王伟-生物无菌制药技术模块的设计、制备和测试(无菌)

BCD/PRESENTATION Biotech and Sterile Skid Design, Manufacture and Testing 生物无菌制药技术模块的设计、制备和测试 Mar. 27th 2015 制药业 AGENDA议程 BCD Overview, history and key metrics BCD概述、历史及关键指标 Project Implementation Approach 项目实施流程 Selected project examples 精选项目案例 Q&A 问答环节 制药业 BCD COMPANY HISTORY 历史 2013 制药业 BCD TEAM 团队 ENGINEERING 工程 PROCUREMENT 采购 OPERATIONS MANAGEMENT 运营管理 ADMINISTRATIVE 行政 FITTERS / WELDERS 钳工/焊工 QUALITY & COMPLIANCE 质量与合规 SAFETY 安全 40 6 4 5 141 4 5 TOTAL 205 EMPLOYEES 总计205名员工 制药业 BCD CAMPUS OVERVIEW BCD园区总览 IRELAND CHARLEVILLE FACILITIES设施介绍 1. ENGINEERING OFFICE 工程办公室 2. MODULE WORKSHOP A 模块车间A 3. VESSELS WORKSHOP 容器车间 4. MODULE WORKSHOP B 模块车间B 5. SERVICE & MAINTENANCE 维修售后 制药业 PRODUCTS & SERVICES 产品与服务 Preliminary Design 初步设计 BoD (Basis of Design) Packs 生物需氧量（基础设计）包括： Process 工艺流程 Mechanical 机械 Electrical 电气 Automation 自动化 Constructability / Project Execution Plans 施工/项目执行计划 Budget and detailed cost estimates 预算和详细的成本估算 Process Vessels 工艺罐 Product formulation, Media / Buffer Prep / Hold, Reactors, CIP, WFI, etc. 工艺配料，培养基/缓冲液制备/存储，反应 器，CIP，WFI，等。 Detailed Design 详细设计 ASME VIII, BPE, CODAP, AD Merkbltter，GB etc. 压力容器标准 PED, ATEX认证 Fabrication 制造 Vessels (up to 300,000L) 罐（最大可达300000L） Skid Modules 模块 High Alloy (AL6XN, C22, SMO, Duplex, Super Duplex) 高合金（AL6XN，C22，SMO，双相，超级双相） 制药业 PRODUCTS & SERVICES产品与服务 Modular Process Systems 模块化系统 Product Formulation, Sterile Filtration, CIP, SIP, Bioprocess Modules: Media Prep, Buffer Prep, Harvest Skids, Effluent and Bio-effluent Treatment Systems 配料系统，无菌过滤，CIP，SIP，生物模块：培养基制备，缓冲液制备，收获模 块，污水与生物污水处理系统 Utility Skids Heating & Cooling, Dosing etc. 设备模块加热和冷却，加药等。 Detailed Design 详细设计 ASME BPE, 31.3, GAMP, etc. Inventor 3D, Electrical & Automation PED, ATEX Fabrication 制造 Skid Modules, Superskids 标准模块，大模块。 High Alloy (AL6XN, C22, SMO, Duplex, Super Duplex) 高合金（AL6XN，C22，SMO，双相，超级双相） Integrated Testing 集成测试 Mechanical and electrical verification 机械和电气的验证 Riboflavin sprayball coverage 核黄素喷淋覆盖 SIP / Thermal mapping SIP /热分布 Integrated functional testing 集成功能测试 IV / OV / ASTM E2500 制药业 PRODUCTS & SERVICES产品与服务 Site services 现场服务 Installation of vessels and skids 罐子及模块的安装 Degreasing, De-rouging & Passivation 脱脂、除锈及钝化 Soft parts replacement 垫片等更换 Commissioning Plans and execution 调试方案及执行 Validation of process systems 工艺验证 Scheduled Maintenance Planning and execution 定期维修计划及执行 Traceable recording of maintenance activities 可追溯的维护活动记录 制药业 PROJECT EXECUTION PROCESS 项目执行过程 制药业 Certified quality management system to I.S. EN ISO 9001:2008 (National Standards Authority of Ireland, NSAI 19.1719). EN ISO 9001:2008质量认证管理体系（爱尔兰国家标准局，质量认证管理体系（爱尔兰国家标准局， NSAI 19.1719） The scope of certification is认证范围认证范围: The design, manufacture and installation of process vessels, modular process units and piping systems. The provision of de- greasing, passivation, de-rouging and sanitisation services. 工艺罐、模块单元及管路系统的设计制造和安工艺罐、模块单元及管路系统的设计制造和安 装。并且提供相应的脱脂、钝化、除锈及灭菌装。并且提供相应的脱脂、钝化、除锈及灭菌 服务。服务。 