制药工厂现场主文件编写说明
平顶山学院分数线-高考试卷
PHARMACEUTICAL INSPECTION CONVENTION
PHARMACEUTICAL INSPECTION CO-
OPERATION SCHEME
药品检查协定和药品检查合作计划组织
PE 0084
1
Annex
1 January 2011
PE 0084
附件一
2011年1月1日
EXPLANATORY NOTES FOR
PHARMACEUTICAL MANUFACTURERS ON THE PREPARATION
OF A SITE MASTER FILE
制药工厂现场主文件编写说明
?PICS January 2011
Reproduction
prohibited for commercial purposes
Reproduction for internal use is authorized
Provided that the source is acknowledged
Editor编著: PICS Secretariat
email邮箱: info@
web site网站:
http:
TABLE OF CONTENTS
目录
1
Document History文件历史..............................
..................................................
...2
2 Introduction简介...............
..................................................
...................................2
3
Purpose目的.........................................
..................................................
..............2
4 Scope范围...........
..................................................
...............................................3
5 Content of Site Master File现场主文件内容.
..................................................
.......3
6 Revision History修订历史.....
..................................................
..............................3
1 11
1 DOCUMENT HISTORY 文件历史
Adoption by the PIC Committee of Officials of
PH 493
PIC委员会正式采用PH493
Entry into force
of PH 493
PH 493 生效
Entry into force of
PE 0081
PE 0081生效
2
INTRODUCTION 简介
2.1 The Site Master
File is prepared by the pharmaceutical
manufacturer and should contain specific
information about the quality management
policies and activities of the site, the
production andor quality
control of
pharmaceutical manufacturing operations carried
out at the named site and any closely integrated
operations at adjacent and nearby buildings.
If only part of a pharmaceutical operation is
carried out on the
site, a Site Master File
need only describe those operations, e.g.
analysis, packaging, etc.
现场主文件是由制药厂家编写，并包含以下
信息：质量管理方针及现场活动、在对在指定现场进行生产或和对
在指定现场的制药生产操作进行的质量
控制以及在临近及附近建筑内进行的一体化操作。如果仅有一部份制药
操作在该现场进行，那么SMF仅
需描叙该类操作即可，如：分析、包装、等。
2.2 When
submitted to a regulatory authority, the Site
Master File should provide clear information on
the manufacturer’s GMP related activities that
can be useful in general supervision and in the
efficient
planning and undertaking of GMP
inspections. 提交至监管机构时，SMF需提供明确信息，说明厂家进行的有
助于一般监
管和GMP审查有效计划和应对的相关GMP活动
2.3 A Site
Master File should contain adequate information
but, as far as possible, not exceed 25-30
pages plus appendices. Simple plans, outline
drawings or schematic layouts are preferred
instead of
narratives. The Site Master File,
including appendices, should be readable when
printed on A4 paper sheets.
SMF应包含足够的信息，但是加上附
件不得超过25-30页。相较于详述，简单性计划、简略的原理图布局图为
首选。SMF，包括附件，
用A4纸打印出来应当可读。
2.4 The Site Master
File should be a part of documentation belonging
to the quality management system
of the
manufacturer and kept updated accordingly. The
Site Master File should have an edition number,
the
date it becomes effective and the date by
which it has to be reviewed. It should be subject
to regular review to
ensure that it is up to
date and representative of current activities.
Each Appendix can have an individual
effective
date, allowing for independent updating.
SMF厂家
质量管理系统文件的一部分，应进行相应更新。SMF应当有一个版本号、生效日期以及需进行审核
的日
期。应对SMF进行定期审核以保证其为最新版本并体现最新行动。每个附件可有单独的生效日期，允许单
独对附件进行更新。
3 PURPOSE目的
The aim
of these Explanatory Notes is to guide the
manufacturer of medicinal products in the
preparation of a
Site Master File that is
useful to the regulatory authority in planning and
conducting GMP inspections.
本说明的目的是指导医药生产厂家进行S
MF的编写。SMF在监管机构进行GMP审查计划和执行GMP
审查中是有用的。
22-23 April 1993
1993年4月22-23
April
1993
1993年3月
1 November 2002
2002年11月1日
2 11
4
SCOPE 适用范围
These Explanatory Notes apply to
the preparation and content of the Site Master
File. Manufacturers
should refer to regional
national regulatory requirements to establish
whether it is mandatory for
manufacturers of
medicinal products to prepare a Site Master File.
