欧盟药品GDP及药品冷链技术(全)

1、,the compliance group,Stan ONeill CPAPE 2011 年会,欧盟药品药品流通法规,EU Regulations on Drug Distributions,Guidelines on Good Distribution Practice of Medicinal Products for Human UseArticle 10 EU Dir 92/25/EEC人用药品流通质量管理指南 欧盟第92/25/EEC号法令第10款,Personnel 人员 Documentation 文件 Premises and Equipment 房屋与设备 Deliverie

2、s to Customers 向客户交付 Returns 退货 Self Inspections 自检,Ensure products are authorised 保证产品经过批准 Storage conditions are observed (all times) 关注产品储存条件(任何时候) Prevent contamination from other products 预防来自其它产品的污染 Ensure adequate turnover of products 保证足够的产品流转量 Deliver right products 交付产品正确无误,Quality System

3、Operated by Wholesalers should 批发商的质量系统应,Right Address 发货地址正确 Satisfactory Period 发货斯让用户满意 Provide tracing system for faulty products 具备追踪系统，追踪有问题的产品 Effective Recall Procedure 有效的召回程序,Quality System Operated by Wholesalers should 批发商的质量系统,Appoint Management Representative - “Responsible Person”- ea

4、ch distribution centre 每个分销中心须指定-“负责人”-即管理代表 Appropriately qualified 适当的资质 Implement and maintain Quality System 来实施与保持质量系统 Key Personnel 关键人员 Appropriate ability and experience to guarantee products are properly handled 有适当的能力与经验来保证产品正确处理,Personnel 人员,Training 培训 Provide training for various GDP op

5、erations 提供不同GDP操作的培训 Training programmes 培训计划 Maintain training records 保存培训记录,Personnel 人员,Procedures 程序 Written procedures should describe the different operations which may affect 应当有书面规程来描述不同的操作，它们可能影响： the quality of the products 产品质量 the distribution activity 分销活动 Procedures for 有以下规程： - Rece

6、ipt and checking of deliveries 发送产品的接收/检查 - Storage 储存 Cleaning and maintenance of premises 贮存厂房的清洁与维护,Documentation 文件,Procedures Contd 程序(续) Recording of storage conditions 记录储存条件 Security on site or in transit 现场或运送安全 Withdrawal from saleable stock 从销售仓库撤回 Records of - orders 记录 -定单 - returned pr

7、oducts - 退货 Recall plans 召回计划 Procedures for various operations should be approved, signed and dated by the Responsible Person 各种规程均应经过负责人的批准，签字与签发日期,Documentation 文件,Records 记录 Made when each operation is taking place 每次操作时均应记录 Activities and events are traceable 活动/事件均可追踪 Readily available 方便查阅 Re

8、tained for 5 years at least 至少保留5年 Each purchase and sale 每次采购与销售有： Date 日期 product/quantity 产品/数量 name and address of supplier/consignee 发货企业/收货人的名称与地址,Documentation 文件,Records Contd 记录(续) Transactions between 以下交易的记录： (i) Manufacturers and Wholesalers 制造企业与批发企业 (ii) Between Wholesalers 批发企业之间 ensu

9、re traceability of origin/destination products i.e. Batch numbers to identify suppliers and those supplied with medicinal products 能保证产品起点/终点的追踪性，如用批号来识别供应商及其发的药品,Documentation 文件,Suitable and adequate to ensure proper conservation/ distribution 适用并足以保证贮存/分销正确无误 Monitoring devices should be calibrat

10、ed 监控装置应当进行校准 Receiving 接收 Receiving bays protect deliveries 有保护收货的区域 Receiving area separate from storage areas 收货区域与储存区域分开 Deliveries examined on receipt 在收货时检查产品 Damage 有无损坏 corresponds to the order 与定单是否相符,Premises and Equipment库房设施与设备,Storage 储存 Medicinal products separate from other goods 药品与其

