欧洲药典质量标准的起草技术指南,英文版

EU GMP ANNEX 1 MANUFACTURE OF STERILE MEDICINAL PRODUCTS （中英文对照）(a) These are average values. （一）这些都是平均值。

(b) Individual settle plates may be exposed for less than 4 hours. （二）单个沉降皿放置的时间可以少于4小时。

20. Appropriate alert and action limits should be set for the results of particulate and microbiological monitoring. If these limits are exceeded operating procedures should prescribe corrective action。

对尘埃粒子和微生物的监控结果，要设置适当的警戒限度和行动限度。

当超出这些限度时，操作规程应说明需要采取的措施。

Isolator technology 隔离技术21. The utilisation of isolator technology to minimize human interventions in processing areas may result in a significant decrease in the risk of microbiological contamination of aseptically manufactured products from the environment. There are many possible designs of isolators and transfer devices. The isolator and the background environment should be designed so that the required air quality for the respective zones can be realised. Isolators are constructed of various materials more or less prone to puncture and leakage. Transfer devices may vary from a single door to double door designs to fully sealed systems incorporating sterilization mechanisms. 在生产区采用人员方面的隔离技术，在无菌产品的生产中，会显著降低周围环境微生物污染的风险。

欧洲药品管理局《GUIDELINE ON QUALITY OF COMBINATION HERBAL（复方草药质量指南）》内容解析COMMITTEE ON HERBAL MEDICINAL PRODUCTS(HMPC)草药产品委员会This guideline applies to herbal medicinal products containingcombinations of herbal substances本指导适用于含有草药和草药提取物的草药制品本指南引用的其它指南附件(1), “Guideline on specifications: test procedures and acceptance criteria for herbal substances, herbal preparations and herbal medicinal products/traditional herbal medicinal products”“草药材、草药制剂和草药产品/传统草药产品的分析程序和验收标准的指导原则”(2), Annex 7 “Manufacture of herbal medicinal products” of Good Manufacturing Practices (GMP) for medicinal products, Volume 4, Rules governing medicinal products in the European Union附件7：草药产品良好生产规范(GMP),第4卷,欧盟医药产品管理规定MAIN GUIDELINE TEXTHerbal medicinal products contain herbal substances/preparations each consisting of a large number of chemical constituents of which only a few may be characterized.草药产品中含有的草药材/草药提取物包含大量的化学组成，但是其中只有少数可明确其成分及结构。

第一部分Appendix XVI C. Efficacy of Antimicrobial Preservation(Ph. Eur. general text 5.1.3)如果药物制剂本身没有足够的抗菌活性，那么就应该加抗菌防腐剂。

在药品正常的储存和使用过程中，液体制剂特别是多剂量液体制剂，尤其需要添加防腐剂。

这样不仅可以阻止细菌繁殖、限制微生物污染；还可以防止细菌污染给患者身体带来的危害和对药品本身的污染。

抗菌防腐剂在GMP 中不能被替代。

抗菌防腐剂的效果根据药物制剂的组成成分的不同、防腐剂加入的形式的不同、或使用容器或封口的不同而增强或减弱。

在最终的包装容器内的制剂，我们需要验证它在整个有效期内的抗菌活性。

这样才能保证在贮存过程中抗菌活性不会减弱。

样品从最终容器中取出时就需要立即进行验证了。

在药物制剂发展期间(注：研发Research & Development ， D 就是发展期间，将活性分子变成处方制剂的过程) ，应该需要证明药物制剂本身的抗菌活性。

如果没有就需要添加合适的防腐剂、或防腐剂能够保护制剂免于遭受微生物污染的不良效果和在贮存和使用过程中细菌的繁殖。

抗菌活性应该通过以下一系列测试来证实。

这些测试并不用于常规的对照目的。

测试抗菌防腐剂的有效性测试包括三方面内容：一、不论最后的包装容器是什么，都需要用规定的接种物，也就是合适的微生物对制剂进行攻击。

二、在规定的温度下贮存已接种制剂。

三、在一段时间间隔内抑制容器内的样本生长，然后计数这样被除去的样本中的菌数。

在测试条件下，如果在规定时间和温度下，接种后制剂中的菌落数有重大的下降或没有增加，那么药物制剂中防腐剂的作用就是可以接受的。

接受标准 (即在规定时间内减少微生物的数量) 随着制剂类型的不同而不同。

因为制剂类型的不同所达到的保护的程度也不同。

(见表 5.1.3-1/2/3 )。

微生物检测(见附录二)绿脓假单胞杆菌金黄色酿脓葡萄球菌白色念珠菌黑曲霉ATCC 9027; NCIMB 8626; CIP 82.118.ATCC 6538; NCTC 10788; NCIMB 9518; CIP 4.83. ATCC 10231; NCPF 3179; IP 48.72.ATCC 16404; IMI 149007; IP 1431.83.使用单菌株攻击而且设计微生物可以在合适的地方补充其他菌株或品种，这样就能代表可能的制剂污染。

EP检测方法：Related substances. Liquid chromatography (2.2.29). Prepare the solutions immediately before use.Test solution. Dissolve 0.200 g of the substance to be examined in 2.5 mL of methanol R containing 4.6 g/L of a 400 g/L solution of tetrabutylammonium hydroxide R and dilute to 10.0 mL with a mixture of equal volumes of a 17.9 g/L solution of disodium hydrogen phosphate R and of a 7.8 g/L solution of sodium dihydrogen phosphate R.Reference solution (a). Dilute 1.0 mL of the test solution to 50.0 mL with the mobile phase. Dilute 5.0 mL of this solution to 100.0 mL with the mobile phase.Reference solution (b). Dilute 1.0 mL of reference solution (a) to 10.0 mL with the mobile phase.Reference solution (c). Dissolve 5.0 mg of 4-aminophenol R,5 mg of paracetamol CRS and 5.0 mg of chloroacetanilide R in methanol R and dilute to 20.0 mL with the same solvent. Dilute 1.0 mL to 250.0 mL with the mobile phase.Reference solution (d). Dissolve 20.0 mg of 4-nitrophenol R in methanol R and dilute to 50.0 mL with the same solvent.Dilute 1.0 mL to 20.0 mL with the mobile phase.有关物质。

欧洲药典-凡例1.1. GENERAL STATEMENTSThe General Notices apply to all monographs and other texts of the European Pharmacopoeia.总论的内容适用于各论和欧洲药典中的其它章节。

The official texts of the European Pharmacopoeia are published in English and French. Translations in other languages may be prepared by the signatory States of the European Pharmacopoeia Convention. In case of doubt or dispute, the English and French versions are alone authoritative.欧洲药典以英语和法语形式发行，欧洲药典委员会的签署国可将药典内容译成其它语言，但若发生争议，应以英语和法语版为权威。

In the texts of the European Pharmacopoeia, the word "Pharmacopoeia" without qualification means the European Pharmacopoeia. The official abbreviation Ph. Eur. may be used to indicate the European Pharmacopoeia.在欧洲药典中，如无特殊规定，“药典”是指欧洲药典，缩写Ph. Eur.也指欧洲药典。

