老规矩，上图：
一、基本概念标准操作规程（Standard Operating procedures），为确保实施的一致性从而达到特定目的而制定的详细的书面操作说明。生产中，标准操作规程是指经批准用来指导设备操作、维护与清洁、验证、环境控制、取样和检验等药品生产活动的通用性文件。参考中国GMP 第十四章 附则在非临床研究、临床研究、药品经营等活动中，同样采用标准操作规程。There shall be written proceduresfor production and process control designed to assure that the drug productshave the identity, strength, quality, and purity they purport or arerepresented to possess. Such procedures shall include all requirements in thissubpart. These written procedures, including any changes, shall be drafted,reviewed, and approved by the appropriate organizational units and reviewed andapproved by the quality control unit. See FDA CFR 211Written procedures
二、相关法规指南
A.【中国GMP 第八章 文件管理】
第一百八十一条 操作规程的内容应当包括：题目、编号、版本号、颁发部门、生效日期、分发部门以及制定人、审核人、批准人的签名并注明日期，标题、正文及变更历史。
第一百八十三条 下述活动也应当有相应的操作规程，其过程和结果应当有记录：
（一）确认和验证；
（二）设备的装配和校准；
（三）厂房和设备的维护、清洁和消毒；
（四）培训、更衣及卫生等与人员相关的事宜；
（五）环境监测；
（六）虫害控制；
（七）变更控制；
（八）偏差处理；
（九）投诉；
（十）药品召回；
（十一）退货。
B.【NMPA 药物临床试验质量管理规范】
第13、15、32、33、36、49、50、79条。
C.【药物非临床研究质量管理规范】
第22~25条。
D.【药物临床试验伦理审查工作指导原则】
第十二条 伦理委员会应制定标准操作规程和制度，以确保伦理审查工作的规范性与一致性。 内容至少包括以下几个方面：
（一）标准操作规程与伦理审查申请指南的制定；
（二）伦理委员会的组织与管理：伦理委员会的组建，伦理审查的保密措施，利益冲突的管理，委员与工作人员的培训，独立顾问的选聘；
（三）伦理审查的方式：会议审查与紧急会议审查，快速审查；
（四）伦理审查的流程：审查申请的受理与处理，初始审查，跟踪审查 , 审查决定的传达；
（五）会议管理：会议准备，会议程序 , 会议记录；
（六）文件与档案管理：建档，保存 , 查阅与复印。
E.【药品GMP指南】标准操作规程是企业活动和决策的基础 , 确保每个人正确、及时的执行质量相关的活动和流程。 标准操作规程根据企业的规定应该有相应的模板和编写要求。 参考药品GMP指南 质量管理体系 6.3 文件种类对所有的生产和检验设备，建立设备操作、清洁及其它相关的标准操作程序。包括：设备、设施标准操作的相关内容建议；设备、设施标准清洁的相关内容建议；对设备附带的自动化系统和计算机系统操作和管理的相关内容建议。 参考药品GMP指南 厂房设备 2.5.2 标准操作程序更衣的标准操作程序：人员进入无菌生产洁净区先要通过气锁间 , 无菌的衣服、鞋套、手套、帽子、口罩以及眼罩对所有要进入无菌生产洁净区的人来说是必需的 , 企业应根据具体情况制定合理的更衣程序 , 建立完备的更衣SOP , 并遵照执行。药品GMP指南 无菌制剂 4.3 无菌生产洁净区着装和更衣确认必须有关于制药用水和纯蒸汽系统的SOP（包括使用、维护、清洗消毒等）。在OQ阶段不必是经批准的最终版SOP，但是SOP的草案应该是有的 , 因为OQ的目的之一是确认SOP草案的可接受或者需改进的内容。通常，SOP的最终完成和批准在PQ的第一阶段。验收标准是在OQ和水系统的正常操作中，适当的SOP草案已经到位并且已经实施了培训。SOP在PQ期间最后定稿。参考药品GMP指南 水系统 4.2.8 试运行和验证为确保除菌滤芯测试、灭菌SOP的可操作性，便于员工理解和操作 , 在SOP中除了采用厂家推荐的示意图标明所有相关的阀门编号外，还可采用结合照片的形式 , 使得员工培训和操作参照时更直观、更方便。 如类似下图的标注方式。参考药品GMP指南 原料药 17.4 产品灭菌管理控制和标准操作规程（SOPs）定义了控制程序方面各层次 , 旨在确保工作人员了解危险是什么 , 这些危险在哪里 , 和管理的目的所在。SOP可能描述如下：工程控制的合理运用、进入并操作设备时使用个人防护设备。SOP的相关培训是管理控制的主要活动 , 以保证工作人员了解风险和如何安全工作。 应重点关注行为管理、空气监测和医学监控。参考药品GMP指南 口服固体制剂 9.2 健康（HEALTH）
F.【药物Ⅰ期临床试验管理指导原则（试行）】
第十九条 管理制度和SOP的制订、审核和批准、实施以及修订与废止。
（一）制定。应制定管理制度和SOP，保证所有管理制度与SOP有统一格式和编码，内容符合相关的法律法规，管理制度与SOP均应标明现行版本号码及生效日期，并及时更新。
（二）审核和批准。 管理制度与SOP起草后，应对SOP草稿进行审阅和讨论，保证文件简练、易懂、完整和清晰，具有逻辑性和可行性，与已生效的其他文件具有兼容性。审核后确定的文件，应规定生效日期，并由研究室负责人签署批准。
（三）实施。 管理制度与SOP生效后应立即执行，所有工作人员必须接受管理制度与相关SOP的培训，更新管理制度与SOP时，需进行针对性的培训。
（四）修订与废止。 根据需要对管理制度和SOP进行定期和不定期修订与废止。将相关信息记录在案，并及时更新版本和版本序列号。 需撤销的管理制度与SOP需归档保管并有作废标记。 保证现行所用的管理制度与SOP为最新版本，并保留最新版本的管理制度与SOP清单。
G.【FDA CFR Sec.211.67 Equipment cleaning and maintenance.】
211.67(b) Written procedures shall be established and followed forcleaning and maintenance of equipment, including utensils, used in themanufacture, processing, packing, or holding of a drug product. Theseprocedures shall include, but are not necessarily limited to, the following:......