11、它产品分开 Conditions specified - protect from light, moisture, below 25 规定条件-避光,防潮,低于25 Temperature monitoring documented 温度监测有记录 Records reviewed regularly 定期审核记录 Temperature Mapping. Storage areas/cold rooms 温度分布、储存区/冷库,Premises and Equipment库房设施与设备,Ensure all locations within specific temperature ran

12、ge 保证所有区域都在规定的温度范围内 25oC 2 - 8oC,Premises and Equipment库房设施与设备,Storage Facility 储存设施 Clean 清洁 Free from litter, dust, pests 无废弃物、灰尘、虫害 Free from spillage or breakage 没有溢出或损坏 Microcontamination 微生物污染 Cross contamination 交叉污染 Stock Rotation 库存流转 “First in First out” Regular checks “先进先出”定期检查,Premises

13、and Equipment库房设施与设备,Out of Date or Damaged Stock 将过期或损坏库存 Quarantine 隔离/待检 Destroy 销毁,Premises and Equipment库房设施与设备,Authorised Wholesalers 批准的批发商 Persons authorised to supply Medicinal Products 经批准可从事药品流通的人员 IMB will look randomly at customer list 爱尔兰药品管理局将在客户清单中随机抽查 Supply Document 提供的文件应有： Date 日

14、期 Name and Pharmaceutical Form 名称与药品剂型 Quantity supplied 供应数量,Deliveries to Customers向客户发货,Supplier and addressee 供应商以及地址 Name and address 名称与地址 Product Shelf Life 产品有效期 Product dispatched must have a minimum defined shelf life remaining 所发送的产品必须具有所规定最短有效期,Deliveries to Customers向客户发货,Transportation

15、 运输 Ensure that 保证： Identification is not lost 不丢失标识 Cross Contamination is avoided 避免交叉污染 Products are secure 产品安全 Breakage Height; Doors) 调查(冷却单元的气流；高度；门)正常运行时的影响 Extensive coverage of all storage areas 所有储存区域均应复盖 Capacity 考察冷藏/冷冻能力,Fridge/Freezer Units: Temperature Mapping Studies 冷藏/冷冻单元：温度分布试验,

16、Simulation of the product temperatures within the load 模拟实际产品装载的温度 Effects of repairs 对冷藏/冷冻效果进行调整 Modifications in layout 或调整装载的布局 Opportunity to assess the capability of the unit in the event of powering down 创造条件，评估电源/动力故障情况下，设备的冷藏/冷冻能力,Fridge/Freezer Units: Temperature Mapping Studies 冷藏/冷冻单元：温度

17、分布试验,Many Types Available 有许多类型 Max/min thermometers (minimum requirement) 最高/最低温度计(最低要求) Electronic continuous recording temperature devices 电子温度连续记录装置 Portable Data Loggers 便携式手动记录仪,Temperature Monitoring Devices温度监测装置,Continuous monitoring system 连续监测系统 Coverage of the storage area 覆盖储存区域 Coverag

18、e of self-contained storage areas 覆盖隔离式储存区域 Monitoring of worst-case locations identified by the temperature mapping study 对在温度分布试验中识别的最差位置进行监测 Frequency of temperature reading and recording 温度读数与记录应有适当的频率,Fridge/Freezer Temperature Monitoring 冷藏/冷冻温度的监测,Type of instrumentation (accuracy of +/-0.5C)

19、 仪器类型(准确度+/-0.5C) Use of product temperature monitoring 用于产品温度监测 Alarm System 报警系统 Effects of Normal Operation 正常运行的效果 Out of Hours Response 对非正常运行的响应 Tested 进行测试,Fridge/Freezer Temperature Monitoring 冷藏/冷冻温度的监测,Annually 每年校准 Against a certified, traceable reference standard 用经过鉴定的，具有可追踪的参照标准进行校准（对照

20、） Records of calibration should be maintained 应保存校准记录,Calibration 校准,Procedure for temperature recording should be documented 应有书面的温度记录的规程 Format of the records 记录有规定的格式 Review 有人审核 Independent review by the person responsible for the storage area 储存区责任人进行独立审核 Procedure for notification of excursion

