Guidelines
of 19 March 2015
on principles of Good Distribution Practice of active substances for medicinal products for human use
人用药活性物质GDP原则指南
(Text with EEA relevance)
(2015/C 95/01)
Introduction 概述
These guidelines are based on the fourth paragraph of Article 47 of Directive 2001/83/EC (1).
这些指南是基于指令2001/83/EC(1)第47条的第4段。
They follow the same principles that underlie the guidelines of EudraLex Volume 4, Part II, Chapter 17, with regard to the distribution of active substances and the Guidelines of 5 November 2013 on Good Distribution Practice of medicinal products for human use (2).
他们遵守在欧盟药品法第4卷第2部分第17章指南中规定的关于原料药销售，和2013年11月5日人用药GDP规范相同的原则。
These guidelines provide stand-alone guidance on Good Distribution Practice (GDP) for importers and distributors of active substances for medicinal products for human use. They complement the rules on distribution set out in the guidelines of EudraLex Volume 4, Part II, and apply also to distributors of active substances manufactured by themselves.
这些指南为人用药所用的原料药的分销商和进口商提供了单独的GDP指南。它们补充了欧盟药品法第4卷第2部分指南中所设定的销售规定，也适用于销售自己生产的原料药的分销商。
Any manufacturing activities in relation to active substances, including re-packaging, re-labelling or dividing up, are subject to Commission Delegated Regulation (EU) No 1252/2014 (3) and EudraLex Volume 4, Part II.
所有与原料药相关的生产活动，包括再包装、再标签或分装均受法规(EU) No 1252/2014 (3) 和欧盟药品法卷4第2部分的管理。
Additional requirements apply to the importation of active substances, as laid down in Article 46b of Directive 2001/83/EC.
适用于原料药进口的额外要求在指令2001/83/EC第46b中列出。
Distributors of active substances for medicinal products for human use should follow these guidelines as of 21 September 2015.
人用药原料药分销商自2015年9月21日起应遵守本指南。
CHAPTER 1 — SCOPE
第1章---范围
These guidelines apply to distribution of active substances, as defined in Article 1(3a) of Directive 2001/83/EC, for medicinal products for human use. According to that provision, an active substance is any substance or mixture of substances intended to be used in the manufacture of a medicinal product and that, when used in its production, becomes an active ingredient of that product intended to exert a pharmacological, immunological or metabolic action with a view to restoring, correcting or modifying physiological functions or to make a medical diagnosis.
这些指南适用于人用药活性物质的分销活动，该活动在指令2001/83/EC第1（3a）条款中进行了定义。根据该条款，原料药是指将用于药品生产的单一物质或混合物质，当其用于生产时，成为发挥药理、免疫或代谢活动的药品的一种活性成分，可以恢复、矫正或修复生理功能或进行医学诊断。
For the purpose of these guidelines, distribution of active substances shall comprise all activities consisting of procuring, importing, holding, supplying or exporting active substances, apart from brokering.
本指南所指原料药分销活动包括所有活动由采购、进口、存贮、供应或出口组成，中间商除外。
These guidelines do not apply to intermediates of active substances.
这些指南不适用于原料药的中间体。
CHAPTER 2 — QUALITY SYSTEM
第2章---质量体系
Distributors of active substances should develop and maintain a quality system setting out responsibilities, processes and risk management principles. Examples of the processes and applications of quality risk management can be found in EudraLex Volume 4, Part III: GMP related documents, ICH guideline Q9 on Quality Risk Management (ICH Q9).