The use of the title or the subtitle of a monograph implies that the article complies with the requirements of the relevant monograph. Such references to monographs in the texts of the Pharmacopoeia are shown using the monograph title and reference number in italics.文章中如果引用了各论中的标题和副标题意味着文章内容符合相关各论的要求。

GUIDE TO GOOD MANUFACTURINGPRACTICE FOR MEDICINAL PRODUCTS药品GMP检查指南.PIC/S July 2004Reproduction prohibited for commercial purposes.Reproduction for internal use is authorised,provided that the source is acknowledged.Editor: PIC/S SecretariatP.O. Box 5695CH-1211 Geneva 11e-mail: daniel.brunner@web site: :// 1 July 2004 PE 009-2TABLE OF CONTENT目录INTRODUCTION介绍 (1)CHAPTER 1 QUALITY MANAGEMENT 质量管理 (4)PRINCIPLE 原则 (4)QUALITY ASSURANCE 质量保证 (4)GOOD MANUFACTURING PRACTICE FOR MEDICINAL PRODUCTS (GMP) 药品GMP (6)QUALITY CONTROL 质量控制 (7)CHAPTER 2 PERSONNEL 人员 (10)PRINCIPLE 原则 (10)GENERAL 通则 (10)KEY PERSONNEL 关键人员 (10)TRAINING 培训 (13)PERSONAL HYGIENE 个人卫生 (14)CHAPTER 3 PREMISES AND EQUIPMENT 厂房和设备 (16)PRINCIPLE 原则 (16)PREMISES General总则 (16)Production Area 生产区域 (17)Storage Areas 储存区域 (19)Quality Control Areas 质量控制区域 (20)Ancillary Areas 辅助区域 (20)EQUIPMENT 设备 (21)CHAPTER 4 DOCUMENTATION 文件 (23)PRINCIPLE 原则 (23)GENERAL 总则 (23)DOCUMENTS REQUIRED 必需的文件 (25)MANUFACTURING FORMULA AND PROCESSING INSTRUCTIONS 生产方法和加工指示 (27)PACKAGING INSTRUCTIONS 包装指示 (28)BA TCH PROCESSING RECORDS 批加工记录 (29)BA TCH PACKAGING RECORDS 批包装记录 (30)PROCEDURES AND RECORDS 程序和记录 (32)CHAPTER 5 PRODUCTION 生产 (36)PRINCIPLE 原则 (36)GENERAL 通则 (36)PREVENTION OF CROSS-CONTAMINATION IN PRODUCTION 生产过程中防止交叉污染 (38)V ALIDATION 验证 (39)STARTING MA TERIALS 起始物料 (40)PROCESSING OPERA TIONS - INTERMEDIATE AND BULK PRODUCTS 加工操作：中间体和散装产品 (42)PACKAGING MATERIALS 包装材料 (42)PACKAGING OPERATIONS 包装操作 (43)FINISHED PRODUCTS 最终成品 (45)REJECTED, RECOVERED AND RETURNED MATERIALS 拒绝的，回收的和退回的物料46CHAPTER 6 QUALITY CONTROL 质量控制 (48)PRINCIPLE 原则 (48)GENERAL 通则 (48)GOOD QUALITY CONTROL LABORATORY PRACTICE 优良质量控制实验室实践 (49)DOCUMENTATION 文件 (49)SAMPLING 取样 (50)TESTING 检测 (52)CHAPTER 7 CONTRACT MANUFACTURE AND ANAL YSIS 合同加工和分析 (55)PRINCIPLE 原则 (55)GENERAL 通则 (55)THE CONTRACT GIVER 合同提供人 (55)THE CONTRACT ACCEPTOR 合同接受人 (56)THE CONTRACT 合同 (57)CHAPTER 8 COMPLAINTS AND PRODUCT RECALL 抱怨和产品召回 (59)PRINCIPLE 原则 (59)COMPLAINTS 抱怨 (59)RECALLS 召回 (60)CHAPTER 9 SELF INSPECTION 自检 (61)PRINCIPLE 原则 (61)ANNEX 1 MANUFACTURE OF STERILE MEDICINAL PRODUCTS无菌药品的生产 (63)PRINCIPLE (63)GENERAL (63)BLOW/FILL/SEAL TECHNOLOGY (67)TERMINALL Y STERILISED PRODUCTS (67)ASEPTIC PREPARA TION (68)PERSONNEL (68)PREMISES (70)EQUIPMENT (71)SANITATION (71)PROCESSING (71)STERILISATION (73)STERILISATION BY HEA T (74)MOIST HEAT (75)DRY HEAT (75)STERILISATION BY RADIATION (75)STERILISATION WITH ETHYLENE OXIDE (76)FILTRATION OF MEDICINAL PRODUCTS WHICH CANNOT BE STERILISED IN THEIR FINAL CONTAINER (77)FINISHING OF STERILE PRODUCTS (77)QUALITY CONTROL (78)ANNEX 2 MANUFACTURE OF BIOLOGICAL MEDICINAL PRODUCTS FOR HUMAN USE人用生物药品的生产 (79)SCOPE (79)PRINCIPLE (79)PERSONNEL (80)PREMISES AND EQUIPMENT (81)ANIMAL QUARTERS AND CARE (82)DOCUMENTATION (82)PRODUCTION (83)QUALITY CONTROL (84)ANNEX 3 MANUFACTURE OF RADIOPHARMACEUTICALS 放射性药品的生产 (85)PRINCIPLE (85)PERSONNEL (85)PREMISES AND EQUIPMENT (85)PRODUCTION (86)QUALITY CONTROL (86)DISTRIBUTION AND RECALLS (86)ANNEX 4 MANUFACTURE OF VETERINARY MEDICINAL PRODUCTS OTHER THAN IMMUNOLOGICALS MANUFACTURE OF PREMIXES FOR MEDICATED FEEDING STUFFS 除为预混合加药饲料原料生产的免疫产品以外的，兽药产品的生产 (87)THE MANUFACTURE OF ECTOPARASITICIDES (88)THE MANUFACTURE OF VETERINARY MEDICINAL PRODUCTS CONTAINING PENICILLINS (88)RETENTION OF SAMPLES (point 1.4. viii and point 6.14.) (88)STERILE VETERINARY MEDICINAL PRODUCTS (88)ANNEX 5 MANUFACTURE OF IMMUNOLOGICAL VETERINARY MEDICAL PRODUCTS免疫兽药产品的生产 (89)PRINCIPLE (89)PERSONNEL (89)PREMISES (90)EQUIPMENT (93)ANIMALS AND ANIMAL HOUSES (94)DISINFECTION - WASTE DISPOSAL (94)PRODUCTION (95)STARTING MA TERIALS (95)QUALITY CONTROL (98)ANNEX 6 MANUFACTURE OF MEDICINAL GASES药用气体的生产 (99)1. PRINCIPLE (99)2. PERSONNEL (99)3. PREMISES AND EQUIPMENT (99)4. DOCUMENTA TION (100)5. PRODUCTION (101)6. QUALITY CONTROL (104)7. STORAGE AND RELEASE (105)ANNEX 7 MANUFACTURE OF HERBAL MEDICINAL PRODUCTS草药产品的生产 (108)PRINCIPLE (108)PREMISES (108)DOCUMENTATION (108)SAMPLING (109)QUALITY CONTROL (110)ANNEX 8 SAMPLING OF STARTING AND PACKAGING MA TERIALS起始物料和包装材料的取样 (111)PRINCIPLE (111)PERSONNEL (111)STARTING MA TERIALS (111)PACKAGING MATERIAL (112)ANNEX 9 MANUFACTURE OF LIQUIDS, CREAMS AND OINTMENTS流体，霜体和膏体药品的生产 (113)PRINCIPLE (113)PRODUCTION (113)ANNEX 10 MANUFACTURE OF PRESSURISED METERED DOSE AEROSOL PREPARATIONS FOR INHALATION吸入式剂量仪的气雾剂的生产 (115)PRINCIPLE (115)GENERAL (115)PREMISES AND EQUIPMENT (115)PRODUCTION AND QUALITY CONTROL (116)ANNEX 11 COMPUTERISED SYSTEMS 计算机化系统 (117)PRINCIPLE (117)PERSONNEL (117)V ALIDATION (117)ANNEX 12 USE OF IONISING RADIATION IN THE MANUFACTURE OF MEDICINAL PRODUCTS使用离子放射生产药品 (120)INTRODUCTION (120)RESPONSIBILITIES (120)DOSIMETRY (121)V ALIDATION OF THE PROCESS (121)COMMISSIONING OF THE PLANT (122)PREMISES (124)PROCESSING (124)DOCUMENTATION (126)MICROBIOLOGICAL MONITORING (126)ANNEX 13 MANUFACTURE OF INVESTIGA TIONAL MEDICINAL PRODUCTS观察期药品的生产 (127)PRINCIPLE (127)GLOSSARY (128)QUALITY MANAGEMENT (130)PERSONNEL (130)PREMISES AND EQUIPMENT (130)DOCUMENT A TION (131)PRODUCTION (132)QUALITY CONTROL (136)RELEASE OF BATCHES (137)SHIPPING (139)COMPLAINTS (139)RECALLS AND RETURNS (139)DESTRUCTION (140)ANNEX 14 MANUFACTURE OF PRODUCTS DERIVED FROM HUMAN BLOOD OR HUMAN PLASMA生产自人类血液或人体组织分离的产品 (143)PRINCIPLE (143)GLOSSARY (144)QUALITY MANAGEMENT (144)PREMISES AND EQUIPMENT (145)BLOOD AND PLASMA COLLECTION (145)TRACEABILITY AND POST COLLECTION MEASURES (146)PRODUCTION AND QUALITY CONTROL (147)RETENTION OF SAMPLES (148)DISPOSAL OF REJECTED BLOOD, PLASMA OR INTERMEDIATES (148)ANNEX 15 QUALIFICATION AND V ALIDATION 确认和验证 (149)PRINCIPLE (149)PLANNING FOR V ALIDATION (149)DOCUMENTATION (150)QUALIFICATION (150)PROCESS V ALIDATION (151)CLEANING VALIDATION (153)CHANGE CONTROL (154)REV ALIDATION (154)GLOSSARY (154)[ANNEX 16] [QUALIFIED PERSON AND BA TCH RELEASE]*经授权的人员和批放行 (157)ANNEX 17 PARAMETRIC RELEASE参数放行 (158)1. PRINCIPLE (158)2. PARAMETRIC RELEASE (158)3. PARAMETRIC RELEASE FOR STERILE PRODUCTS (158)4. GLOSSARY (160)[ANNEX 18] [GMP GUIDE FOR ACTIVE PHARMACEUTICAL INGREDIENTS] 17原料药GMP 指南 (161)GLOSSARY术语表 (162)GUIDE TO GOOD MANUFACTURING PRACTICE FOR MEDICINAL PRODUCTS药品GMP指南INTRODUCTION介绍为进一步消除药品贸易壁垒，促进许可证的一致性，以及确保整个欧洲在研发，生产和控制药品中保持高标准的质量保证，根据药品检查协会（PIC）同意，药品检查使用一致的GMP原则，和药品检查合作计划表中的欧洲药品GMP及其附录。