21、s outside of specified limits 有温度偏离规定限度的通报程序 Investigation of excursions, consideration of the impact on product, and implementation of corrective actions 调查温度偏离，考虑其对产品的影响，实行纠偏措施,Temperature Recording 温度记录,Considerations in Selecting a Transportation System 选择一个运输系统应考虑的问题： Nature & Size of the load

22、所装载的性质与大小 Temperature control requirements of the load 装载对温度的控制要求 Method of transportation 运输方法 Duration of transportation 运输时间 Local seasonal temperatures 地区不同季节的温度 情况,Cold Storage Transportation Systems冷藏运输系统,Small Volume Systems 小容量系统 Chill packs may also be incorporated 可考虑采用冷却袋 May be of differ

23、ent sizes to incorporate smaller, medium, and larger volumes with the relevant capacity range 可能需根据能力来考虑大、中、小规格的不同组合 Typically suitable for smaller volume loads where the transit times are of limited duration e.g. deliveries from a wholesaler to a pharmacy 通常适用于小量药品的运输，如从一个批发仓库发往药房的短距、短时运输,Small Vol

24、ume Transportation Systems小量运输系统,Qualification 确认 The system should be qualified to demonstrate its ability to maintain the required product temperature storage conditions 系统应经过确认，证实其保持产品储存温度的能力 Qualification should take into account 确认应当考虑以下因素： Maximum transit times 最长运输时间 Minimum and maximum packa

25、ging capacities 最大、最小包装的装货能力,Operational Issues 运行问题,Maximum seasonal variation in temperatures 季节的最大温差变化 Packaging configuration for the systems 该系统中包装的配置 Required freezing times for the ice packs and cooling times for the chill packs 冰袋所需冷冻时间及冷却袋所需的冷却时间 Conditioning time for the ice packs 冰袋能起作用的持

26、续时间,Operational Issues 运行问题,The system should be used in accordance with the parameters utilised in the qualification study 应按在确认试验中采用的参数要求使用系统 Additional requirements to support use of the system include:- 系统其它辅助性使用的要求包括： Rotation and control of the ice packs and chill packs 冰袋与冷却袋的周转与控制 Corrective

27、 actions in the case of goods having been transported outside of the required temperature range 在货运过程中超出规定温度范围时的纠正措施,System In-Use 系统的使用,Labelling 标签/标签 All operational aspects should be proceduralised 系统所有的运行情况应当按规程处理 Temperature monitoring within the load 在装载中，监测温度 Training 对人员进行培训,System In-Use 系

28、统的使用,Refrigerated transport vehicles or transportation containers which incorporate a chiller unit. 带制冷单元的冷藏车或集装箱 Suitable for large volume loads where the transit times are prolonged in duration 适用于货运量大、运输时间长时的装载 May be used as a primary or secondary means of environmental control 可用于一级或二级（直接或间接）环境

29、控制手段,Cold Storage: Large Volume Transportation Systems 冷藏：大容量运输系统,Mapping to determine hot/cold spots with respect to storage. 用温度分布来确定储存区的高温及低温点 Qualification 确认 Consideration should be given to 应考虑以下内容： Ensuring the air flow within the refrigeration unit 保证冷藏单元内空气流动 Capacity of the load 装载能力 Confi

30、guration of the load 装载配置/结构 Orientation of product with respect to the chiller and air circulation units 根据制冷机及空气循环情况，堆放产品,Operational Issues 运行问题,System In-Use 系统的使用 Temperature Monitoring of the refrigeration unit. 对冷藏单元要监测温度 Use of temperature monitoring within the load. 监测装载的温度 The system should be used in accordance with the parameters utilised in the mapping & qualification studies. 应按在温度分布与确认试验中获得的参数使用系统 All operational aspects should be proceduralised. 所有运行情况均应有程序化的管理 Training 培训,Operational Issues 运行问题,Can a wholesaler release returned medicinal products requirin