原料药分销商应建立和维护质量体系，设定职责、流程和风险管理原则。在EUDRALEX 第4卷第3部分：GMP相关文件，ICH指南Q9质量风险管理中可以找到质量风险管理流程和应用实例。
The quality system should be adequately resourced with competent personnel, and suitable and sufficient premises, equipment and facilities. It should ensure that:
质量体系应具有足够的有资质的人员，具备适当的充足的设施、设备和场所。它应保证：
l active substances are procured, imported, held, supplied or exported in a way that is compliant with the requirements of GDP for active substances;
l 原料药的生产、进口、存贮、供应和出口应符合原料药GDP要求
l management responsibilities are clearly specified;
l 管理职责清楚界定
l active substances are delivered to the right recipients within a satisfactory time period;
l 原料药在令人满意的时间内被发送给正确的收货人
l records are made contemporaneously;
l 记录同步制作
l deviations from established procedures are documented and investigated;
l 偏出已建立的程序的偏差要记录并调查
l 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;
l 应采取适当的纠正和预防措施，通常大家作为CAPA，来纠正和防止偏差，保证符合质量风险管理原则
l changes that may affect the storage and distribution of active substances are evaluated.
l 可能对原料药存贮和销售有影响的变更应进行评估
The size, structure and complexity of the distributor’s activities should be taken into consideration when developing or modifying the quality system.
在建立和修改质量体系时，要考虑分销商活动的规模、组织结构和复杂程度。
CHAPTER 3 — PERSONNEL
第3章---人员
The distributor should designate a person at each location where distribution activities are performed who should have defined authority and responsibility for ensuring that a quality system is implemented and maintained. The designated person should fulfil his responsibilities personally. The designated person can delegate duties but not responsibilities.
分销商应在每个实施分销活动的地点指定一个人，该人员应被授权并有责任保证实施和维护一个质量体系。指定的人员应亲自履行其职责。指定人员可以转移其工作任务，但不能将其责任转移。
The responsibilities of all personnel involved in the distribution of active substances should be specified in writing. The personnel should be trained on the requirements of GDP for active substances. They should have the appropriate competence and experience to ensure that active substances are properly handled, stored and distributed.
所有参与原料药分销的人员的职责均应以书面形式定义。人员应接受原料药GDP要求的培训。他们应具有适当的资质和经验，以保证原料药被恰当地处理、存贮和销售。
Personnel should receive initial and continuing training relevant to their role, based on written procedures and in accordance with a written training programme.
人员应接受与其工作相关的初始入岗培训和持续培训。培训应根据书面程序进行，符合书面培训计划。
A record of all training should be kept, and the effectiveness of training should be periodically assessed and documented.
所有培训应保存记录，培训有效性应定期评估并记录。
CHAPTER 4 — DOCUMENTATION
第4章---文件记录
Documentation comprises all written procedures, instructions, contracts, records and data, in paper or in electronic form. Documentation should be readily available or retrievable. All documentation related to compliance of the distributor with these guidelines should be made available on request of competent authorities.
文件记录包括所有书面程序、指令、合同、记录和数据，书面的或电子形式的。文件记录应易于获得或恢复。所有与分销商符合这些指南相关的文件记录应均在药监当局要求时可以提供。
Documentation should be sufficiently comprehensive with respect to the scope of the distributor’s activities and in a language understood by personnel. It should be written in clear, unambiguous language and be free from errors.
文件记录应包括与分销活活动范围相关的充分的综合信息，其语言应易于被人理解。书写应清楚无歧义，没有错误。
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.
文件记录中所有修订应签字日期，修改应使得原有信息可以读取。适当时，还要记录修改理由。
Each employee should have ready access to all necessary documentation for the tasks executed.
每位员工应有权限进入完成其工作所必须的所有文件记录。
Procedures 程序
Written procedures should describe the distribution activities which affect the quality of the active substances. This could include receipt and checking of deliveries, storage, cleaning and maintenance of the premises (including pest control), recording of the storage conditions, security of stocks on site and of consignments in transit, withdrawal from saleable stock, handling of returned products, recall plans, etc.
书面程序应描述对原料药质量有影响的分销活动。这可以包括对收到货物的接收、检查、存贮、设施清洁和维保（包括虫鼠控制）、存贮条件记录、现场库存和在途货物安全性、从可销售库存中撤回、退货处理、召回计划等。
Procedures should be approved, signed and dated by the person responsible for the quality system.
