Good Distribution Practice of active substances for medicinal products for human use

药品储运温度验证与偏差处理药品储运过程中经常出现温度超标的情况，基于用药安全和药品稳定有效等方面考虑，药品储运过程中的温度控制和运输验证尤为重要。

本文汇总了中国、欧盟、美国对药品储运过程中温度超标相关的问题的态度，供大家参考。

中国GMP：问题：对于30℃以下储存的产品（成品），在夏天运输过程会超过30℃，像此类药品还需对运输条件确认吗？另外对运输条件的确认以什么方式体现合适？答：需要。

对运输条件进行评估。

点评：对运输条件进行评估是通过运输验证来实现的？简单地说，就是按正常的运输、包装条件下，用温、湿度记录仪等仪器证实整个运输过程的条件满足产品的要求。

对于出现的短时间的背离可以通过长期、加速稳定性数据予以评估。

问题：2～8℃保存的产品，如企业有加速实验数据，短期常温运输对产品质量无影响，可以不用冷链吗？答：不可以。

必须在冷链条件下运输，点评：冷链条件运输时出现的短时间背离按偏差处理。

可用加速实验数据评估，但不允许直接用常温运输条件运输。

问题：运输条件是否与贮存条件一致？答：运输条件应当满足储存条件。

点评：运输条件应满足储存条件，如果在运输途中出现了偏离，可以依据相应的稳定性数据进行评估，确定偏离对产品的影响。

问题165：产品规定储存条件为阴凉处，在运输过程中是否必须采取措施将运输温度控制在20℃以下？答：在不影响产品质量的情况下，运输过程中的温度可以在20℃以上，需要有相应的稳定性数据作为支持，必须采取必要的控制措施。

点评：运输过程中的温度是否可以在20℃以上，温度可以偏离多长时间，最大可偏离的温度上限，这些都需要有相应的稳定性数据作为支持。

同时可以通过运输验证证实在最恶劣条件下产品可能经受的最大温度变化和时间长短，结合稳定性数据做合理的判断。

问题：疫苗的运输条件如何监控？答：疫苗产品的冷链运输，应该配备全过程连续温度记录装置，由接收方在验收产品时对运输过程的温度记录结果进行确认。

点评：依据《中国药典》三部的要求，生物制品贮存温度通常为2～8℃，运输过程需注意快速、冷链、防冻结，因此疫苗产品的运输应采用适当的保温（或控温）措施，且需经过最差条件验证，并建议对运输过程配备连续温度记录装置，记载每一发运单位的温度变化情况，由接收方在验收产品时对运输过程的温度记录结果进行确认，发运单位也应对此结果定期进行评估。

