中英对照-APIC原料药厂清洁验证指南：7.0分组法(括号法)

APIC 201405原料药厂清洁验证指南：7.0 分组法（括号法）和最差情况分级（中英文）

2014-07-15julia翻译蒲公英

7.0 Bracketing and Worst Case Rating 分组法（括号法）和最差情况分级

7.1 Introduction 介绍

The cleaning processes of multiple product use equipment in API facilities are subject to requirements for cleaning validation. The validation effort could be huge. In order to minimize the amount of validation required, a worst case approach for the validation can be used.

原料药工厂中的多产品设备清洁要求进行清洁验证。清洁工作量会比较大。为了减少验证的工作量，可以采用最差情形方法进行验证。

By means of a bracketing procedure the substances are grouped.

采用分组法时，物质按类进行分组。

A worst case rating procedure is used to select the worst case in each group.

然后在每组中采用最差情形分级法选择各组中最差的情况。

Validation of the worst case situation takes place. However, it is of utmost importance that a documented scientific rational for the chosen worst cases exists.

对最差情形进行验证。至关重要的是，选择最差情形的科学合理性要进行记录。This chapter gives an overview of the suggested work to be carried out, the acceptance criteria and the methodology for evaluation of the data. It should be emphasized that this is only an example to give guidance. The equipment, the substances produced and the procedures in place may vary; and this results in other solutions than those given in this example.

本章介绍了所需要进行的工作、可接受标准和数据评估方法。需要强调的是，这只是一个指导性的例子，而实际情况下，设备、生产的物质和清洁程序可能有所不同，则可能需要采用与例中不同的解决方案。

The worst case rating priority will then support a conclusion that the cleaning procedures are effective for all drug substances and other chemicals within the bracket, including those not individually tested.

最差情形分级优先性是用来支持清洁方法对组内所有原料药和化学物均有效的

结论的，包括那些并没有进行单独检测的物质。

7.2 Bracketing Procedure 分组法

The objective of a bracketing project, is for the company to demonstrate that it has a scientific rationale for its worst case rating of the substances in the cleaning validation program. The first thing to do is to make groups and sub groups - which we will term “bracketing”, from which worst cases will later be selected based on the results from the rating. The bracketing procedure should be included in a company policy, or an SOP or an equivalent document on cleaning validation. A multipurpose facility, Clean Company, is presented as an example we will follow.

分组法的目的是让公司可以证明清洁验证方案中，对原料药进行最差情形分级具有科学合理性。首先要做的是进行分组和分小组----我们称为“分组法（括号法）”，在一个组中，再根据分级结果选择一个最差情形。分组流程应包括在公司方针中，或在SOP或相当清洁验证文件中。以下的例子中我们假定有一个多功能工厂、一个清洁公司。

a) Equipment Train The Clean Company is a multipurpose site for synthesis and isolation of organic substances (see figure 1). It is divided into six equipment trains separated from each other and intended for different use (earlier API steps, final API purification, drying etc.). In TrainA 9 substances can be produced, in TrainB 9 substances can be produced, in TrainC 8 substances can be produced, in TrainD 8 substances can be produced, in TrainE 10 substances can be produced, and in TrainF