本说明使用与SMF的编写及内容。厂家应参考地区／国家法规要求以确定是否强制要求医药用品厂家编
写SMF。
These Explanatory Notes apply for
all kind of manufacturing operations such as
production, packaging
and labelling, testing,
relabelling and repackaging of all types of
medicinal products. The outlines of this guide
could also be used in the preparation of a
Site Master File or corresponding document by
Blood and Tissue
Establishments and
manufacturers of Active Pharmaceutical
Ingredients.
本说明适用于下述此类生产操作：所有类型医药产品的生产、包装和贴标
、检验、再贴标和再包装。本指
南的大纲也可以用于编写SMF或API血液和组织制造机构以及生产厂
家相关文件的编写。
5 CONTENT OF SITE MASTER
FILE SMF内容
Refer to Annex for the format to
be used.
SMF格式见附件。
6 REVISION
HISTORY 修订历史
Date
日期
1 November
2002
2002年11月1日
Version Number
版本号
PE 0081 Revision of format (in line with SOP
on SOPs) and
introduction; delete reference to
the Site Master File as
being Part B of the
PICS inspection report; new point C.5.3
on
reprocessingrework; better distinction between
Quality
Assurance and Quality Control;
explanation of
abbreviations; minor editorial
changes. All changes
adopted at PICS Committee
meeting on 8 October 2002.
格式（与SOP一致）及简介修订；取消
将SMF作为
PICS审查报告的Ｂ部；C.5.3再加工／返工的新要点；质量
保证和质量控
制的进一步区分；缩略词的解释；小幅编辑修
改。所有变更均在PICS委员2002年10月8日召开
的会议
上被采用。
1 July 2004
PE 0082
2004年６月1日
25 September
2007 2007年９月２５日
编者协调变更
Change in the Editor’s coordinates
PE 0083
编者协调变更
Change in the Editor’s
coordinates
3 11
1
January 2011
2011年１月１日
PE 0084
Simplification of the document and implementation
of
requirements related to quality risk
assessment policy
简化文件以及质量风险评估政策相关要求的执行
Annex to PE 0084
CONTENT OF SITE MASTER
FILE
PE0084附件：现场主文件内容
1
GENERAL INFORMATION ON THE MANUFACTURER工厂一般信息
1.1 Contact information on the
manufacturer生产商联系信息
— Name and official
address of the manufacturer;
—
生产商名称和办公地址；
— Names and street addresses
of the site, buildings and production units
located on the site;
—
厂址名称和街道地址、厂内建筑和生产单元的名称；
— Contact
information of the manufacturer including 24 hrs
telephone number of the contact
personnel in
the case of product defects or recalls;
—
生产商联系信息，包括产品缺陷或召回时联系人的24小时电话号码；
—
Identification number of the site as e.g. GPS
details, DUNS (Data Universal Numbering System)
Number (a unique identification number
provided by Dun & Bradstreet) of the site or any
other geographic
location system[1].
—
工厂识别信息，如全球定位信息（GPS信息）或其他的地理定位系统，以及邓氏编号。
1.2 Authorised pharmaceutical
manufacturing activities of the site. 授权的药物生产活动
— Copy of the valid manufacturing
authorisation issued by the relevant Competent -
Authority in
Appendix 1; or when applicable,
reference to the EudraGMP database. If the
Competent Authority does not
issue
manufacturing authorisations, this should be
stated;
— 在附件1中，附上相关主管当局颁发的有效生产许可证的复件；或
者可能的话，引用欧洲GMP数
据库；如果主管当局不颁发生产许可证，这应该加以说明。
—
Brief description of manufacture, import, export,
distribution and other activities as authorised by
the relevant Competent Authorities including
foreign authorities with authorised dosage
formsactivities,
respectively; where not
covered by the manufacturing authorisation;
—
药政机构许可的生产、进口、出口、分销和其他活动的简要描述，包括生产许可证上没有的国外当
局许可
的剂型活动；
4 11
— Type of
products currently manufactured onsite (list in
Appendix 2) where not covered by
Appendix 1 or
the Eudra GMP database;
—
目前在厂生产的产品类型（在附件2中列出），如果未被包含在附件1中或欧洲GMP准入中
—
List of GMP inspections of the site within the
last 5 years; including dates and namecountry of
the Competent Authority having performed the
inspection. A copy of current GMP certificate
(Appendix 3) or
reference to the EudraGMP
database should be included, if available.
—
列出过去5年的现场GMP检查清单，包括日期和进行检验的药政机构的名称国家。如果有，应当
提供现
行的GMP证书（附件3）或引用欧洲GMP数据库中的副本。
1.3
Any other manufacturing activities carried out on
the site厂区内进行的任何其他生产活动
— Description of
nonpharmaceutical activities onsite, if any.