制药业 NDT Supplier Process NDT Execution Management NDT Report Validation NDT Report Welding & Welder Qualification Management Welding Validation Databook NDT Databook WPS & PQR Databook Welder Certification WPS & PQR Database Procurement Process Weld Log Production Material Management Supplier Process Material Certification Material Incoming Inspection Process Material Certification Validation Databook Material Certification Databook Test Certification Estimation Process Production Planning & Scheduling Fabrication Process NoBo Design Approval Process Test Certification and PED Documentation CE Certificate REALISATION (OP110)STORES (OP120)PROCUREMENT (OP120)VALIDATION (OP100)CLIENT ACCEPTANCE (OP100)MECHANICAL ENGINEERING (OP90) Pricing Information & Delivery Norms Proposal & Quotation Material / Equipment Transfer Process Welder Qualification Database In Process Inspection & Pre-FAT Static FAT Design Library Project Management Processes User Requirements Specification DEFINITION (OP60) Schedule Definition Scope Definition Cost Definition (incl. Cash Flow) Quality Definition Risk Register Schedule (incl. WBS) Cost Report & Invoicing Project / Quality Plan Risk Assessment Action Log & Meeting Schedule Cost Management Schedule Management Quality Management Risk Management Communication & Coordination Scope Management Variation/ Change Control Log PROCESS ENGINEERING (OP80) Feedback Process Design P&ID Line List Process Calculations Project Engineering Equipment & Component List Equipment Datasheets Risk Assessments (PED, MD, ATEX) Mechanical Design Model / GA Drawings Detail / Isometric Drawings MTO (incl. Material Log) Risk Assessment (HAZOP) Test Protocols (FAT, SAT, Pressure Test etc.) Welding Requirements Specification NDT Requirements Specification Equipment PRF & RFD CE Certification (incl. IOM) Mechanical Calculations Procurement Status Report Purchase Order Equipment Certification NoBo Construction Verification Equipment Inspection (Engineering) Process Engineering Documentation Project Quality Plan Databook Equipment Certification Project Engineering Documentation Mechanical Engineering Documentation Electrical Engineering HFS / HDS Electrical Drawings I/O List Parts List Subcontract Scope of Works Automation Engineering FDS / DDS / SMDS Subcontract Scope of Works Process Steps / PFS / PFD Configuration Panel Build Electrical Installation Test Protocols (SFAT, SMTS) Test Protocols (HFAT) Electrical Panel pre-FAT Electrical Panel FAT Electrical Installation pre-FAT Electrical Installation FAT Electrical Engineering Documentation Automation pre-FAT Automation FAT Automation Documentation Statutory Requirements (PED, ATEX, MD etc.) Code Requirements (EN, ASME etc.) PROJECT ENGINEERING (OP80) SUPPLIER DEFINITION (OP60) ELECTRICAL ENGINEERING (OP85)AUTOMATION ENGINEERING (OP85) MECHANICAL ENGINEERING (OP90)PROJECT ENGINEERING (OP80) Electrical Contractor Process Automation Contractor Process Preliminary Engineering / Design Project Execution Strategy Functional FAT Client Feedback Document Validation Process Document Management Process Document Register Definition Phase 定义阶段定义阶段 Planning Phase 计划阶段计划阶段 Design Phase 设计阶段设计阶段 Procurement Phase 采购阶段采购阶段 Fabrication Phase 制备阶段制备阶段 Validation / Verification Phase 验证或确认阶段验证或确认阶段 Product Realisation Process is fully documented in the Quality Management System (QMS). 