CPMP ICH 283 95残留溶剂指南

两份（

V

）

ICH

的残留溶剂指南：

ICH Q3C

杂质：残 留溶剂指南（

CPMP/ICH/283/95

）和

GL18

：杂质指南：新兽药制剂、活 性成分和辅料中的残留溶剂（

CVMP/VICH/502/99

）已经分别自

1998

年

3

月和

2001

年

6

月开始使用多年了。

However, it has become evident that further clarification was required regarding the

specifications for Class 1 and class 2 residual solvents in active substances.

但是，现在要求对活性物质中

1

类和< /p>

2

类残留溶剂的质量标准需要进行进一步的澄清。

A clear interpretation of the issues regarding residues of solvents used in the

manufacture of finished medicinal products, both human and veterinary, was also

required.

同时也要求对制 剂生产中使用的溶剂的残留问题进行清楚的阐述。

Annex I: Specifications for class 1 and class 2 residual solvents in active

substances

附录

I

：活性物质中

1

类和

2

类残留溶剂质量标准

Specifications for class 1 solvents

1

类溶剂质量标准

In both the ICH and VICH guidelines on impurities: residual solvents it is stated that

“solvents in class 1 should not be employed in the manufacture of drug/active

substances, excipients, and drug/veterinary medicinal products because of their

unacceptable toxicity or their deleterious environmental effect. However, if their use is

unavoidable in order to produce a drug/veterinary medicinal product with a significant

therapeutic advance, then their levels should be restricted as shown…….., unless

otherwise justified”.

在

ICH

和

V ICH

的杂质指南：残留溶剂中，已经说明了

“

在药品

/

活性物质、辅料和人药

/

兽药生产中

不应使用

1

……

”

。

The justification for using a class 1 solvent as a solvent in a manufacturing process may

be based on the current scientific and technical knowledge and the step in which this

solvent is involved. For example, use of that class 1 solvent is unavoidable for the

specific chemical reaction, or the desired purity profile can only be obtained by using

that class 1 solvent. If a class 1 solvent is involved in a very early step of the

manufacturing process and if the absence of this solvent is shown in a suitable

intermediate, such an approach may be acceptable (for example, friedel crafts chemical

reaction).

对于生产工艺 中使用

1

类溶剂的论证可以是基于现行科学和技术知识，以及使 用溶剂的步骤。例如，

某个化学反应不能避免要使用

1

类溶剂，或只能使用

1

类溶剂来获得所需的纯度 。如果

1

类溶剂的使

用是在生产工艺的 较早步骤中，如果在适当的中间体中并不存在该溶剂残留，则是可以接受的（例如，

傅< /p>

-

克反应）。

The maximum acceptable limit, in a suitable intermediate or in the final active

substance, for a class 1 solvent, whether it is used as a solvent, a starting material, is

present as a by-product, or it is present in a solvent, should comply with the limits

prescribed in the relevant aforementioned ICH/VICH guideline on impurities: residual

solvents, unless otherwise justified (for example, by the benefit : risk ratio).

在适当的中间体中或在最终活性物质中，不管 是用作溶剂还是起始物料，不管是以副产物出现，还是

在一种溶剂中出现，

1

类溶剂的最大可接受限度均应符合其在之前提到的

ICH/VICH

指南杂质：残留

溶剂中所规定的限度，否则应 另行论证（例如，根据利益

-

风险平衡）。

In all cases, the content of class 1 solvents in the final active substance should comply

with the requirements of the relevant aforementioned Guideline, if tested.

在所有情况下，如果测试的话，活性物质成品 中的

1

类溶剂含量应符合之前提到的指南中的要求。