—
如果有的话，描述厂区内的非制药活动。
2 QUALITY
MANAGEMENT SYSTEM OF THE MANUFACTURER公司的质量管理体系
2.1 The quality management system of
the manufacturer公司质量管理体系
— Brief
description of the quality management systems run
by the company and reference to the
standards
used;
— 公司质量管理运行系统的简要说明和所参考的标准;
—
Responsibilities related to the maintaining of
quality system including senior management;
—
包括高级管理层在内的质量体系维护职责；
— Information of
activities for which the site is accredited and
certified, including datas and content
of
accreditations, name of accrediting bodies.
—
公司认证的活动信息，包括日期和认证内容，认证机构名称。
2.2
Release procedure of finished products最终产品放行程序
— Detailed description of qualification
requirements (education and work experience) of
the
Authorised Person(s) Qualified Person(s)
responsible for batch certification and releasing
procedures;
—
负责批量证明和放行程序的授权人有资质人（简称：QP）的资格要求（教育工作经验）的详细说
明；
— General description of batch
certification and releasing procedure;
—
批合格和放行过程的一般描述；
— Role of Authorised
Person Qualified Person in quarantine and release
of finished products and
in assessment of
compliance with the Marketing Authorisation;
—
授权人有资质人（简称：QP）在待验、放行最终产品、上市授权符合性评估中的角色。
5 11
— The arrangements between
Authorised Persons Qualified Persons when several
Authorised
Persons Qualified Persons are
involved;
— 涉及到多个授权人有资质人时，他们之间的安排
—
Statement on whether the control strategy employs
Process Analytical Technology (PAT) andor
Real
Time Release or Parametric Release.
—
采用PAT（过程分析技术）控制策略和或实时放行或参数放行的描述
2.3
Management of suppliers and contractors承包商和供应商的管理
— A brief summary of the
establishmentknowledge of supply chain and the
external audit program;
—
供应链和外部审计程序建立和信息的一个简要介绍;
— Brief
description of the qualification system of
contractors, manufacturers of active
pharmaceutical ingredients (API) and other
critical materials suppliers;
—
简要说明承包商、活性药物成分（API供应商）和其他关键材料供应商的资格审查系统；
—
Measures taken to ensure that products
manufactured are compliant with TSE (Transmitting
animal spongiform encephalopathy) guidelines.
— 采取的措施，以确保生产出的产品符合TSE（动物海绵状脑病传染）指南
— Measures adopted where
counterfeitfalsified products, bulk products (i.e.
unpacked tablets),
active pharmaceutical
ingredients or excipients are suspected or
identified;
—
假冒伪造产品，散装产品（即拆开的片剂），药物活性成分或辅料的怀疑或确定方法
—
Use of outside scientific, analytical or other
technical assistance in relation to manufacture
and
analysis;
—
外部研究、分析或其他有关生产的技术支援;
— List of contract
manufacturers and laboratories including the
addresses and contact information
and flow
charts of supplychains for outsourced
manufacturing and Quality Control activities; e.g.
sterilisation
of primary packaging material
for aseptic processes, testing of starting
rawmaterials etc, should be presented
in
Appendix 4;
— 合同生产商和实验室的名单，包括地址和联系方式，以及
外包生产和质量控制活动的供应链流程图。
如无菌工艺的内包装材料灭菌，起始物料的检测，应显示附件
4
— Brief overview of the responsibility
sharing between the contract giver and acceptor
with respect
to compliance with the Marketing
Authorisation (where not included under 2.2).
— 上市授权符合性中，合同双方责任划分（如果未在2.2项下描述）的简要概述。
2.4 Quality Risk Management
(QRM) 生产商质量风险管理（QRM）
— Brief description
of QRM methodologies used by the manufacturer;
— 生产商QRM方针的简要描述
6 11
— Scope and focus of QRM
including brief description of any activities
which are performed at
corporate level, and
those which are performed locally. Any application
of the QRM system to assess
continuity of
supply should be mentioned.
— QRM的范围和关注
点的详细描述，包括全体公司层所有活动和仅在局部执行活动的简要描述。任
何采用QRM体系对供应连
续性进行的评估，都应当被讨论。
2.5 Product
Quality Reviews产品质量回顾
— Brief
description of methodologies used
—
方法的简要描述
3 PERSONNEL人员
—
- Organisation chart showing the arrangements for
quality management, production and quality
control positionstitles in Appendix 5,
including senior management and Authorised
Person(s) Qualified
Person(s);
—
显示质量管理、生产和质量控制安排以及职位职称的图表附于附件5，包括高级管理人员和QP的
安排;
— - Number of employees engaged in the
quality management, production, quality control,
storage
and distribution respectively.
