the
compliance
group
Stan O’Neill
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 Guidelines on Good Distribution Practice of Medicinal
Products for Human Use[Article 10 EU Dir 92/25/EEC]Products for Human Use[Article 10 EU Dir 92/25/EEC]人用药人用药
品流通质量管理指南品流通质量管理指南 [[欧盟第欧盟第92/25/EEC92/25/EEC号法令第号法令第1010款款]]
• Personnel 人员
• Documentation 文件
• Premises and Equipment 房屋与设备
• Deliveries 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 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”- each 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 operations
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：
- Receipt 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 Cont’d 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 products - 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
» Retained 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 Cont’d 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
ensure traceability of origin/destination products .
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 calibrated 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 range
• 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
F “First in First out” Regular checks
“先进先出”定期检查
Premises and Equipment
库房设施与设备
u Out of Date or Damaged Stock 将过期或损坏库存
F Quarantine 隔离/待检
F 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 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 & theft are avoided 避免损坏与偷窃
» Protected from unacceptable environmental
conditions 防止环境条件不符合要求
» Temperature is controlled during transport
在运输中温度受控
Deliveries to Customers
向客户发货
– Cold Chain 冷链
Products requiring refrigeration must be delivered in
需要冷冻产品必须在下列条件下发运
» Refrigerated transport 冷冻运输
» Insulated boxes 绝热箱
Validate worst case situation during transport
验证在运输中最坏情况状态
Ensure product does not come in contact with ice packs
保证产品不接触冰袋
Responsible Person - ensure adequate delivery conditions
maintained 负责人-保证保持足够的交付条件
Deliveries to Customers
向客户发货
– Controlled Drugs 受控药物
Maintain Security Chain 保持发货各环节的安全
» Separate control drugs in deliveries to facilitate
transfer
受控药品要采用单独发送方式，方便移交
» Deliver direct to pharmacist at the hospital or
retail outlet
直接交到医院或零售店的药剂师
Deliveries to Customers
向客户发货
Non Defective Medicinal Products 无缺陷药品
– Segregation from Saleable Stock until checked
– 与销售库存相隔离，直到经过检查
» Products in good condition - original unwrapped
containers
产品保持良好状态 -- 容器为原始包装未经开封
» Products stored under proper conditions
产品在正确条件下储存
» Remaining shelf life acceptable
仍有可接受的有效期
Returns 退货
u Products examined and assessed by authorised,
trained personnel
产品由经过批准及培训人员的检测与评估
– Special storage conditions - time elapsed since issue
特别储存条件-自从发货起的持续时间
– Maintain records of returned goods
保存退货记录
– Return to stock operating FIFO System
退回仓库，按先进先出要求管理
Returns 退货
– Product Disposal 产品处置
Returned, Rejected or Recalled Products
退回，拒绝或召回产品
» Decision documented & recorded by Responsible
Person
决定文件与负责人的记录
» Disposal in a timely manner
以及时的方式处置
Returns 退货
• Conduct and Record Self Inspections to monitor
the implementation of and compliance with GDP
Guidelines
• 对执行流通管理规范情况进行自检并做好记录：
» Self Inspection Procedure 自检程序
» Inspection Reports 检查报告
» Follow up Actions 跟踪措施
» Inspection Log 检查日志
Self Inspection 自检
• Quality Management 质量管理
– No Quality System available 没有质量系统
– No System for Control of Documentation -
Issue/Retrieval 无系统控制文件的发放/与收回
– Master copies SOPS not approved by R. Person
基准SOP（原版）没有经过负责人批准
– No Policy re.没有以下相关的方针：
» Minimum acceptable product dating
最短可接受产品有效期
