Sterile Processing of Pharmaceutical Products: Engineering Practice, Validation, and Compliance in Regulated Environments

Description

Describes the methodologies and best practices of the sterile manufacture of drug products Thoroughly trained personnel and carefully designed, operated, and maintained facilities and equipment are vital for the sterile manufacture of medicinal products using aseptic processing. Professionals in pharmaceutical and biopharmaceutical manufacturing facilities must have a clear understanding of current good manufacturing practice (cGMP) and preapproval inspection (PAI) requirements. Sterile Processing of Pharmaceutical Products: Engineering Practice, Validation, and Compliance in Regulated Environments provides up-to-date coverage of aseptic processing techniques and sterilization methods. Written by a recognized expert with more than 20 years of industry experience in aseptic manufacturing, this practical resource illustrates a comprehensive approach to sterile manufacturing engineering that can achieve drug manufacturing objectives and goals. Topics include sanitary piping and equipment, cleaning and manufacturing process validation, computerized automated systems, personal protective equipment (PPE), clean-in-place (CIP) systems, barriers and isolators, and guidelines for statistical procedure. Offering authoritative guidance on the key aspects of sterile manufacturing engineering, this volume: Covers fundamentals of aseptic techniques, quality by design, risk assessment and management, and operational requirementsAddresses various regulations and guidelines instituted by the FDA, ISPE, EMA, MHRA, and ICHProvides techniques for systematic process optimization and good manufacturing practice Emphasizes the importance of attention to detail in process development and validationFeatures real-world examples highlighting different aspects of drug manufacturing Sterile Processing of Pharmaceutical Products: Engineering Practice, Validation, and Compliance in Regulated Environments is an indispensable reference and guide for all chemists, chemical engineers, pharmaceutical professionals and engineers, and other professionals working in pharmaceutical sciences and manufacturing. Cover Title Page Copyright Contents Preface Acknowledgments Chapter 1 Introduction Chapter 2 Sterilization Steam Sterilization Flash Sterilization Low‐Temperature Sterilization Technologies Ethylene Oxide Gas Sterilization Hydrogen Peroxide Gas Plasma Disinfection and Surface Sterilization Using Peracetic Acid Ionizing Radiation Dry‐Heat Sterilizers Filtration Microwave Vaporized Hydrogen Peroxide (VHP®) Ozone Formaldehyde Steam Gaseous Chlorine Dioxide Vaporized Peracetic Acid Infrared Radiation Sterilization Cycle Verification Monitoring Chapter 3 Sterile Manufacturing Facilities Chapter 4 Sanitary Process Piping and Equipment QA Procedures Standard Operating Procedures – cGMP Installations Heat Exchangers Sanitary Pumps Sanitary Tanks Instruments Pressure Transmitter (Various Sources) Temperature Transmitter (Various Sources) Standard Operating Procedures – cGMP Installations Surface Finish Welding Applicability Process/Procedure Records (General) Records Automatic Orbital Welding Weld Acceptance Criteria for Automatic Orbital Weld Qualifications Chapter 5 Passivation In‐house Passivation Using Vats Spot Passivation Astro Pak UltraPass Gel Passivation Alternative Process Control of Passivated Items Preparing, Testing, and Adjusting Cleaning and Passivation Chemicals (Passivation in Vats) Chapter 6 Chilled Water System Process Description Commissioning of HVAC Installation Verification – X Ton Chiller System System Startup – X Ton Chiller Functional Testing – X Ton Chiller Chapter 7 Clean‐In‐Place (CIP) Systems Life Cycle Requirements Product and Process User Requirements Process Quality Requirements Process Parameter Requirements Installation User Requirements Operational Requirements Chapter 8 Computerized Automated Systems Functional Requirement Specification Process Automation System EMS User Requirement Specification Automation Overview Software Hardware SCADA Control Panels Main Control Panel Remote I/O Panels Power Distribution Panels Instrumentation Panels System Functions System Overview Control Modules Interfaces User Interface (SCADA) PAS System Overview Graphical Screen Navigation Client EMS Area Graphical Screens Graphical Control