UK GUIDANCE ON GOOD MANUFACTURING PRACTICE•Manufacturers’ Obligations•Qualified Persons•Code of Practice for Qualified Persons in the Pharmaceutical Industry •Appendix 1: UK Statements on CPD•Import from Third Countries•Mutual Recognition Agreements on Good Manufacturing Practice (GMP) and Manufacturing Authorisation•Content of the Fabricator’s/Manufacturer’s Batch Certificate for Drug/Medicinal Products Exported to Countries Under the Scope of aMutual Recognition Agreement (MRA)•UK Guidance on Certificates of Analysis•GMP for Starting Materials•Manufacture and Importation of Unlicensed Medicines for Human Use Manufacturers’ ObligationsThe holder of a manufacturer’s licence must comply with certain obligations in relation to the manufacture and assembly of relevant medicinal products. These obligations are set out in Regulation 2 of The Medicines for Human Use (Manufacturing, Wholesale Dealing and Miscellaneous Amendments) Regulations 2005 [SI 2005 No. 2789]. They require that the licence holder shall:ply with the principles of good manufacturing practice;2.only use active starting materials which have been manufactured orassembled in accordance with good manufacturing practice, unless they are for use in an exempt medicinal product;3.maintain such staff, premises, equipment and facilities necessary toconduct the manufacture and assembly of relevant medicinal products in accordance with the requirements of their manufacturer’s licence and the marketing authorizations of the medicinal product being manufactured;4.maintain such staff, premises, equipment and facilities for the handling,control, storage and distribution of the relevant medicinal productsmanufactured or assembled in accordance with their manufacturer’slicence as necessary to maintain the quality of those medicinal products;5.ensure that any arrangements made for the control, storage anddistribution of the relevant medicinal products are adequate to maintain the quality of those products;6.not carry out any manufacture or assembly of medicinal products otherthan in accordance with their manufacturer’s licence and at the premises specified in the licence;7.not use any premises for the handling, control, storage or distribution ofrelevant medicinal products other than those named on theirmanufacturer’s licence which have been approved by the licensingauthority for that purpose;rm the licensing authority before making any material alteration to thepremises or facilities used under their manufacturer’s licence, or in theoperations for which they are used;rm the licensing authority of any proposed changes to any personnelnamed in their manufacturer’s licence as responsible for quality control, including the person named as the qualified person;10.permit the licensing authority to carry out inspections, take samples orcopies of documentation as necessary to enable the licensing authority to ascertain whether there are any grounds for suspending, revoking orterminating the manufacturer’s licence or to verifying any statementcontained in an application for a licence;11.ensure that any blood or blood component that they import into the UnitedKingdom and use as a starting material or raw material in the manufacture of a relevant medicinal product meets equivalent standards of quality and safety to those laid down in Commission Directive 2004/33/EC,implementing Directive 2002/98/EC of the European Parliament and of the Council as regards certain technical requirements for blood and bloodcomponents.12.ensure that he has at all times at his disposal the services of at least onequalified person who is responsible for carrying out, in relation to themedicinal products being manufactured or assembled, the duties specified in Article 51 of the Directive 2001/83/EC as amended. (See Section 8). Where the manufacturer’s licence holder distributes the relevant medicinal product manufactured or assembled in accordance with the manufacturer’s licence he shall:•comply with the principles of good distribution practice;•ensure the appropriate and continued supply of the medicinal product that he manufactures or assembles;•sell only, or offer for sale or supply, the medicinal product in accordance and conformity with a marketing authorization unless it is an exemptmedicinal product or is distributed to another Member State where it can be legally used as an unlicensed relevant medicinal product in the MemberState concerned;•distribute only their medicinal products to a holder of a wholesale dealer’s licence relating to those products; a holder of an authorization granted bythe competent authority of another EEA State authorising the supply ofthose products by way of wholesale dealing; any person who may lawfully sell those products by retail or who may lawfully supply them incircumstances corresponding to retail sale; or any person who may lawfully administer those products;•where the relevant medicinal product is supplied to a person for retail sale or supply, the manufacturer’s licence holder must enclose with the producta document which makes it possible to ascertain the date on which thesupply took place; the name and pharmaceutical form of the productsupplied; the quantity of product supplied; and the names and addresses of the person or persons from whom the products were supplied.The Standard Provisions are incorporated into all manufacturer’s licences in the form set out in Schedule 1 of the “Manufacturing and Wholesale Dealing Regulations”, that is, those provisions which may be included in all licences unless an individual licence provides variations to them. They require that the manufacturer’s licence holder shall:1.place their quality control system referred to in Article 11(1) of CommissionDirective 2003/94/EC under the authority of the head of the Quality Control (QC);2.provide information about the products being manufactured or assembledunder their manufacturer’s licence and about the operations beingconducted in relation to such manufacture or assembly as may berequested by the licensing authority;rm the licensing authority of any proposed changes to be made to anypersonnel named in his licence, responsible for supervising the production operations; in charge of the animals from which are derived anysubstances used in the production of the medicinal products beingmanufactured or assembled; or responsible for the culture of any livingtissues used in the manufacture of the medicinal products beingmanufactured or assembled;4.keep readily available for inspection by a person authorised by the licensingauthority the batch documentation referred to in Article 9(1) ofCommission Directive 2003/94/EC, and permit that person to take copies or make extracts from such documentation;5.keep readily available for examination by a person authorised by theLicensing Authority, samples of each batch of finished relevant medicinal product referred to in Article 11(4) of Commission Directive 2003/94/EC;6.withhold any batch of any medicinal product from sale or export so far asmay be reasonably practicable for up to 6 weeks when informed that itdoes not comply with its licence specifications or with the provisions of the Act or of any regulations under the Act;7.ensure that any tests for determining conformity with the standards andspecifications applying to any particular product used in the manufacture ofa medicinal product shall, except so far as the conditions of the productspecification for that product otherwise provide, be applied to samples taken from the medicinal product after all manufacturing processes have been completed, or at such earlier stage in the manufacture as may be approved by the licensing authority;8.where the manufacturer’s licence relates to the assembly of any relevantmedicinal product or class of product, and the licence holder supplies that relevant medicinal product at such a stage of assembly that does not fully comply with the provisions of the product specification that relate tolabelling, the licence holder shall communicate the particulars of those provisions to the person to whom that product has been so supplied;9.where the manufacturer’s licence relates to the assembly of a relevantmedicinal product; and that medicinal product is not manufactured by the licence holder; and particulars as to the name and address of themanufacturer of, or of the person who imports, that relevant medicinal product have been given by the licence holder to the licensing authority, the licence holder shall forthwith notify the licensing authority in writing of any changes in such particulars;10.keep readily available for examination by a person authorised by thelicensing authority durable records of the details of manufacture of any intermediate products held by him which are for use in the manufacture of biological medicinal products for human use and shall be in such form as to ensure that the manufacturer’s licence holder has a comprehensive record of all matters that are relevant to an evaluation of the safety, quality and efficacy of any finished biological medicinal product for human use which he manufactures using those intermediate products. The records shall not be destroyed without the consent of the licensing authority until therecords of the details of manufacture of any finished medicinal products which were or may be manufactured using those intermediate products may be destroyed in accordance with the requirements of theseRegulations;11.arrange for animals which are used in the production of any medicinalproducts, to be housed in premises of such a nature, and be managed in such a manner, as to facilitate compliance with the provisions relating to them in the relevant marketing authorizations;12.take all reasonable precautions and exercise all due diligence to ensurethat any information he provides to the licensing authority which isrelevant to an evaluation of the safety, quality or efficacy of any medicinal product for human use which he manufactures or assembles; or anystarting materials or intermediate products that he holds which are for usein the manufacture of relevant medicinal products, is not false ormisleading in any material particular.The manufacturer’s licence holder may use a contract laboratory pursuant to Article 11(2) of Commission Directive 2003/94/EC if operated by a person approved by the licensing authority, i.e. if not on the manufacturer’s licence a contract laboratory will not be acceptable1.For any changes to the information shown on a licence, prior approval from the licensing authority must be obtained.Qualified PersonsSub-sections•GeneralGeneralAll holders of a manufacturer’s licence for licensed products, including for the purposes of import, are required to have available the services of a Qualified Person (QP), who must be named on the licence. When considering a nomination, the licensing authority (the MHRA) routinely takes into account the assessment of the nominee’s eligibility made by the joint assessment panel of the Institute of Biology, the Royal Pharmaceutical Society of Great Britain and the Royal Society of Chemistry. Exceptionally, the MHRA will assess a nominee directly if he or she is not a member of any of these professional bodies.Title IV of Directive 2001/83/EC as amended lays down the requirements for QPs in relation to products for human use. Article 51 defines the duties of the QP; Articles 49 and 50 define the requirements for eligibility under the permanent and transitional arrangements respectively, and Article 52 requires Member States to ensure that the duties of QPs are fulfilled, either through administrative measures or by making such persons subject to a professional code of conduct. Title IV of Directive 2001/82/EC as amended lays down equivalent requirements in relation to veterinary products. Guidance on the duties of QPs is given in the EU Guide to GMP and in particular in its Annex 16.By inspection and other means the licensing authority routinely assesses whether or not QPs are fulfilling their duties. In making this assessment, reference is made to the Code of Practice for Qualified Persons produced jointly by the Institute of Biology, the Royal Pharmaceutical Society of Great Britain and the Royal Society of Chemistry in collaboration with the MHRA and the VeterinaryMedicines Directorate. This reference is made whether or not the QP in question is a member of one or more of these bodies (see next section).All QPs should be guided in fulfilling their duties by the Code of Practice, although the references in Sections 11.1 and 12.4 to the disciplinary machinery of the professional bodies, and in Section 11.6 to the advice which professional bodies can give, would not be relevant in the case of a QP who is not a member of one of these bodies. The European Industrial Pharmacists Group adopted a similar code2 in 1995 for the guidance of its members.Code of Practice for Qualified Persons in the Pharmaceutical IndustrySub-sections• 1.0 Introduction• 2.0 Regulatory Basis for the Qualified Person• 3.0 Purpose of the Code• 4.0 Application of the Code• 5.0 Terminology• 6.0 General Principles•7.0 Routine Duties of a Qualified Person•8.0 Performance of Duties and Regulatory Compliance•9.0 Number and Location of Qualified Persons•10.0 Contracted Qualified Persons•11.0 Contract Manufacture and/or Testing•12.0 Continuing Professional Development•13.0 Professional Conduct•14.0 Disciplinary Procedures1.0 Introduction1.1The concept of the Qualified Person (QP), first established in 1975, is a unique regulatory requirement that applies only within the European Union (EU). The only comparable situation exists within Member States of the European Economic Area (EEA) with whom the EU has reciprocal agreements.1.2Each holder of an Authorisation to Manufacture products for use in a Clinical Trial or products subject to Marketing Authorisations, within Member States of the EU, must name a person or persons who are eligible to act in the capacity of QP. 1.3The requirement for QP covers both Human and Veterinary Medicinal Products including those intended for export.1.4Particular conditions for formal qualifications and practical experience for eligibility to act as a QP are specified in the relevant EU Council Directives (see 2 below). Ensuring compliance with these conditions is the responsibility of the Competent Authorities of the Member States.1.5The primary legal responsibility of the QP is to certify batches of Medicinal Product prior to use in a Clinical Trial (Human Medicinal Products only) or prior to release for sale and placing on the market (Human and Veterinary Medicinal Products). However, the wider technical, ethical and professional obligations in terms of patient Safety, Quality and Efficacy must also be considered. Hence this professional Code of Practice, which is designed to take account of these issues.2.0 Regulatory Basis for the Qualified PersonFor ease of reference the key regulatory documents concerning the QP are as follows:1.Principles and Guidelines of Good Manufacturing Practice for MedicinalProducts for Human Use: Directive 2003/94/EC Article 7.2.Principles and Guidelines of Good Manufacturing Practice for VeterinaryMedicinal Products: Directive 91/412/EEC Article 7.3.Good Clinical Practice in the Conduct of Clinical Trials on Medicinal Productsfor Human Use: Directive 2001/20/EC Article 13.munity Code Relating to Veterinary Medicinal Products: Directive2001/82/EC - Title IV - Manufacture and Imports Articles 44–57.munity Code Relating to Medicinal Products for Human Use: Directive2001/83/EC Title IV Manufacture and Importation Articles 40–53.6.Good Manufacturing Practices: Eudralex Volume 4Annex 13: Manufacture of Investigational Medicinal ProductsAnnex 16: Certification by a Qualified Person and Batch Release3.0 Purpose of the Code3.1The legal functions of the Qualified Person (QP) are stated in Article 51 of Directive 2001/83/EC or Article 55 of Directive 2001/82/EC and reproduced in the preface to the UK Joint Professional Bodies’ Study Guide 2000.3.2The aims and objectives of the Code of Practice are to provide operational guidelines for carrying out the functions of the Qualified Person within a professional code of conduct in accordance with Article 56 of Council Directive 2001/82/EC and/or Article 52 of Council Directive 2001/83/EC.3.3The Code is in the interests of Qualified Persons, their employers, patients and the Competent Authorities of the Member States.4.0 Application of the Code4.1The Code is equally applicable to Qualified Persons who have achieved that status under the transitional arrangements, and under the permanent provisions.4.2Qualified Persons have a professional duty to decline to act as Qualified Persons in the release of product types for which they do not possess the relevant experience and knowledge.4.3It should be noted that Qualified Persons are eligible to certify batches of medicinal product as follows:1.those who have achieved Qualified Person status under the permanentprovisions are eligible to certify batches of human or veterinary medicinal products in any member state within the European Union (EU);2.those who have achieved Qualified Person status under the transitionalarrangements for human medicines are eligible to certify batches of human or veterinary medicinal products, and such certification is restricted toacting in the United Kingdom (UK) although such products, once certified, can legally be sold or supplied throughout the EU;3.those who have achieved Qualified Person status under the transitionalarrangements for veterinary medicines are only eligible to certify batches of veterinary medicinal products, and such certification is restricted toacting in the UK although such products, once certified, can legally be sold or supplied throughout the EU.4.4The Code applies equally to Qualified Persons involved in human and/or veterinary medicines.4.5The Licensing Authority may refer to this Code in connection with disciplinary proceedings against a Qualified Person under Article 52 of Directive 2001/83/EC or Article 56 of Directive 2001/82/EC.5.0 Terminology5.1The terminology used in this Code of Practice corresponds with that used in the current versions of the EC directives on Good Pharmaceutical Manufacturing Practice (GMP) and the Guide to Good Pharmaceutical Manufacturing Practice.5.2Within the EU the terms Marketing Authorisation, Manufacturing Authorisation and Investigational Medicinal Products Authorisation are generally used and shall henceforth be referred to throughout this Code.The UK licensing system currently uses the equivalent terms Product Licence (= Marketing Authorisation) and Manufacturer’s Licence (= Manufacturing Authorisation).6.0 General Principles6.1Pharmaceutical Manufacturers and the Competent Authorities of the Member States have a duty to ensure that patients are properly protected and that medicinal products meet appropriate requirements for safety, quality and efficacy.6.2The legal framework is provided by the European Directives and “The Rules Governing Medicinal Products in the European Union”, which are implemented by individual Member States’ national legislation.6.3An operational framework is provided in the current Volume 4 of the Rules Governing Medical Products in the European Union “Good Manufacturing Practices”. In Chapter 1 of the Guidelines, Quality Management, it states that:“The 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, the company’s suppliers and the distributors.To achieve the quality objective reliably there must be a comprehensively designed and correctly implemented system of Quality Assurance incorporating Good Manufacturing Practice and thus Quality Control. 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 and Quality Control 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.”6.4Qualified Persons should be aware that whilst Quality Management applies to full-scale manufacture, it also extends to original product design, development, formulation and preparation of medicinal products for use in clinical trials. This includes the establishment of well-defined manufacturing processes, sampling programmes and analytical tests methods and appropriate specifications for ingredients, printed and unprinted packaging components and finished dosage forms.7.0 Routine Duties of a Qualified PersonQualified Persons have routine duties, some of which may be delegated (see later), in line with the above general principles. Before certifying a batch prior to release the Qualified Person doing so should always ensure that the following requirements have been met:“The meaning of the word ensure in this context is that the Qualified Person must be confident that various actions, which may not be under his/her direct control, have in fact been taken.” See also Section 8.The Marketing Authorisation and Manufacturing Authorisation or Investigational Medicinal Products Authorisation requirements for the Medicinal Products have been met for the batch concerned.7.2The principles and guidelines of GMP as stated in Directive 2003/94/EC (Human) or Directive 91/412/EEC (Veterinary) and as interpreted in the EU Guide to GMP have been followed.7.3The principal manufacturing and testing processes have been validated.7.4All the necessary quality control checks and tests have been performed, and account taken of the manufacturing and packaging conditions including a review of batch records. The EU Guide to GMP suggests that the Head of Production and the Head of Quality Control assume line management responsibilities for these activities.7.5Any changes or deviations in manufacturing, packaging or quality control have been notified in accordance with a well-defined reporting system before any product batch is released. Such changes may need notification to and approval by the Competent Authorities of the Member States.7.6Any additional sampling, inspection, tests and checks have been carried out or initiated, as appropriate, to cover changes or deviations.All necessary manufacturing, packaging and associated documentation has been completed and endorsed by suitably authorised staff trained in the concept of Quality Assurance and Good Manufacturing Practices.7.8Regular audits, self-inspections and spot checks are being carried out by experienced staff.7.9All relevant factors have been considered including any not specifically associated with the output batch directly under review (e.g. calibration and maintenance records, environmental monitoring).7.10The legal requirements regarding imported products have been fully met. For products imported from outside the EU or EEA, the Qualified Person should ensure testing within the EU/EEA to the requirements of the Marketing Authorisation and any other tests to assure quality of the products, unless a mutual recognition agreement between the EU and the third country concerned allows the acceptance of manufacturer’s batch certification in lieu.The Qualified Person should also be satisfied that the medicinal products have been manufactured in accordance with GMP standards which are equivalent to those of the EU or EEA.7.11The Qualified Person should also recognise the need to consult other company experts in the various areas of the Study Guide to reinforce his/her knowledge on appropriate points when a doubtful situation arises (e.g. stability, unusual analytical results, process or equipment changes, potential environmental or microbiological risks, re-labelling, abnormal yields, cross contamination risks etc.).To maintain a register (or equivalent document) as a record of product batches certified by the Qualified Person prior to batch release.7.13To retain reference samples of each product batch at the site of manufacture for a period of time in compliance with EU regulations and the Licensing Authority’s requirements.7.14In considering how to perform the above duties, 7.1 to 7.13, the Qualified Person will have to take account of the nature and size of the operations being performed. For example, in a very small company with a limited range of products it may be possible that the Qualified Person can take direct responsibility for some or all of the tasks outlined above. In larger organisations, the Qualified Person will be dependent upon the knowledge and expertise of his/her colleagues in undertaking some or all of the tasks.However, it is of paramount importance that the Qualified Person takes steps, within a well planned Quality Management System, to assure himself or herself that the tasks allocated are in fact being performed satisfactorily. Hence the routine duties of the Qualified Person depend very much upon a team effort wherein the individuals concerned realise the position and responsibility of the Qualified Person and provide every support.What cannot be over emphasised in this context is the Qualified Person’s commitment to meet regularly with professional colleagues in all functional groups and to understand their contribution and impact upon quality.The certification of a batch prior to release must be performed by a Qualified Person.8.0 Performance of Duties and Regulatory Compliance 8.1Management, as a requirement of Quality Assurance, should clearly define the areas of work and the method of operating in the absence of the regular Qualified Person.In the absence of one Qualified Person, the task of certifying batches can only be delegated to another Qualified Person nominated on the Manufacturing Authorisation and who is knowledgeable and experienced with regard to the medicinal products under review.8.2Whilst each Qualified Person has a personal and professional responsibility for being certain that the various checks and tests have been carried out, the detail of this work is described in the EU Guide to GMP as normally the responsibility of the Head of Production and the Head of Quality Control who must ensure that appropriately trained and experienced staff are available.Ultimately the Qualified Person must be satisfied either directly or, more usually, by the proper operation of quality systems, which include appropriate approvals, audits, self inspections and spot checks that manufacturing, packaging and quality control testing have complied with relevant requirements.Batch certification without such adequate steps may be regarded as professional misconduct.8.3It must be recognised that the Qualified Person depends upon many of his/her working colleagues for the achievement of quality and regulatory compliance in the manufacture of medicinal products. It is therefore of paramount importance that he or she achieves a good working relationship with other persons in positions of responsibility. These are likely to include those responsible for: •processing and packing operations•quality control laboratories•validation。

