aghastIQ中英文对照

2021年1月27日发(作者：百衲衣)

Q7a

（中英文对照）

FDA

原料药

GMP

指南

< p>

Table of Contents

1. INTRODUCTION

Objective

Regulatory Applicability

Scope

2. QUALITY MANAGEMENT

Principles

Responsibilities

of

the

Quality

Unit(s)

Responsibility for Production

Activities

Internal Audits (Self

Inspection)

Product Quality Review

3. PERSONNEL

Personnel Qualifications

Personnel Hygiene

Consultants

目录

1.

简介

目的

法规的适用性

范围

2.

质量管理

总则

质量部门的责任

生产作业的职责

内部审计（自检）

产品质量审核

3.

人员

3.

人员的资质

人员卫生

顾问

4. BUILDINGS AND FACILITIES

Design and Construction

Utilities

Water

Containment

Lighting

Sewage and Refuse

Sanitation and Maintenance

5. PROCESS EQUIPMENT

Design and Construction

Equipment Maintenance and

Cleaning

Calibration

Computerized Systems

6. DOCUMENTATION AND RECORDS

Documentation System and

Specifications

Equipment cleaning and Use

Record

Records of Raw Materials,

4.

建筑和设施

设计和结构

公用设施

水

限制

照明

排污和垃圾

卫生和保养

5.

工艺设备

设计和结构

设备保养和清洁

校验

计算机控制系统

6.

文件和记录

文件系统和质量标准

设备的清洁和使用记录

原料、中间体、原料药的标签和

Intermediates, API Labeling and

包装材料的记录

Packaging Materials

Master Production Instructions

生产工艺规程（主生产和控制记

(Master Production and Control

Records)

Batch

Production

Records

(Batch

Production and Control Records)

Laboratory Control Records

Batch Production Record Review

7. MATERIALS MANAGEMENT

General Controls

Receipt and Quarantine

Sampling and Testing of

Incoming Production Materials

Storage

Re- evaluation

8. PRODUCTION AND IN-PROCESS

CONTROLS

Production Operations

Time Limits

8.3 In-process Sampling and

录）

批生产记录（批生产和控制记录）

实验室控制记录

批生产记录审核

7.

物料管理

控制通则

接收和待验

进厂物料的取样与测试

储存

复验

8.

生产和过程控制

生产操作

时限

工序取样和控制

Controls

Blending Batches of

Intermediates or APIs

Contamination Control

9. PACKAGING AND IDENTIFICATION

LABELING OF APIs AND

INTERMEDIATES

General

Packaging Materials

Label Issuance and Control

Packaging and Labeling

Operations

10. STORAGE AND DISTRIBUTION

Warehousing Procedures

Distribution Procedures

11. LABORATORY CONTROLS

General Controls

Testing of Intermediates and

APIs

Validation of Analytical

中间体或原料药的混批

污染控制

9.

原料药和中间体的包装和贴签

总则

包装材料

标签发放与控制

包装和贴签操作

10.

储存和分发

入库程序

分发程序

11.

实验室控制

控制通则

中间体和原料药的测试

分析方法的验证

Procedures

Certificates of Analysis

Stability Monitoring of APIs

Expiry and Retest Dating

Reserve/Retention Samples

12. VALIDATION

Validation Policy

Validation Documentation

Qualification

Approaches to Process

Validation

Process Validation Program

Periodic Review of Validated

Systems

Cleaning Validation

Validation of Analytical

Methods

13. CHANGE CONTROL

14. REJECTION AND RE-USE OF

MATERIALS

分析报告单

原料药的稳定性监测

有效期和复验期

留样

12.

验证

验证方针

验证文件

确认

工艺验证的方法

工艺验证的程序

验证系统的定期审核

清洗验证

分析方法的验证

13.

变更的控制

14.

拒收和物料的再利用

Rejection

Reprocessing

Reworking

Recovery of Materials and

Solvents

Returns

15. COMPLAINTS AND RECALLS

16. CONTRACT MANUFACTURERS

(INCLUDING LABORATORIES)

17. AGENTS, BROKERS, TRADERS,

DISTRIBUTORS, REPACKERS, AND

RELABELLERS

Applicability

Traceability of Distributed

APIs and Intermediates

Quality Management

Repackaging, Relabeling, and

Holding of APIs and

Intermediates

Stability

拒收

返工

重新加工

物料与溶剂的回收

退货

15.

投诉与召回

16.

协议生产商（包括实验室）

17.

代理商、经纪人、贸易商、经

销商、重新包装者和重新贴签者

适用性

已分发的原料药和中间体的可追溯

性

质量管理

原料药和中间体的重新包装 、重新

贴签和待检

稳定性

Transfer of Information

Handling of Complaints and

Recalls

Handling of Returns

18. Specific Guidance for APIs

Manufactured by Cell

Culture/Fermentation

General

Cell Bank Maintenance and

Record Keeping

Cell Culture/Fermentation

Harvesting, Isolation and

Purification

Viral Removal/Inactivation

steps

19. APIs for Use in Clinical

Trials

General

Quality

Equipment and Facilities

Control of Raw Materials

信息的传达

投诉和召回的处理

退货的处理

18.

用细胞繁殖

/

发酵生产的原料

药的特殊指南

总则

细胞库的维护和记录的保存

细胞繁殖

/

发酵

收取、分离和精制

病毒的去除

/

灭活步骤

19.