Annex 15: Qualification and Validation
附录15:确认和验证
Legal basis for publishing the detailed guidelines:Article 47 of Directive 2001/83/EC on the Community code relating to medicinal products for human use and Article 51 of Directive 2001/82/EC on the Community code relating to veterinary medicinal products. This document provides guidance for the interpretation of the principles and guidelines of good manufacturing practice (GMP) for medicinal products as laid down in Directive 2003/94/EC for medicinal products for human use and Directive 91/412/EEC for veterinary use.
Reasons for changes:Since Annex 15 was published in 2001 the manufacturing and regulatory environment has changed significantly and an update is required to this Annex to reflect this changed environment. This revision to Annex 15 takes into account changes to other sections of the EudraLex, Volume 4, Part I, relationship to Part II, Annex 11, ICH Q8, Q9, Q10 and Q11, QWP guidance on process validation, and changes in manufacturing technology.

欧盟《制药用水质量指南》2020版（中英文对照）！Guidelineon the quality of water for pharmaceutical use制药用水质量指南This guideline replaces the Note for guidanceon quality of water for pharmaceutical use (CPMP/QWP/158/01 EMEA/CVMP/115/01)and CPMP Position Statement on the Quality of Water used in the production ofVaccines for parenteral use (EMEA/CPMP/BWP/1571/02 Rev.1).本指南取代“制药用水质量指南说明”（CPMP/QWP/158/01 EMEA/CVMP/115/01）和CPMP 《注射疫苗生产用水质量立场声明》（EMEA/CPMP/BWP/1571/02 rev.1）。

Executive summary 执行摘要 This guideline replaces the Note for Guidanceon quality of water for pharmaceutical use (CPMP/QWP/158/01, EMEA/CVMP/115/01)originally adopted inMay 2002, and the CPMP Position Statement on the Qualityof Water used in the production of Vaccines for parenteral use(EMEA/CPMP/BWP/1571/02 rev.1).本指南取代 2002 年 5 月生效的《制药用水质量指南说明》（CPMP/QWP/158/01, EMEA/CVMP/115/01），和CPMP《注射疫苗生产用水质量立场声明》（EMEA/CPMP/BWP/1571/02 rev.1）。

