工艺参数确认1111

工艺参数的确认Process Parameter Qualification

谢永

2013-7-24

工艺参数的确认

工艺参数确认的背景和目的

工艺参数确认的一般流程

工艺参数确认的前提

质量风险分析和工艺确认方案

工艺参数确认

质量风险再分析和工艺确认报告

关键工艺参数的定义

其他

工艺参数的分类

温度

数量（重量，体积等）

压力

pH

搅拌速度

时间

其他

工艺参数范围的确定

科学原理

文献资料

历史数据

小试数据（对实验数据的统计学分析）

来源于其他公司或客户的数据

经验：工艺中偏差和OOS。

参数范围确认试验（正交试验，失败边际试验等）

几个名词

Design space 设计空间

Hold-Point 工艺暂存点

Edge of failure 失败边际

Critical

Design Space

The multidimensional combination and interaction of input variables (e.g. material attributes) and process parameters that have been demonstrated to provide assurance of quality. Working within the design space is not considered as a change. Movement out of the design space is considered to be a change and would normally initiate a regulatory post approval change process. Design space is proposed by the applicant and is subject to regulatory assessment and approval.

Design Space

ICH Q8中的定义

The design space is the established range of process parameters that has been demonstrated to provide assurance of quality. In some cases design space can also be applicable to formulation attributes. Working within the design space is not generally considered as a change of the approved ranges for process parameters and formulation attributes. Movement out of the design space is considered to be a change and would normally initiate a regulatory post approval change process.

Hold-Point

A point in the process for which sufficient stability data was collected to allow storage of the material for a certain length of time under defined conditions. For data collection purposes hold-points are treated as process parameters.

Edge of failure

The boundary to a variable or parameter, beyond which the relevant quality attributes or specifications cannot be met.

Critical

Any process step, process condition, test requirement, or other relevant parameter or item that must be controlled within predetermined and tight criteria to ensure that the API meets its specifications.

工艺参数确认的背景

ICH Q7 12.11

12.11 The critical parameters/attributes should normally be

identified during the development stage or from historical data, and the ranges necessary for the reproducible

operation should be defined. This should include:

− Defining the API in terms of its critical product attributes; − Identifying process parameters that could affect the critical quality attributes of the API;

− Determining the range for each critical process parameter expected to be used during routine

manufacturing and process control.