用于临床研究的原料药

总则

质量

设备和设施

原料的控制

Production

Validation

Changes

Laboratory Controls

Documentation

20. Glossary

Q7a GMP Guidance for APIs

Q7a

原料药的

GMP

指南

1. INTRODUCTION

Objective

This document is intended to

provide guidance regarding good

manufacturing

practice

(GMP)

for

the manufacturing of active

pharmaceutical ingredients

(APIs) under an appropriate

system for managing quality. It

is also intended to help ensure

that APIs meet the quality and

purity

characteristics

that

they

purport, or are represented, to

生产

验证

变更

实验室控制

文件

20.

术语

1.

简介

目的

本文件旨在为在合适的质量管理 体

系下制造活性药用成分

（以下称原料

药）

提供有关优良药品生产管理规范

（

GMP

）提供指南。它也着眼于帮助

确保原料药符合其旨在达到 或表明

拥有的质量与纯度要求。

possess.

In this guidance, the term

本指南中所指的“制造”包括物料

接收、生产、包装、重新包装 、贴

manufacturing

is defined to

include

all

operations

of

receipt

签、重新贴签、质量控制、放行、

of materials, production,

packaging, repackaging,

labeling, relabeling, quality

control, release, storage and

distribution of APIs and the

related controls. In this

guidance, the term

should

原料药的储存和分发及 其相关控制

的所有操作。本指南中，“应当”

一词表示希望采用 的建议，除非证

明其不适用或者可用一种已证明有

同等或更高质 量保证水平的供选物

来替代。本指南中的“现行优良生

产管理规 范

（

cGMP

）

”和“优良生产

identifies

recommendations

that,

管理规范（

GMP

）”是等同的。

< br>

when followed, will ensure

compliance with CGMPs. An

alternative approach may be used

if such approach satisfies the

requirements of the applicable

statues.

For

the

purposes

of

this

guidance, the terms

current good

manufacturing

practices

and

good

manufacturing practices

are

equivalent.

The guidance as a whole does not

本指南在总体上未涉及生产人员的

cover safety aspects for the

personnel engaged in

manufacturing, nor aspects

related to protecting the

environment. These controls are

inherent

responsibilities

of

the

manufacturer and are governed by

national laws.

This guidance is not intended to

define registration and/or

filing requirements or modify

pharmacopoeial requirements.

This

guidance

does

not

affect

the

ability of the responsible

regulatory agency to establish

specific registration/filing

requirements regarding APIs

within the context of

marketing/manufacturing

安全问题 ，亦不包括环保方面的内

容。这方面的管理是生产者固有的

责任 ，也是国家法律规定的。

本指南未 规定注册

/

归档的要求、或

修改药典的 要求。本指南不影响负

责药政审理部门在原料药上市

/

制造

授权或药品申请方面建立特定注册

/

归档要求的能力。注册

/

归档的所有

承诺必须做到。

authorizations or drug

applications.

All

commitments

in

registration/filing documents

should be met.

Regulatory Applicability

Within the world community,

materials may vary as to their

legal classification as an API.

When a material is classified as

an

API

in

the

region

or

country

in

which it is manufactured or used

in a drug product, it should be

manufactured according to this

guidance.

Scope

This guidance applies to the

manufacture of APIs for use in

human

drug

(medicinal)

products.

It applies to the manufacture of

sterile

APIs

only

up

to

the

point

immediately prior to the APIs

法规的适用性

在世界范围内对原料药的法定定义

是各不相同的。当某种物料在 其制

造或用于药品的地区或国家被称为

原料药，就应该按照本指 南进行生

产。

范围

本文件适用于人用药品（医疗用 品）

所含原料药的生产。它适用于无菌

原料药在灭菌前的步骤。 本指南不

包括无菌原料药的消毒和灭菌工

艺，但是，应当符合地 方当局所规

定的药品（医疗用品）生产的

GMP

being rendered sterile. The

sterilization and aseptic

processing of sterile APIs are

not

covered

by

this

guidance,

but

指南。

should

be

performed

in

accordance

with GMP guidances for drug

(medicinal) products as defined

by local authorities.

This guidance covers APIs that

are manufactured by chemical

synthesis, extraction, cell

culture/fermentation, recovery

from natural sources, or any

combination of these processes.

Specific guidance for APIs

manufactured by cell

culture/fermentation is

described in Section 18.

This guidance excludes all

vaccines, whole cells, whole

blood and plasma, blood and

本文件适用于通过化学合成、提

取、细胞培养

< br>/

发酵，通过从自然资

源回收，或通过这些工艺的结合而

得到的原料药。通过细胞培养

/

发酵< /p>

生产的原料药的特殊指南则在第

18

章论 述。

本指南不包括所有疫苗、完整

细胞、全血和血浆、全血和血浆的

衍生物

（血浆成分）

和基因治疗的原

plasma derivatives (plasma

料药。但是却包括以血或血浆为原

fractionation),

and

gene

therapy

材料生产的原料药。值得注意的是

APIs. However, it does include

APIs that are produced using

blood

or

plasma

as

raw

materials.

Note that cell substrates

(mammalian, plant, insect or

microbial

cells,

tissue

or

animal

sources including transgenic

animals) and early process steps

may

be

subject

to

GMP

but

are

not

covered by this guidance. In

addition, the guidance does not

apply to medical gases,

bulk-packaged drug (medicinal)

products ., tablets or capsules

in bulk containers), or

radiopharmaceuticals.

Section

19

contains

guidance

that

only applies to the manufacture

of

APIs

used

in

the

production

of

细胞培 养基

（哺乳动物、植物、昆虫

或微生物的细胞、组织或动物源包

括转基因动物）

和前期生产可能应遵

循

GMP

规范，但不包括在本指南之

内。 另外，本指南不适用于医用气

体、散装的制剂药

（例如，散装的 片

剂和胶囊）和放射性药物的生产。

第

19

章的 指南只适用于用在药品

（医疗用品）

生产中的原料药制造，

特别是临床实验用药

（研究用医疗产

dru g (medicinal) products

specifically

for

clinical

trials

品）的原料药制造。

(investigational medicinal

products).

