制药工程技术网

The ECA Academy is receiving a lot of questions on SOPs (Standard Operating Procedures)needed in a GMP environment. The most interesting is the one on which SOPs are required by law. Here is an Overview:

ECA学会收到大量GMP环境下所需SOP（标准操作规程）的问题，其中最有意思的问题是法规要求哪些SOP。以下是一个概览：

U.S. Food and Drug Administration (FDA): 美国FDA

A three year old Notice focusing on specific record keeping requirements in the Federal Register also gives a very good summary of SOPs required by 21 CFR Part 211:
三年前，在联邦注册上有一个关于记录管理要求方面的通知对于21CFR第211部分要求有哪些SOP做了一个很好的总结：

"Written procedures (standard operating procedures - SOPs),are required for many Part 211 records. The current SOP requirements were initially provided in a final rule published in the Federal Register of September 29, 1978 (43 FR 45014), and are now an integral and familiar part of the drug manufacturing process."

“许多第211部分的记录要求具有书面程序（标准操作规程SOP）。现行SOP要求最初是在联邦注册1978年9月29日（43FR45014）中公布的，现在已经成为药品生产过程中必要的类似部分”。

• The 25 SOPs provisions under Part 211 include:

• 第211部分中25个SOP条款包括

• Section211.22(d)-Responsibilities and procedures of the quality control unit;

• 第211.22（d）- 质量控制部门的职责和程序

• Section211.56(b)-Sanitation procedures

• 第211.56(b) - 消毒程序

• Section211.56(c)-Use of suitable rodenticides, insecticides, fungicides, sanitizing agents;

• 第211.56(c)---使用适当杀虫剂、灭鼠药、杀真菌剂、消毒剂

• Section211.67(b)-Cleaning and maintenance of equipment;

• 第211.67(b)----设备的清洁和维护

• Section211.68(a)-Proper performance of automatic, mechanical, and electronic equipment;

• 第211.68(a)----自动化、机械化和电子设备具备适当性能

• Section211.80(a)-Receipt, identification, storage, handling, sampling, testing, and approval or rejection of components and drug product containers or closures;

• 第211.80(a)---部件和药品容器密闭材料的接收、鉴别、存贮、处置、取样、测试和批准或拒收

• Section211.94(d)-Standards or specifications, methods of testing, and methods of cleaning, sterilizing, and processing to remove pyrogenic properties for drug product containers and closures;

• 第211.80(d)---药品容器密闭材料的规格或质量标准、检验方法、清洁方法、灭菌方法及清除热原

• Section211.100(a)-Production and process control;

• 第211.100(a)---生产和工艺控制

• Section211.110(a)-Sampling and testing of in-process materials and drug products;

• 第211.110(a)---中控和成品取样和检测

• Section211.113(a)-Prevention of objectionable microorganisms in drug products not required to be sterile;

• 第211.113(a)----非无菌药品中防止有害微生物

• Section211.113(b)-Prevention of microbiological contamination of drug product spurporting to be sterile, including validation of any sterilization process;

• 第211.113(b)---无菌药品中防止微生物污染，包括所有无菌工艺的验证

• Section211.115(a)-System for reprocessing batches that do not conform to standards or specifications, to insure that reprocessed batches conform with all established standards, specifications, and characteristics;

• 第211.115(a)----不符合质量标准的批准的返工管理，以保证返工后批次符合所有既定标准、质量规格和特性

• Section211.122(a)-Receipt, identification, storage, handling, sampling, examination and/or testing of labeling and packaging materials;

• 第211.122(a)---标签和包装材料的接收、鉴别、存贮、处置、取样、检查和/或检测

• Section211.125(f)-Control procedures for the issuance of labeling;

• 第211.125(f)---标签发放控制程序

• Section211.130-Packaging and label operations, prevention of mixup and cross contamination, identification and handling of filed drug product containers that are set aside and held in unlabeled condition, and identification of the drug product with a lot or control number that permits determination of the history of the manufacture and control of the batch;

• 第211.130---包装和贴标操作、防止混淆和交叉污染、鉴别和处置已印制但弃置且无标识的药品包材、采用批号或控制号鉴别药品，使其可追溯生产和批控制历史

• Section211.142-Warehousing;

• 第211.142----仓库管理

• Section211.150-Distribution of drug products;

• 第211.150----药品分销

• Section211.160-Laboratory controls;