产品实现过程完全记录在产品实现过程完全记录在质量管理质量管理系统中（系统中（QMS）。）。 制药业 Quality Plan describes how the requirements of the contract will be met throughout the project lifecycle. 质量计划描述了怎样通过项目周期来满足合同要求。质量计划描述了怎样通过项目周期来满足合同要求。 Schedule Development in MS Project Ms Project格式的进度计划格式的进度计划 Project Meetings (Internal & Client). 项目会议（与内部或与客户）项目会议（与内部或与客户） Action Log. 操作记录操作记录 Constraint & Risk Review. 约束条件与风险回顾约束条件与风险回顾 Change Management 变更管理变更管理 Project Reporting. 项目报告项目报告 制药业 Procedures are in place to define the design process 定义设计过程的程序已落实定义设计过程的程序已落实 Where in BCD scope, HAZOPs are executed. 在在BCD范围内，已经执行范围内，已经执行HAZOP分析。分析。 Design risk assessments are completed for pressure equipment, machinery and ATEX risks, where applicable. 设计风险评估在压力设备、机器以及适用设计风险评估在压力设备、机器以及适用 的防爆风险中已经是完善的。的防爆风险中已经是完善的。 Design is subject to peer review. 设计是经过内部审核的设计是经过内部审核的 Internal & client design review meetings and model reviews are conducted. 会进行内部及客户设计审查会议和模块审查。会进行内部及客户设计审查会议和模块审查。 制药业 Supplier & Subcontractor assessment and management processes. 评估和管理供应商及分包商。 Material & Equipment Inspection is in accordance with OP120-004 and to ASME BPE. 根据标准OP120-004 和ASME BPE检查材料。 Visual and Physical Inspection. 外观和物理检查 Calibrated inspection equipment includes: Micrometers, Profilometers, Ferrite scope, Digital Protractors, Positive Material Identification (PMI). 校准检测设备包括:千分尺、表面粗造度检测仪,铁素体 检测仪,数显角度仪, 材料光谱分析仪(PMI)。 The material traceability and certification lifecycles are in accordance with OP100-18 Material Certification Review. 材料的可追溯性和认证周期符合OP100-18材料认证审 核。 制药业 Fabrication Phase制造阶段制造阶段 BCD has a comprehensive welding and welder qualification system: BCD有完善的焊接和焊工资格审核系统有完善的焊接和焊工资格审核系统 Library of Procedure Qualification Records (PQRs). 工艺评定记录的程序库工艺评定记录的程序库 Library of Welding Procedure Specifications (WPSs). 焊接工艺评定的程序库焊接工艺评定的程序库 Notified Body Approved. 公告机构批准公告机构批准 Dual Qualified (EN/ASME). 双双标准（标准（EN/ASME） Stainless Steel, Higher Alloys, Titanium, Carbon. 不锈钢、高合金、钛、碳不锈钢、高合金、钛、碳 Manual & Semi-Automatic Welding. 手动焊及半自动焊手动焊及半自动焊 Low Ferrite Welding. 低铁素体焊接低铁素体焊接 Range of Processes. 广阔的工艺范围广阔的工艺范围 制药业 Welding Implementation焊接实施焊接实施 Welding Equipment Includes焊接设备焊接设备: Calibrated Orbital Welders标准轨道自动焊机标准轨道自动焊机 Calibrated Purge Monitors标准吹扫检测仪标准吹扫检测仪 Magnahelic Gauges 气压表气压表 High Purity Purge Gas高纯度气体高纯度气体 Welding Documentation Includes焊接文件焊接文件: Weld Maps焊接图焊接图 Weld Logs焊接日志焊接日志 Weld Coupon Logs焊样日志焊样日志 Welding Inspection To Approved Procedures By焊接检焊接检 验批准程序验批准程序: Qualified BCD Personnel BCD相关资格人员相关资格人员 Independent Third-Party NDT Contractors 独立第三独立第三方无损检测承包商方无损检测承包商 Cleaning, Pickling, Passivation Cert (F110-004-A) PRELIMINARIES Job Pack (OP70-018) Materials & Equipment (OP120-003) PRODUCTION PRE-CUTTING CHECKSIn-Process