An

API

starting

material

is

a

raw

material, an intermediate, or an

API

that

is

used

in

the

production

of

an

API

and

that

is

incorporated

as a significant structural

fragment into the structure of

the

API.

An

API

starting

material

can be an article of commerce, a

material purchased from one or

more suppliers under contract or

commercial agreement, or

produced in-house. API starting

materials normally have defined

chemical properties and

structure.

The company should designate and

document the rationale for the

“原料药的起始物料”是指一种原

料 、中间体或原料药，用来生产一

种原料药，或者以主要结构单元的

形式被结合进原料药结构中。原料

药的起始物料可能是在市场上有

售、能够通过合同或商业协议从一

个或多个供应商处购得，或由生产

厂家自制。原料药的起始物料一般

来说有特定的化学特性和结构。

生产厂商要指定并用书面文件说明

原料药的生产从何处开始的理论依

point at which production of the

据。对于合成工艺而言，就是“原

API begins. For synthetic

料药的起始物料”进入工艺的那一

processes, this is known as the

点。对其他工艺

（如：发酵，提取，

point at which API starting

materials are entered into the

process. For other processes .,

fermentation, extraction,

purification), this rationale

should be established on a

case-by-case

basis.

Table

1

gives

guidance

on

the

point

at

which

the

API

starting

material

is

normally

introduced into the process.

From this point on, appropriate

GMP as defined in this guidance

should be applied to these

intermediate and/or API

manufacturing steps. This would

include the validation of

critical process steps

determined to impact the quality

纯化等）可能需要具体问题具体对

待。表

1

给出了原料药的起始物料

从哪一点引入工艺过程的指导原

则。

从这步开始，本指南 中的有关

GMP

规范应当应用在这些中间体和

< br>/

或原

料药的制造中。这包括对原料药质

量有影响的关键工艺步骤的验证。

但是，值得注意的是厂商选择某一

< p>
步骤进行验证，并不一定将该步骤

定为关键步骤。

of

the

API.

However,

it

should

be

noted

that

the

fact

that

a

company

chooses to validate a process

step does not necessarily define

that steps as critical.

The guidance in this document

would normally be applied to the

steps shown in gray in Table 1.

However, all steps shown may not

be completed. The stringency of

GMP in API manufacturing should

increase as the process proceeds

from early API steps to final

steps, purification, and

packaging. Physical processing

of APIs, such as granulation,

coating

or

physical

manipulation

of particle size ., milling,

micronizing)

should

be

conducted

according to this guidance.

This GMP guidance does not apply

本文件的指南通常适用于表

1

中的

灰色步骤。但在表中体现的所有步

< br>骤并不是将应用

GMP

管理的所有步

骤全部体现出来了。原料药生产中

的

GMP

要求应当随着工艺的进行，

从原料药的前几步到最后几步，精

< br>制和包装，越来越严格。原料药的

物理加工，如制粒、包衣或颗粒度

的物理处理

（例如制粉、微粉化）

应

当按本指南的标准进行。

本

GMP

指南不适用于引入定义了的

t o steps prior to the

“原料药的起始物料”以前的步

introduction of the defined API

骤。

starting material.

Table 1: Application of this Guidance to API Manufacturing

Type of

Manufacturing

Chemical

manufacturing

Application of this guidance to steps (shown in gray) used in thi

manufacturing

Production of

Introduction of the

Production of

the API

Starting

material

API starting

material into

process

Introduction of

Isolation

the

API

starting

and

material into

process

purification

Isolation

Intermediate(s)

and

purification

API derived from

Collection of

Cutting, mixing,

animal sources

organ, fluid,

and/or initial

or tissue

processing

API

extracted

from

Collection of

Cutting and initial

Introduction of

Isolation

plant sources

plant

extraction(s)

the

API

starting

and

material into

process

Herbal extracts

used as API

Collection of

Cutting and initial

plants

extraction

purification

Further

extraction

API consisting of

Collection of

Cutting/comminuting

comminuted or

powdered herbs

plants and/or

cultivation

and

harvesting

Biotechnology:

Establishment

Maintenance of

Cell culture

and/or

fermentation

Isolation

and

purification

fermentation/cell

of

master

cell

working cell bank

culture

bank and

working cell

bank

“Classical”

fermentation to

produce an API

Establishment

Maintenance of the

Introduction of

Isolation

of cell bank

cell bank

the cells into

and

fermentation

purification

Increasing GMP

表

1:

本指南在原料药生产中的应用

生产类型

化学品的生

产

本指南在用于各类生产的工艺步骤（灰色背景）中的应用

原料药起始

物料的生产

原料药起始物

中间体的生产

分离和纯

物理加工和包装

料引入工艺过

程

动物源原料

器官、分泌

切割、混合和

原料药起始物

分离和纯

物理加工和包装

化

药

物或组织的

收集

/

或初步加工

料引入工艺过

化

程

从植物源提

取的原料药

植物的收集

切割和初步提

< p>
原料药起始物

分离和纯

物理加工和包装

< p>

取

料引入工艺过

化

程

草药提取物

用作原料药

由粉碎的或

粉末状草药

组成的原料

< br>药

生物技术：

发酵

< p>
/

细胞

培养

“经典”

发酵生产原

料药

植物的收集

切割和初步提

取

进一步提

物理加工和包装

取

植物的收集

和

/

或培养

和收获

< br>

切割

/

粉碎

物理加工和包装

主细胞库和

工作细胞库

的建立

细胞库的建

立

工作细胞库的

细胞培养和

/

维护

或发酵

分离和纯

物理加工和包装

化

细胞库的维护

细胞引入发酵

分离和纯

物理加工和包装

化

2. QUALITY MANAGEMENT

Principles

Quality should be the

2

．质量管理

GMP

的要求增加

总则

参与 原料药生产的每一个人都应当

responsibilities of all persons

对质量负责。

involved in manufacturing.