H.【FDA CFR 211 Sec.211.192 Production record review.】
All drug product production and control records, including those forpackaging and labeling, shall be reviewed and approved by the quality controlunit to determine compliance with all established, approved written proceduresbefore a batch is released or distributed. Any unexplained discrepancy(including a percentage of theoretical yield exceeding the maximum or minimumpercentages established in master production and control records) or thefailure of a batch or any of its components to meet any of its specificationsshall be thoroughly investigated, whether or not the batch has already beendistributed. The investigation shall extend to other batches of the same drugproduct and other drug products that may have been associated with the specificfailure or discrepancy. A written record of the investigation shall be made andshall include the conclusions and followup.
I.【FDA Guidance CMCPostapproval Manufacturing Changes To Be Documented in Annual Reports】
To submit a notification of change in an annual report in accordance with21 CFR 314.81(b)(2)(iv)(b) and 314.70(d)(3), the applicant must include a fulldescription of the CMC changes that were made that the applicant believes didnot require a supplemental application under sections 314.70(b) and (c). Thisdescription should include a (1) list of each change by the date the change wasmade; (2) relevant summary of data from studies and tests performed to evaluatethe effects of the change, including cross references to validation protocolsand standard operating procedures and policies; and (3) list of all drugproducts involved. See FDA Guidance CMC Postapproval Manufacturing Changes ToBe Documented in Annual Reports.
J.【FDA Guidance forIndustry Bioanalytical Method Validation】
The analytical laboratory should have a written set of standard operatingprocedures (SOPs) to ensure a complete system of quality control and assurance.The SOPs should cover all aspects of analysis from the time the sample iscollected and reaches the laboratory until the results of the analysis arereported. The SOPs also should include record keeping, security and chain ofsample custody (accountability systems that ensure integrity of test articles),sample preparation, and analytical tools such as methods, reagents, equipment,instrumentation, and procedures for quality control and verification ofresults.
K.【FDA FR Improvingthe Quality of ANDA Submissions】
Bioequivalence: Inaccurate and/or incomplete information contained inelectronic tables; submission of pharmacokinetic repeats; inaccurate and/orincomplete biowaiver requests (e.g., inappropriate method of solubilitydetermination, lack of dissolution data for all strengths, missing standardoperating procedures for analytical methods.
L.【EU GMP Generationand Control of Documentation】
4.4 Documents containing instructions should be laid out in an orderlyfashion and be easy to check. The style and language of documents should fitwith their intended use. Standard Operating procedures, Work Instructions andMethods should be written in an imperative mandatory style.
M. 【EU GMP Chapter 4:Documentation】
Other
4.29 There should be written policies, procedures , protocols, reportsand the associated records of actions taken or conclusions reached, where appropriate,for the following examples:
Validation and qualification of processes, equipment and systems;
Equipment assembly and calibration;
Technology transfer;
Maintenance, cleaning and sanitation;
Personnel matters including signature lists, training in GMP andtechnical matters, clothing and hygiene and verification of the effectivenessof training.
Environmental monitoring;
Pest control;
Complaints;
Recalls;
Returns;
Change control;
Investigations into deviations and non-conformances;
Internal quality/GMP compliance audits;
Summaries of records where appropriate (e.g. product quality review);
Supplier audits.
N.【WHO GMP15.Documentation】
Standard operating procedures (SOPs) and records
15.31 Standard operating procedures and associated records of actionstaken or, where appropriate, conclusions reached should be available for:
(a) equipment assembly and validation;
(b) analytical apparatus and calibration;
(c) maintenance, cleaning and sanitization;
(d) personnel matters including qualification, training, clothing andhygiene;
(e) environmental monitoring;
(f) pest control;
(g) complaints;
(h) recalls;
(i) returns.