II(Information)INFORMATION FROM EUROPEAN UNION INSTITUTIONS, BODIES, OFFICESAND AGENCIESOTHER ACTSGuidelinesof 7 March 2013on Good Distribution Practice of Medicinal Products for Human Use(2013/C 68/01)INTRODUCTIONThese guidelines are based on Article 84 and Article 85(b)(3) of Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use (1) (Directive 2001/83/EC).The wholesale distribution of medicinal products is an important activity in integrated supply chain management. Today’s distribution network for medicinal products is increasingly complex and involves many players. These guidelines lay down appropriate tools to assist wholesale distributors in conducting their activities and to prevent falsified medicines from entering the legal supply chain. Compliance with these guidelines will ensure control of the distribution chain and consequently maintain the quality and the integrity of medicinal products.According to Article 1(17) of Directive 2001/83/EC, wholesale distribution of medicinal products is all activities consisting of procuring, holding, supplying or exporting medicinal products, apart from supplying medicinal products to the public. Such activities are carried out with manufacturers or their depos­itories, importers, other wholesale distributors or with pharmacists and persons authorized or entitled to supply medicinal products to the public in the Member State concerned.Any person acting as a wholesale distributor has to hold a wholesale distribution authorisation. Article 80(g) of Directive 2001/83/EC provides that distributors must comply with the principles of and guidelines for good distribution practice (GDP). Possession of a manufacturing authorisation includes author­isation to distribute the medicinal products covered by the au­thorisation. Manufacturers performing any distribution activities with their own products must therefore comply with GDP.The definition of wholesale distribution does not depend on whether that distributor is established or operating in specific customs areas, such as in free zones or in free warehouses. All obligations related to wholesale distribution activities (such as exporting, holding or supplying) also apply to these distributors. Relevant sections of these guidelines should also be adhered to by other actors involved in the distribution of medicinal products.Other actors such as brokers may also play a role in the distribution channel for medicinal products. According to Article 85(b), persons brokering medicinal products must be subject to certain provisions applicable to wholesale distributors, as well as specific provisions on brokering.CHAPTER 1 — QUALITY MANAGEMENT1.1. PrincipleWholesale distributors must maintain a quality system setting out responsibilities, processes and risk management principles in relation to their activities (2). All distribution activities should be clearly defined and systematically reviewed. All critical steps of distribution processes and significant changes should be justified and where relevant validated. The quality system is the responsibility of the organisation’s management and requires their leadership and active participation and should be supported by staff commitment.(1) OJ L 311, 28.11.2001, p. 67. (2) Article 80(h) of Directive 2001/83/EC.1.2. Quality systemThe system for managing quality should encompass the organ­isational structure, procedures, processes and resources, as well as activities necessary to ensure confidence that the product delivered maintains its quality and integrity and remains within the legal supply chain during storage and/or transportation.The quality system should be fully documented and its effecti­veness monitored. All quality system-related activities should be defined and documented. A quality manual or equivalent docu­mentation approach should be established.A responsible person should be appointed by the management, who should have clearly specified authority and responsibility for ensuring that a quality system is implemented and maintained.The management of the distributor should ensure that all parts of the quality system are adequately resourced with competent personnel, and suitable and sufficient premises, equipment and facilities.The size, structure and complexity of distributor’s activities should be taken into consideration when developing or modifying the quality system.A change control system should be in place. This system should incorporate quality risk management principles, and be proportionate and effective.The quality system should ensure that:(i) medicinal products are procured, held, supplied or exportedin a way that is compliant with the requirements of GDP;(ii) management responsibilities are clearly specified;(iii) products are delivered to the right recipients within a satisfactory time period;(iv) records are made contemporaneously;(v) deviations from established procedures are documented and investigated;(vi) appropriate corrective and preventive actions (commonly known as CAPA) are taken to correct deviations and prevent them in line with the principles of quality risk management.1.3. Management of outsourced activitiesThe quality system should extend to the control and review of any outsourced activities related to the procurement, holding, supply or export of medicinal products. These processes should incorporate quality risk management and include:(i) assessing the suitability and competence of the ContractAcceptor to carry out the activity and checking authorisation status, if required;(ii) defining the responsibilities and communication processes for the quality-related activities of the parties involved;(iii) monitoring and review of the performance of the Contract Acceptor, and the identification and implementation of any required improvements on a regular basis.1.4. Management review and monitoringThe management should have a formal process for reviewing the quality system on a periodic basis. The review should include:(i) measurement of the achievement of quality systemobjectives;(ii) assessment of performance indicators that can be used to monitor the effectiveness of processes within the quality system, such as complaints, deviations, CAPA, changes to processes; feedback on outsourced activities; self-assessment processes including risk assessments and audits; and external assessments such as inspections, findings and customer audits;(iii) emerging regulations, guidance and quality issues that can impact the quality management system;(iv) innovations that might enhance the quality system;(v) changes in business environment and objectives.The outcome of each management review of the quality system should be documented in a timely manner and effectively communicated internally.1.5. Quality risk managementQuality risk management is a systematic process for the assessment, control, communication and review of risks to the quality of medicinal products. It can be applied both proactively and retrospectively.Quality risk management 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 process should be commensurate with the level of risk. Examples of the processes and applications of quality risk management can be found in guideline Q9 of the International Conference on Harmonisation (ICH).CHAPTER 2 — PERSONNEL2.1. PrincipleThe correct distribution of medicinal products relies upon people. For this reason, there must be sufficient competent personnel to carry out all the tasks for which the wholesale distributor is responsible. Individual responsibilities should be clearly understood by the staff and be recorded.2.2. Responsible personThe wholesale distributor must designate a person as Responsible Person. The Responsible Person should meet the qualifications and all conditions provided for by the legislation of the Member State concerned (1). A degree in pharmacy is desirable. The Responsible Person should have appropriate competence and experience as well as knowledge of and training in GDP.The Responsible Person should fulfil their responsibilities personally and should be continuously contactable. The Responsible Person may delegate duties but not responsibilities.The written job description of the Responsible Person should define their authority to take decisions with regard to their responsibilities. The wholesale distributor should give the Responsible Person the defined authority, resources and responsibility needed to fulfil their duties.The Responsible Person should carry out their duties in such a way as to ensure that the wholesale distributor can demonstrate GDP compliance and that public service obligations are met.The responsibilities of the Responsible Person include:(i) ensuring that a quality management system isimplemented and maintained;(ii) focusing on the management of authorised activities and the accuracy and quality of records;(iii) ensuring that initial and continuous training programmes are implemented and maintained;(iv) coordinating and promptly performing any recall operations for medicinal products;(v) ensuring that relevant customer complaints are dealt with effectively;(vi) ensuring that suppliers and customers are approved;(vii) approving any subcontracted activities which may impact on GDP;(viii) ensuring that self-inspections are performed at appropriate regular intervals following a prearranged programme and necessary corrective measures are put in place;(ix) keeping appropriate records of any delegated duties;(x) deciding on the final disposition of returned, rejected, recalled or falsified products;(xi) approving any returns to saleable stock;(xii) ensuring that any additional requirements imposed on certain products by national law are adhered to (2).2.3. Other personnelThere should be an adequate number of competent personnel involved in all stages of the wholesale distribution activities of medicinal products. The number of personnel required will depend on the volume and scope of activities.The organisational structure of the wholesale distributor should be set out in an organisation chart. The role, responsibilities, and interrelationships of all personnel should be clearly indicated.The role and responsibilities of employees working in key positions should be set out in written job descriptions, along with any arrangements for deputising.2.4. TrainingAll personnel involved in wholesale distribution activities should be trained on the requirements of GDP. They should have the appropriate competence and experience prior to commencing their tasks.Personnel should receive initial and continuing training relevant to their role, based on written procedures and in accordance with a written training programme. The Responsible Person should also maintain their competence in GDP through regular training.(1) Article 79(b) of Directive 2001/83/EC. (2) Article 83 of Directive 2001/83/EC.In addition, training should include aspects of product identifi­cation and avoidance of falsified medicines entering the supply chain.Personnel dealing with any products which require more stringent handling conditions should receive specific training. Examples of such products include hazardous products, radio­active materials, products presenting special risks of abuse (including narcotic and psychotropic substances), and temperature-sensitive products.A record of all training should be kept, and the effectiveness of training should be periodically assessed and documented.2.5. HygieneAppropriate procedures relating to personnel hygiene, relevant to the activities being carried out, should be established and observed. Such procedures should cover health, hygiene and clothing.CHAPTER 3 — PREMISES AND EQUIPMENT3.1. PrincipleWholesale distributors must have suitable and adequate premises, installations and equipment (1), so as to ensure proper storage and distribution of medicinal products. In particular, the premises should be clean, dry and maintained within acceptable temperature limits.3.2. PremisesThe premises should be designed or adapted to ensure that the required storage conditions are maintained. They should be suitably secure, structurally sound and of sufficient capacity to allow safe storage and handling of the medicinal products. Storage areas should be provided with adequate lighting to enable all operations to be carried out accurately and safely.Where premises are not directly operated by the wholesale distributor, a contract should be in place. The contracted premises should be covered by a separate wholesale distribution authorisation.Medicinal products should be stored in segregated areas which are clearly marked and have access restricted to authorised personnel. Any system replacing physical segregation, such as electronic segregation based on a computerised system, should provide equivalent security and should be validated.Products pending a decision as to their disposition or products that have been removed from saleable stock should be segregated either physically or through an equivalent electronic system. This includes, for example, any product suspected of falsification and returned products. Medicinal products received from a third country but not intended for the Union market should also be physically segregated. Any falsified medicinal products, expired products, recalled products and rejected products found in the supply chain should be immediately physically segregated and stored in a dedicated area away from all other medicinal products. The appropriate degree of security should be applied in these areas to ensure that such items remain separate from saleable stock. These areas should be clearly identified.Special attention should be paid to the storage of products with specific handling instructions as specified in national law. Special storage conditions (and special authorisations) may be required for such products (e.g. narcotics and psychotropic substances).Radioactive materials and other hazardous products, as well as products presenting special safety risks of fire or explosion (e.g. medicinal gases, combustibles, flammable liquids and solids), should be stored in one or more dedicated areas subject to local legislation and appropriate safety and security measures.Receiving and dispatch bays should protect products from prevailing weather conditions. There should be adequate separation between the receipt and dispatch and storage areas. Procedures should be in place to maintain control of inbound/ outbound goods. Reception areas where deliveries are examined following receipt should be designated and suitably equipped.Unauthorised access to all areas of the authorised premises should be prevented. Prevention measures would usually include a monitored intruder alarm system and appropriate access control. Visitors should be accompanied.Premises and storage facilities should be clean and free from litter and dust. Cleaning programmes, instructions and records should be in place. Appropriate cleaning equipment and cleaning agents should be chosen and used so as not to present a source of contamination.Premises should be designed and equipped so as to afford protection against the entry of insects, rodents or other animals. A preventive pest control programme should be in place.Rest, wash and refreshment rooms for employees should be adequately separated from the storage areas. The presence of food, drink, smoking material or medicinal products for personal use should be prohibited in the storage areas.(1) Article 79(a) of Directive 2001/83/EC.3.2.1. Temperature and environment controlSuitable equipment and procedures should be in place to check the environment where medicinal products are stored. Environ­mental factors to be considered include temperature, light, humidity and cleanliness of the premises.An initial temperature mapping exercise should be carried out on the storage area before use, under representative conditions. Temperature monitoring equipment should be located according to the results of the mapping exercise, ensuring that monitoring devices are positioned in the areas that experience the extremes of fluctuations. The mapping exercise should be repeated according to the results of a risk assessment exercise or whenever significant modifications are made to the facility or the temperature controlling equipment. For small premises of a few square meters which are at room temperature, an assessment of potential risks (e.g. heaters) should be conducted and temperature monitors placed accordingly.3.3. EquipmentAll equipment impacting on storage and distribution of medicinal products should be designed, located and maintained to a standard which suits its intended purpose. Planned main­tenance should be in place for key equipment vital to the functionality of the operation.Equipment used to control or to monitor the environment where the medicinal products are stored should be calibrated at defined intervals based on a risk and reliability assessment.Calibration of equipment should be traceable to a national or international measurement standard. Appropriate alarm systems should be in place to provide alerts when there are excursions from predefined storage conditions. Alarm levels should be appropriately set and alarms should be regularly tested to ensure adequate functionality.Equipment repair, maintenance and calibration operations should be carried out in such a way that the integrity of the medicinal products is not compromised.Adequate records of repair, maintenance and calibration activities for key equipment should be made and the results should be retained. Key equipment would include for example cold stores, monitored intruder alarm and access control systems, refrigerators, thermo hygrometers, or other temperature and humidity recording devices, air handling units and any equipment used in conjunction with the onward supply chain. 3.3.1. Computerised systemsBefore a computerised system is brought into use, it should be demonstrated, through appropriate validation or verification studies, that the system is capable of achieving the desired results accurately, consistently and reproducibly.A written, detailed description of the system should be available (including diagrams where appropriate). This should be kept up to date. The document should describe principles, objectives, security measures, system scope and main features, how the computerised system is used and the way it interacts with other systems.Data should only be entered into the computerised system or amended by persons authorised to do so.Data should be secured by physical or electronic means and protected against accidental or unauthorised modifications. Stored data should be checked periodically for accessibility. Data should be protected by backing up at regular intervals. Backup data should be retained for the period stated in national legislation but at least 5 years at a separate and secure location.Procedures to be followed if the system fails or breaks down should be defined. This should include systems for the restoration of data.3.3.2. Qualification and validationWholesale distributors should identify what key equipment qualification and/or key process validation is necessary to ensure correct installation and operation. The scope and extent of such qualification and/or validation activities (such as storage, pick and pack processes) should be determined using a documented risk assessment approach.Equipment and processes should be respectively qualified and/or validated before commencing use and after any significant changes (e.g. repair or maintenance).Validation and qualification reports should be prepared summarising the results obtained and commenting on any observed deviations. Deviations from established procedures should be documented and further actions decided to correct deviations and avoid their reoccurrence (corrective and preventive actions). The principles of CAPA should be applied where necessary. Evidence of satisfactory validation and acceptance of a process or piece of equipment should be produced and approved by appropriate personnel.CHAPTER 4 — DOCUMENTATION4.1. PrincipleGood documentation constitutes an essential part of the quality system. Written documentation should prevent errors from spoken communication and permits the tracking of relevant operations during the distribution of medicinal products.4.2. GeneralDocumentation comprises all written procedures, instructions, contracts, records and data, in paper or in electronic form. Documentation should be readily available/retrievable.With regard to the processing of personal data of employees, complainants or any other natural person, Directive 95/46/EC on the protection of individuals applies to the processing of personal data and to the free movement of such data.Documentation should be sufficiently comprehensive with respect to the scope of the wholesale distributor’s activities and in a language understood by personnel. It should be written in clear, unambiguous language and be free from errors.Procedures should be approved signed and dated by the responsible person. Documentation should be approved, signed and dated by appropriate authorised persons, as required. It should not be handwritten; although, where it is necessary, sufficient space should be provided for such entries.Any alteration made in the documentation should be signed and dated; the alteration should permit the reading of the original information. Where appropriate, the reason for the alteration should be recorded.Documents should be retained for the period stated in national legislation but at least 5 years. Personal data should be deleted or anonymised as soon as their storage is no longer than necessary for the purpose of distribution activities.Each employee should have ready access to all necessary documentation for the tasks executed.Attention should be paid to using valid and approved procedures. Documents should have unambiguous content; title, nature and purpose should be clearly stated. Documents should be reviewed regularly and kept up to date. Version control should be applied to procedures. After revision of a document a system should exist to prevent inadvertent use of the superseded version. Superseded or obsolete procedures should be removed from workstations and archived. Records must be kept either in the form of purchase/sales invoices, delivery slips, or on computer or any other form, for any transaction in medicinal products received, supplied or brokered.Records must include at least the following information: date; name of the medicinal product; quantity received, supplied or brokered; name and address of the supplier, customer, broker or consignee, as appropriate; and batch number at least for medicinal product bearing the safety features (1).Records should be made at the time each operation is undertaken.CHAPTER 5 — OPERATIONS5.1. PrincipleAll actions taken by wholesale distributors should ensure that the identity of the medicinal product is not lost and that the wholesale distribution of medicinal products is performed according to the information on the outer packaging. The wholesale distributor should use all means available to minimise the risk of falsified medicinal products entering the legal supply chain.All medicinal products distributed in the EU by a wholesale distributor must be covered by a marketing authorisation granted by the EU or by a Member State (2).Any distributor, other than the marketing authorisation holder, who imports a medicinal product from another Member State must notify the marketing authorisation holder and the competent authority in the Member State to which the medicinal product will be imported of their intention to import that product (3). All key operations described below should be fully described in the quality system in appropriate documentation.5.2. Qualification of suppliersWholesale distributors must obtain their supplies of medicinal products only from persons who are themselves in possession of a wholesale distribution authorisation, or who are in possession of a manufacturing authorisation which covers the product in question (4).Wholesale distributors receiving medicinal products from third countries for the purpose of importation, i.e. for the purpose of placing these products on the EU market, must hold a manufacturing authorisation (5).(1) Articles 80(e) and 82 of Directive 2001/83/EC.(2) Articles 76(1) and) (2) of Directive 2001/83/EC.(3) Article 76(3) of Directive 2001/83/EC.(4) Article 80(b) of Directive 2001/83/EC.(5) Article 40, third paragraph of Directive 2001/83/EC.Where medicinal products are obtained from another wholesale distributor the receiving wholesale distributor must verify that the supplier complies with the principles and guidelines of good distribution practices and that they hold an authorisation for example by using the Union database. If the medicinal product is obtained through brokering, the wholesale distributor must verify that the broker is registered and complies with the requirements in Chapter 10 (1).Appropriate qualification and approval of suppliers should be performed prior to any procurement of medicinal products. This should be controlled by a procedure and the results documented and periodically rechecked.When entering into a new contract with new suppliers the wholesale distributor should carry out ‘due diligence’ checks in order to assess the suitability, competence and reliability of the other party. Attention should be paid to:(i) the reputation or reliability of the supplier;(ii) offers of medicinal products more likely to be falsified;(iii) large offers of medicinal products which are generally only available in limited quantities; and(iv) out-of-range prices.5.3. Qualification of customersWholesale distributors must ensure they supply medicinal products only to persons who are themselves in possession of a wholesale distribution authorisation or who are authorised or entitled to supply medicinal products to the public.Checks and periodic rechecks may include: requesting copies of customer’s authorisations according to national law, verifying status on an authority website, requesting evidence of qualifications or entitlement according to national legislation.Wholesale distributors should monitor their transactions and investigate any irregularity in the sales patterns of narcotics, psychotropic substances or other dangerous substances. Unusual sales patterns that may constitute diversion or misuse of medicinal product should be investigated and reported to competent authorities where necessary. Steps should be taken to ensure fulfilment of any public service obligation imposed upon them.5.4. Receipt of medicinal productsThe purpose of the receiving function is to ensure that the arriving consignment is correct, that the medicinal products originate from approved suppliers and that they have not been visibly damaged during transport.Medicinal products requiring special storage or security measures should be prioritised and once appropriate checks have been conducted they should be immediately transferred to appropriate storage facilities.Batches of medicinal products intended for the EU and EEA countries should not be transferred to saleable stock before assurance has been obtained in accordance with written procedures, that they are authorised for sale. For batches coming from another Member State, prior to their transfer to saleable stock, the control report referred to in Article 51(1) of Directive 2001/83/EC or another proof of release to the market in question based on an equivalent system should be carefully checked by appropriately trained personnel.5.5. StorageMedicinal products and, if necessary, healthcare products should be stored separately from other products likely to alter them and should be protected from the harmful effects of light, temperature, moisture and other external factors. Particular attention should be paid to products requiring specific storage conditions.Incoming containers of medicinal products should be cleaned, if necessary, before storage.Warehousing operations must ensure appropriate storage conditions are maintained and allow for appropriate security of stocks.Stock should be rotated according to the first expiry, first out (FEFO) principle. Exceptions should be documented.Medicinal products should be handled and stored in such a manner as to prevent spillage, breakage, contamination and mix-ups. Medicinal products should not be stored directly on the floor unless the package is designed to allow such storage (such as for some medicinal gas cylinders).Medicinal products that are nearing or are beyond their expiry date/shelf life should be withdrawn immediately from saleable stock either physically or through other equivalent electronic segregation.(1) Article 80, fourth paragraph of Directive 2001/83/EC.。