—
参与质量管理、生产、质量控制、储存和发放的各自员工数目；
4
PREMISES AND EQUIPMENT厂房和设施
4.1
Premises厂房
— Short description of
plant; size of the site and list of buildings. If
the production for different
markets, i.e. for
local, EU, USA, etc. takes place in different
buildings on the site, the buildings should be
listed with destined markets identified (if
not identified under 1.1);
— 厂房的简单描述：场地
大小和建筑清单。如果不同市场的产品，如本地、欧盟、美国等地，在不同
的建筑中生产，清单中应在建
筑上列出目标市场（如果未在1.1中描述）；
— Simple plan or
description of manufacturing areas with indication
of scale (architectural or
engineering
drawings are not required);
—
示意图或生产区的简单描述，要指出生产规模（不要求建筑或工程图纸）;
— Lay
outs and flow charts of the production areas (in
Appendix 6) showing the room classification
and pressure differentials between adjoining
areas and indicating the production activities
(i.e. compounding,
filling, storage,
packaging, etc.) in the rooms;
— 应在附件6提
供生产区域的布局图和流程图。图上应当显示房间级别，相邻区域之间的压差，并指
出房间内进行的生产
活动即混合、填料、储存、包装等。
— Layouts of warehouses
and storage areas, with special areas for the
storage and handling of
highly toxic,
hazardous and sensitising materials indicated, if
applicable;
7 11
—
仓库和储存区域的示意图和高毒高危害高敏感物料储存和处理区域的描述，如果适用。
—
Brief description of specific storage conditions
if applicable, but not indicated on the layouts.
— 特定储存条件（如果适用）的简要描述，不需要在示意图中指出。
4.1.1 Brief description of heating,
ventilation and air conditioning (HVAC)
systems供暖，通风和空调
（HVAC）系统的简要描述
—
Principles for defining the air supply,
temperature, humidity, pressure differentials and
air change
rates, policy of air recirculation
(%).
—
系统设计标准，例如，空气供应、温度、湿度、压差和换气次数、空气循环方法（%）;
4.1.2 Brief description of water
systems水系统的简要描述
— - Quality references
of water produced;
— 产水的质量标准
—
- Schematic drawings of the systems in Appendix 7.
— 水系统的示意图附于附件7
4.1.3
Brief description of other relevant utilities,
such as steam, compressed air, N2, etc.
其他相关单元
的简要描述，如蒸汽??，压缩空气，氮气等。
4.2
Equipment设备
4.2.1 Listing of major
production and control laboratory equipment with
critical pieces of equipment
identified should
be provided in Appendix 8.
在附件8中列出生产和实验室控制设备中已确定的关键设备
4.2.2
Cleaning and sanitation清洁和卫生
— Brief
description of cleaning and sanitation methods of
product contact surfaces (i.e. manual
cleaning, automatic CleaninPlace, etc).
—
产品接触表面的清洁和卫生方法的简要描述（即人工清洗，自动清洁等）。
4.2.3
GMP critical computerised systems GMP的关键电脑系统
—
Description of GMP critical computerised systems
(excluding equipment specific Programmable
Logic Controllers (PLCs)).
GMP关键电脑系统的描述（不包括特定设备的可编程逻辑控制器PLC）
5
DOCUMENTATION文件
— Description of
documentation system (i.e. electronic, manual);
8 11
— 公司文件体系的描述
—
When documents and records are stored or archived
offsite (including pharmacovigilance data,
when applicable): List of types of
documentsrecords; Name and address of storage site
and an estimate of
time required retrieving
documents from the offsite archive.
— 文
件和记录在厂外存储或归档（包括药物警戒的数据，如果适用）：文件记录的类型列表，存储
地点的名称
和地址以及异地存档时检索取回文件所需时间的评估。
6
PRODUCTION生产
6.1 Type of
products产品类型
(references to Appendix 1 or 2
can be made可参考附件1或2):
— Type of products
manufactured including
— 生产的产品类型包括
n
list of dosage forms of both human and veterinary
products which are manufactured on the site;
n 工厂生产的人用和兽用产品的剂型的列表
n
list of dosage forms of investigational medicinal
products (IMP) manufactured for any clinical
trials on the site, and when different from
the commercial manufacturing, information of
production areas and
personnel;
n
临床试验用的研究性新药（IMP）的剂型列表，如果不同于商业生产工艺，要给出生产区域和人员
信息
— Toxic or hazardous substances handled
(e.g. with high pharmacological activity andor
with
sensitising properties);
—
有毒有害物质处理（如，高药物活性或致敏物质）
— Product types
manufactured in a dedicated facility or on a
campaign basis, if applicable;
—
在专用车间生产的产品剂型，如果适用
— Process Analytical
Technology (PAT) applications, if applicable:
general statement of the
relevant technology,
and associated computerised systems.
