISO/TR21582：2021《致热性医疗器械热原试验的原理和方法》，文件类型由

ISO的技术报告调整为我国的指导性技术文件。

本文件做了下列最小限度的编辑性改动：

—3.1中增加了注2。

请注意本文件的某些内容可能涉及专利。本文件的发布机构不承担识别专利的责任。

本文件由国家药品监督管理局提出。

本文件由全国医疗器械生物学评价标准化技术委员会（SAC/TC248）归口。

本文件起草单位：山东省医疗器械和药品包装检验研究院、天津市医疗器械质量监督检验中心、苏

州百特医疗用品有限公司。

本文件主要起草人：刘佳、袁博、徐海燕、许晶、李振强、李凌梅、田硕、杨婧。

Ⅲ

GB/Z44363—2024/ISO/TR21582:2021

引言

目前，医疗器械的安全评估以ISO10993（所有部分）中推荐的毒理学研究和其他研究为指导。

材料介导的致热性表现为一种全身反应，虽然在GB/T16886.11—2021附录G中有涉及，但本文

件致力于对热原试验进行总体描述。

热原反应是指化学物质或其他物质引发的不良反应，如微生物成分引起的发热反应。热原反应试验

已被要求用于评价直接或间接接触循环血液和淋巴系统、脑脊液（CSF）和与人体相互作用的产品的安

全性。

目前，家兔体内致热性试验和体外细菌内毒素试验已作为评价医疗器械及其材料致热性的公认方

法。国际上对已经建立的试验方法包含试验样品的制备方式已经达成共识，并且在相关的指南和药典均

有体现。

近来，一种使用人免疫细胞进行的体外热原试验，即基于人体细胞的热原试验（HCPT），已经被

开发出来并应用于胃肠外药物的热原试验。由于该方法直接或间接接触人体血细胞，目前正在考虑将其

应用于医疗器械热原检测。

Ⅳ

GB/Z44363—2024/ISO/TR21582:2021

致热性医疗器械热原试验的

原理和方法

1范围

本文件规定了医疗器械及其材料的热原试验的原理和方法。

本文件适用于医疗器械及其材料的热原试验。

2规范性引用文件

本文件没有规范性引用文件。

3术语和定义

下列术语和定义适用于本文件。

ISO和IEC维护的用于标准化的术语数据库，地址如下：

—IEC电子百科：/；

—ISO在线浏览平台：/obp。

3.1

医疗器械medicaldevice

制造商的预期用途是为下列一个或多个特定医疗目的用于人类的，不论单独使用或组合使用的仪

器、设备、器具、机器、用具、植入物、体外应用试剂或校准品、软件、材料或者其他相似或相关物

品。这些目的是：

—疾病的诊断、预防、监护、治疗或缓解；

—损伤的诊断、监护、治疗、缓解或补偿；

—解剖或生理过程的研究、替代、调节或者支持；

—支持或维持生命；

—妊娠控制；

—医疗器械的消毒；

—通过对取自人体的样本进行体外检查的方式提供医疗信息。

其作用于人体体表或体内的主要设计作用不是用药理学、免疫学或代谢的手段获得，但可以有这些

手段参与并起一定的辅助作用。

注1：在某些监管机构认为是医疗器械，但在其他监管机构则不被认为是医疗器械的产品是：

—消毒物质；

—残疾人员的辅助用品；

—含有动物和/或人类组织的器械；

—体外受精或辅助生殖技术的器械。

注2：《医疗器械监督管理条例》中医疗器械的定义如下：

医疗器械，是指直接或者间接用于人体的仪器、设备、器具、体外诊断试剂及校准物、材料以及其他类似或者

相关的物品，包括所需要的计算机软件；其效用主要通过物理等方式获得，不是通过药理学、免疫学或者代谢

的方式获得，或者虽然有这些方式参与但是只起辅助作用；其目的是：

（一）疾病的诊断、预防、监护、治疗或者缓解；

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