1. 在制药工艺中，哪项是质量控制的关键步骤？A. 原料采购B. 产品包装C. 中间体检测D. 成品储存2. 制药工艺中的“GMP”代表什么？A. Good Manufacturing PracticeB. General Manufacturing ProcessC. Global Medical ProductD. Good Market Potential3. 哪种设备常用于制药工艺中的混合操作？A. 离心机B. 搅拌机C. 干燥机D. 压片机4. 在制药工艺中，哪项技术用于去除药物中的微生物？A. 过滤B. 蒸馏C. 冷冻D. 萃取5. 制药工艺中的“API”代表什么？A. Active Pharmaceutical IngredientB. Advanced Pharmaceutical InterfaceC. Application Programming InterfaceD. Automated Production Integration6. 哪种材料常用于制药工艺中的胶囊壳制造？A. 塑料B. 玻璃C. 明胶D. 金属7. 在制药工艺中，哪项技术用于提高药物的稳定性？A. 冷冻干燥B. 高温灭菌C. 超声波处理D. 微波加热8. 制药工艺中的“SOP”代表什么？A. Standard Operating ProcedureB. System Optimization ProtocolC. Special Operation ProgramD. Standardized Object Protocol9. 哪种设备常用于制药工艺中的粉碎操作？A. 混合机B. 研磨机C. 干燥机D. 包装机10. 在制药工艺中，哪项技术用于分离药物中的杂质？A. 过滤B. 蒸馏C. 萃取D. 离子交换11. 制药工艺中的“HPLC”代表什么？A. High Performance Liquid ChromatographyB. High Pressure Liquid ChromatographyC. High Precision Laboratory ChemistryD. High Polymer Liquid Chromatography12. 哪种材料常用于制药工艺中的片剂包衣？A. 塑料B. 明胶C. 聚合物D. 糖13. 在制药工艺中，哪项技术用于检测药物的纯度？A. 色谱法B. 光谱法C. 电泳法D. 质谱法14. 制药工艺中的“FDA”代表什么？A. Food and Drug AdministrationB. Federal Drug AssociationC. Food Distribution AuthorityD. Federal Dietary Agency15. 哪种设备常用于制药工艺中的干燥操作？A. 混合机B. 研磨机C. 干燥机D. 包装机16. 在制药工艺中，哪项技术用于提高药物的溶解度？A. 冷冻干燥B. 高温灭菌C. 超声波处理D. 微粉化17. 制药工艺中的“cGMP”代表什么？A. Current Good Manufacturing PracticeB. Comprehensive Good Manufacturing ProcessC. Continuous General Manufacturing PracticeD. Control Group Manufacturing Process18. 哪种材料常用于制药工艺中的注射剂容器？A. 塑料B. 玻璃C. 金属D. 陶瓷19. 在制药工艺中，哪项技术用于检测药物的微生物污染？A. 色谱法B. 光谱法C. 电泳法D. 微生物检测20. 制药工艺中的“USP”代表什么？A. United States PharmacopeiaB. Universal Standard ProtocolC. Uniform System ProcedureD. United Scientific Protocol21. 哪种设备常用于制药工艺中的灭菌操作？A. 混合机B. 研磨机C. 干燥机D. 灭菌器22. 在制药工艺中，哪项技术用于提高药物的生物利用度？A. 冷冻干燥B. 高温灭菌C. 超声波处理D. 微粉化23. 制药工艺中的“ICH”代表什么？A. International Conference on HarmonizationB. International Chemical HarmonizationC. Integrated Chemical HandlingD. International Chemical Hazard24. 哪种材料常用于制药工艺中的口服液容器？A. 塑料B. 玻璃C. 金属D. 陶瓷25. 在制药工艺中，哪项技术用于检测药物的含量？A. 色谱法B. 光谱法C. 电泳法D. 滴定法26. 制药工艺中的“EMA”代表什么？A. European Medicines AgencyB. European Medical AssociationC. Emergency Medical AidD. European Medical Analysis27. 哪种设备常用于制药工艺中的包装操作？A. 混合机B. 研磨机C. 干燥机D. 包装机28. 在制药工艺中，哪项技术用于提高药物的稳定性？A. 冷冻干燥B. 高温灭菌C. 超声波处理D. 微粉化29. 制药工艺中的“GCP”代表什么？A. Good Clinical PracticeB. General Clinical ProtocolC. Global Clinical ProgramD. Good Control Practice30. 哪种材料常用于制药工艺中的片剂制造？A. 塑料B. 玻璃C. 明胶D. 淀粉31. 在制药工艺中，哪项技术用于检测药物的晶型？A. 色谱法B. 光谱法C. 电泳法D. X射线衍射32. 制药工艺中的“GLP”代表什么？A. Good Laboratory PracticeB. General Laboratory ProtocolC. Global Laboratory ProgramD. Good Logistic Practice33. 哪种设备常用于制药工艺中的萃取操作？A. 混合机B. 研磨机C. 干燥机D. 萃取器34. 在制药工艺中，哪项技术用于提高药物的生物活性？A. 冷冻干燥B. 高温灭菌C. 超声波处理D. 微粉化35. 制药工艺中的“GSP”代表什么？A. Good Storage PracticeB. General Storage ProtocolC. Global Storage ProgramD. Good Supply Practice36. 哪种材料常用于制药工艺中的软胶囊制造？A. 塑料B. 玻璃C. 明胶D. 淀粉37. 在制药工艺中，哪项技术用于检测药物的粒度？A. 色谱法B. 光谱法C. 电泳法D. 粒度分析38. 制药工艺中的“GDP”代表什么？A. Good Distribution PracticeB. General Distribution ProtocolC. Global Distribution ProgramD. Good Dispensing Practice39. 哪种设备常用于制药工艺中的压片操作？A. 混合机B. 研磨机C. 干燥机D. 压片机40. 在制药工艺中，哪项技术用于提高药物的溶解速度？A. 冷冻干燥B. 高温灭菌C. 超声波处理D. 微粉化41. 制药工艺中的“GAP”代表什么？A. Good Agricultural PracticeB. General Agricultural ProtocolC. Global Agricultural ProgramD. Good Analytical Practice42. 哪种材料常用于制药工艺中的注射用水制造？A. 自来水B. 蒸馏水C. 矿泉水D. 纯净水43. 在制药工艺中，哪项技术用于检测药物的残留溶剂？A. 色谱法B. 光谱法C. 电泳法D. 气相色谱法44. 制药工艺中的“GVP”代表什么？A. Good Validation PracticeB. General Validation ProtocolC. Global Validation ProgramD. Good Verification Practice45. 哪种设备常用于制药工艺中的过滤操作？A. 混合机B. 研磨机C. 干燥机D. 过滤器46. 在制药工艺中，哪项技术用于提高药物的生物相容性？A. 冷冻干燥B. 高温灭菌C. 超声波处理D. 表面改性47. 制药工艺中的“GTP”代表什么？A. Good Testing PracticeB. General Testing ProtocolC. Global Testing ProgramD. Good Technical Practice48. 哪种材料常用于制药工艺中的冻干粉末制造？A. 塑料B. 玻璃C. 明胶D. 淀粉49. 在制药工艺中，哪项技术用于检测药物的重金属含量？A. 色谱法B. 光谱法C. 电泳法D. 原子吸收光谱法50. 制药工艺中的“GMP”代表什么？A. Good Manufacturing PracticeB. General Manufacturing ProcessC. Global Medical ProductD. Good Market Potential51. 哪种设备常用于制药工艺中的蒸馏操作？A. 混合机B. 研磨机C. 干燥机D. 蒸馏器52. 在制药工艺中，哪项技术用于提高药物的稳定性？A. 冷冻干燥B. 高温灭菌C. 超声波处理D. 微粉化53. 制药工艺中的“GCP”代表什么？A. Good Clinical PracticeB. General Clinical ProtocolC. Global Clinical ProgramD. Good Control Practice54. 哪种材料常用于制药工艺中的片剂包衣？A. 塑料B. 明胶C. 聚合物D. 糖55. 在制药工艺中，哪项技术用于检测药物的纯度？A. 色谱法B. 光谱法C. 电泳法D. 质谱法56. 制药工艺中的“FDA”代表什么？A. Food and Drug AdministrationB. Federal Drug AssociationC. Food Distribution AuthorityD. Federal Dietary Agency57. 哪种设备常用于制药工艺中的干燥操作？A. 混合机B. 研磨机C. 干燥机D. 包装机58. 在制药工艺中，哪项技术用于提高药物的溶解度？A. 冷冻干燥B. 高温灭菌C. 超声波处理D. 微粉化59. 制药工艺中的“cGMP”代表什么？A. Current Good Manufacturing PracticeB. Comprehensive Good Manufacturing ProcessC. Continuous General Manufacturing PracticeD. Control Group Manufacturing Process60. 哪种材料常用于制药工艺中的注射剂容器？A. 塑料B. 玻璃C. 金属D. 陶瓷答案1. C2. A3. B4. A5. A6. C7. A8. A10. A11. A12. D13. A14. A15. C16. D17. A18. B19. D20. A21. D22. D23. A24. A25. D26. A27. D28. A29. A30. D31. D32. A33. D34. D35. A36. C37. D38. A39. D40. D41. A42. D43. D44. A45. D46. D47. A48. D49. D50. A51. D52. A53. A54. D55. A56. A57. C58. D60. B。