Screens Interfaces to Equipment Interfaces to Other Systems Ethernet Network Nonfunctional Attributes Power Failure Recovery PLC Only Failure HMI Only Failure Network Only Failure Maintainability Backup and Recovery Functional Requirement Specification GLC Environmental Monitoring System Automation Overview System Components Software Hardware Control Panels Gateways System Functions System Overview Control Modules Interfaces User Interface (SCADA) GLC EMS Area Graphical Screen Global Logistics Center (GLC) Environmental Monitoring System Interfaces to Equipment Interfaces to Other Systems Ethernet Network Wireless Connections Nonfunctional Attributes Power Failure Recovery PLC Only Failure HMI Only Failure Network Only Failure Maintainability Backup and Recovery Software Module Design Specification Functional Requirement Specification Process Automation System Automation Overview System Components Software Hardware Control Panels System Functions System Overview Control Modules Interfaces User Interface (SCADA) PAS System Overview Screen Graphical Screen Navigation Graphical Control Screens Interfaces to Equipment Interfaces to Other Systems Ethernet Network Nonfunctional Attributes Power Failure Recovery PLC Only Failure HMI Only Failure Network Only Failure Maintainability Backup and Recovery Software Design Specification Prosoft Configuration Enabling and Disabling of the Gateway Default Server Interface Temperature Sensor Settings Humidity Sensor Settings Software Design Specification Continuous Logic Module Classes and Control Modules Virtual Differential Pressure Alarm Disable Room Condition Indication Navigation Links Alarm Daily Report WFI Still Equipment Module Class WFI Silo Equipment Module Class EM&uscore;SILO WFI Primary Loop Equipment Module Class EM&uscore;PRIM&uscore;LOOP WFI Supply Header Equipment Module Class EM&uscore;HEADER Electrical – Controls Equipment Specifications Documentation Drives/Motors Chapter 9 Personal Protective Equipment (PPE) and Process Flow Chapter 10 Sterile Aseptic Processing Chapter 11 Integrated Facility Design Case Study Issue Root Cause Corrective Action Preventive Actions Chapter 12 Barriers and Isolators Isolator Design Considerations Chapter 13 Guidelines for Statistical Procedure Process Capability Analysis Long‐term Studies Acceptance Sampling Attribute and Variable Sampling Plans Variable Sampling Plans – ANSI Z1.9 Normality Transformation of Non‐normal Data (Normalization) Protocol Sampling Failure Mode and Effect Analysis (FMEA) Calculating or Recalculating Control Limits Chapter 14 Calibration Contingency Plan/Disaster Recovery Chapter 15 Cleaning Validation New Products and Product Changes Cleaning Processes and Changes Risk Assessment/Matrix Approach Matrix Development Cleaning Processes (Manual and Automated) CPP/CQA Cleaning Validation Life Cycle – Cleaning Method Development Strategy for Process Controls Worst‐Case Identification – Product/Component Equipment Validation Tests/Inspections – Visual Inspection Chemical Testing Microbiological Testing Endotoxin Testing Sampling Methods Direct Swab Sampling Rinse Sampling Coupon Testing Sampling Sites Acceptance Criteria Residual Levels Endotoxin Levels Microbiological Levels Cleaning Agents/Sanitizer Validation Studies Hold Time Development Dirty Hold Time Clean Hold Time Additional Hold Times/Cleaning Frequencies Continuous Process Verification Failure Investigations Chapter 16 Validation of Filling Equipment Chapter 17 Manufacturing Process Validation Stage 2 – Process Qualification Appendix A Installation Test Plans Appendix B Operational Tests Plans Appendix C WFI Turbulence Flow Requirements Appendix D Water For Injection (WFI) – Design Requirements Process Description Specifications Life Cycle Requirements Product and Process User Requirements Product Description Operating Ranges Material of Construction Metallics Plastics Elastomers Glass Welding Requirements Construction Requirements Lubrication Requirements Electrical Requirements Safety Requirements Operational Requirements Process Constraints and Limitations Process Control System Operator Interface Power Loss and Recovery Cleaning and Sanitizing Maintenance Requirements Training and Documentation Requirements Appendix E Solution Transfer System (STS) – Design Requirements System Description Bulk Powder Handling System Glossary Nomenclature References Further Reading Index EULA