—
过程分析技术（简称：PAT）的应用，如果适用：相关计算机系统和相关技术的简要描述。
6.2 Process validation工艺验证
— Brief description of general policy for
process validation;
—
工艺验证方法的简要描述。如适用，连续的验证方法；
— Policy for
reprocessing or reworking.
— 返工或再加工的方法
6.3 Material management and
warehousing物料管理和仓储
9 11
—
Arrangements for the handling of starting
materials, packaging materials, bulk and f inished
products including sampling, quarantine,
release and storage;
—
起始物料、包装材料、原料药和成品的处置管理，包括取样、待验、放行和储存。
—
Arrangements for the handling of rejected
materials and products.
— 不合格物料和产品处置管理
7 QUALITY CONTROL (QC) 质量控制
— Description of the Quality Control
activities carried out on the site in terms of
physical, chemical,
and microbiological and
biological testing.
—
关于物理、化学、微生物和生物检测项目，在工厂执行的质量控制活动的描述。
8
DISTRIBUTION, COMPLAINTS, PRODUCT DEFECTS AND
RECALLS分销，投诉，偏差和召回
8.1
Distribution (to the part under the responsibility
of the manufacturer) 分销（生产商所承担的责任）
—
Types (wholesale licence holders, manufacturing
licence holders, etc) and locations (EUEEA,
USA, etc.) of the companies to which the
products are shipped from the site;
—
工厂生产的产品发往的公司类型（零售证持有者、生产许可证持有者等）和位置（欧盟、美国等），
—
Description of the system used to verify that each
customer recipient is legally entitled to
receive medicinal products from the
manufacturer;
—
描述：确认每个客户接收人是合法的从生产商处接收医药产品
— Brief
description of the system to ensure appropriate
environmental conditions during transit, e.g.
temperature monitoring control;
—
简要描述运输过程中环境条件的监测控制，例如温度监测控制；
—
Arrangements for product distribution and methods
by which product traceability is maintained;
— 产品分销和产品追踪性的管理方法
— Measures
taken to prevent manufacturers’ products to fall
in the illegal supply chain.
—
防止生产商的产品进入非法供应链的措施
8.2
Complaints, product defects and recalls投诉、偏差和召回
— Brief description of the system for
handling complains, product defects and recalls.
— 处置投诉、偏差和召回的体系的简要描述
9
SELF INSPECTIONS自检
— Short description
of the self inspection system with focus on
criteria used for selection of the
areas to be
covered during planned inspections, practical
arrangements and followup activities.
10 11
—
自检体系的简要描述，重点描述在计划检查、实际安排和跟踪活动中检查区域选择的标准。
Appendix 1 Copy of valid manufacturing
authorisation
附件1. 有效生产许可证的复件
Appendix 2
List of dosage forms manufactured including the
INNnames or common name (as
available) of
active pharmaceutical ingredients (API) used
附件2.
生产的产品清单（制剂和或原料药），包括用于制剂的原料药国际通用名称或公司名称（如果有）
Appendix 3 Copy of valid GMP Certificate
附件3. 有效的GMP证书复件
Appendix 4 List of
contract manufacturers and laboratories including
the addresses and contact
information, and
flowcharts of the supplychains for these
outsourced activities
附件4合同生产商和实验室的名单，包括地址和联系信息，以及这些外部活动的供应链示意图
Appendix 5 Organisational charts
附件5组织机构图
Appendix 6 Lay outs of production areas
including material and personnel flows, general
flow charts
of manufacturing processes of each
product type (dosage form)
附件6.
生产区域示意图，包括物料和人员流向、每种产品类型的工艺流程图
Appendix 7
Schematic drawings of water systems
附件7水系统示意图
Appendix 8 List of major production and
laboratory equipment
附件8 主要生产和实验室设备清单
[1] A D-U-N-S reference is required for Site
Master Files submitted to EUEEA authorities for
manufacturing sites located outside of the
EUEEA.
邓白氏号在欧盟欧洲经济区以外生产场所向EUEEA当局提交工厂主文件时需要。
11 11