» Return of refrigerated products 冷冻产品退货
GDP Deficiencies – General
执行流通规范常中的见缺陷
n Personnel 人员
u Company training programme not available
公司没有培训计划
– No training SOP for GDP operations
没有培训流通管理规范的SOP
u Personnel training not documented
人员培训没有记录
GDP Deficiencies – General
执行流通规范常中的见缺陷
• Documentation 文件
– Relevant SOPs not available in areas of operation
在操作区域没有相关的SOP
– SOPs not available for 没有下列SOP：
» Receipt and checking of deliveries
对到货的接收与检查
» Warehouse cleaning/pest control
仓库的清洁/虫害控制
» Temperature monitoring 温度监测
» Customer complaints 客户投诉
GDP Deficiencies – General
执行流通规范常中的见缺陷
u Customer complaints not closed out in a timely
manner 没有及时处理（了结）客户的投诉
F No customer complaint log maintained
没有保留客户投诉记录
u Service/calibration reports not reviewed
没有审核校准/ 维修报告
– Pest control reports not reviewed
没有经过审核虫害控制报告
u Calibration certs - acceptable error limit not
specified 校准证明-没有具体规定误差限度
GDP Deficiencies – General
执行流通规范常中的见缺陷
• Premises and Equipment 库房与设备
– Unauthorised products supplied 发了未批准的产品
– Premises maintained in an untidy/dirty condition
库房处于肮乱状态
– Products not stored on pallets 产品没有用托盘储存
– Inadequate segregation receiving / picking/ dispatch
areas 接收/检料/发放区域没有适当隔离
– Out of date/short dated stock in inventory
过期/短有效期产品没有库存清单
GDP Deficiencies – General
执行流通规范常中的见缺陷
– Temperature Mapping 温度分布
» Not performed
没有进行
» Product stored in close proximity to unit heaters
产品近热源储存
– Temperature probes not calibrated
– 温度传感器没有经过校准
GDP Deficiencies – General
执行流通规范常中的见缺陷
• Premises and Equipment Cont’d 库房与设备(续)
– Temperature excursions in cold room not
investigated 冷库温度超出范围，没做调查
– Data loggers not calibrated within operating range
没有对数据自动记录仪在其运行范围内对校准
MDA Drugs MDA药品
F Inadequate control. Poor security
没有足够控制，安全性不良
GDP Deficiencies – General
执行流通规范常中的见缺陷
F Discrepancies not adequately investigated
对差异情况没有适当调查
u Dangerous storage practices 储存做法危险：
F Rat poison stored over Baby Food Products
将毒鼠药储存在婴儿食品上
» Organophosphorus compds stored over open
将有机磷化合物存放在上面
» containers packaging components
容器包装成分。
GDP Deficiencies – General
执行流通规范常中的见缺陷
• Deliveries to Customers 向客户发货
– Cold storage units for delivery refrigerated products
not validated
发货用冷藏产品的冷储存单元没有经过验证
– Inadequate control re. ice packs
没有足够控制，如冰袋
– Inadequate security of MDA drugs
对于MDA药品没有足够的安全性
n
GDP Deficiencies – General
执行流通规范常中的见缺陷
n Returns 退货
u No SOP Re. return of product to saleable stock
将退货产品到销售仓库无SOP
u Personnel not trained Re. checking returned goods
没有对人员进行退回货物检查的培训
GDP Deficiencies – General
执行流通规范常中的见缺陷
• Self Inspection 自检
– No SOP defining Self Inspection
没有SOP来规定自检
– Regular inspections not performed
没有进行定期检查
– Reports not issued 自检无报告
– Follow up actions not documented 跟踪措施无记录
– Log of inspections not maintained
没有保存检查记录
GDP Deficiencies – General
执行流通规范常中的见缺陷
• Current GDP Guideline 现行GDP指南
• Guidelines on GDP of Medicinal Products for HumanUse
(94/C 63/03) 人用药品流通管理规范(94/C 63/03)
•
– since 1994 从1994年开始
– out dated 已过期
– limited scope, not detailed, no clear guidance
范围狭，不详细，缺乏明确的指导性
– not reflecting current activities observed in wholesale
distribution 不能反映现行药品流通的相关活动
Developments – new guidelines
制订-新的指南
• Complex distribution networks where all players not
wholesale distributors as defined in Directive
2001/83/EC
• 在复杂的药品流通网络中的各种角色，并非都是
2001/83/EC号法令中定义的批发商
• This leads to inconsistencies in MS with respect to
licensing and control of . virtual wholesalers,
outsourcing activities, brokers, transportation
• 这在药品销售中，导致虚拟的批发商、外部采购活动、
中间商、运输企业发放许可证及管理等方面的矛盾
Why a new guideline?