EudraLexThe Rules Governing Medicinal Products in the European UnionVolume 4EU Guidelines toGood Manufacturing PracticeMedicinal Products for Human and Veterinary UsePart IChapter 1 Quality ManagementPrincipleThe holder of a Manufacturing Authorisation must manufacture medicinal products so as to ensure that they are fit for their intended use, comply with the requirements of the Marketing Authorisation and do not place patients at risk due to inadequate safety, quality or efficacy. The attainment of this quality objective is the responsibility of senior management and requires the participation and commitment by staff in many different departments and at all levels within the company, by the company‟s suppliers and by the distributors. To achiev e the quality objective reliably there must be a comprehensively designed and correctly implemented system of Quality Assurance incorporating Good Manufacturing Practice, Quality Control and Quality Risk Management. It should be fully documented and its effectiveness monitored. All parts of the Quality Assurance system should be adequately resourced with competent personnel, and suitable and sufficient premises, equipment and facilities. There are additional legal responsibilities for the holder of the Manufacturing Authorisation and for the Qualified Person(s).The basic concepts of Quality Assurance, Good Manufacturing Practice, Quality Control and Quality Risk Management are inter-related. They are described here in order to emphasise their relationships and their fundamental importance to the production and control of medicinal products.Quality Assurance1.1 Quality Assurance is a wide-ranging concept, which covers all matters, which individually or collectively influence the quality of a product. It is the sum total of the organised arrangements made with the objective of ensuring that medicinal products are of the quality required for their intended use. Quality Assurance therefore incorporates Good Manufacturing Practice plus other factors outside the scope of this Guide.The system of Quality Assurance appropriate for the manufacture of medicinal products should ensure that:(i) medicinal products are designed and developed in a way that takes account of the requirements of Good Manufacturing Practice;(ii) production and control operations are clearly specified and Good Manufacturing Practice adopted;(iii) managerial responsibilities are clearly specified;(iv) arrangements are made for the manufacture, supply and use of the correct starting and packaging materials;(v) all necessary controls on intermediate products, and any other in-process controls and validations are carried out;(vi) the finished product is correctly processed and checked, according to the defined procedures; (vii) medicinal products are not sold or supplied before a Qualified Person has certified that each production batch has been produced and controlled in accordance with the requirements of the Marketing Authorisation and any other regulations relevant to the production, control and release of medicinal products;(viii) satisfactory arrangements exist to ensure, as far as possible, that the medicinal products are stored, distributed and subsequently handled so that quality is maintained throughout their shelf life;(ix) there is a procedure for Self-Inspection and/or quality audit, which regularly appraises the effectiveness and applicability of the Quality Assurance system.Good Manufacturing Practice for Medicinal Products (GMP)1.2 Good Manufacturing Practice is that part of Quality Assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the Marketing Authorisation or product specification.Good Manufacturing Practice is concerned with both production and quality control. The basic requirements of GMP are that:(i) all manufacturing processes are clearly defined, systematically reviewed in the light of experience and shown to be capable of consistently manufacturing medicinal products of the required quality and complying with their specifications;(ii) critical steps of manufacturing processes and significant changes to the process are validated; (iii) all necessary facilities for GMP are provided including:• a ppropriately qualified and trained personnel;• adequate premises and space;• suitable equipment and services;• correct materials, containers and labels;• approved procedures and instructions;• suitable storage and transport;(iv) instructions and procedures are written in an instructional form in clear and unambiguous language, specifically applicable to the facilities provided;(v) operators are trained to carry out procedures correctly;(vi) records are made, manually and/or by recording instruments, during manufacture which demonstrate that all the steps required by the defined procedures and instructions were in fact taken and that the quantity and quality of the product was as expected. Any significant deviations are fully recorded and investigated;(vii) records of manufacture including distribution which enable the complete history of a batch to be traced, are retained in a comprehensible and accessible form;(viii) the distribution (wholesaling) of the products minimises any risk to their quality;(ix) a system is available to recall any batch of product, from sale or supply;(x) complaints about marketed products are examined, the causes of quality defects investigated and appropriate measures taken in respect of the defective products and to prevent reoccurrence. Quality Control1.3 Quality Control is that part of Good Manufacturing Practice which is concerned with sampling, specifications and testing, and with the organisation, documentation and release procedures which ensure that the necessary and relevant tests are actually carried out and that materials are not released for use, nor products released for sale or supply, until their quality has been judged to be satisfactory.The basic requirements of Quality Control are that:(i) adequate facilities, trained personnel and approved procedures are available for sampling, inspecting and testing starting materials, packaging materials, intermediate, bulk, and finished products, and where appropriate for monitoring environmental conditions for GMP purposes; (ii) samples of starting materials, packaging materials, intermediate products, bulk products and finished products are taken by personnel and by methods approved by Quality Control;(iii) test methods are validated;(iv) records are made, manually and/or by recording instruments, which demonstrate that all the required sampling, inspecting and testing procedures were actually carried out. Any deviations are fully recorded and investigated;(v) the finished products contain active ingredients complying with the qualitative and quantitative composition of the Marketing Authorisation, are of the purity required, and are enclosed within their proper containers and correctly labelled;(vi) records are made of the results of inspection and that testing of materials, intermediate, bulk, and finished products is formally assessed against specification. Product assessment includes a review and evaluation of relevant production documentation and an assessment of deviations from specified procedures;(vii) no batch of product is released for sale or supply prior to certification by a Qualified Person that it is in accordance with the requirements of the relevant authorisations;(viii) sufficient reference samples of starting materials and products are retained to permit future examination of the product if necessary and that the product is retained in its final pack unless exceptionally large packs are produced.Product Quality Review1.4 Regular periodic or rolling quality reviews of all licensed medicinal products, including export only products, should be conducted with the objective of verifying the consistency of the existing process, the appropriateness of current specifications for both starting materials and finished product to highlight any trends and to identify product and process improvements. Such reviews should normally be conducted and documented annually, taking into account previous reviews, and should include at least:(i) A review of starting materials including packaging materials used in the product, especially those from new sources.(ii) A review of critical in-process controls and finished product results.(iii) A review of all batches that failed to meet established specification(s) and their investigation.(iv) A review of all significant deviations or non-conformances, their related investigations, and the effectiveness of resultant corrective and preventative actions taken.(v) A review of all changes carried out to the processes or analytical methods.(vi) A review of Marketing Authorisation variations submitted/granted/refused, including those for third country (export only) dossiers.(vii) A review of the results of the stability monitoring programme and any adverse trends. (viii) A review of all quality-related returns, complaints and recalls and the investigationsperformed at the time.(ix) A review of adequacy of any other previous product process or equipment corrective actions. (x) For new marketing authorisations and variations to marketing authorisations, a review of post-marketing commitments.(xi) The qualification status of relevant equipment and utilities, e.g. HV AC, water, compressed gases, etc.(xii) A review of any contractual arrangements as defined in Chapter 7 to ensure that they are up to date.The manufacturer and marketing authorisation holder should evaluate the results of this review, where different, and an assessment made of whether corrective and preventative action or any revalidation should be undertaken. Reasons for such corrective actions should be documented. Agreed corrective and preventative actions should be completed in a timely and effective manner. There should be management procedures for the ongoing management and review of these actions and the effectiveness of these procedures verified during self- inspection. Quality reviews may be grouped by product type, e.g. solid dosage forms, liquid dosage forms, sterile products, etc. where scientifically justified.Where the marketing authorisation holder is not the manufacturer, there should be a technical agreement in place between the various parties that defines their respective responsibilities in producing the quality review. The Qualified Person responsible for final batch certification together with the marketing authorisation holder should ensure that the quality review is performed in a timely manner and is accurate.Quality Risk Management1.5 Quality risk management is a systematic process for the assessment, control, communication and review of risks to the quality of the medicinal product. It can be applied both proactively and retrospectively.1.6 The quality risk management system should ensure that:- the evaluation of the risk to quality is based on scientific knowledge, experience with the process and ultimately links to the protection of the patient- the level of effort, formality and documentation of the quality risk management process is commensurate with the level of riskExamples of the processes and applications of quality risk management can be found inter alia in Annex 20.CHAPTER 2 PERSONNELPrincipleThe establishment and maintenance of a satisfactory system of quality assurance and the correct manufacture of medicinal products relies upon people. For this reason there must be sufficient qualified personnel to carry out all the tasks which are the responsibility of the manufacturer. Individual responsibilities should be clearly understood by the individuals and recorded. All personnel should be aware of the principles of Good Manufacturing Practice that affect them and receive initial and continuing training, including hygiene instructions, relevant to their needs. General2.1 The manufacturer should have an adequate number of personnel with the necessary qualifications and practical experience. The responsibilities placed on any one individual should not be so extensive as to present any risk to quality.2.2 The manufacturer must have an organisation chart. People in responsible positions should havespecific duties recorded in written job descriptions and adequate authority to carry out their responsibilities. Their duties may be delegated to designated deputies of a satisfactory qualification level. There should be no gaps or unexplained overlaps in the responsibilities of those personnel concerned with the application of Good Manufacturing Practice.Key Personnel2.3 Key Personnel include the head of Production, the head of Quality Control, and if at least one of 1 these persons is not responsible for the duties described in Article 51 of Directive 2001/83/EC , the Qualified Person(s) designated for the purpose. Normally key posts should be occupied by full-time personnel. The heads of Production and Quality Control must be independent from each other. In large organisations, it may be necessary to delegate some of the functions listed in 2.5, 2.6 and 2.7.2.4 The duties of the Qualified Person(s) are fully described in Article 51 of Directive 2001/83/EC, and can be summarised as follows:(a) for medicinal products manufactured within the European Community, a Qualified Person must ensure that each batch has been produced and tested/checked in accordance with the directives and the marketing authorisation ;(b) for medicinal products manufactured outside the European Community, a Qualified Person must ensure that each imported batch has undergone, in the importing country, the testing specified in paragraph 1 (b) of Article 51;(c) a Qualified Person must certify in a register or equivalent document, as operations are carried out and before any release, that each production batch satisfies the provisions of Article 51.The persons responsible for these duties must meet the qualification requirements laid down in Article 493 of the same Directive, they shall be permanently and continuously at the disposal of the holder of the Manufacturing Authorisation to carry out their responsibilities. Their responsibilities may be delegated, but only to other Qualified Person(s).2.5 The head of the Production Department generally