【分享】通则<467>-残留溶剂介绍

The Current Requirements of <467>

<467>的现行要求

•Driving force: Safety of the patient, recommends use of less toxic solvents

驱动力：病人的安全，建议使用低毒性的溶剂

•Testing is to be performed only for solvents "likely to be present“

测试只需针对“可能存在的”溶剂

•Used or produced in the final manufacturing step

在最终生产步骤中使用或产生的

•Used in previous steps and not removed by a validated procedure

在先前的步骤中使用，且没有被经验证过的方法去除的

•The limits for acceptable concentrations listed in the chapter are for drug products, not for their components

在通则中列出的可接受浓度限度是针对制剂，而不是组成成分

•The concentration in the drug product may be:

药品中的浓度可以是：

–Calculated from the contributions of components

通过制剂中各组分中的残留溶剂浓度进行计算

–Determined experimentally, mandatory if:

下列情况是强制要求通过实验确定的：

•Solvents are used in its manufacture

生产过程中使用的溶剂

•Cumulative calculation exceeds limits

计算结果超出限度的

–Manufacturers of drug products may rely on data provided by the suppliers of components

成品生产商可以依赖成分生产商提供的数据

–Provides unambiguous identification and quantification methods

提供明确的鉴别和定量方

–Includes options to allow use of materials that exceed the limits tabulated.

包括可允许使用超过列表中限度的物料

–“The procedures described in this general chapter are to be applied wherever possible. Otherwise, manufacturers may select the most appropriate validated analytical procedure for a particular application.”

“可能的话，尽量使用通则中的方法”。否则生产商需选择最适当的经验证的方法进行特殊的应用。

–Submission of alte-rnative methods is not required.

替代性的方法不需要提交。

Introduction to <467> Residual Solvents

<467>残留溶剂的介绍

•This general chapter applies to existing drug substances, excipients, and products. All substances and products are subject to relevant control of solvents likely to be present in a substance or product.

该通则适用于现有的主药，辅料和成品。所有成分和成品都要对成分和成品中可能存在的溶剂进行控制。

•Main objective is to maintain acceptable amount of residual solvents in pharmaceuticals for the safety of the patient

主要目的是为了病人的健康将药物中的残留溶剂维持在可接受的量

•Recommendation is the use of less toxic solvents

建议使用低毒的溶剂

•Description of levels considered to be toxicologically acceptable for some residual solvents

根据毒理给出了某些残留溶剂可接受的量

•When a manufacturer has received approval from a competent regulatory authority for the use of a new solvent not currently listed or for higher levels than those described in the chapter, the manufacturer is responsible to notify the USP regarding the identity of this solvent, approved residual solvent limit in the article, and the appropriate test procedure for this residual solvent in the article. USP will address the topic in the individual (or respective) monograph.

当生产商收到法规部门批准的允许使用不在清单上或残留量高于通则清单上所列的溶剂时，生产商有责任通知USP关于该溶剂的鉴别，被批准的文件中的残留溶剂限度，及适当的该残留溶剂的测试方法。USP会在相应的各论中引入该主题。