Each manufacturer should

establish, document, and

每一个生产商都应当建立并执 行一

套有管理人员和有关员工积极参与

implement

an

effective

system

for

的有效的质量管理体系，并使其文

managing quality that involves

the active participation of

management and appropriate

manufacturing personnel.

The system for managing quality

should encompass the

organizational structure,

procedures, process and

resources, as well as activities

to

ensure

confidence

that

the

API

will meet its intended

specifications for quality and

purity. All quality-related

activities should be defined and

documented.

There should be a quality

件化。

质量管理体系应当包括组织机构、

规程、工艺和资源，以及确保 原料

药会符合其预期的质量与纯度要求

所必需的活动。所有涉及 质量管理

的活动都应当明确规定，并使其文

件化。

应当设立一个独立于生产部门的质

unit(s) that is independent of

量部门，同时履行质量保证

(

QA

)

和

production

and

that

fulfills

both

质量控制

(

QC

)

的职责。依照组织机

quality assurance (

QA

) and

quality control (

QC)

responsibilities. The quality

unit can be in the form of

separate QA and QC units or a

single individual or group,

depending upon the size and

structure of the organization.

The persons authorized to

release intermediates and APIs

should be specified.

All quality-related activities

should be recorded at the time

they are performed.

Any deviation from established

procedures should be documented

and explained. Critical

deviations should be

构的大小，可以是分开的

QA

和

Q C

部门，或者只是一个人或小组。

应当指定授权发放中间体和原料药

的 人员。

所有有关质量的活动应当在其执行

时就记录。

任何偏离既定规程的情况都应当有

文字记录并加以解释。对于关键性

偏差应当进行调查，并记录调 查经

过及其结果。

investigated, and the

investigation and its

conclusions should be

documented.

No materials should be released

or used before the satisfactory

completion of evaluation by the

quality unit(s) unless there are

appropriate systems in place to

allow for such use ., release

under quarantine as described in

Section 10 or the use of raw

materials or intermediates

pending completion of

evaluation).

Procedures should exist for

notifying

responsible

management

in a timely manner of regulatory

inspections, serious GMP

deficiencies, product defects

and related actions .,

在质量部门对物料完成满意的评价

之前，任何物料都不应当发放或使

用，除非有合适的系统允许此 类使

用（如条款所述的待检情况下的使

用，或是原料或中间体在 等待评价

结束时的使用）。

应当有规程能确保公司的责任管理

部 门能及时得到有关药政检查、严

重的

GMP

缺陷、产品缺陷及其相关

活动

（如质量投诉，召回，药政活 动

等）的通知。

quality- related complaints,

recalls, and regulatory

actions).

Responsibilities

of

the

Quality

质量部门的责任

Unit(s)

The quality unit(s) should be

involved in all quality-related

matters.

The quality unit(s) should

review and approve all

appropriate quality-related

documents.

The

main

responsibilities

of

the

independent quality unit(s)

should not be delegated. These

responsibilities should be

described in writing and should

include, but not necessarily be

limited to:

1.

Releasing or rejecting all

质量部门应当参与所有与质量 有关

的事物。

所有与质量有关的文件应当由质量

部 门审核批准。

< br>独立的质量部门的主要职责不应当

委派给他人。这些责任应当以文字

形式加以说明，而且应当包括，但

不限于：

1.

所有原料药的放行与否。用于生

产商控制范围以外的中间体的放

行与否；

2.

建立一个放行与拒收原材料、中

APIs. Releasing or rejecting

intermediates for use outside

3.

间体、包装材料和标签的系统；

在供销售的原料药放行前，审核

the control of the

manufacturing company

2.

Establishing a system to

release or reject raw

materials, intermediates,

packaging, and labeling

materials

3.

Reviewing completed batch

production and laboratory

control records of critical

process steps before release

of the API for distribution

4.

Making sure that critical

deviations are investigated

and resolved

5.

Approving all specifications

and master production

instructions

6.

Approving all procedures

affecting the quality of

已完成的关键步骤的批生产记录

和实验室检验记录；

< br>

4.

确保已对重大偏差进行 了调查并

已解决；

5.

批准所有的规格标准和主生产指

令；

6.

批准所有可能影响原料药和中间

体质量的规程；

7.

确保进行内部审计（自检）；

8.

批准中间体或原料药的委托生产

商；

9.

批准可能影响到中间体或原料药

质量的变更；

10.

审核并批准验证方案和报告；

11.

确保调查并解决质量问题的投

诉；

12.

确保用有效的体系来维护和校 验

关键设备；

13.

确保物料都经过了适当的检验 并

报告结果；

intermediates or APIs

7.

14.

确保有稳定性数据支持中间体或

Making sure that internal

audits

(self- inspections)

are

performed

原料药的复验期或有效期和储存

条件；

15.

开展产品质量审核（详见节）。

8.

Approving intermediate and

API contract manufacturers

9.

Approving changes that

potentially affect

intermediate or API quality

10.

Reviewing and approving

validation protocols and

reports

11.

Making sure that

quality-related complaints

are investigated and resolved

12.

Making sure that effective

systems are used for

maintaining and calibrating

critical equipment

13.