has the following responsibilities:i. to ensure that products are produced and stored according to the appropriate documentation in order to obtain the required quality;ii. to approve the instructions relating to production operations and to ensure their strict implementation;iii. to ensure that the production records are evaluated and signed by an authorised person before they are sent to the Quality Control Department;iv. to check the maintenance of his department, premises and equipment;v. to ensure that the appropriate validations are done;vi. to ensure that the required initial and continuing training of his department personnel is carried out and adapted according to need.2.6 The head of the Quality Control Department generally has the following responsibilities:i. to approve or reject, as he sees fit, starting materials, packaging materials, and intermediate, bulk and finished products;ii. to evaluate batch records;iii. to ensure that all necessary testing is carried out;iv. to approve specifications, sampling instructions, test methods and other Quality Control procedures;v. to approve and monitor any contract analysts;vi. to check the maintenance of his department, premises and equipment;vii. to ensure that the appropriate validations are done;viii. to ensure that the required initial and continuing training of his department personnel is carried out and adapted according to need.Other duties of the Quality Control Department are summarised in Chapter 6.2.7 The heads of Production and Quality Control generally have some shared, or jointly exercised, responsibilities relating to quality. These may include, subject to any national regulations:— the authorisation of written procedures and other documents, including amendments;— the monitoring and control of the manufacturing environment;— plant hygiene;— process validation;— training;— the approval and monitoring of suppliers of materials;— the approval and monitoring of contract manufacturers;— the designation and monitoring of storage conditions for materials and products;— the retention of records;— the monitoring of compliance with the requirements of Good Manufacturing Practice;— the inspection, investigation, and taking of samples, in order to monitor factors which may affect product quality.Training2.8 The manufacturer should provide training for all the personnel whose duties take them into production areas or into control laboratories (including the technical, maintenance and cleaning personnel), and for other personnel whose activities could affect the quality of the product.2.9 Besides the basic training on the theory and practice of Good Manufacturing Practice, newly recruited personnel should receive training appropriate to the duties assigned to them. Continuing training should also be given, and its practical effectiveness should be periodically assessed. Training programmes should be available, approved by either the head of Production or the head of Quality Control, as appropriate. Training records should be kept.2.10 Personnel working in areas where contamination is a hazard, e.g. clean areas or areas where highly active, toxic, infectious or sensitising materials are handled, should be given specific training.2.11 Visitors or untrained personnel should, preferably, not be taken into the production and quality control areas. If this is unavoidable, they should be given information in advance, particularly about personal hygiene and the prescribed protective clothing. They should be closely supervised.2.12 The concept of Quality Assurance and all the measures capable of improving its understanding and implementation should be fully discussed during the training sessions. Personnel Hygiene2.13 Detailed hygiene programmes should be established and adapted to the different needs within the factory. They should include procedures relating to the health, hygiene practices and clothing of personnel. These procedures should be understood and followed in a very strict way by every person whose duties take him into the production and control areas. Hygiene programmes should be promoted by management and widely discussed during training sessions.2.14 All personnel should receive medical examination upon recruitment. It must be the manufacturer‟s responsibility t hat there are instructions ensuring that health conditions that can be of relevance to the quality of products come to the manufacturer‟s knowledge. After the first medical examination, examinations should be carried out when necessary for the work and personal health.2.15 Steps should be taken to ensure as far as is practicable that no person affected by an infectious disease or having open lesions on the exposed surface of the body is engaged in the manufacture of medicinal products.2.16 Every person entering the manufacturing areas should wear protective garments appropriate to the operations to be carried out.2.17 Eating, drinking, chewing or smoking, or the storage of food, drink, smoking materials or personal medication in the production and storage areas should be prohibited. In general, any unhygienic practice within the manufacturing areas or in any other area where the product might be adversely affected, should be forbidden.2.18 Direct contact should be avoided between the operator‟s hands and the exposed product as well as with any part of the equipment that comes into contact with the products.2.19 Personnel should be instructed to use the hand-washing facilities.2.20 Any specific requirements for the manufacture of special groups of products, for example sterile preparations, are covered in the annexes.CHAPTER 3 PREMISES AND EQUIPMENTPrinciplePremises and equipment must be located, designed, constructed, adapted and maintained to suit the operations to be carried out. Their layout and design must aim to minimise the risk of errors and permit effective cleaning and maintenance in order to avoid cross- contamination, build up of dust or dirt and, in general, any adverse effect on the quality of products.PremisesGeneral3.1 Premises should be situated in an environment which, when considered together with measures to protect the manufacture, presents minimal risk of causing contamination of materials or products.3.2 Premises should be carefully maintained, ensuring that repair and maintenance operations do not present any hazard to the quality of products. They should be cleaned and, where applicable, disinfected according to detailed written procedures.3.3 Lighting, temperature, humidity and ventilation should be appropriate and such that they do not adversely affect, directly or indirectly, either the medicinal products during their manufacture and storage, or the accurate functioning of equipment.3.4 Premises should be designed and equipped so as to afford maximum protection against the entry of insects or other animals.3.5 Steps should be taken in order to prevent the entry of unauthorised people. Production, storage and quality control areas should not be used as a right of way by personnel who do not work in them.Production Area3.6 In order to minimise the risk of a serious medical hazard due to cross-contamination, dedicated and self contained facilities must be available for the production of particular medicinal products, such as highly sensitising materials (e.g. penicillins) or biological preparations (e.g. from live micro-organisms). The production of certain additional products, such as certain antibiotics, certain hormones, certain cytotoxics, certain highly active drugs and non-medicinal products should not be conducted in the same facilities. For those products, in exceptional cases, the principle of campaign working in the same facilities can be accepted provided that specific precautions are taken and the necessary validations are made. The manufacture of technicalpoisons, such as pesticides and herbicides, should not be allowed in premises used for the manufacture of medicinal products.3.7 Premises should preferably be laid out in such a way as to allow the production to take place in areas connected in a logical order corresponding to the sequence of the operations and to the requisite cleanliness levels.3.8 The adequacy of the working and in-process storage space should permit the orderly and logical positioning of equipment and materials so as to minimise the risk of confusion between different medicinal products or their components, to avoid cross-contamination and to minimise the risk of omission or wrong application of any of the manufacturing or control steps.3.9 Where starting and primary packaging materials, intermediate or bulk products are exposed to the environment, interior surfaces (walls, floors and ceilings) should be smooth, free from cracks and open joints, and should not shed particulate matter and should permit easy and effective cleaning and, if necessary, disinfection.3.10 Pipework, light fittings, ventilation points and other services should be designed and sited to avoid the creation of recesses which are difficult to clean. As far as possible, for maintenance purposes, they should be accessible from outside the manufacturing areas.3.11 Drains should be of adequate size, and have trapped gullies. Open channels should be avoided where possible, but if necessary, they should be shallow to facilitate cleaning and disinfection.3.12 Production areas should be effectively ventilated, with air control facilities (including temperature and, where necessary, humidity and filtration) appropriate both to the products handled, to the operations undertaken within them and to the external environment.3.13 Weighing of starting materials usually should be carried out in a separate weighing room designed for that use.3.14 In cases where dust is generated (e.g. during sampling, weighing, mixing and processing operations, packaging of dry products), specific provisions should be taken to avoid cross- contamination and facilitate cleaning.3.15 Premises for the packaging of medicinal products should be specifically designed and laid out so as to avoid mix-ups or cross-contamination.3.16 Production areas should be well lit, particularly where visual on-line controls are carried out.3.17 In-process controls may be carried out within the production area provided they do not carry any risk for the production.Storage Areas3.18 Storage areas should be of sufficient capacity to allow orderly storage of the various categories of materials and products:starting and packaging materials, intermediate, bulk and finished products, products in quarantine, released, rejected, returned or recalled.3.19 Storage areas should be designed or adapted to ensure good storage conditions. In particular, they should be clean and dry and maintained within acceptable temperature limits. Where special storage conditions are required (e.g. temperature, humidity) these should be provided, checked and monitored.3.20 Receiving and dispatch bays should protect materials and products from the weather. Reception areas should be designed and equipped to allow containers of incoming materials to be cleaned where necessary before storage.3.21 Where quarantine status is ensured by storage in separate areas, these areas must be clearly marked and their access restricted to authorised personnel. Any system replacing the physicalquarantine should give equivalent security.3.22 There should normally be a separate sampling area for starting materials. If sampling is performed in the storage area, it should be conducted in such a way as to prevent contamination or cross-contamination.3.23 Segregated areas should be provided for the storage of rejected, recalled or returned materials or products.3.24 Highly active materials or products should be stored in safe and secure areas.3.25 Printed packaging materials are considered critical to the conformity of the medicinal product and special attention should be paid to the safe and secure storage of these materials.Quality Control Areas3.26 Normally, Quality Control laboratories should be separated from production areas. This is particularly important for laboratories for the control of biologicals, microbiologicals and radioisotopes, which should also be separated from each other.3.27 Control laboratories should be designed to suit the operations to be carried out in them. Sufficient space should be given to avoid mix-ups and cross-contamination. There should be adequate suitable storage space for samples and records.3.28 Separate rooms may be necessary to protect sensitive instruments from vibration, electrical interference, humidity, etc.3.29 Special requirements are needed in laboratories handling particular substances, such as biological or radioactive samples.Ancillary Areas3.30 Rest and refreshment rooms should be separate from other areas.3.31 Facilities for changing clothes, and for washing and toilet purposes should be easily accessible and appropriate for the number of users. Toilets should not directly communicate with production or storage areas.3.32 Maintenance workshops should as far as possible be separated from production areas. Whenever parts and tools are stored in the production area, they should be kept in rooms or lockers reserved for that use.3.33 Animal houses should be well isolated from other areas, with separate entrance (animal access) and air handling facilities.Equipment3.34 Manufacturing equipment should be designed, located and maintained to suit its intended purpose.3.35 Repair and maintenance operations should not present any hazard to the quality of the products.3.36 Manufacturing equipment should be designed so that it can be easily and thoroughly cleaned. It should be cleaned according to detailed and written procedures and stored only in a clean and dry condition.3.37 Washing and cleaning equipment should be chosen and used in order not to be a source of contamination.3.38 Equipment should be installed in such a way as to prevent any risk of error or of contamination.3.39 Production equipment should not present any hazard to the products. The parts of the production equipment that come into contact with the product must not be reactive, additive or absorptive to such an extent that it will affect the quality of the product and thus present any hazard.。