程序应经过质量体系负责人批准、签字和日期。
Attention should be paid to the use of valid and approved procedures. 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.
应注意要使用有效的经过批准的程序。文件记录应进行定期审核，保持更新。程序应实施版本控制。在文件修订后，应有一个系统来防止使用失效的文件。前版本或失效程序应从工作场所移除并存档。
Records 记录
Records should be clear, be made at the time each operation is performed and in such a way that all significant activities or events are traceable. Records should be retained for at least 1 year after the expiry date of the active substance batch to which they relate. For active substances with retest dates, records should be retained for at least 3 years after the batch is completely distributed.
记录应清楚，在每个操作实施时即行记录，所有重大活动或事件均应可追溯。记录应保存至少至与记录相关的原料药批次有效期后1年。对于具有复验期的原料药，记录应保存至少在该批次完全销售后3年。
Records should be kept of each purchase and sale, showing the date of purchase or supply, name of the active substance, batch number and quantity received or supplied, and name and address of the supplier and of the original manufacturer, if not the same, or of the shipping agent and/or the consignee. Records should ensure the traceability of the origin and destination of products, so that all the suppliers of, or those supplied with, an active substance can be identified. Records that should be retained and be available include:
每次采购和销售的记录均应保存，并显示采购或销售的日期、原料药名称、批号、收到或发出的数量、供应商和原始生产商（如不同）的名称和地址、或货代和/或收货人的名称和地址。记录应保证原产地和目的地可追踪，这样所有原料药供应商，或收货人，可以识别。应保存并可以获得的记录包括：
l identity of supplier, original manufacturer, shipping agent and/or consignee;
l 供应商、原生产商、货代和/或收货人的识别信息
l address of supplier, original manufacturer, shipping agent and/or consignee;
l 供应商、原生产商、货代和/或收货人的地址
l purchase orders;
l 采购订单
l bills of lading, transportation and distribution records;
l 提单，运输和销售记录
l receipt documents;
l 接收文件
l name or designation of active substance;
l 原料药的名称和目的地
l manufacturer’s batch number;
l 生产商批号
l certificates of analysis, including those of the original manufacturer;
l 检验报告，包括原生产厂的检验报告
l retest or expiry date.
l 复验期或有效期
CHAPTER 5 — PREMISES AND EQUIPMENT
第5章---设施和设备
Premises and equipment should be suitable and adequate to ensure proper storage, protection from contamination, e.g. narcotics, highly sensitising materials, materials of high pharmacological activity or toxicity, and distribution of active substances. They should be suitably secure to prevent unauthorised access. Monitoring devices that are necessary to guarantee the quality attributes of the active substance should be calibrated according to an approved schedule against certified traceable standards.
设施和设备应适当并充分，以保证适当的存贮、保护以防止污染，例如，麻醉品、高致敏物料、高药物活性或毒性物料、以及原料药分销。设施和设备应可以保证防止非法进入。保证原料药的质量属性所必须的监控装置应根据批准的时间计划，采取可追溯的标准进行校正。
CHAPTER 6 — OPERATIONS
第6章---操作
Orders 订货
Where active substances are procured from a manufacturer, importer or distributor established in the EU, that manufacturer, importer or distributor should be registered according to Article 52a of Directive 2001/83/EC.
如果原料药从欧盟境内生产商、进口商或分销商处采购，生产商、进口商或分销商应根据指令2001/83/EC的第52a条款要求进行登记。
Receipt 接收
Areas for receiving active substances should protect deliveries from prevailing weather conditions during unloading. The reception area should be separate from the storage area. Deliveries should be examined at receipt in order to check that:
原料药接收区域应能保护收到的货物在不好的天气卸货。接收区域应与存贮区域分开。所收到的货物应在接受进根据订单检查以下内容：
l containers are not damaged;
l 容器未被损坏
l all security seals are present with no sign of tampering;
l 所有安全封签均在且没有破坏伪造的迹象
l correct labelling, including correlation between the name used by the supplier and the in-house name, if these are different;
l 标识正确，包括供应商所用的名称与公司内名称之间的相互关系，如果这两名称不同的话
l necessary information, such as a certificate of analysis, is available; and
l 必要的信息，如分析报告，可以获得
l the active substance and the consignment correspond to the order.
l 原料药和发货条款符合订单
Active substances with broken seals, damaged packaging, or suspected of possible contamination should be quarantined either physically or using an equivalent electronic system and the cause of the issue investigated.