精心整理INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USEICH H ARMONISED T RIPARTITE G UIDELINEG OOD M ANUFACTURING P RACTICE G UIDE FOR A CTIVE P HARMACEUTICAL I NGREDIENTSQ7Having reached Step 4 of the ICH Process at the ICH Steering Committee meeting on 10 November 2000, this guideline is recommended for adoption to the three regulatory parties to ICHTable of Contents 目录1. INTRODUCTION 1. 前言1.1 Objective 1.1 目的1.2 Regulatory Applicability 1.2 法规的适用性1.3 Scope 1.3 范围2. QUALITY MANAGEMENT 2.质量管理2.1 Principles 2.1 总则2.2 Responsibilities of the Quality Unit(s) 2.2 质量部门的责任精心整理2.3 Responsibility for Production Activities 2.3 生产的职责2.4 Internal Audits (Self Inspection) 2.4 内部审计（自检）2.5 Product Quality Review 2.5 产品质量回顾3. PERSONNEL 3. 人员3.1 Personnel Qualifications 3.1人员资格3.2 Personnel Hygiene 3.2 个人卫生3.3 Consultants 3.3 顾问4. BUILDINGS AND FACILITIES 4. 建筑和设施4.1 Design and Construction 4.1 设计和建造4.2 Utilities 4.2 公用设施4.3 Water 4.3 水4.4 Containment 4.4 特殊限制4.5 Lighting 4.5 照明5.3 Calibration7.4 Storage8.2 Time Limits9.1 General9.3 Label Issuance and Control 9.3 标签发放与管理9.4 Packaging and Labeling Operations 9.4 包装和贴签管理10. STORAGE AND DISTRIBUTION 10.储存和分发10.1 Warehousing Procedures 10.1 入库程序10.2 Distribution Procedures 10.2 分发程序11. LABORATORY CONTROLS 11.实验室管理11.1 General Controls 11.1通则11.2 Testing of Intermediates and APIs 11.2 中间体和原料药的检测11.3 Validation of Analytical Procedures 11.3 分析方法的验证11.4 Certificates of Analysis 11.4 检验报告11.5 Stability Monitoring of APIs 11.5 原料药的稳定性考察11.6 Expiry and Retest Dating 11.6 有效期和复验期11.7 Reserve/Retention Samples 11.7 留样12. VALIDATION 12.验证精心整理12.1 Validation Policy 12.1 验证方针12.2 Validation Documentation 12.2 验证文件12.3 Qualification 12.3 确认12.4 Approaches to Process Validation 12.4 工艺验证的方法12.5 Process Validation Program 12.5 工艺验证的程序12.6 Periodic Review of Validated Systems 12.6 对已验证的系统的定期回顾12.7 Cleaning Validation 12.7 清洗验证12.8 Validation of Analytical Methods 12.8 分析方法的验证13. CHANGE CONTROL 13.变更控制14. REJECTION AND RE-USE OF MATERIALS 14.物料的拒收和再利用14.1 Rejection 14.1 拒收14.2 Reprocessing 14.2 返工14.3 Reworking 14.3 重新加工14.5 Returns17.5 Stability18.1 General19.1 General19.2 Quality19.5 Production19.6 Validation19.7 Changes20. Glossary1. INTRODUCTION 1. 简介1.1 Objective 1.1 目的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 possess.本文件旨在提供在适当的体系下为了控制生产原料药的质量而实施的药品生产质量管理规范（GMP）的指南。

医疗仪器器械税收分类编码医疗仪器器械税收分类编码一、引言医疗仪器器械在现代医疗领域中发挥着重要作用，对于人类的健康事业具有不可忽视的影响力。

为了规范医疗仪器器械的管理和分类，各国都建立了相应的税收分类编码体系。

医疗仪器器械税收分类编码旨在为税务部门提供准确、清晰的分类标准，便于对医疗仪器器械进行识别、计税和管理。

本文将深入探讨医疗仪器器械税收分类编码的背景、分类方式以及对企业和行业的影响。

二、医疗仪器器械税收分类编码的背景税收分类是指根据特定的类别将纳税人和商品进行分类的过程，以便进行税收管理和征税。

医疗仪器器械作为一类特殊的商品，其分类尤为重要。

医疗仪器器械的种类繁多，性质复杂，仅凭外观或功能无法准确判断其真实用途和价值。

建立医疗仪器器械税收分类编码体系可以提供准确、可靠的分类标准，方便税务部门对医疗仪器器械进行管理和计税。

三、医疗仪器器械税收分类编码的分类方式医疗仪器器械税收分类编码的分类方式通常采用层次化、综合性的原则。

根据仪器器械的功能和用途，将其分为不同的类别和子类别，并依次细分，以达到准确分类的目的。

在国际上，常用的医疗仪器器械税收分类编码体系包括世界关贸组织（WTO）的国际贸易统一编号和欧盟的CN编码等。

这些编码体系旨在提供国际范围内的统一分类标准，方便跨国贸易和合作。

四、医疗仪器器械税收分类编码的影响医疗仪器器械税收分类编码对于企业和行业有着重要的影响。

对于企业来说，准确的税收分类可以帮助企业了解市场需求和竞争状况，有助于制定市场营销策略和产品研发方向。

税收分类还直接关系到企业的纳税额和财务成本。

不同分类的医疗仪器器械可能适用不同的税率和优惠政策，正确的分类可以减少纳税风险和成本。

医疗仪器器械税收分类编码的建立对于行业的发展和监管也具有积极意义。

它可以提供行业统计数据，为政府部门制定政策和规划提供参考依据，促进行业的健康发展。

五、个人观点和理解医疗仪器器械税收分类编码的建立和完善对于医疗行业的可持续发展至关重要。

1.《中华人民共和国药品管理法》Drug Control Law of the People's Republic of China2.药品生产企业管理control over drug manufacturers3.药品经营企业管理control over drug distributors4.医疗机构的药剂管理control over medicines in medical institutions5.药品管理control over drugs6.药品包装的管理control over drug packaging7.药品价格和广告的管理control over drug price and advertisement8.药品监督inspection of drugs9.法律责任legal liabilities10.药品标识labels or marks of the drugs11.假药counterfeit drugs12.劣药inferior drugs13.药品检验机构drug quality control laboratory14.药品的生产企业drug manufacturers15.经营企业drug distributors16.医疗机构medical institutions17.药品监督管理部门drug regulatory agency18.药品批准证明文件drug approval documents19.行政处分administrative sanctions20.刑事责任criminal liabilities21.药品生产质量管理规范Good Manufacturing Practice for Pharmaceutical Products (GMP)22.药品经营质量管理规范Good Supply Practice for Pharmaceutical Products (GSP)23.药品生产许可证Drug Manufacturing Certificate24.药品经营许可证Drug Supply Certificate25.医疗机构制剂许可证Pharmaceutical Preparation Certificate for Medical Institution26.进口药品注册证书Import Drug License27.临床试验clinical trial28.新药证书New Drug Certificate29.药品批准文号Drug Approval Number30.在中华人民共和国境内从事药品的研制、生产、经营、使用和监督管理的单位或者个人，必须遵守《中华人民共和国药品管理法》All institutions or individuals engaged in research, production, distribution, use, and administration and supervision of drugs in the People's Republic of China shall abide by drug control law of the people's republic of China.31.国务院药品监督管理部门主管全国药品监督管理工作。

国际药物注册英语词汇互译FDA(fooｄaｎd dｒug ａdmiｎistration):(美国)食品药品监督管理局NDA（ｎeｗdrug applicatiｏｎ):新药申请ANDＡ(abｂrｅviated new drug aｐpｌicatｉon）：简化新药申请EP（expoｒｔａpplicａtｉon）:出口药申请（申请出口不被批准在美国销售的药品）treaｔmｅnt ＩND：研究中的新药用于治疗aｂbreviaｔｅｄ(new）ｄｒug：简化申请的新药ＤＭF（ｄruｇmasｔer fiｌe）:药物主文件(持有者为谨慎起见而准备的保密资料，可以包括一个或多个人用药物在制备、加工、包装和贮存过程中所涉及的设备、生产过程或物品。