Date of implementation: 1 March 2010Introduction:The holder of a Certificate of suitability shall inform the EDQM of any change to the information in the certification dossier by sending an application form and all necessary documents demonstrating that the conditions laid down in the present guideline are met.Classification of changesThe changes have been classified in three categories (notification/minor/major) depending on the potential impact of the change on the quality of the final substance. These three categories are based on those (IA-IAIN/IB/II) of the Commission Regulation (EC) No 1234/2008 concerning the examination of variations to the terms of marketing authorisation for medicinal products for human use and veterinary medicinal products.Any change not classified as a notification or a major change should be classified as a minor change except in the following cases where a new application should be submitted:- addition of a new route of synthesis and/or a new manufacturing site where the specifications of the final substance are different from the one already approved- transfer to a new holder that is not the same legal entity as the approved one, where the transfer does not occur because of a merger or because the company is sold, and where the manufacturer does not take out the Certificate of suitability in their own name.The changes related to Ph. Eur. monograph revisions or any other regulatory requirements are treated separately and generally initiated by the EDQM.执行日期：2010年3月1日介绍：欧洲药典适用性证书持有人必须向EDQM报告所有与申报文件有关的变更，申报时应填写申请表格和所有必要的资料，证明变更符合现行指南的规定。

欧洲药品评价局EMEA和欧洲药品质量管理局（EDQM）介绍一九九四年经欧共体与欧洲议会协商后，以设在法国的欧洲药典委员会秘书处为基础成立了欧洲药品质量管理局(EDQM)。