Making

sure

that

materials

are

appropriately tested and the

results are reported

14.

Making sure that there is

stability data to support

retest or expiry dates and

storage conditions on APIs

and/or intermediates, where

appropriate

15.

Performing product quality

reviews

(as

defined

in

Section

Responsibility for Production

Activities

The responsibility for

production activities should be

described in writing and should

include, but not necessarily be

limited to:

1.

Preparing, reviewing,

approving, and distributing

the instructions for the

production of intermediates

or APIs according to written

procedures

生产作业的职责

生产作业的职责应当 以文字形式加

以说明，并应当包括，但不限于以

下内容：

1.

按书面程序 起草、审核、批准和

分发中间体或原料药的生产指

令；

2.

按照已批准的 指令生产原料药或

者中间体；

3.

审核所有的批生产记录确保其完

整并有签名；

4.

确保所有的生产偏差都已报告、

2.

Producing APIs and, when

appropriate, intermediates

according to pre-approved

instructions

3.

Reviewing all production

batch records and ensuring

that these are completed and

signed

4.

Making sure that all

production deviations are

reported and evaluated and

that critical deviations are

investigated and the

conclusions are recorded

5.

Making sure that production

facilities

are

clean

and,

when

appropriate, disinfected

6.

Making

sure

that

the

necessary

calibrations are performed

and records kept

7.

Making sure that the premises

and equipment are maintained

评价，对关键的偏差已做了调

查，并记 录结论；

5.

确保生产设施的清洁，必要时要

消毒；

6.

确保进行必要的校验，并有记

录；

7.

确保对厂房和设备进行保养，并

有记录；

8.

确保验证方案和报告的审核与批

准；

9.

对产品、工艺或设备拟作的变更

进行评估；

10.

确保新的或已改进的生产设施 和

设备经过了确认。

and records kept

8.

Making sure that validation

protocols and reports are

reviewed and approved

9.

Evaluating proposed changes

in product, process or

equipment

10.

Making

sure

that

new

and,

when

appropriate, modified

facilities and equipment are

qualified

Internal Audits (Self

Inspection)

To verify compliance with the

principles of GMP for APIs,

regular

internal

audits

should

be

performed in accordance with an

approved schedule.

Audit findings and corrective

actions should be documented and

brought to the attention of

内部审计（自检）

为确实符合原料药

GMP

< p>
原则，应当

按照批准的计划进行定期的内部审

计。

审计结 果及整改措施应当形成文

件，并引起公司责任管理人员的重

视。 获准的整改措施应当及时、有

responsible management of the

firm. Agreed corrective actions

should be completed in a timely

效地完成。

and effective manner.

Product Quality Review

Regular

quality-reviews

of

APIs

should be conducted with the

objective of verifying the

consistency of the process. Such

reviews should normally be

conducted and documented

annually and should include at

least:

●

A review of critical

in-process control and

critical API test results

●

A review of all batches

that failed to meet

established

specification(s)

●

A review of all critical

产品质量审核

原料药的定期质量审核应当以证实

工 艺的一致性为目的来进行。此种

审核通常应当每年进行一次，并记

录，内容至少应当包括：

●

关键工艺控制以及原料药关

键测试结果的审核；

●

所有不符合既定质量标准的

产品批号的审核；

●

所有关键的偏差或违规行为

及有关调查的审核；

●

任何工艺或分析方法变动的

审核；

●

稳定性监测的审核；

●

所有与质量有关的退货、投

诉和召回的审核；

●

整改措施的适当性的审核。

deviations or

nonconformances and

related investigations

●

A review of any changes

carried out to the

processes or analytical

methods

●

A review of results of the

stability monitoring

program

●

A review of all

quality-related returns,

complaints and recalls

●

A review of adequacy of

corrective actions

The results of this review

should be evaluated and an

assessment made of whether

corrective action or any

revalidation should be

undertaken. Reasons for such

应当对质量审核结果进行评估，并

做出是否需要整改或做任何再验证

的评价。此类整改措施的理由 应当

文件化。获准的整改措施应当及

时、有效地完成。

corrective action should be

documented. Agreed corrective

actions should be completed in a

timely and effective manner.

3. PERSONNEL

Personnel Qualifications

There should be an adequate

number of personnel qualified by

appropriate

education,

training,

and/or experience to perform and

supervise the manufacture of

intermediates and APIs.

The responsibilities of all

personnel engaged in the

manufacture

of

intermediates

and

APIs should be specified in

writing.

Training should be regularly

conducted by qualified

individuals and should cover, at

3.

人员

员工的资质

应当有足够数量的员工具备从事和

监管原料药和中间体生产的教育、

< br>培训和

/

或经历等资格。

参与原料药和中间体生产的所有人

员的职责应当书面规定。

应当由有资格的人员定期进行培

训， 内容至少应当包括员工所从事

的特定操作和与其职能有关的

a minimum, the particular

operations that the employee

performs

and

GMP

as

it

relates

to

GMP

。培训记录应当保存，并应当定

期对培训进行评估。

< br>

the employee

’

s functions.

Records of training should be

maintained. Training should be

periodically assessed.

Personnel Hygiene

Personnel should practice good

sanitation and health habits.

Personnel should wear clean

clothing suitable for the

manufacturing activity with

which they are involved and this

clothing should be changed, when

appropriate. Additional

protective

apparel,

such

as

head,

face, hand, and arm coverings,

should be worn, when necessary,

to

protect

intermediates

and

APIs

from contamination.

