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

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