相对于设在英国伦敦主要负责对新药和新生物制品审评的欧洲药品审评委员会(EMEA)，EDQM主要功能之一是对上市后的仿制药品的监督管理，其主要监管手段是对产品的Certification of Suitability和对通过欧洲各国家官方药品检验所（OMCL）之间的欧洲网络系统来对药品的市场监督。

EMEA（European Medicines uation Agency）翻译为欧洲药品评价局，其机构正在改革变化中，首先，EMEA将从现有的“欧洲药品评价局(European Medicines uation Agency，EMEA)更名为“欧洲药品局(European Medicines Agency，EMA)“。

欧洲药品质量理事会EDQM（European Directorate for the Quality of Medicines）作为另一重要欧洲官方药管机构，欧洲药品质量管理局是由欧洲药典委员会技术秘书处演化而来，它有很多职能，具体职能如下：1、欧洲药典委员会的技术秘书处提供技术支持2、负责欧洲药典及相关产品的出版与发行3、负责化学药物标准品和生物制品标准品的制备与销售4、负责对欧洲药典各论的适用性认证5、负责构建欧洲官方药品检验实验室网络，承担生物制品批签发与上市药品的监督任务。

EMEA和EDQM之间的关系？欧洲药品评价局EMEA(European Agency for the uation of Medicinal Products)是欧洲官方药管机构之一，它有很多职能，其中很重要的一点就是负责药品（制剂）上市核准程序；而欧洲药品质量理事会EDQM（European Directorate for the Quality of Medicines）作为另一重要欧洲官方药事管理机构，它有很多职能，如：建立药品的质量标准以供欧洲药典委员会使用，制备标准品CRS，执行COS 程序最终颁发COS证书等等。

Guideline on Requirements for Revision/Renewal of Certificates of Suitability to the European Pharmacopoeia MonographsEDQM CEP证书变更/更新指南要求目录1.INTRODUCTION: (1)1.介绍 (1)2.CLASSIFICATION OF CHANGES: (1)2.变更分类 (1)3.DOCUMENTATION TO BE PROVIDED: (2)3.需提供的文件 (2)4.LIST OF CHANGES: (3)4.变更清单 (3)4.I.ADMINISTRATIVE CHANGES (4)4.I.行政变更 (4)4.II.QUALITY CHANGES (7)4.II.质量变更 (7)4.II.1Manufacture (8)4.II.1生产 (8)4.II.2Control of the final substance (16)4.II.2产品的控制 (17)4.II.3Container closure system (20)4.II.3容器密封系统 (20)4.II.4Stability (22)4.II.4稳定性 (23)4.II.5Design Space and Post-Approval Change Management Protocols (24)4.II.5设计空间与批准后变更管理方案 (24)4.III.TSE CHANGES (26)4.III.TSE变更 (27)5.RENEWAL (30)5.更新 (32)6.TRANSFER OF HOLDERSHIP (33)6.CEP证书持有人转让 (33)Date of implementation: 1st September 2013实行日期：2013-9-11.INTRODUCTION:1.介绍The holder of a certificate of suitability (CEP) shall inform the EDQM of any change to information in the CEP application by sending an appropriate request for revision demonstrating that the conditions laid down in the present guideline are met. In addition, this guideline describes the requirements for the renewal of CEPs and for a transfer of holdership.欧洲药典适用性证书持有人必须向EDQM 报告所有与申报文件有关的变更，申报时应寄送合理的变更请求，证明变更符合现行指南的规定。

欧洲药典质量标准的起草技术指南Technical Guide for the Elaboration of MonographsEuropean Directorate for the Quality of Medicines & HealthCare4th 2005译者序欧洲药品质量管理局(Eumpean Directorate for the Quality 0f Medicines&HealthCare，简称EDQM＆HealthCare)创立于1964年，原来的名称是“European Pharmacopoeia Secretariat"，隶属于1949年创立的欧洲理事会(Council 0f Europe，Directorate General IⅡSocial Cohesion)．1996年更名为EDQM。

2006年，EDQM新的办公楼和实验室竣工，2007年1月起EDQM更名为EDQM&HealthCare，位于法国Strasbourg，Strasbourg同时也是欧洲理事会和欧洲议会(Parliament of Europe)的总部。

EDQM最主要的职责就是《欧洲药典》的起草、出版以及欧洲药典标准物质的制备和发放。

欧洲药典委员会现有37个成员国，其中包括24个欧盟国家，包括WHO在内的20个国家为观察员，我国于1994年成为EDQM的观察员。

1969年发行第一版《欧洲药典》(V0l.I)。

第六版《欧洲药典》将于2008年1月1日生效。

欧洲药典已经成为最具影响力的药典之一。

受世界卫生组织资助，我有幸于2004年对EDQM进行了短期访问，并结识了时任欧洲药品质量管理局局长的Agnes Artiges博士及其他的EDQM官员和专家。

2005年9月，Arfiges 博士率团来华参加“首届中欧药典论坛”并访问了中国药品生物制品检定所，同年获得Artiges博士的授权翻译了“欧洲药典标准物质指导原则Guideline for Establishment 0f European Pharmacopoeia Reference Standard”并在《中国药品标准杂志》发表。

表中所给数据仅作为指导性建议，更严格的限度规定也可能被证明是合适的。只有在证明药品中的杂质含 量较低时才可以采用容量滴定方法，否则应引入其他的含量测定方法。
欧洲药典质量标准的起草技术指南
48 / 48
重复性 相对准确度
RSD(n=6)