Inspection Sheet (F70-018-B) Welding Qualification Management (OP110-003) Calibration Management (OP10-010) Project Schedule (OP70-004) Pressure/Leak Test Certificate (F100-002/3-A) Notified Body Witness As Required Welding Procedure Specification (OP110-003) Design Documentation (OP70-007) PRODUCTION FABRICATION CHECKS PRE-HYDROTEST Weld Log (OP70-018) HYDROTEST Drainability Certificate (F100-005-A) Surface Finish Certificate (F-WI-100-003A) Attachment Leak Test Certificate (F100-21-A) Material Record Sheet (F120-001-A) Dye Pen Certificate (F100-024-A) Check Head Dimensions/ Surface Finish Check Nozzle Layout Check Shell Dimensions Check Head/Shell Orientation Check Nozzles Straight Check Surface Finish Per Drawing Check Dye Pen of All Polished Welds (OP100-024) In-Process Inspection Sheet (F70-018-B) Certification Required? Check Critical Dimensions Welding Visual Inspection (OP100-022) Verify Material Records Up-to-Date and Correct Verify Drainability (OP100-005) Verify Surface Finish (WI100-003) PS and QE Approval for Hydrotest As Required, Leak Test of Reinforcement Pads (OP100-021) Pressure/Leak Test (OP100-002/3) Verify Barrier Paint Coverage Verify Insulation Thickness Verify Legs Are Straight Verify Critical External Dimensions Verify Cowl Fabrication & Polishing Welding Visual Inspection (OP100-022) Verify Material Record Sheet Up-to-Date and Correct Verify attachments fitted Verify Surface Finish (WI100-003) Verify Dip Tubes and Spray Lances (OP110-011) Verify NDT Complete (OP100-001) Cleaning & Pickling (OP110-004) Spool Weld Log (F110-011-A) As Required, Verify Ferrite Levels (OP100-008) Ferrite Report (F100-008-A) Verify NDT Complete (OP100-001) NDT Reports and Films QE/PS Release for Electropolish Preparation for Electropolish (OP110-007) ELECTROPOLISH Third-Party Electropolish QE Electropolish Approval Third-Party Electropolish Certificate PRODUCTION FABRICATION CHECKS POST-HYDROTEST PS and QE Approval for Pre-FAT Final Visual and Dimensional Checks Sprayball Test Certificate (F100-004-A) Sprayball Test (OP100-004) Verify Drainability (OP100-005) QE/PE PRE-FAT Agitator Run Test (OP100-007) Agitator Run Test Certificate (F100-007-A) Electrical Installation & Pre-FAT E&I SCOPE PM and QE Approval for FAT FAT Release Note (OP100-009) Executed FAT Protocol Release Note (F100-009-A) Vessel Packing (WI-111-024) Final Inspection Pre-Packing (F70-018-B) Passivation (QMS Series 130) Post-Passivation Cleanliness Test (OP100-023) Passivation Certificate PM POST-FAT Production Supervisor Verification of Peer Review Complete As Required, Lift Lug Load Testing (WI100-004) 制药业 In-Process inspection is conducted in accordance with defined procedures按既定程序的过程检查按既定程序的过程检查. Subsidiary procedures define specific test requirements including辅助程序定义具体测试要求辅助程序定义具体测试要求: Visual Examination of Welds焊缝目测检查焊缝目测检查 NDT无损探伤无损探伤 Surface Finish表面抛光度表面抛光度 Drainability排水能力排水能力 Piping Slope Tests管道坡度测试管道坡度测试 Pre-FAT & FAT are executed in accordance with pre- approved protocols. 