封签破坏、包装破损或疑被污染的原料药应进行隔离，可以是物理的，也可以等同的电子系统，要对问题进行调查。
Active substances subject to specific storage measures, e.g. narcotics and products requiring a specific storage temperature or humidity, should be immediately identified and stored in accordance with written instructions and with relevant legislative provisions.
有特定存贮措施要求的原料药，例如麻醉品，或要求特定存贮温度或湿度的原料药，应立即识别出，根据书面存贮要求和相关的法律条款要求进行存贮。
Where the distributor suspects that an active substance procured or imported by him is falsified, he should segregate it either physically or using an equivalent electronic system and inform the national competent authority of the country in which he is registered.
如果分销商怀疑所购进或进口的一种原料药为假药，其应采用物理或等同的电子系统进行隔离，并通知其登记的国家药监当局。
Rejected materials should be identified and controlled and quarantined to prevent their unauthorised use in manufacturing and their further distribution. Records of destruction activities should be readily available.
拒收的物料应进行识别和控制，并隔离，以防止其被未经授权地用于生产和进一步销售中。销毁活动的记录应易于获得。
Storage 存贮
Active substances should be stored under the conditions specified by the manufacturer, e.g. controlled temperature and humidity when necessary, and in such a manner to prevent contamination and/or mix up. The storage conditions should be monitored and records maintained. The records should be reviewed regularly by the person responsible for the quality system.
原料应被存贮在生产商指定的条件下，例如，必要时，受控的温度和湿度下，存贮方式应能防止污染和/或混淆。存贮条件应进行监控，监控记录应保存。记录应由质量体系的相关责任人定期审核。
When specific storage conditions are required, the storage area should be qualified and operated within the specified limits.
如果有要求特定的存贮条件，则存贮区域应进行确认，并在指定的限度内运行。
The storage facilities should be clean and free from litter, dust and pests. Adequate precautions should be taken against spillage or breakage, attack by micro-organisms and cross-contamination.
存贮设施应清洁，没有垃圾、灰尘和虫鼠。应采取充分的预防措施来防止泼撒或破损，滋生微生物及交叉污染。
There should be a system to ensure stock rotation, e.g. ‘first expiry (retest date), first out’, with regular and frequent checks that the system is operating correctly. Electronic warehouse management systems should be validated.
应有一个系统来保证库存周转，例如，近效期（复验期）先出，进行常规和频繁的检查来发现系统是否正常运行。电子仓库管理系统应进行验证。
Active substances beyond their expiry date should be separated, either physically or using an equivalent electronic system, from approved stock and not be supplied.
超出其有效期的原料药应隔离，可以是物理形式的，也可以等同的电子系统，将其与已批准的库存分开，不得销售。
Where storage or transportation of active substances is contracted out, the distributor should ensure that the contract acceptor knows and follows the appropriate storage and transport conditions. There must be a written contract between the contract giver and contract acceptor, which clearly establishes the duties of each party. The contract acceptor should not subcontract any of the work entrusted to him under the contract without the contract giver’s written authorisation.
如果原料药的存贮和运输被外包，则分销商应保证合同接受方知晓并遵守适当的存贮和运输条件。外包方和合同接受方之间应有一份合同，其中应清楚说明各方的义务。在没有得到外包方的书面授权之前，合同接受方不应将受委托的任何工作外包给他人。
Deliveries to customers 发送给客户
Supplies within the EU should be made only by distributors of active substances registered according to Article 52a of Directive 2001/83/EC to other distributors, manufacturers or to dispensing pharmacies.