Δx =
x - xtheory xtheory
标准加入法的平均回收率在9751025之间是可以被接337容量滴定法附录2511附录2219附录2220当建立一个新的含量测定用容量分析方法时推荐在规定的测定条件下按照随机原则对至份不同重量的供试品进行滴定滴定终点消耗的滴定液体积应为所用滴定管体积的2090然后对数据进行统计学处理必须满足多个评价指标的要求才能获得对滴定方法的认可
欧洲药典质量标准的起草技术指南
46 / 48
计算每次标准加入操作的回收率。标准加入法的平均回收率在 97.5%~102.5 之间是可以被接 受的。 3.3.7 容量滴定法（附录 2.5.11，附录 2.2.19，附录 2.2.20） 当建立一个新的含量测定用容量分析方法时，推荐在规定的测定条件下，按照随机原则，对至 少 7 份 不 同 重 量的 供 试 品 进 行 滴 定 ， 滴 定 终 点 消 耗 的 滴 定 液 体 积 应 为 所 用 滴 定 管 体 积 的 20%~90%，然后对数据进行统计学处理，必须满足多个评价指标的要求才能获得对滴定方法 的认可。 供试品称重的天平读数、 终点时消耗的滴定液体积的读数的相对偏差不得超过观察值的 0.5%。 通过线性回归方程对依赖于供试品重量“mi”的滴定终点体积“Vi”进行评价，获得线性回归 方程并用斜率“bobs” 、 外推法获得截距“aobs” 以及精密度（标准偏差，用 sdv（V）表示） 。 第一个判断标准--成比例的系统误差(偏倚) 考虑到标准滴定液的滴定度，对于电位滴定法。计算获得的斜率“bobs”与理论值（给定的滴 btheor = Z Mr C r

1 GENERAL NOTICES凡例1.1 GENERAL STATEMENTS概述The General Notices apply to all monographs and other texts of the European Pharmacopoeia.凡例的内容适用于各论和欧洲药典中的其它章节。

The official texts of the European Pharmacopoeia are published in English and French. Translations in other languages may be prepared by the signatoryStates of the European Pharmacopoeia Convention. In case of doubt or dispute, the English and French versions are alone authoritative.欧洲药典以英语和法语形式发行，欧洲药典委员会的签署国可将药典内容译成其它语言，但若发生争议，应以英语和法语版为权威。

In the texts of the European Pharmacopoeia, the word ‘Pharmacopoeia’ without qualification means the European Pharmacopoeia. The official abbreviation Ph.Eur. may be used to indicate the European Pharmacopoeia.在欧洲药典中，如无特殊规定，“药典”是指欧洲药典，官方缩写 Ph. Eur.也指欧洲药典。

The use of the title or the subtitle of a monograph implies that the articlecomplies with the requirements of the relevant monograph. Such references to monographs in the texts of the Pharmacopoeia are shown using themonograph title and reference number in italics.文章中如果引用了各论中的标题和副标题意味着文章内容符合相关各论的要求。

摘 自 :m,T.L.Isenhour. 通 过 玻 璃 仪 器 的 选 择 降 低 标 准 溶 液 制 备 过 程 中 的 相 对 误 差 . Analytical Chemistry, 1980, 53, 1158-1161. 译者注.根据稀释比例,稀释步骤应为 2 步稀释.
1.5 试剂 当试剂的一个或多个性质对其用途有决定作用时,必须明确该试剂的质量,必要时还可以规定适 当的方法对试剂的适用性进行检测.通常采用分析纯试剂,给出试剂的名称\化学文摘号和分子 式已经足够. 如果限度检查中所需的试剂\试液\滴定液和标准溶液已经在(欧洲药典)的试剂和试液中收载, 就可以使用药典收载的试剂和试液.如果偶尔使用一次的简单试液或溶液,在各论中应给出配制 方法. 应当避免使用公认的的剧毒试剂(致癌物),尤其是那些难于控制毒性的物质,比如在接触细粉状 试剂或显色剂时.避免使用在欧洲药典委员会的一个或多个成员国禁止或限制使用的物质. 1.6 商品名称 在起草的各论中应采用脚注的形式给出色谱柱或薄层板的商品名称,当试剂的商品哆嗦称有助 于 分析 人员的工作 时也应 以 脚注 形式给 出( 比如 只 能 从某 个 供应 商 获得 的 检测 试 剂盒子或试 剂). 在正式发行的药典文本中不出现商品名称.但是,在药典收载该各论后,以在 EDQM 网站的 数据库中找到相关色谱柱\薄层板和试剂的商品名称. 1.7 标准物质 关于标准物质的政策和指导原则详见附录 5.12 Reference standards(已于 2006 年 3 月正式 生效,译者注).EDQM 负责对照品候选原料的采购\标准物质的建立\保存和监测.许多标准物质, 尤其是用于杂质控制的标准物质的数量有限.在药液药典论坛发表各论草案前,应当向 EDQM 提供足量的标准物质候选原料,EDQM 将根据获得的标准物质原料的数量情况,制定标准物质 使用的最佳方案(比如混合标准物质替代单个标准物质的供应).EDQM 的目标是在各论草案被 讨论通过的同时,提交标准物质 报告供委员会 审核.如果不能同时提供,在标准颁布后最短时 间

欧洲药典标准物质指导原则介绍宁保明;严菁;张启明;金少鸿【期刊名称】《中国药品标准》【年(卷),期】2006(7)4【摘要】欧洲药品质量管理局（European Directorate for the Quality of Medicines，简称EDQM）是负责欧洲药典质量标准起草及标准物质制备的机构，目前有35个成员国和18个观察员国，其中有欧盟以及欧盟的24个成员国。

欧洲药典作为法定质量标准在欧洲34个成员国中执行，是国际上最具影响力的药典之一。

我国于1994年成为EDQM的观察员国。

所有在欧洲销售的原料药、植物药和药物制剂中使用的原料药包括辅料都必须通过EDQM的CEP（Certification of Suitability of European Pharmacopoeiamonographs）认证。

该机构同时还负责欧洲药品质量监督的技术组织工作。

【总页数】6页(P74-79)【作者】宁保明;严菁;张启明;金少鸿【作者单位】中国药品生物制品检定所,中国,北京,100050;中国药品生物制品检定所,中国,北京,100050;中国药品生物制品检定所,中国,北京,100050;中国药品生物制品检定所,中国,北京,100050【正文语种】中文【中图分类】R446.5【相关文献】1.胶印标准及标准化指导（四）：介绍西德对胶印产品的质量控制 [J], 朱元泓2.上海市计量测试技术研究院国家一级标准物质、二级标准物质介绍 [J], 王根荣3.WHO国际生物制品标准物质制备指导原则介绍与我国兽用生物制品标准物质制备程序思考 [J], 李翠; 王琴; 郎洪武; 赵启祖; 王兆; 万建青; 徐嫄; 邹兴启; 朱元源; 徐璐; 张乾义; 夏应菊4.加强标准物质监管保障量值准确可靠市场监管总局印发《关于加强标准物质建设和管理的指导意见》 [J],5.国家标准物质系列讲座之三国家标准物质有关名词与术语介绍 [J], 王根荣因版权原因，仅展示原文概要，查看原文内容请购买。