员工的卫生

员工应当养成良好的卫生和健康习

惯。

员工应当穿着适合其所从事生产操

作的干净服装，必要时应当更换。

其它保护性用品如头、脸、手 和臂

等遮护用品必要时也应当佩带，以

免原料药和中间体受到污 染。

Personnel should avoid direct

contact with intermediates and

APIs.

Smoking, eating, drinking,

chewing and the storage of food

should be restricted to certain

designated areas separate from

the manufacturing areas.

Personnel suffering from an

infectious

disease

or

having

open

lesions

on

the

exposed

surface

of

the body should not engage in

activities that could result in

compromising

the

quality

of

APIs.

Any person shown at any time

(either

by

medical

examination

or

supervisory

observation)

to

have

an apparent illness or open

lesions should be excluded from

activities where the condition

员工应当避免与中间体或原料药的

直接接触。

吸烟、吃、喝、咀嚼及存放食品仅

限 于与生产区隔开的指定区域。

< /p>

患传染性疾病或身体表面有开放性

创伤的员工不应当从事危及原料 药

质量的生产活动。在任何时候

（经医

学检验或监控检查）

任何患有危及到

原料药质量的疾病或创伤的 人员都

不应当参与作业，直到健康状况已

恢复，或者有资格的医 学人员确认

该员工不会危及到原料药的安全性

和质量。

could adversely affect the

quality of the APIs until the

condition is corrected or

qualified medical personnel

determine that the person

’

s

inclusion would not jeopardize

the

safety

or

quality

of

the

APIs.

Consultants

Consultants advising on the

manufacture and control of

intermediates

or

APIs

should

have

sufficient education, training,

and experience, or any

combination

thereof,

to

advise

on

the subject for which they are

retained.

Records should be maintained

stating the name, address,

qualifications, and type of

service provided by these

consultants.

顾问

< /p>

中间体或原料药生产和控制的顾问

应当有足够的学历，受训和经验 ，

能胜任所承担的工作。

顾问的姓名、地址、资格和提供服

务 的类型都应当有文字记录。

4. BUILDINGS AND FACILITIES

Design and Construction

4.

建筑和设施

设计和结构

Buildings

and

facilities

used

in

用于中间体和原料药生产的厂房和

the

manufacture

of

intermediates

and APIs should be located,

designed, and constructed to

facilitate cleaning,

maintenance, and operations as

appropriate

to

the

type

and

stage

of manufacture. Facilities

should also be designed to

minimize potential

contamination. Where

microbiological specifications

have been established for the

intermediate or API, facilities

should also be designed to limit

exposure to objectionable

microbiological

contaminants,

as

appropriate.

设施的选址、设计和建造应当便于

清洁，维护和适应一定类型和阶段< /p>

的生产操作。设施的设计应尽量减

少潜在的污染。如果中间体或原 料

药的生产有微生物限度要求，那么

设施设计应相应的限制有害 微生物

的污染。

Buildings

and

facilities

should

厂房和设施应有足够空间，以便有

have adequate space for the

秩序地放置设备和物料，防止混淆

orderly placement of equipment

和污染。

and materials to prevent mix-ups

and contamination.

Where the equipment itself .,

closed or contained system)

provides adequate protection of

the material, such equipment can

be located outdoors.

The flow of materials and

personnel

through

the

building

or

facilities should be designed to

prevent mix-ups and

contamination.

There

should

be

defined

areas

or

other control systems for the

following activities:

●

Receipt, identification,

sampling, and quarantine of

自 身能对物料提供足够保护的设备

（如关闭的或封闭的系统）

，可 以在

户外放置。

通过厂房和设施的物流和人流的设

计 应当能防止混杂和污染。

以下活动应当有指定区域或其它控

制系统：

●

来料的接收、鉴别、取样和待

验，等待放行或拒收；

●

中间体和原料药放行或拒收前的

incoming materials, pending

release or rejection

●

●

●

待验；

中间体和原料药的取样

不合格物料处理（如退货、返工

Quarantine before release or

rejection of intermediates

and APIs

●

Sampling of intermediates and

APIs

●

Holding rejected materials

before further disposition .,

return, reprocessing or

destruction)

●

Storage of released materials

●

Production operations

●

Packaging and labeling

operations

●

Laboratory operations

Adequate and clean washing and

toilet facilities should be

provided for personnel. These

facilities should be equipped

with hot and cold water, as

或销毁）前的贮存；

●

已放行物料的贮存；

●

生产操作；

●

包装及贴标签操作；

●

实验室操作。

应当为员工提供足够和清洁的盥洗

设 施。这些盥洗设施应当装有冷热

水

（视情况而定）

、肥皂或洗涤剂，

干手机和一次性毛巾。盥洗室应当

与生产区隔离，但要便于达到。应

appropriate, soap or detergent,

当根据情况提供足够的淋浴和

/

或更

air dryers, or single service

towels. The washing and toilet

facilities should be separate

from, but easily accessible to,

manufacturing areas. Adequate

facilities for showering and/or

changing clothes should be

provided, when appropriate.

Laboratory areas/operations

should

normally

be

separated

from

production areas. Some

laboratory areas, in particular

those used for in-process

controls, can be located in

production areas, provided the

operations of the production

process do not adversely affect

the accuracy of the laboratory

measurements,

and

the

laboratory

and its operations do not

衣设施。

实验室区域

/

操作通常应当与生产

区隔离。有些实验室区域，特别是

用于中间控制的，可以位于生产区

内，只要生产工艺操作对实验室测

量的准确性没有负面影响，而 且，

实验室及其操作对生产过程，或中

间体，或原料药也没有负 面影响。

adversely affect the production

process, intermediate, or API.