只有在DＭF持有者或授权代表以授权书的形式授权给FDA,ＦＤA在审查IND、NDA、AＮDA时才能参考其内容）holdｅr:DＭF持有者CＦＲ（cｏdｅof federaｌｒegｕlatioｎ）:(美国)联邦法规PANEＬ:专家小组ｂａｔch pｒｏduction：批量生产；分批生产batchｐｒoductioｎrecoｒdｓ:生产批号记录pｏst oｒpre-ｍarkｅt ｓurｖeillancｅ：销售前或销售后监督ｉnfｏrmed conｓｅnt:知情同意（患者对治疗或受试者对医疗试验了解后表示同意接受治疗或试验）ｐrescription ｄｒuｇ：处方药OＴC drｕg（oｖer—tｈe—cｏunｔer drｕg):非处方药U.Ｓ. ｐuｂlｉｃheaｌth servｉce：美国卫生福利部NIH(nａtional insｔitute of heaｌth):(美国）全国卫生研究所ａniｍaｌtrａｉl:动物试验ａccelerateｄaｐprｏｖａl：加速批准standardｄrug：标准药物invesｔiｇatoｒ：研究人员;调研人员prｅｐａring ａnｄsubmiｔｔinｇ:起草和申报submission：申报;递交bｅnｅｆit(s):受益riｓｋ（s）:受害drｕg ｐroduｃｔ：药物产品druｇsuｂstance:原料药establｉsｈed naｍe:确定的名称geｎericｎame：非专利名称ｐｒoprietary name：专有名称；INＮ(inｔeｒnａtｉｏｎal nonpropｒiｅtarｙname）：国际非专有名称naｒraｔive sｕmmarｙ: 记叙体概要adverｓe eｆfect:副作用adｖerｓeｒeactｉon：不良反应proｔocoｌ:方案archｉvaｌcopｙ:存档用副本reｖiｅｗcopｙ:审查用副本oｆfiｃiａl compenｄium:法定药典（主要指USP、NF)．USP(ｔhe unitｅd staｔe phaｒｍａｃopｅｉa):美国药典（现已和ＮＦ合并一起出版)NF（naｔioｎalｆormuｌary):(美国）国家药品集ｏｆｆiciａl=ｐhaｒmaｃopeiａl = cｏmpｅｎdｉal:药典的;法定的;官方的aｇenｃy:审理部门（指FＤA)sｐonsor：主办者（指负责并着手临床研究者)ideｎtitｙ：真伪；鉴别;特性sｔrength:规格;规格含量(每一剂量单位所含有效成分的量)labelｅｄamount:标示量ｒeｇｕｌａtory specｉficatｉon：质量管理规格标准(NDＡ提供）regｕｌatｏry methoｄｏlogy：质量管理方法(FDＡ用于考核原料药或药物产品是否符合批准了的质量管理规格标准的整套步骤）ｒegulａtory methods validatｉoｎ:管理用分析方法的验证(FDA对ＮDA提供的方法进行验证）Dietary ｓuｐｐｌｅmeｎt:食用补充品ＩCＨ(ＩnternaｔionaｌCoｎfｅrｅｎｃe on Ｈａrmｏnizatiｏn of Tec ｈnicａl Requiremｅｎts foｒＲｅgｉｓtrａtｉon oｆＰhaｒmaceutｉcalｓfoｒＨumanＵｓｅ）人用药物注册技术要求国际协调会议ICH：Quａｌity-质量Q１A(R２): Stability Ｔｅsting ｏf Ｎew Ｄrｕg Subｓtａncｅs ａnｄProdｕctｓ（SecｏndReｖiｓion）新原料药和制剂的稳定性试验（第二版）Ｑ1B: Photostabiliｔy Tｅｓtiｎｇof New Ｄrｕg Substancｅs and Prodｕcts新原料药和制剂的光稳定性试验Q１C:StabiliｔｙＴesting foｒNew Ｄosage Fｏrms新制剂的稳定性试验Q１D: Brａckeｔinｇａnd Ｍａtｒixing Deｓigｎs for Ｓtabiｌity Tesｔing oｆDrugSubstａncｅs and DｒuｇProdｕcｔs原料药和制剂稳定性试验的交叉和矩阵设计Q1E: Evaluatｉon of StaｂｉｌiｔｙDaｔa对稳定性数据的评估处理Q１Ｆ:StａbiliｔｙDatａPackａge fｏｒRegistraｔionＡppｌicaｔions iｎＣｌimaｔｉｃZones III anｄIV在气候带III和IV,药物注册申请所提供的稳定性数据Q2A: Teｘt on Ｖaｌidation of Analyｔｉcal Pｒｏceｄures分析程序的验证Q２B: Ｖalｉdａtｉon of AnalytｉcaｌＰrｏｃｅdurｅｓ:Ｍeｔhodo ｌoｇy分析程序的验证:方法学Ｑ3A（R)：Impuritieｓｉn Nｅw ＤruｇＳｕｂstａnces (ＲeｖiseｄG ｕiｄeline)新原料药中的杂质(修订版）Q3B(R): Impurｉｔies in New Ｄｒug Prｏｄucts （Ｒevised Guideline)新制剂中的杂质（修订版)Q3C: Impuriｔies: Guidｅｌine fｏｒＲｅsidual Ｓolventｓ杂质：残留溶剂指南Q3C(Ｍ）:Ｉmｐurities: Ｇｕｉdeｌine ｆor RｅｓｉduａｌSolventｓ（Maｉntenａnce)杂质:残留溶剂指南(修改内容)Q4: Phaｒmaｃopoｅias药典Q4Ａ：Pｈarmａcｏpoeial Harｍoｎiｓaｔion药典的协调Q４Ｂ:Reｇulatory Accｅｐtａnce ofＰharmａｃopoｅial Iｎteｒｃhangeaｂiｌity药典互替在法规上的可接受性Q5Ａ: Viral Ｓａｆｅty Evａluation ｏfＢiotechｎｏloｇy ProｄｕcｔsＤeriｖｅd from ＣellLiｎes of Human ｏr ＡｎimaｌOriｇin来源于人或者动物细胞系的生物技术产品的病毒安全性评估Q5B: Quａliｔy ｏf Ｂiotechnologｉcal Proｄuｃts:Analysｉs of ｔhｅEｘpressionConｓtruct in Cells Ｕsｅｄfor Ｐroduｃtｉon ｏｆr-DＮA Deｒived Pｒotｅin Productｓ生物技术产品的质量：源于重组DNA的蛋白质产品的生产中所用的细胞中的表达构建分析Ｑ5Ｃ：Qｕaliｔy of Bｉotechｎological Pｒoducts: Ｓtabｉlity TｅsｔinｇofＢiotechnｏlｏgical/BioｌogiｃaｌProducts生物技术产品的质量:生物技术／生物产品的稳定性试验Q5D：Dｅｒｉｖatｉon and Chａraｃterisationｏf Ｃell Sｕbｓtrａtes Ｕsed fｏｒＰroｄuctioｎoｆＢｉｏｔecｈnologiｃaｌ／BioloｇicaｌＰrodｕctｓ用于生产生物技术/生物产品的细胞底物的起源和特征描述Ｑ5E：Comparａｂility of Ｂiotｅchｎｏlogｉcal/Biｏlｏgｉｃal Pro ｄucｔs SubjｅｃtｔｏCｈangｅs in Their Ｍａnufａcｔuriｎg Ｐｒｏcesｓ基于不同生产工艺的生物技术产品/生物产品的可比较性Q６: Sｐecｉficａtｉons fｏr New Dｒug Sｕbstａnces and Prｏductｓ新原料药和制剂的质量规格Q6Ａ: Sｐecｉficａｔiｏns:ＴesｔProcedurｅｓａｎd AｃcｅpｔanceＣｒiteｒｉa for New DrugSubstaｎces aｎd Nｅw Drｕg Produｃts: Chemical Suｂｓtaｎcｅs质量规格:新原料药和新制剂的检验程序和可接收标准:化学物质Ｑ6Ｂ: Specｉｆｉｃａｔioｎs: TeｓｔProcedｕreｓａnd Acｃepｔａnce Criteria forBｉｏｔechnolｏgical/BiｏloｇicaｌＰroｄucts质量规格：生物技术／生物产品的检验程序和可接收标准Q7:Gｏod Manufactｕring Ｐｒacｔices fｏｒPharmaｃｅuｔical Ingrｅdｉeｎtｓ活性药物成份的GMPQ7A: Good ＭanufacturｉnｇPractｉce Ｇｕide foｒActivｅＰｈａrｍaceutｉcalIｎｇｒedｉeｎts活性药物成份的GMP指南Q8：Pｈａrmaceuｔical Develｏｐmeｎt药物研发Ｑ9: Ｑualiｔy Risk Ｍanａｇement质量风险管理ICH:Saｆety-安全S１A：Guｉdeliｎe onｔhｅNｅed fｏrＣaｒcinogenicｉty Stｕdies ofＰhaｒmaceｕticａls药物致癌性研究需要的指南S1B:Tｅｓｔing for Ｃａrciｎogenｉｃity of Pharmａｃeuｔicals药物致癌性的检验S1C:DosｅＳeｌeｃｔiｏn ｆｏr Carcｉnogｅｎiｃity Stｕdies o ｆPhaｒｍａｃｅutiｃals药物致癌性研究之剂量选择S1C（R)：Adｄｅndｕm: Addｉｔｉｏn of a LiｍｉｔＤｏse ａndＲelａted Notｅｓ附录：极限剂量和有关注释的的补充Ｓ2Ａ:Guidａｎｃe on Specific Aspeｃts ｏf ＲegｕlatoryＧeｎotoｘiciｔｙTestｓfoｒＰharmacｅutiｃals受法规管辖的药物基因毒性检验的特定方面的指南Ｓ2Ｂ：Geｎotoxｉｃitｙ: A Standａｒd Batｔery foｒGenotoｘici ｔy Tesｔing ｆｏrPharmacｅuｔicals基因毒性：药物基因毒性检验的标准S3A：Note for Guiｄancｅon Tｏxicokinｅtics: The Assessment of SystemiｃExｐｏsurｅｉｎToxｉcｉtｙSｔudieｓ毒物代谢动力学指南的注释：毒性研究中的全身性暴露量的评估S3Ｂ:Pharmacokinｅtics: Guidancｅfor Reｐeated Dose Tｉssｕe D ｉｓtributionStｕdiｅｓ药物代谢动力学：重复剂量的组织分布研究指南S4: Ｓinｇle DoseＴoxicitｙTｅsts单剂量毒性检验S4Ａ: Ｄuratｉon of Chrｏnic Toxicity Ｔestiｎg in Aniｍａlｓ(Rodeｎt anｄNoｎ-Roｄent Toｘiｃiｔy Tｅstiｎg）动物体内慢性毒性持续时间的检验（啮齿动物和非啮齿动物毒性检验)S5Ａ: Ｄｅteｃtion of Toxiｃity to Ｒeprｏducｔion forＭedicinａl Ｐroducts药物对生殖发育的毒性的检验S5B(M）：Maiｎtenａnｃe oｆthe ICH Guidｅｌiｎe ｏnＴoxicity t ｏMaleＦeｒtｉlity:An Adｄendum tｏｔhe Guidelｉne onＤetecｔion of Toxiｃity to ReprodｕcｔioｎforMeｄicｉnａl Pｒｏｄucts对男性生殖能力的毒性的指南的变动：药物对生殖发育的毒性的检验指南增加了一个附录Ｓ６:Ｐrｅｃｌinical Safety Evａluaｔioｎof Biｏtecｈnology-Ｄerived Pharmacｅｕtiｃaｌs生物技术生产的药物的临床前安全评价S7A：Saｆety Pharmacolｏgy Sｔudieｓfｏr Human Pｈarmaceｕtｉcalｓ人用药的安全药理学研究S7B: The Noncliｎical Eｖaluａtioｎof ｔｈeＰoｔentiaｌｆor D ｅlayed VentｒicuｌarRｅｐoｌarｉzａｔｉon（QＴIｎterval Prolｏｎgatｉon) ＢyＨｕman Phａrmaceuticaｌs药物延迟心室复极化(QT间期）潜在作用的非临床评价S８：Ｉmｍｕnｏｔｏｘicoｌｏgy Ｓtudies ｆoｒHuman Pｈaｒmaceut ｉcals人用药免疫毒理学研究M３（M):Ｍａｉｎtenａncｅof thｅICH Gｕiｄｅline on Nｏn-Ｃｌｉnicａl Saｆｅty Ｓtudies foｒthｅConduｃｔoｆHuman CｌinicaｌTriａｌs fｏｒＰhaｒmａceu ｔｉcalｓ药物的对人临床试验的非临床安全研究指南的变动Ｅ-Efficａcy（有效)E1: Tｈe Extent ｏf Popuｌatｉｏn Ｅxposure toＡssess Cｌiｎiｃal Ｓaｆｅｔy for ＤｒugｓIntended for Lｏng-Ｔｅrm Ｔreａtment ｏf Nｏn－Liｆe-Threaｔening Cｏndｉtions对用于无生命危险情况下长期治疗的药物进行临床安全评估的族群暴露量范围E2A:Clinical SａfetｙData Manaｇｅmenｔ: Ｄefｉｎiｔioｎs and Ｓｔandards forＥxpediｔｅｄＲeｐoｒting临床安全数据管理:速报制度的定义和标准E2B（R)：Rｅvisionｏf ｔhe Ｅ２B(M）ＩCＨGuideliｎeｏn Clｉnｉcａl SaｆetyＤataＭanagemenｔDａｔａElemｅnts foｒTransmｉssioｎof Ｉｎdivid ｕal Case SafeｔyRｅｐoｒts个案安全报告送交的临床安全数据管理的数据要素指南(E2B（M)）的修订版E２B （M)：Mａｉｎtenaｎｃe ｏf the Clｉnｉcal SaｆｅtｙDat ａMａnagement iｎcludｉｎg:Data ElementｓfoｒTｒansmissioｎof IndiｖｉduａｌCａse Sａfety Rｅpoｒｔｓ临床安全数据管理的变动包括：个案安全报告送交的数据要素E２B(Ｍ)：Ｍａinｔenanｃe of thｅCliniｃａl Sａfｅty DaｔａMａｎa ｇemｅnt incｌudiｎｇＱｕestiｏｎs and Ａnｓwerｓ临床安全数据管理的变动,包括问答E2Ｃ: Cｌiniｃａl SａｆeｔｙDatａＭａnagｅment:Pｅｒioｄic Sa ｆety UpdateＲeporｔs ｆorMarkｅｔed Drｕgs临床安全数据管理：已上市药品的周期性安全数据更新报告Ａdｄenｄum tｏE２Ｃ: Periodic Safety Update RepｏrtｓfoｒMarketｅd DrugsE2C的附录:已上市药品的周期性安全数据更新报告E２D: Pｏst－Apｐrｏval Safeｔy DataＭａｎagemｅｎt：Ｄefｉni ｔｉｏns ａｎｄSｔandａrｄs forＥxpeｄiｔｅd Reｐｏｒtiｎg批准后的安全数据管理:速报制度的定义和标准E2E:PhaｒmacoviｇiｌａncｅPlaｎning药物警戒计划E３:Sｔrｕcture ａnd ＣontenｔｏｆClｉniｃａl Sｔudy Reｐorts临床研究报告的结构和内容E4: Ｄｏse-Respoｎse Iｎfｏrmaｔion to Support Ｄrｕg Ｒegｉstrａｔion支持药品注册的剂量-效应资料E5:Ethnic Ｆactoｒｓinｔhe ＡccepｔaｂilityｏfＦorｅiｇn ClinｉcａｌＤata引入海外临床数据时要考虑的人种因素Ｅ6: GｏｏｄCｌiｎical Pｒactice: Consｏliｄａｔed Guideｌine ＧCＰ：良好的临床规范：统一的指南E７: Sｔudiｅs inＳupport of Ｓpeｃial Pｏpｕlａtioｎｓ: Gerｉatrics对特定族群的支持的研究:老人病学E８: Gｅneral Consiｄeratｉoｎs for Clinical Trialｓ对临床试验的总的考虑E9: Statｉstical Princiｐｌeｓfor CｌiｎicａｌTrｉａlｓ临床试验的统计原则E１0: Choice of ControｌGｒoup and Rｅｌated Issｕeｓｉn Cliniｃal Trials临床试验中控制组和有关课题的选择E１１: Clinicａl Investigaｔｉonｏf MｅdicinaｌＰｒoducts in the ＰediatricＰopｕｌatｉon小儿科药物的临床调查E１2A：Princiｐlｅs fｏｒＣlｉnical Evaluaｔion ｏf Nｅw Ａntihyp ｅｒtenｓivｅDrｕgs新抗高血压药物的临床评价原则E14: ThｅClinical EｖaluaｔioｎｏｆQＴ/ＱＴｃInteｒｖal Pｒolongatiｏn andPrｏaｒrhythｍｉc Ｐotｅnｔial ｆｏr Noｎ-Antiarrhythmic Drugs非抗心率失常药物的QT/ＱTc间期和致心率失常潜在作用的临床评价ＭｕltidisｃiｐｌinａrｙＧuidｅｌｉｎeｓ多学科兼容的指南M１:ＭedｉcaｌTｅｒminology医学术语M２: ＥｌeｃtronｉｃSｔandards fｏr Ｔranｓmissiｏn of ＲegulaｔoryＩnfｏrmatiｏn（ＥSＴRI)药政信息传递之电子标准Ｍ3：ＴimingｏｆＰre-cliniｃalＳtｕdies in Ｒelatｉoｎｔo Cli ｎical Ｔrｉals（SeeSａfｅtyＴｏpicｓ)有关临床试验的临床前研究的时间安排M４: The Common Techｎical Docuｍent （Sｅe CＴD seｃｔioｎfｏrｃｏmpletｅStatus ofthｅguidelｉnes）通用技术文件(见有关CTD章节)Ｍ5:Data Eｌeｍｅnts and Stａndａrds for ＤrugＤｉctionaries药物词典的数据要素和标准临床试验常用的英文缩略语TTP：time-to－proｇresｓｉon疾病进展时间SAE: seｖeriｔy Aｄveｒｓe Evｅnt 严重不良事件AE：ＡdveｒｓｅEｖｅnt 不良事件SOP：Staｎdard OｐeratinｇProcedｕｒｅ标准操作规程ＣＲＦ：Cａse Rｅport foｒm病例报告表ＤLＴ: 剂量限制毒性MTD: 最大耐受剂量KPS：Ｋａrnｏｆｓky Ｐerfoｒmaｎce Ｓｔatus行为状态评分CR：complｅteｒｅsponsｅ完全缓解PR: partiａl ｒesponse部分缓解SD：病情稳定PD：pｒoｇressive diｓeａse病情进展CTC: 常用药物毒性标准IＥC: indｅpｅndent ethics committｅｅ独立伦理委员会IRB ：ｉｎstituｔｉｏnal reｖiew boａｒd伦理委员会ＣRA: 临床研究助理ＣRＯ：Contrａct Ｒeseａrch Orｇaniｚation 合同研究组织ＤFＳ: Diseａse Frｅe Sｕrvival 无病生存期OS：（OvｅｒａlｌSurvivａl)总生存时间ＩC: Iｎformed ｃonｓｅnt知情同意ADR: Ａｄverｓe Drｕg Rｅaｃｔion不良反应GAＰ:ＧｏoｄAｇｒiｃulturaｌPracｔice中药材种植管理规范ＧCP:Good Clｉnicａl Practice 药物临床试验质量管理规范GLP:Good Ｌａbｏratoｒy Prａctice 药品实验室管理规范GMP:Good Ｍａｎuｆacturｉng Praｃticｅ药品生产质量管理规范ＧＳＰ:Good Supply Praｃtice药品经营质量管理规范ＧUP：Ｇood Use Praｃtice 药品使用质量管理规范PI：Principal inｖestigator 主要研究者ＣI：Co－iｎｖeatigａｔor 合作研究者SI ：Sｕb-invesｔｉgator 助理研究者CＯI :Ｃｏoｒdinating inｖｅｓtiｇtoｒ协调研究者DＧMP:医疗器械生产质量管理规范ICＦ: Ｉnｆoｒmed conｓenｔforｍ知情同意书RCT : randｏmizedｃontrolleｄtｒiａl, 随机对照试验NRＣCT：nｏn-rａndｏmized concurrｅntｃontrolleｄtrｉａl, 非随机同期对照试验ＥBＭ：evidenｃe-ｂasｅd meｄicine 循证医学RCD：randomized croｓs-over disgｎ随机交叉对照试验HCT: historial ｃontrolｔrial,历史对照研究RECISＴ: Ｒｅｓpoｎse Ｅvaluation CriｔeriａＩn Solid Tｕmｏrs．实体瘤疗效反应的评价标准QＣ：Quａlｉty Cｏnｔｒol质量控制ＵＡDR: UnexｐectｅｄAｄverse Dｒｕg Reacｔｉon，非预期药物不良反应。