在欧盟境内销售原料药给其它分销商、生产商或药房，只能由根据指令2001/83/EC的52a条款登记过的分销商实施。
Active substances should be transported in accordance with the conditions specified by the manufacturer and in a manner that does not adversely affect their quality. Product, batch and container identity should be maintained at all times. All original container labels should remain readable.
原料药应根据生产商指定的条件进行运输，运输方式应不会对其质量形成不良影响。在所有时间均应保证产品名称、批号和容器可以识别。所有原装的容器标签均应保证可读。
A system should be in place by which the distribution of each batch of active substance can be readily identified to permit its recall.
应有一个系统来保证原料药的每个批次均易于识别，使得召回可以执行。
Transfer of information 信息转达
Any information or event that the distributor becomes aware of, which have the potential to cause an interruption to supply, should be notified to relevant customers.
当分销商知晓任何可能会导致供应中断的信息或事件时，均应通知给相关的客户。
Distributors should transfer all product quality or regulatory information received from an active substance manufacturer to the customer and from the customer to the active substance manufacturer.
分销商应将从原料药生产商处收到的所有的产品质量或法规信息转达给客户，并将从客户处收到的信息转达给原料药生产商。
The distributor who supplies the active substance to the customer should provide the name and address of the original active substance manufacturer and the batch number(s) supplied. A copy of the original certificate of analysis from the manufacturer should be provided to the customer.
供应原料药给客户的分销商应提供原料药的原始生产商的名称和地址以及所供货物的批号给客户。生产商原厂检验报告应提供给客户。
The distributor should also provide the identity of the original active substance manufacturer to competent authorities upon request. The original manufacturer can respond to the competent authority directly or through its authorised agents. (In this context ‘authorised’ refers to authorised by the manufacturer.)
在被要求时，分销商还应提供原始原料药生产商的识别给药监机构。原始生产商可以直接回复给药监当局，或通过其授权的代理回复。（在此处，“授权”指由生产商授予权利）
The specific guidance for certificates of analysis is detailed in Section 11.4 of Part II of Eudralex Volume 4.
关于检验报告的特定指南详细参见欧盟药品法第4卷第2部分第11.4部分。
CHAPTER 7 — RETURNS, COMPLAINTS AND RECALLS
第7章---退货、客诉和召回
Returns 退货
Returned active substances should be identified as such and quarantined pending investigation.
退回的原料药应进行标识，在调查期间隔离存放。
Active substances which have left the care of the distributor, should only be returned to approved stock if all of the following conditions are met:
由分销商监管的原料药，只有在满足以下全部条件时才可以退回至批准的库存中
l the active substance is in the original unopened container(s) with all original security seals present and is in good condition;
l 原料药保存在原始未打开的容器中，所有原始的安全封印均在并保持良好状态
l it is demonstrated that the active substance has been stored and handled under proper conditions. Written information provided by the customer should be available for this purpose;
l 已证明原料药所曾经的存贮和处理都是在适当的条件下进行的。客户提供的书面信息可证明上述情况；
l the remaining shelf life period is acceptable;
l 剩余货架期可以接受
l the active substance has been examined and assessed by a person trained and authorised to do so;
l 原料药由经过培训并具有授权的人员检查并评估
l no loss of information/traceability has occurred.
l 没有丢失信息/可追踪性
This assessment should take into account the nature of the active substance, any special storage conditions it requires, and the time elapsed since it was supplied. As necessary and if there is any doubt about the quality of the returned active substance, advice should be sought from the manufacturer.
