APIC 原料药厂清洁验证指南-中英文2014.05

APIC 201405原料药厂清洁验证指南（中英文）GUIDANCE ON ASPECTS OF CLEANING VALIDATION IN ACTIVE PHARMACEUTICAL INGREDIENT PLANTS

原料药工厂中清洁验证指南

May 2014

Table of Contents 1.0 FOREWORD

前言 2.0 OBJECTIVE

目的 3.0 SCOPE

范围 4.0 ACCEPTANCE CRITERIA

可接受标准 4.1 Introduction 介绍

4.2 Methods of Calculating Acceptance Criteria 可接受标准的计算方法

4.2.1. Acceptance criteria using health-based data

使用基于健康数据的可接受

标准 4.2.2 Acceptance criteria based on

Therapeutic Daily Dose

基于日治疗剂量的可接受标准 4.2.3. Acceptance criteria based on LD50

基于半数致死量的可接受标准 4.2.4 General Limit as acceptance criteria

作为可接受标准的通用限度 4.2.5 Swab Limits

擦拭限度 4.2.6 Rinse Limits 淋洗限度

4.2.7 Rationale for the use of different limits in pharmaceutical and chemical production 在药品和化学生产中使用不同限度的合理性

5.0 LEVELS OF CLEANING

清洁级别 5.1 Introduction

介绍 5.2 Cleaning Levels

清洁级别 5.3 Cleaning Verification/Validation

清洁验收/验证 6.0 CONTROL OF CLEANING PROCESS 清洁过程的控制

7.0 BRACKETING AND WORST CASE

RATING

分类法和最差情况分级法 7.1 Introduction

介绍 7.2 Bracketing Procedure

分类法程序 7.3 Cleaning Procedures

清洁程序 7.4 Worst Case Rating 最差情况分级

8.0 DETERMINATION OF THE AMOUNT OF RESIDUE

残留量检测

8.1 Introduction 介绍

8.2 Validation Requirements 验证要求

8.3 Sampling Methods 取样方法

8.4 Analytical Methods 分析方法

9.0 CLEANING VALIDATION PROTOCOL 清洁验证方案9.1 Background 背景

9.2 Purpose 目的

9.3 Scope 范围

9.4 Responsibility 职责

9.5 Sampling Procedure 取样程序

9.6 Testing procedure 分析方法

9.7 Acceptance criteria 可接受标准9.8 Deviations 偏差

9.9 Revalidation 再验证

10.0 VALIDATION QUESTIONS 验证问题

11.0 REFERENCES 参考文献

12.0 GLOSSARY 词汇

13.0 COPYRIGHT AND DISCLAIMER 版本及声明

1.0 FOREWORD 前言

The original version of this guidance document has now been updated by the APIC Cleaning Validation Task Force on behalf of the Active Pharmaceutical Ingredient Committee (APIC) of CEFIC.

本指南文件的原版本现已由APIC清洁验证工作组代表CEFIC的APIC委员会进行了更新。

The Task Force members are:- 以下是工作组的成员

Annick Bonneure, APIC, Belgium

Tom Buggy, DSM Sinochem Pharmaceuticals, The Netherlands

Paul Clingan, MacFarlan Smith, UK

Anke Grootaert, Janssen Pharmaceutica, Belgium

Peter Mungenast, Merck KGaA, Germany.

Luisa Paulo, Hovione FarmaCiencia SA, Portugal

Filip Quintiens, Genzyme, Belgium

Claude Vandenbossche, Ajinomoto Omnichem, Belgium

Jos van der Ven, Aspen Oss B.V., The Netherlands

Stefan Wienken, BASF, Germany.

With support and review from:- 以下为提供支持和进行审核的人员

Pieter van der Hoeven, APIC, Belgium

Anthony Storey, Pfizer, U.K.

Rainer Fendt, BASF, Germany.

The subject of cleaning validation in active pharmaceutical ingredient manufacturing plants has continued to receive a large amount of attention from regulators, companies and customers alike.

原料药生产工厂的清洁验证一直是法规人员、公司和客户等关注的问题。

The integration of Cleaning Validation within an effective Quality System supported by Quality Risk Management Processes should give assurance that API Manufacturing Operations are performed in such a way that Risks to patients related to cleaning validation are understood, assessed for impact and are mitigated as necessary.

原料药生产企业应将清洁验证与有效的质量体系相结合，由质量风险管理来支持，了解与清洁验证相关的患者风险，评估其影响，并在必要时降低风险。