FDA（food and drug adminisration）：（美国）食品药品监督管理局NDA（new drug application）：新药申请ANDA（abbreviated new drug application）：简化新药申请EP（export application）：出口药申请（申请出口不被批准在美国销售的药品）treatment IND：研究中的新药用于治疗abbreviated（new）drug：简化申请的新药DMF（drug master file）：药物主文件（持有者为谨慎起见而准备的保密资料，可以包括一个或多个人用药物在制备、加工、包装和贮存过程中所涉及的设备、生产过程或物品。

只有在DMF持有者或授权代表以授权书的形式授权给FDA，FDA在审查IND、NDA、ANDA时才能参考其内容）holder：DMF持有者CFR（code of federal regulation）：（美国）联邦法规PANEL：专家小组batch production：批量生产；分批生产batch production records：生产批号记录post or pre-market surveillance：销售前或销售后监督informed consent：知情同意（患者对治疗或受试者对医疗试验了解后表示同意接受治疗或试验）prescription drug：处方药OTC drug（over—the—counter drug）：非处方药U.S. public health service：美国卫生福利部NIH（national institute of health）：（美国）全国卫生研究所animal trail：动物试验accelerated approval：加速批准standard drug：标准药物investigator ：研究人员；调研人员preparing and submitting：起草和申报submission：申报；递交benefit(s)：受益risk（s）：受害drug product：药物产品drug substance：原料药established name：确定的名称generic name：非专利名称proprietary name：专有名称；INN（international nonproprietary name）：国际非专有名称narrative summary: 记叙体概要adverse effect：副作用adverse reaction：不良反应protocol：方案archival copy：存档用副本review copy：审查用副本official compendium：法定药典（主要指USP、NF）．USP（the united state pharmacopeia）：美国药典（现已和NF合并一起出版）NF（national formulary）：（美国）国家药品集official＝pharmacopeial = compendial：药典的；法定的；官方的agency：审理部门（指FDA）sponsor：主办者（指负责并着手临床研究者）identity：真伪；鉴别；特性strength：规格；规格含量（每一剂量单位所含有效成分的量）labeled amount：标示量regulatory specification：质量管理规格标准（NDA提供）regulatory methodology：质量管理方法（FDA用于考核原料药或药物产品是否符合批准了的质量管理规格标准的整套步骤）regulatory methods validation：管理用分析方法的验证（FDA对NDA提供的方法进行验证）Dietary supplement：食用补充品ICH（International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use)人用药物注册技术要求国际协调会议ICH：Quality-质量Q1A(R2): Stability Testing of New Drug Substances and Products (SecondRevision)新原料药和制剂的稳定性试验（第二版）Q1B: Photostability Testing of New Drug Substances and Products新原料药和制剂的光稳定性试验Q1C: Stability Testing for New Dosage Forms新制剂的稳定性试验Q1D: Bracketing and Matrixing Designs for Stability Testing of DrugSubstances and Drug Products原料药和制剂稳定性试验的交叉和矩阵设计Q1E: Evaluation of Stability Data对稳定性数据的评估处理Q1F: Stability Data Package for Registration Applications in ClimaticZones III and IV在气候带III和IV，药物注册申请所提供的稳定性数据Q2A: Text on Validation of Analytical Procedures分析程序的验证Q2B: Validation of Analytical Procedures: Methodology分析程序的验证：方法学Q3A(R): Impurities in New Drug Substances (Revised Guideline)新原料药中的杂质（修订版）Q3B(R): Impurities in New Drug Products (Revised Guideline)新制剂中的杂质（修订版）Q3C: Impurities: Guideline for Residual Solvents杂质：残留溶剂指南Q3C(M): Impurities: Guideline for Residual Solvents (Maintenance)杂质：残留溶剂指南（修改内容）Q4: Pharmacopoeias药典Q4A: PharmacopoeialHarmonisation药典的协调Q4B: Regulatory Acceptance of Pharmacopoeial Interchangeability药典互替在法规上的可接受性Q5A: Viral Safety Evaluation of Biotechnology Products Derived from CellLines of Human or Animal Origin来源于人或者动物细胞系的生物技术产品的病毒安全性评估Q5B: Quality of Biotechnological Products: Analysis of the ExpressionConstruct in Cells Used for Production of r-DNA Derived Protein Products生物技术产品的质量：源于重组DNA的蛋白质产品的生产中所用的细胞中的表达构建分析Q5C: Quality of Biotechnological Products: Stability Testing ofBiotechnological/Biological Products生物技术产品的质量：生物技术/生物产品的稳定性试验Q5D: Derivation and Characterisation of Cell Substrates Used forProduction of Biotechnological/Biological Products用于生产生物技术/生物产品的细胞底物的起源和特征描述Q5E: Comparability of Biotechnological/Biological Products Subject toChanges in Their Manufacturing Process基于不同生产工艺的生物技术产品/生物产品的可比较性Q6: Specifications for New Drug Substances and Products新原料药和制剂的质量规格Q6A: Specifications: Test Procedures and Acceptance Criteria for New DrugSubstances and New Drug Products: Chemical Substances质量规格：新原料药和新制剂的检验程序和可接收标准：化学物质Q6B: Specifications: Test Procedures and Acceptance Criteria forBiotechnological/Biological Products质量规格：生物技术/生物产品的检验程序和可接收标准Q7: Good Manufacturing Practices for Pharmaceutical Ingredients活性药物成份的GMPQ7A: Good Manufacturing Practice Guide for Active PharmaceuticalIngredients活性药物成份的GMP指南Q8: Pharmaceutical Development药物研发Q9: Quality Risk Management质量风险管理ICH：Safety-安全S1A: Guideline on the Need for Carcinogenicity Studies of Pharmaceuticals药物致癌性研究需要的指南S1B: Testing for Carcinogenicity of Pharmaceuticals药物致癌性的检验S1C: Dose Selection for Carcinogenicity Studies of Pharmaceuticals药物致癌性研究之剂量选择S1C(R): Addendum: Addition of a Limit Dose and Related Notes附录：极限剂量和有关注释的的补充S2A: Guidance on Specific Aspects of Regulatory Genotoxicity Tests forPharmaceuticals受法规管辖的药物基因毒性检验的特定方面的指南S2B: Genotoxicity: A Standard Battery for Genotoxicity Testing forPharmaceuticals基因毒性：药物基因毒性检验的标准S3A: Note for Guidance on Toxicokinetics: The Assessment of SystemicExposure in Toxicity Studies毒物代谢动力学指南的注释：毒性研究中的全身性暴露量的评估S3B: Pharmacokinetics: Guidance for Repeated Dose Tissue DistributionStudies药物代谢动力学：重复剂量的组织分布研究指南S4: Single Dose Toxicity Tests单剂量毒性检验S4A: Duration of Chronic Toxicity Testing in Animals (Rodent andNon-Rodent Toxicity Testing)动物体内慢性毒性持续时间的检验（啮齿动物和非啮齿动物毒性检验）S5A: Detection of Toxicity to Reproduction for Medicinal Products药物对生殖发育的毒性的检验S5B(M): Maintenance of the ICH Guideline on Toxicity to Male Fertility:An Addendum to the Guideline on Detection of Toxicity to Reproduction forMedicinal Products对男性生殖能力的毒性的指南的变动：药物对生殖发育的毒性的检验指南增加了一个附录S6: Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals生物技术生产的药物的临床前安全评价S7A: Safety Pharmacology Studies for Human Pharmaceuticals人用药的安全药理学研究S7B: The Nonclinical Evaluation of the Potential for Delayed VentricularRepolarization(QT Interval Prolongation) By Human Pharmaceuticals药物延迟心室复极化（QT间期）潜在作用的非临床评价S8: Immunotoxicology Studies for Human Pharmaceuticals人用药免疫毒理学研究M3(M): Maintenance of the ICH Guideline on Non-Clinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals药物的对人临床试验的非临床安全研究指南的变动E-Efficacy（有效）E1: The Extent of Population Exposure to Assess Clinical Safety for DrugsIntended for Long-Term Treatment of Non-Life-Threatening Conditions对用于无生命危险情况下长期治疗的药物进行临床安全评估的族群暴露量范围E2A: Clinical Safety Data Management: Definitions and Standards forExpedited Reporting临床安全数据管理：速报制度的定义和标准E2B(R): Revision of the E2B(M) ICH Guideline on Clinical Safety DataManagement Data Elements for Transmission of Individual Case SafetyReports个案安全报告送交的临床安全数据管理的数据要素指南（E2B（M））的修订版E2B (M): Maintenance of the Clinical Safety Data Management including:Data Elements for Transmission of Individual Case Safety Reports临床安全数据管理的变动包括：个案安全报告送交的数据要素E2B(M): Maintenance of the Clinical Safety Data Management includingQuestions and Answers临床安全数据管理的变动，包括问答E2C: Clinical Safety Data Management: Periodic Safety Update Reports forMarketed Drugs临床安全数据管理：已上市药品的周期性安全数据更新报告Addendum to E2C: Periodic Safety Update Reports for Marketed DrugsE2C的附录：已上市药品的周期性安全数据更新报告E2D: Post-Approval Safety Data Management: Definitions and Standards for Expedited Reporting批准后的安全数据管理：速报制度的定义和标准E2E: Pharmacovigilance Planning药物警戒计划E3: Structure and Content of Clinical Study Reports临床研究报告的结构和内容E4: Dose-Response Information to Support Drug Registration支持药品注册的剂量－效应资料E5: Ethnic Factors in the Acceptability of Foreign Clinical Data引入海外临床数据时要考虑的人种因素E6: Good Clinical Practice: Consolidated GuidelineGCP：良好的临床规范：统一的指南E7: Studies in Support of Special Populations: Geriatrics对特定族群的支持的研究：老人病学E8: General Considerations for Clinical Trials对临床试验的总的考虑E9: Statistical Principles for Clinical Trials临床试验的统计原则E10: Choice of Control Group and Related Issues in Clinical Trials临床试验中控制组和有关课题的选择E11: Clinical Investigation of Medicinal Products in the PediatricPopulation小儿科药物的临床调查E12A: Principles for Clinical Evaluation of New Antihypertensive Drugs新抗高血压药物的临床评价原则E14: The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs非抗心率失常药物的QT/QTc间期和致心率失常潜在作用的临床评价Multidisciplinary Guidelines 多学科兼容的指南M1: Medical Terminology医学术语M2: Electronic Standards for Transmission of Regulatory Information (ESTRI)药政信息传递之电子标准M3: Timing of Pre-clinical Studies in Relation to Clinical Trials (SeeSafety Topics)有关临床试验的临床前研究的时间安排M4: The Common Technical Document (See CTD section for complete Status of the guidelines)通用技术文件（见有关CTD章节）M5: Data Elements and Standards for Drug Dictionaries药物词典的数据要素和标准临床试验常用的英文缩略语TTP：time-to-progression 疾病进展时间SAE：severity Adverse Event 严重不良事件AE：Adverse Event 不良事件SOP：Standard Operating Procedure 标准操作规程CRF：Case Report form 病例报告表DLT：剂量限制毒性MTD：最大耐受剂量KPS：Karnofsky Performance Status行为状态评分CR：complete response完全缓解PR：partial response部分缓解SD：病情稳定PD：progressive disease病情进展CTC：常用药物毒性标准IEC：independent ethics committee 独立伦理委员会IRB ：institutional review board 伦理委员会CRA：临床研究助理CRO：Contract Research Organization 合同研究组织DFS：Disease Free Survival 无病生存期OS：（Overall Survival）总生存时间IC：Informed consent 知情同意ADR：Adverse Drug Reaction 不良反应GAP：Good Agricultural Practice 中药材种植管理规范GCP：Good Clinical Practice 药物临床试验质量管理规范GLP：Good Laboratory Practice 药品实验室管理规范GMP：Good Manufacturing Practice 药品生产质量管理规范GSP：Good Supply Practice 药品经营质量管理规范GUP：Good Use Practice 药品使用质量管理规范PI ：Principal investigator 主要研究者CI：Co-inveatigator合作研究者SI ：Sub-investigator 助理研究者COI ：Coordinating investigtor协调研究者DGMP：医疗器械生产质量管理规范ICF：Informed consent form 知情同意书RCT ：randomized controlled trial, 随机对照试验NRCCT：non-randomized concurrent controlled trial, 非随机同期对照试验EBM：evidence-based medicine 循证医学RCD：randomized cross-over disgn随机交叉对照试验HCT：historial control trial, 历史对照研究RECIST：Response Evaluation Criteria In Solid Tumors. 实体瘤疗效反应的评价标准QC：Quality Control质量控制UADR：Unexpected Adverse Drug Reaction，非预期药物不良反应。