为什么要一个新指南?
• New legislative requirements arising from proposal from
Commission (identification of GDP requirements and
obligations for brokers, verification of suppliers). These
need to be incorporated into GDP Guidelines
• 新立法要求来自委员会的提议(鉴别药品流通的要求以
及中间商，各供应企业的义务)，这需整合到GDP指南
中
• Lack of harmonisation –different procedures/formats at
Community level and international level
• 缺乏协调–在欧盟层面与国际层面上有不同的程序/格式
Why a new guideline?
为什么要一个新指南?
• Computerised systems 计算机化的系统
• Management of contract arrangements
• 委托管理
• Transparency in supply chain 供应链透明度
• Transportation 运输
• Counterfeit controls 假药控制
Likely new components
可能的新的内容
• Subject all actors in distribution chain to conditions of wholesaling
(except pharmacies, retailers)
取决于所有分销链的参与者至批发商条件(除药房，零售商外)
• More stringent verification of suppliers by wholesalers
批发商对供货商将会有更严格的检查
• GDP Community database (EudraGDP)
药品流通欧盟数据库
• Strengthen GDP compliance inspections:
强化药品流通的达标检查:
• “Compilation of Community Procedures for GDP“
“欧盟将流通规程进行汇编”
Potential impacts 潜在影响
• GDP Drafting Group Established 2008 (EMA)
• 欧盟药品管理局流通规范起草小组于2008年成立
• Concept Paper on revision published –February 2009
• 修订的概念文件已于2009年2月公布
• Deadline for Comments –May 2009
• 征求意见截止日期–2009年5月
• Guideline on GDP 药品流通指南
– well advanced 相当先进
Work in progress 工作进展
– harmonised with WHO Guideline
与WHO指南相协调/一致
– draft for public consultation expected Q2 2010
预期在2010年第2季度发布草案进行磋商
– some clarifications / definitions pending
有一些定义/需澄清的问题待定
– must await EU Directive 必须等候欧盟的法令
• Layout of Guideline expected to mirror GMPs
• 预计指南的大体结构参照GMP的形式
Work in progress 工作进展
• Procedures on 这类程序包括：
– Inspection process 检查程序
– Issue of GDP Certificate 签发药品流通规范GDP证书
– Serious GDP non-compliance 严重违反药品流通规范
– Training and qualification of Inspectors
检查员的培训与资质确认
– Wholesale Distribution Authorisation format
批发商许可批准格式文件
– GDP Inspection report format
药品流通规范检查报告格式
Likely amendment of Compilation of Community Likely amendment of Compilation of Community
Procedures Procedures 可能修订欧盟程序汇编可能修订欧盟程序汇编
• Obligations for wholesalers distributing to third
countries (import for export)
• 批发商对第三国的义务(进口用于出口)
• Inspection process for brokers
• 检查中间商的程序
• EudraGDP format Eudra药品流通格式文件
• GDP Certificates format 药品流通证书格式
• Non-conformance certificates 不达标证书
Future developments 前景
• Impact on Wholesalers 影响到批发商
• New detailed GDP Guidelines 有新的详细的药品流通指南
• New chapters (Quality Risk Management, Validation of
Computerised Systems, Deviations, Change Control)
会有一些新的章节(质量风险管理，计算机化系统验证，偏差，
变更控制)
• New format of Wholesaler’s Authorisation
批准新批发商许可的格式
• GDP Certificate after each inspection每次检查发GDP证书
• Information uploaded onto EudraGDP
信息上传到 EudraGDP（欧盟药品流通数据库）
Future developments 前景