Utilities

公用设施

All utilities that could affect

对产品质量会有影响的所有公用设

product quality ., steam, gas,

compressed air, heating,

ventilation, and air

conditioning) should be

qualified and appropriately

monitored and action should be

taken when limits are exceeded.

Drawings for these utility

systems should be available.

Adequate ventilation, air

filtration and exhaust systems

should be provided, where

appropriate. These systems

should be designed and

constructed to minimize risks of

contamination and

cross- contamination and should

施（如蒸汽，气体，压缩空气和 加

热，通风及空调）

都应当确认合格，

并进行适当监控，在超出限度时应

当采取相应措施。应当有这些公用

设施的系统图。

< p>
应当根据情况，提供足够的通风、

空气过滤和排气系统。这些系统应

当根据相应的生产阶段，设计和建

造成将污染和交叉污染降至最低限< /p>

度，并包括控制气压、微生物

（如果

适用 ）

、灰尘、湿度和温度的设备。

特别值得注意的是原料药暴露的 区

域。

include equipment for control of

air

pressure,

microorganisms

(if

appropriate), dust, humidity,

and temperature, as appropriate

to the stage of manufacture.

Particular attention should be

giving to areas where APIs are

exposed to the environment.

If air is recirculated to

production areas, appropriate

measures should be taken to

control risks of contamination

and cross-contamination.

Permanently installed pipework

should be appropriately

identified. This can be

accomplished by identifying

individual

lines,

documentation,

computer control system, or

alternative means. Pipework

should be located to avoid risks

如果空气再循环到生 产区域，应当

采取适当的控制污染和交叉污染的

风险。

永久性安装的管 道应当有适宜的标

识。这可以通过标识每根管道、提

供证明文件 、计算机控制系统，或

其它替代方法来达到。管道的安装

处应当 防止污染中间体或原料药。

of contamination of the

intermediate or ApI.

Drains should be of adequate

排水沟应当有足够的尺寸，而且应

size and should be provided with

当根据情况装有空断器或适当的装

an

air

break

or

a

suitable

device

to prevent back-siphonage, when

appropriate.

Water

Water

used

in

the

manufacture

of

APIs

should

be

demonstrated

to

be

suitable for its intended use.

Unless otherwise justified,

process water should, at a

minimum, meet World Health

Organization (WHO) guidelines

for drinking (portable) water

quality.

If drinking (portable) water is

insufficient to ensure API

quality and tighter chemical

置，防止倒虹吸。

水

原料药生产中使用的水应当证明适

合于其预定的用途。

除非有其它理由，工 艺用水最低限

度应当符合世界卫生组织（

WHO

）的

饮用水质量指南。

如果饮用水不足以确保原料的质

量， 并要求更为严格的化学和

/

或微

生物水 质规格标准，应当指定合适

and/or microbiological water

quality specifications are

called for, appropriate

specifications for

physical/chemical attributes,

total microbial counts,

objectionable organisms, and/or

endotoxins should be

established.

Where water used in the process

is

treated

by

the

manufacturer

to

achieve a defined quality, the

treatment process should be

validated and monitored with

appropriate action limits.

Where the manufacturer of a

nonsterile API either intends or

claims

that

it

is

suitable

for

use

in further processing to produce

a sterile drug (medicinal)

product, water used in the final

的物理

/

化学特性、微生物总数、控

制菌和

/

或内毒素的规格标准。

在工艺用水为达到规定质量由 制造

商进行处理时，处理工艺应当经过

验证，并用合适的处置限 度来监

测。

当非无菌原料药的制造商打算或者

声 称该原料药适用于进一步加工生

产无菌药品

（医疗用品）

时，最终分

离和精制阶段的用水应当进行微生

物总数、致病菌和内毒素方面的监

测和控制。

isolation

and

purification

steps

should be monitored and

controlled for total microbial

counts,

objectionable

organisms,

and endotoxins.

Containment

Dedicated production areas,

which

can

include

facilities,

air

handling equipment and/or

process equipment, should be

employed in the production of

highly sensitizing materials,

such as penicillins or

cephalosprins.

The use of dedicated production

areas should also be considered

when material of an infectious

nature or high pharmacological

activity or toxicity is

involved ., certain steroids or

cytotoxic anti-cancer agents)

限制

在高致敏性物质，如青霉素或头孢

菌 素类的生产中，应当使用专用的

生产区，包括设施、空气处理设备

和

/

或工艺设备。

当涉及具有感染性、高药理活性或

毒性的物料时

（如，激素类或抗肿瘤

类 ）

，也应当考虑专用的生产区，除

非已建立并维持一套经验证的 灭活

和

/

或清洗程序。

unless validated inactivation

and/or cleaning procedures are

established and maintained.

Appropriate measures should be

应当建立并实施相应的措施，防止

established and implemented to

prevent

cross-contamination

from

personnel and materials moving

from one dedicated area to

another.

Any production activities

(including

weighing,

milling,

or

packaging) of highly toxic

nonpharmaceutical materials,

such as herbicides and

pesticides, should not be

conducted using the buildings

and/or equipment being used for

the production of APIs. Handling

and

storage

of

these

highly

toxic

nonpharmaceutical materials

should be separate from APIs.

由于在各专用区域间流动的人员和

物料而造成的交叉污染。

剧毒的非药用物质，如除草剂、杀

虫剂的任何生产活动

（包括称重、研

磨或包装）

都不应当使用生产原 料药

所使用的厂房和

/

或设备。这类剧 毒

非药用物质的处理和储存都应当与

原料药分开。

Lighting

Adequate lighting should be

provided in all areas to

facilitate cleaning,

maintenance, and proper

operations.