EUROPEAN COMMISSION 欧盟委员会ENTERPRISE AND INDUSTRY DIRECTORATE-GENERAL 企业与工业管理局Consumer goods 消费品Pharmaceuticals 药品Brussels, 03 February 2010 布鲁塞尔2010.02.03ENTR/F/2/AM/an D(2010) 3374EudraLex（European Union Law On drug regulatory affairs）欧盟药品法规The Rules Governing Medicinal Products in the European Union欧盟医药产品管理规则Volume 4卷4Good Manufacturing Practice良好生产规范Medicinal Products for Human and Veterinary Use人用和兽用医药产品Part II: Basic Requirements for Active Substances used as Starting Materials 第二部分：作为起始物料的原料药的基本要求Table of Contents目录1 Introduction1简介1.1 Objective1.1目的1.2 Regulatory Applicability1.2法规适用性1.3 Scope1.3范围2 Quality Management2质量管理2.1 Principles2.1原则2.2 Quality Risk Management2.2质量风险管理2.3 Responsibilities of the Quality Unit(s) 2.3质量部门的职责2.4 Responsibility for Production Activities 2.4生产活动的职责2.5 Internal Audits (Self-Inspection)2.5内部审计（自检）2.6 Product Quality Review2.6产品质量回顾3 Personnel3 人员3.1 Personnel Qualifications3.1 人员资质3.2 Personnel Hygiene3.2 人员卫生3.3 Consultants3.3 顾问4 Buildings and Facilities4 厂房设施4.1 Design and Construction4.1 设计和建造4.2 Utilities4.2 公用工程4.3 Water4.3 水4.4 Containment4.4 限制4.5 Lighting4.5 照明4.6 Sewage and Refuse4.6 废水废物4.7 Sanitation and Maintenance4.7 公共卫生及保养5 Process Equipment5 工艺设备5.1 Design and Construction5.1 设计和建造5.2 Equipment Maintenance and Cleaning5.2 设备的保养和清洁5.3 Calibration5.3 校验5.4 Computerized Systems5.4 计算机系统6 Documentation and Records6 文件和记录6.1 Documentation System and Specifications6.1 文件系统与规格标准6.2 Equipment Cleaning and Use Record6.2 设备清洁和使用记录6.3 Records of Raw Materials, Intermediates, API Labelling and Packaging Materials 6.3 原料、中间产品、原料药的标签和包装材料的记录6.4 Master Production Instructions (Master Production and Control Records)6.4 生产指令（生产和控制记录）6.5 Batch Production Records (Batch Production and Control Records)6.5批生产记录（批生产和控制记录）6.6 Laboratory Control Records6.6 实验室控制记录（批检验记录）6.7 Batch Production Record Review6.7批生产记录审核7 Materials Management7 物料管理7.1 General Controls7.1 控制通则7.2 Receipt and Quarantine7.2 接受和待检7.3 Sampling and Testing of Incoming Production Materials7.3 到货物料的取样和检测7.4 Storage7.4 贮存7.5 Re-evaluation7.5 再评估8 Production and In-Process Controls8 生产和过程控制8.1 Production Operations8.1 生产操作8.2 Time Limits8.2 时间限制8.3 In-process Sampling and Controls8.3 中控取样和控制8.4 Blending Batches of Intermediates or APIs8.4 中间产品和原料药的混批8.5 Contamination Control8.5 污染控制9 Packaging and Identification Labelling of APIs and Intermediates 9 中间产品和原料药的包装和贴签9.1 General9.1 总则9.2 Packaging Materials9.2 包装材料9.3 Label Issuance and Control9.3 标签放行和控制9.4 Packaging and Labelling Operations9.4 包装和贴签操作10 Storage and Distribution10 贮存和销售10.1 Warehousing Procedures10.1 入库程序10.2 Distribution Procedures10.2 销售程序11 Laboratory Controls11 实验室控制11.1 General Controls11.1 控制通则11.2 Testing of Intermediates and APIs11.2 中间产品和原料药的检测11.3 Validation of Analytical Procedures11.3 分析方法的验证11.4 Certificates of Analysis11.4 分析报告11.5 Stability Monitoring of APIs11.5 原料药的稳定性监测11.6 Expiry and Retest Dating11.6 失效和复检日期11.7 Reserve/Retention Samples11.7 留样12 Validation12 验证12.1 Validation Policy12.1 验证方针12.2 Validation Documentation12.2 验证文件12.3 Qualification12.3 确认12.4 Approaches to Process Validation12.4 工艺验证方法12.5 Process Validation Program12.5 工艺验证计划12.6 Periodic Review of Validated Systems12.6 验证系统的定期审核12.7 Cleaning Validation12.7 清洁验证12.8 Validation of Analytical Methods12.8 分析方法验证13 Change Control13 变更控制14 Rejection and Reuse of Materials14 物料的拒收和再利用14.1 Rejection14.1 拒收14.2 Reprocessing14.2 返工14.3 Reworking14.3 重新加工14.4 Recovery of Materials and Solvents14.4 物料和溶剂的回收利用14.5 Returns14.5 退回15 Complaints and Recalls15 投诉和召回16 Contract Manufacturers (including Laboratories)16 合同生产企业（包含实验室）17 Agents, Brokers, Traders, Distributors, Repackers, and Relabellers 17 代理商、经纪商、贸易商、经销商、重新包装商和重新贴签商17.1 Applicability17.1 适用性17.2 Traceability of Distributed APIs and Intermediates17.2 已销售中间产品和原料药的追踪17.3 Quality Management17.3 质量管理17.4 Repackaging, Relabelling and Holding of APIs and Intermediates 17.4 中间产品和原料药的重新包装、重新贴签和处理17.5 Stability17.5 稳定性17.6 Transfer of Information17.6 信息的传输17.7 Handling of Complaints and Recalls17.7 投诉和召回的处理17.8 Handling of Returns17.8 退货的处理18 Specific Guidance for APIs Manufactured by Cell Culture/Fermentation 18 用于细胞培养/发酵而得原料药的特殊指南18.1 General18.1 总则18.2 Cell Bank Maintenance and Recordkeeping18.2 细胞库的维护和记录保存18.3 Cell Culture/Fermentation18.3 细胞培养/发酵18.4 Harvesting, Isolation, and Purification18.4 收获、分离和精制18.5 Viral Removal/Inactivation Steps18.5 病毒除去/灭火步骤19 APIs for Use in Clinical Trials19 用于临床试验的原料药19.1 General19.1 总则19.2 Quality19.2 质量19.3 Equipment and Facilities19.3 设备设施19.4 Control of Raw Materials19.4 原料的控制19.5 Production19.5 生产19.6 Validation19.6 验证19.7 Changes19.7 变更19.8 Laboratory Controls19.8 实验室控制19.9 Documentation19.9 文件20 Glossary20 词汇表1 Introduction1 介绍This guideline was published in November 2000 as Annex 18 to the GMP Guide reflecting the EU’s agreement to ICH Q7A and has been used by manufacturers and GMP inspectorates on a voluntary basis. Article 46 (f) of Directive 2001/83/EC and Article 50 (f) of Directive 2001/82/EC; as amended by Directives 2004/27/EC and 2004/28/EC respectively, place new obligations on manufacturing authorisation holders to use only active substances that have been manufactured in accordance with Good Manufacturing Practice for starting materials. The directives go on to say that the principles of Good Manufacturing Practice for active substances are to be adopted as detailed guidelines. Member States have agreed that the text of former Annex 18 should form the basis of the detailed guidelines to create Part II of the GMP Guide.本指南已经在2000年11月以GMP指南附录18的形式公布过，它反应了欧盟对ICH Q7A的认可以，该指南已经被生产商和GMP检查员在自愿的原则下所使用。