该评估应考虑原料药的属性，所有特殊的存贮条件要求，其进入供应链所经历的时间长度。必要时，如果对退回的原料药质量有怀疑，可以向生产商寻求建议。
Records of returned active substances should be maintained. For each return, documentation should include:
原料药退货记录应保存，每次退货的文件记录应包括：
l name and address of the consignee returning the active substances;
l 原料药退回方的名称和地址
l name or designation of active substance, active substance batch number and quantity returned;
l 原料药名称和目的地，原料药批号和退回数量
l reason for return;
l 退回理由
l use or disposal of the returned active substance and records of the assessment performed.
l 退回原料药的使用或处理情况，所实施的评估记录
Only appropriately trained and authorised personnel should release active substances for return to stock. Active substances returned to saleable stock should be placed such that the stock rotation system operates effectively.
只有接受过适当培训且具有授权的人员才可以将退回的原料药放行进入正常库存。退回的原料药进入可销售库存后，其放置方式应能保证库存周围系统有效运转。
Complaints and recalls 客诉和召回
All complaints, whether received orally or in writing, should be recorded and investigated according to a written procedure. In the event of a complaint about the quality of an active substance the distributor should review the complaint with the original active substance manufacturer in order to determine whether any further action, either with other customers who may have received this active substance or with the competent authority, or both, should be initiated. The investigation into the cause for the complaint should be conducted and documented by the appropriate party.
所有客诉，无论以口头形式还是书面形式收到，均应根据书面程序进行记录和调查。如果客诉是与活性物质的质量相关，则分销商应与原料药原始生产商一起审核该客诉，以决定是否需要采取进一步行动，或者与其它可能收到该活性物质的客户，或与药监当局，或都一起来采取行动。对投诉原因应由适当方进行调查并记录。
Complaint records should include: 客诉记录应包括
l name and address of complainant;
l 投诉人姓名和地址
l name, title, where appropriate, and phone number of person submitting the complaint;
l 提交投诉的人员的姓名、职位、适当时记录其电话号码
l complaint nature, including name and batch number of the active substance;
l 投诉情况，包括活性物质的名称和批号
l date the complaint is received;
l 投诉收到日期
l action initially taken, including dates and identity of person taking the action;
l 收到投诉后首先采取的措施，包括采取措施的日期和人员
l any follow-up action taken;
l 随后采取的措施
l response provided to the originator of complaint, including date response sent;
l 给投诉人的回复，包括回复发出日期
l final decision on active substance batch.
l 对活性物质批次做出的最终决定
Records of complaints should be retained in order to evaluate trends, product related frequencies, and severity with a view to taking additional, and if appropriate, immediate corrective action. These should be made available during inspections by competent authorities.
客诉记录应保存，以评估趋势、与产品相关的发生频次、以及其严重性是否需要立即采取适当的纠正措施。这些记录在官方检查期间应可以提供。
Where a complaint is referred to the original active substance manufacturer, the record maintained by the distributor should include any response received from the original active substance manufacturer, including date and information provided.
如果客诉涉及到原始的活性物质生产商，则分销商所保存的记录应包括所有从原始活性物质生产商处收到的回复，包括收到日期及所提供的信息。
In the event of a serious or potentially life-threatening situation, local, national, and/or international authorities should be informed and their advice sought.
如果情况严重，或可能危及生命，则应通知当地、国家和/或国际药监机构，并寻求其建议。
There should be a written procedure that defines the circumstances under which a recall of an active substance should be considered.
应有书面程序定义何种情况下需要考虑对活性物质进行召回。
The recall procedure should designate who should be involved in evaluating the information, how a recall should be initiated, who should be informed about the recall, and how the recalled material should be treated. The designated person (cf. Section 3.1) should be involved in recalls.
召回程序应指明谁需要涉入信息评估中，一个召回要如何启动，要将召回通知给谁，召回的物料要如何处理。指定的人员（参见第3.1部分）应参与召回活动。
CHAPTER 8 — SELF-INSPECTIONS 第8章---自检
The distributor should conduct and record self-inspections in order to monitor the implementation of and compliance with these guidelines. Regular self-inspections should be performed in accordance with an approved schedule.
分销商应实施并记录自检，以监控本指南的实施和符合情况。常规自检应根据批准的计划实施。
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