Sewage and Refuse

Sewage, refuse, and other

waste ., solids, liquids, or

gaseous by-products from

manufacturing) in and from

buildings and the immediate

surrounding area should be

disposed

of

in

a

safe,

timely,

and

sanitary manner. Containers

and/or pipes for waste material

should be clearly identified.

Sanitation and Maintenance

Buildings used in the

manufacture

of

intermediates

and

照明

所有 区域都应当提供充足的照明，

以便于清洗、保养或其它操作。

排污和垃圾

进入和流出厂房及邻近区域的污

水、垃圾和其它废物

（如生产 中的固

态、液态或气态的副产物）

，应当安

全、及时、卫生的处理。废物的容

器和

/

< br>或管道应当显着地标明。

卫生和保养

生产中间体和原料药的厂房应当适

当地保养、维修并保持清洁。

APIs should be properly

maintained and repaired and kept

in a clean condition.

Written procedures should be

established assigning

responsibility for sanitation

and describing the cleaning

schedules, methods, equipment,

and materials to be used in

cleaning buildings and

facilities.

When necessary, written

procedures

should

be

established

for the use of suitable

rodenticides, insecticides,

fungicides, fumigating agents,

and cleaning and sanitizing

agents to prevent the

contamination of equipment, raw

materials, packaging/labeling

materials, intermediates, and

应当制定书面程序来分配卫生工作

的职责，并描述用于清洁厂房和设

施的清洁的计划、方法、设备 和材

料。

必要时，还应当对合适的灭鼠药、

杀虫剂、杀真菌剂、烟熏剂和 清洁

消毒剂的使用制定书面程序，以避

免对设备、原料、包装< /p>

/

标签、中间

体和原料药的污染。

APIs.

5. PROCESS EQUIPMENT

Design and Construction

Equipment used in the

manufacture

of

intermediates

and

APIs should be of appropriate

design and adequate size, and

suitably

located

for

its

intended

use,

cleaning,

sanitation

(where

appropriate), and maintenance.

Equipment

should

be

constructed

so

that

surfaces

that

contact

raw

materials, intermediates, or

APIs do not alter the quality of

the

intermediates

and

APIs

beyond

the

official

or

other

established

specifications.

Production equipment should

only

be

used

within

its

qualified

operating range.

5.

工艺设备

设计和结构

中间体和原料药生产中使用的设备

应 当有合理的设计和足够的尺寸，

并且放置在适宜于其使用、清洁、

消毒（根据情况而定）和保养的地

方。

设备的构造中与原料、中间体或原

料药接触的表面不会改变中间体和

原料药的质量而使其不符合法 定的

或其他已规定的质量标准。

生产设备应该只在其确认的操作范

围 内运行。

Major equipment ., reactors,

storage containers) and

中间体或原料药生产过程中使用的

主要设备

（ 如反应釜、贮存容器）

和

permanently

installed

processing

永久性安装的工艺管道，应当作适

lines used during the production

当的识别标志。

of an intermediate or API should

be appropriately identified.

Any substances associated with

the operation of equipment, such

as lubricants, heating fluids or

coolants, should not contact

intermediates or APIs so as to

alter the quality of APIs or

intermediates beyond the

official or other established

specifications. Any deviations

from this practice should be

evaluated to ensure that there

are

no

detrimental

effects

on

the

material

’

s fitness for use.

Wherever possible, food grade

lubricants and oils should be

设备运转所需的任何物质， 如润滑

剂、加热液或冷却剂，不应当与中

间体或原料药接触，以 免影响其质

量，导致无法达到法定的或其它已

规定的质量标准。 任何违背该规定

的情况都应当进行评估，以确保对

该物质效果的 适用性没有有害的影

响。可能的话，应当使用食用级的

润滑剂和 油类。

used.

Closed or contained equipment

should be used whenever

appropriate. Where open

equipment is used, or equipment

is opened, appropriate

precautions should be taken to

minimize the risk of

contamination.

5.16

A set of current drawings

should be maintained for

equipment and critical

installations

.,

instrumentation

and utility systems).

Equipment Maintenance and

Cleaning

Schedules and procedures

(including assignment of

responsibility) should be

established

for

the

preventative

应当尽量使用关闭的或封闭的设

备。 若使用开放设备或设备被打开

时，应当采取适当的预防措施，将

污染的风险降至最小。

应当保存一套现在的设备和关键装

置的图纸（如测试设备和公用系

统）。

设备保养和清洁

< br>应当制订设备预防性保养的计划和

程序（包括职责的分配）。

maintenance of equipment.

Written procedures should be

established for cleaning

应当制订设备清洗及允许用于中间

体和原料药生产的书面程序。清洁

equipment release for use in the

程序应当尽量详细，使操作者能对

manufacture

of

intermediates

and

APIs.

Cleaning

procedures

should

contain sufficient details to

enable operators to clean each

type of equipment in a

reproducible and effective

manner. These procedures should

include:

●

Assignment of responsibility

for cleaning of equipment

●

Cleaning schedules,

including,

where

appropriate,

sanitizing schedules

●

A complete description of the

methods and materials,

including dilution of

cleaning agents used to clean

各类设备进行可重复的、有效

的清

洗。这些程序应当包括：

●

设备清洗职责分配；

●

清洗计划，必要时包括消毒计

划；

●

方法和材料的详尽描述，包括用< /p>

于清洗设备的清洗剂的稀释方

法；

●

为确保正确的清洗，根据具体情< /p>

况还应当包括包装设备拆卸和安

装的方法；

●

拿走或抹掉上一批的标识；

●

使用前防止已清洁的设备被污

染；

●

如果可行，使用前对设备进行检

查；

●

根据情况，规定生产结束和清洗