符合预先批准协议的预符合预先批准协议的预FAT及及FAT。 SAT, Commissioning & Qualification services are provided. 提供提供SAT、调试及认证服务。、调试及认证服务。 制药业 Test Facilities Include: 测试设施包括：测试设施包括： RO Water RO水水 Plant Steam 工厂工厂蒸汽蒸汽 Clean Steam 洁净洁净蒸汽蒸汽 Clean Dry Air 清洁清洁干燥空气干燥空气 Vessel Test Bay 容器容器试验台试验台 Sprayball testing 喷喷淋测试淋测试 Calibrated inspection equipment includes: Micrometers, Profilometers, Ferritescope, Digital Protractors, Positive Material Identification (PMI). 校准校准检测设备包括：千分尺检测设备包括：千分尺，表面粗糙度仪，铁离子检测仪，数显角度，表面粗糙度仪，铁离子检测仪，数显角度 仪，材料检测仪（仪，材料检测仪（PMI）。）。 制药业 Experienced in delivering large scale projects throughout the globe. 有交付全球大规模项目的丰富有交付全球大规模项目的丰富经经 验验。 All aspects of logistics. 全方位物流全方位物流 制药业 Project Sample项目案例 制药业 COMPOUNDING SKID P&ID组装模块PID图 制药业 COMPOUNDING SKID PLAN组装模块方案 制药业 COMPOUNDING SKID ELEVATIONS 组装模块立面图 制药业 COMPOUNDING SKID 3D MODEL 组装模块3D模型 制药业 COMPOUNDING SKID 3D MODEL 组装模块3D模型 制药业 COMPOUNDING SKID 3D MODEL 组装模块3D模型 制药业 COMPOUNDING SKID PHOTO组装模块照片 制药业 BCD SELECTED REFERENCE PROJECTS BCD精选项目案例 制药业 MEDIA / BUFFER HOLD SUPERSKID 培养基/缓冲液保存 大型设备模块 2012 WAVRE BELGIUM VALUE 7,000,000 OVERVIEW概述 BASIS OF DESIGN基础设计 DETAILED DESIGN详细设计 MANUFACTURING HOURS: 24,000 制造耗时24000H ENGINEERING HOURS: 16,000 工程耗时16000H AUTOMATION SYSTEM自动系统: INTEGRATED FAT完整FAT SITE INSTALLATION现场安装 COMMISSIONING IV/OV ASTM E2500 调试IV/OV ASTM E2500 制药业 MEDIA / BUFFER HOLD SUPERSKID 培养基/缓冲液保存 大型设备模块 制药业 2008 CORK, IRELAND VALUE 5,100,000 MEDIA PREP & HARVEST HOLD 培养基制备和收获存储 OVERVIEW概述 DETAILED DESIGN 详细设计 MANUFACTURING HOURS: 19,000 制造耗时19000H ENGINEERING HOURS: 12,000 工程耗时12000H AUTOMATION SYSTEM自动化系统: INTEGRATED FAT 完整FAT SITE INSTALLATION 现场安装 COMMISSIONING 调试 制药业 2009 DENMARK VALUE 4,500,000 OVERVIEW概述 DETAILED DESIGN 详细设计 MANUFACTURING HOURS: 15,000 HRS 制造耗时15000H ENGINEERING HOURS: 10,000 HRS 工程耗时12000H AUTOMATION SYSTEM: DELTAV, 570 I/O 自动化系统： DELTAV, 570 I/O CIP SUPERSKIDS (2 X 5 SKID UNITS) CIP大型模块（25 模块单元） CIP RINSE SKIDS (2 SKIDS) CIP冲洗模块（2模块） CHROMATOGRAPHY BLEND SKIDS (3 MODULES) 层析模块（3个模块） BIOWASTE INACTIVATION SKID 生物废料失活模块 CIP, CHROMATOGRAPHY & BIOWASTE CIP、层析及生物废料 制药业 2008 VALUE 4,200,000 OVERVIEW DETAILED DESIGN详细设计 6 VACCINE SKIDS 6个疫苗模块 MANUFACTURING HOURS: 12,600 HRS 制造耗时12600H ENGINEERING HOURS: 5000 HRS 工程耗时5000H INTEGRATED TESTING集成测试 AUTOMATION SYSTEM自动化系统: DELTAV, COMMISSIONING调试 SITE INTEGRATION现场集成 VACCINE ADJUVANT SKIDS 疫苗助剂模块 BELGIUM, us, CANADA, 比利时，美国，加拿大，比利时，美国，加拿大， FRANCE, GERMANY, JAPAN 法国，德国，日本法国，德国，日本 制药业 VACCINE ADJUVANT SKIDS 疫苗辅料模块 制药业 2007 SWEDEN VALUE 2,950,000 OVERVIEW DETAILIED DESIGN详细设计 11 VESSELS 11罐 MANUFACTURING HOURS: 10,900 HRS 制造耗时10900H ENGINEERING HOURS: 6000 HRS 工程耗时6000H INTEGRATED TESTING集成测试 AUTOMATION SYSTEM自动化系统: DELTAV, COMMISSIONING 调试 FLAMMABLE MEDIA / BUFFER & CIP 易燃培养基或缓冲液&CIP 制药业 DSP & BUFFER HOLD DSP及缓冲液保存 CURRENT SINGAPORE VALUE 10,800,000 OVERVIEW概述 DETAILED DESIGN详细设计 19 VESSELS 19罐 SUPERSKIDS 大型模块 TCMS INTEGRATED TESTING集成测试 THERMAL MAPPING热辐射 COMMISIOING调试 制药业 2011 GENZYME BELGIUM VALUE 5,200,000 NANOFILTRATION - FORMULATION - BUFFER HOLD 纳滤-配料-缓冲液