How to Integrate Quality by Efficient Design Qbed in Product Development

Cover
Principles of Parenteral Solution Validation
Copyright
Dedication
Contents
List of Contributors
Editor Biographies
About the Expertise in Pharmaceutical Process Technology Series
	Format
	Subject Matter
	Target Audience
Introduction
	References
	Further Reading
1 Process Validation: Design and Planning
	Part 1: Background—The Need for Process Understanding
	Why Is Aseptic Process Validation so challenging?
	Process Validation, Process Capability, and Process Control
	Role of Process Understanding
	Process Life Cycle Approach
	Proper Process Design as the Key to Process Performance Assurance: Sterility by Design
	Using a Line of Sight Approach
	Defining Process Requirements
	The Role of Process Design and Planning in Validation: Basis of Design
	Timely User Requirement Specification
	Equipment and Facility Qualification
	Mapping the Process
	Periodic Assessment and Requalification
	Aseptic Practices: A Key Element in the Validation of Aseptic Processes
	First Air Principles
	References
2 Aseptic Process Validation: Aseptic Process Simulation Design
	Microbial Contamination Case Study: Sterile Vessel Holding Qualification
		Question #1: How Did the Interior of the Vessel Become Contaminated?
		The More Challenging Question Is #2: If the Conclusions Are Correct, Then Why Did the Initial Media Fills Pass?
	Aseptic Process Simulation Study Design
	Aseptic Process Simulations Performance Schedule and Frequency
	Media Fills Run Number
	Inclusion of Process Steps
	“Worst-Case” Parameters or Conditions
	Fill Volume
	Duration
	Interventions
	Intervention Evaluation and Risk Assessment Methods
	Incubation
	Growth Promotion Studies
	Preincubation Inspection and Rejection
	Postincubation Inspection
	Acceptance Criteria
	Filled Unit Accountability
	Failure Investigation
	Aborted and Invalid Media Fills
	Special Considerations
	Powder Filling
	Ointment Filling
	Lyophilized Product Filling
	Anaerobic Processes
	Conclusion
	References
3 Quality Risk Management of Parenteral Process Validation, Part 1: Fundamentals
	Quality Risk Management and Process Validation
		Overview: Risk Management Evolution
		Principles of Risk Management and the Quality Risk Management Life Cycle
		Risk: Understanding Hazard, Harm, and Controls
		Risk Management: The Fine Print
		Risk Team Membership
		Goal, Scope, and Boundaries
		Exploring the Process Map
			The Risk Question and Tool Selection
		Scales for Assessing Risk
		Quality Risk Management Life Cycle
			Risk Assessment
			Risk Control
			Risk Communication
			Risk Review
		Conclusion
	References
4 Equipment Cleaning Process
	Establishing Limits
	References
	Further Reading
5 Quality Risk Management of Parenteral Process Validation, Part 2: A Risk-Based Quality Management System
	Overview
	Deviation Management
		Low Risk Deviation
		Medium Risk Deviation
		High Risk Deviation
	Corrective and Preventive Action
		Risk Benefit Analysis
	Change Control
	Change Control and Corrective and Preventive Action Effectiveness Monitoring
	Self-Inspection Process
		Define Key Quality Management Systems
		Define Functional Area Categories
		Perform Risk Assessment Using Compliance Scoring Criteria
		Risk Factors and Scoring
		Determine Audit Frequency Using Risk Matrix
		Develop Audit Schedule; Review Annually
	Summary
	References
	Further Reading
6 Use of Statistics in Process Validation
	Overview
	Use of Statistics in Parenteral Process Validation—Ten Basic Concepts
		First Concept—A Concept of Statistical Inference
	Second Concept—Graph It First!
	Third Concept—Let DataTalk to You!
	Fourth Concept—Normality?
	Fifth Concept—Descriptive Statistics
	Sixth Concept—Control Charting
	Seventh and Eight Concepts—Tolerance and Capability
	Ninth Concept—Hypothesis Testing
	Tenth Concept—Design of Experiments
	Conclusion
	References
	Further Reading
7 Process Validation Stage 1: Parenteral Process Design
	Introduction Into Pharmaceutical Development
	Master Planning, Organization, and Schedule Planning
	Risk/Impact Assessment
	Process/System Design
	Perform Risk Assessment (Identification of Critical Quality Attributes and Critical Process Parameters)
	Design of Experiments
	Developing Control Strategies and Determine Process Design
	Scale-Up and Technology Transfer
	Stage 1: Design of Experiments Case Study
	Final Notes About Stage 1 Process Design
	References
8 Process Validation Stage 2: Parenteral Process Performance Qualification
	General Principles of Stage 2 Life Cycle Approach to Process Validation for Parenteral Products
	The Line of Sight Approach to Process Understanding and Process Validation
	Stage 2: Process Qualification
	Some Points to Consider for the Qualification of Equipment and Systems
	Critical Utilities
	Clean Rooms and Classified Areas
	Component Preparation
	Product Sterilization and Filtration
		Moist Heat Sterilization
		Dry Heat Sterilization
		Radiation and Ethylene Oxide
		Sterile Filtration
	Filling Equipment and Systems
	Inspection, Labeling, and Secondary Packaging Systems
	Lyophilization
	Material Storage, Handling, and Transport
	Testing Laboratories
	Additional Parenteral Processes
	Cleaning Validation
	Computer System Validation
	Terminal Sterilization
	Container Closure Integrity
	Periodic Assessment and Requalification
	Stage 2b—PPQ or Process Performance Qualification
	Number of Batches
	Conclusion
	References
	Further Reading
9 Process Validation Stage 3: Continued Process Verification
	Introduction
	Definitions Typically Used in Process Validation
	Determining When Continued Process Verification Starts
	Legacy Systems Versus New Systems
	Continued Process Verification Strategy and Enhanced Sampling
	Maintenance of Validation and Change Control, and Periodic Assessment
	Develop Control Rules for Continued Process Verification
	Develop Strategies for Continued Process Verification
	Examples of Case Study Evaluations for Parenteral Products
	Conclusion
	References
10 Preuse/Poststerilization Integrity Testing of Sterilizing Grade Filter
	Introduction
	Possible Reasons to Apply Preuse/Poststerilization Integrity Testing
	The Risks Attached to Preuse/Poststerilization Integrity Testing
	Recommendations
	References
11 Environmental Monitoring
	References
	Further reading
12 Isolators
	Further Reading
13 Post Aseptic Fill Sterilization and Lethal Treatment
	Introduction
	Sterilization and Lethal Treatment
		Post Aseptic Fill Sterilization
		Post Aseptic Fill Lethal Treatment
		Parametric Release
	Summary
Conclusion
Index