• 第211.160----实验室控制

• Section211.165(c)-Testing and release for distribution;

• 第211.165（c）-----检测和放行用于销售

• Section211.166(a)-Stability testing;

• 第211.166（a）---稳定性测试

• Section211.167-Special testing requirements;

• 第211.167----特殊检测要求

• Section211.180(f)-Notification of responsible officials of investigations, recalls,reports of inspectional observations, and any regulatory actions relating to good manufacturing practice;

• 第211.180(f)----将调查、召回、检查缺陷和所有与GMP相关的法规行动通知相关官方

• Section211.198(a)-Written and oral complaint procedures, including quality involving specifications failures, and serious and unexpected adverse drug experiences;

• 第211.198(a)----书面和口头投诉处理程序，包括与不符合质量标准的质量问题，和严重的非预期副反应

• Section211.204-Holding, testing, and reprocessing of returned drug products; and

• 第211.204----退回药品的保存、检测和返工

• Section211.208-Drug product salvaging.

• 第211.208----药品回收利用

European Union: 欧盟

SOPs required by EU-GMP are mainly defined in the EU Guidelines to Good Manufacturing Practice of Eudralex Vol. 4 (EU-GMP Guide). There is no comprehensive list provided but Chapter 4 of Part 1 (Documentation) of theGuide gives some examples:

EU-GMP所要求的SOP主要是在EUDRALE 卷4（EU-GMP指南）中定义的。指南中并没有给出一份清单，但在第1部分（文件记录）中给出了一些例子：

"There should be written policies, procedures, protocols,reports and the associated records of actions taken or conclusions reached,where appropriate, for the following examples:

“以下例子中，在适当时，对所采取的措施和获得的结论应有书面方针、程序、方案、报告及相应的记录”

• Validation and qualification of processes, equipment and systems;

• 工艺、设备和公用系统的验证和确认

• Equipment assembly and calibration;

• 设备安装和校正

• Technology transfer;

• 技术转移

• Maintenance, cleaning and sanitation;

• 维护、清洁和消毒

• Personnel matters including signature lists, training in GMP and technical matters, clothing and hygiene and verification of the effectiveness of training.

• 人员，包括签名清单、GMP和技术方面的培训、着装和卫生及培训有效性评估

• Environmental monitoring;

• 环境监控

• Pest control;

• 虫鼠控制

• Complaints;

• 客诉

• Recalls;

• 召回

• Returns;

• 退货

• Change control;

• 变更控制

• Investigations into deviations and non-conformances;

• 偏差和不符合事件调查

• Internal quality/GMP compliance audits;

• 内部质量/GMP符合性审计

• Summaries of records where appropriate (e.g. product quality review);

• 适当时，记录总结（例如，产品年度回顾）

• Supplier audits."

• 供应商审计

• Chapter 4.30 requires that operating procedures "should be available for major items of manufacturing and test equipment."

• 第4.30章要求“对主要的生产和检测设备应有”操作程序。

World Health Organisation (WHO) 世界卫生组织

A very comprehensive list can be found in the WHO guide to good manufacturing practice (GMP) requirements, Part 1: Standard operating procedures and master formulae. Although written as part ofthe Global Programme for Vaccines and Immunization, Vaccine Supply and Quality,this overview gives valuable guidance also for other pharmaceutical companies.

在WHO的GMP指南要求第1部分：标准操作程序和主配方中，可以发现一份涉及面很广的清单

More than 75 SOPs are listed from the following areas in Appendix 1 ("List of Document Requirements"):

在附录1（文件要求清单）中针对以下方面列出了75个SOP：

• Raw Materials

• 原料

• Biological Starting Materials

• 生物起始物料

• Facility

• 设施

• Equipment (Production and QC)

• 设备（生产和QC）

• Production

• 生产

• Labelling and Packaging

• 贴标和包装

• Quality Control

• 质量控制

• Quality Assurance

• 质量保证

The examples from FDA, EU and WHO provided above are not a finite list. Some topics might be split in a number of SOPs forthe sake of practicality. Some other company or quality system specific processes might be defined in SOPs as well.

上述FDA、欧盟和WHO清单举例并无意对SOP进行限制，有些主题可能会被拆分为一系列的SOP，以使其具有可操作性。另有一些公司或质量体系相关的流程可能也会在SOP中进行规定。