How to Integrate Quality by Efficient Design Qbed in Product Development

288 Pages·2019·9.977 MB·English

by  Bhavishya Mittal

Principles of Parenteral Solution
Validation
RelatedTitles:
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Part of the
Expertise in Pharmaceutical Process
Series
Technology
Principles of Parenteral
Solution Validation
A Practical Lifecycle Approach
Edited by
Igor Gorsky
Senior Consultant, ConcordiaValsource LLC., Downingtown,
PA, United States
Harold S. Baseman
Chief Operating Officer, Valsource Inc, Jupiter, FL, United States
Series Editor
Michael Levin
Milev, LLC Pharmaceutical Technology Consulting,
NJ, United States
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DEDICATION
I would like to dedicate this book to my family—my wife Faina, my
children Jessica and Joshua Gorsky’s, my sister Alina Gorokhovsky,
my mother Polina Gorokhovsky, and my beloved late father Iosif
Gorokhovsky who unfortunately passed away before this book was
published. Without them I wouldn’t be able to compile this volume. In
addition, I would like to thank my co-editor Hal Baseman and Dr.
Mike Long for their help and mentorship. Finally, I would like to
thank all contributors for their chapters.
Igor Gorsky
CONTENTS
List of Contributors...........................................................................xiii
Editor Biographies...............................................................................xv
About the Expertise in Pharmaceutical Process Technology Series....xvii
Introduction...........................................................................................1
Igor Gorsky
References.............................................................................................7
Further Reading...................................................................................7
Chapter 1 Process Validation: Design and Planning.............................9
Harold S. Baseman
Part 1: Background—The Need for Process Understanding.................9
Why Is Aseptic Process Validation so Challenging?...........................12
Process Validation, Process Capability, and Process
Control...............................................................................................14
Role of Process Understanding...........................................................15
Process Life Cycle Approach..............................................................16
Proper Process Design as the Key to Process Performance
Assurance: Sterility by Design............................................................17
Using a Line of Sight Approach.........................................................17
Defining Process Requirements..........................................................20
The Role of Process Design and Planning in Validation:
Basis of Design...................................................................................21
Timely User Requirement Specification.............................................22
Equipment and Facility Qualification.................................................23
Mapping the Process...........................................................................25
Periodic Assessment and Requalification............................................27
Aseptic Practices: A Key Element in the Validation of Aseptic
Processes.............................................................................................28
First Air Principles.............................................................................30
References...........................................................................................31
viii Contents
Chapter 2 Aseptic Process Validation: Aseptic Process Simulation
Design................................................................................33
HaroldS. Baseman
Microbial Contamination Case Study: Sterile Vessel Holding
Qualification.......................................................................................35
Aseptic Process Simulation Study Design...........................................38
Aseptic Process Simulations Performance Schedule and Frequency...39
Media Fills Run Number...................................................................39
Inclusion of Process Steps...................................................................41
“Worst-Case” Parameters or Conditions............................................42
Fill Volume.........................................................................................43
Duration.............................................................................................43
Interventions.......................................................................................46
Intervention Evaluation and Risk Assessment Methods.....................47
Incubation..........................................................................................50
Growth Promotion Studies.................................................................51
Preincubation Inspection and Rejection.............................................52
Postincubation Inspection...................................................................53
Acceptance Criteria............................................................................53
Filled Unit Accountability..................................................................54
Failure Investigation...........................................................................54
Aborted and Invalid Media Fills........................................................55
Special Considerations........................................................................55
Powder Filling....................................................................................56
Ointment Filling.................................................................................56
Lyophilized Product Filling................................................................56
Anaerobic Processes............................................................................57
Conclusion..........................................................................................57
References...........................................................................................58
Chapter 3 Quality Risk Management of Parenteral Process
Validation, Part 1: Fundamentals.......................................61
Amanda McFarland
Quality Risk Management and Process Validation............................61
References...........................................................................................79
Chapter 4 Equipment Cleaning Process..............................................81
Igor Gorsky
Establishing Limits.............................................................................82
Contents ix
References...........................................................................................96
Further Reading.................................................................................96
Chapter 5 Quality Risk Management of Parenteral Process
Validation, Part 2: A Risk-Based Quality Management
System...............................................................................97
Lori Richter
Overview.............................................................................................97
Deviation Management......................................................................99
Corrective and Preventive Action.....................................................102
Change Control................................................................................105
Change Control and Corrective and Preventive Action
Effectiveness Monitoring..................................................................106
Self-Inspection Process......................................................................107
Summary..........................................................................................113
References.........................................................................................113
Further Reading...............................................................................113
Chapter 6 Use of Statistics in Process Validation.............................115
Igor Gorsky
Overview...........................................................................................115
Use of Statistics in Parenteral Process Validation—Ten Basic
Concepts...........................................................................................120
Second Concept—Graph It First!.....................................................120
Third Concept—Let DataTalk to You!............................................121
Fourth Concept—Normality?...........................................................122
Fifth Concept—Descriptive Statistics...............................................123
Sixth Concept—Control Charting....................................................123
Seventh and Eight Concepts—Tolerance and Capability.................125
Ninth Concept—Hypothesis Testing................................................130
Tenth Concept—Design of Experiments...........................................131
Conclusion........................................................................................134
References.........................................................................................135
Further Reading...............................................................................136
Chapter 7 Process Validation Stage 1: Parenteral Process Design....137
Igor Gorsky
Introduction Into Pharmaceutical Development...............................137
Master Planning, Organization, and Schedule Planning...................139
x Contents
Risk/Impact Assessment...................................................................141
Process/System Design......................................................................144
Perform Risk Assessment (Identification of Critical Quality
Attributes and Critical Process Parameters).....................................146
Design of Experiments......................................................................151
Developing Control Strategies and Determine Process Design.........156
Scale-Up and Technology Transfer..................................................157
Stage 1: Design of Experiments Case Study.....................................162
Final Notes About Stage 1 Process Design......................................172
References.........................................................................................175
Chapter 8 Process Validation Stage 2: Parenteral Process
Performance Qualification...............................................177
HaroldS. Baseman and Igor Gorsky
General Principles of Stage 2 Life Cycle Approach to Process
Validation for Parenteral Products...................................................177
The Line of Sight Approach to Process Understanding and
Process Validation............................................................................183
Stage 2: Process Qualification...........................................................184
Some Points to Consider for the Qualification of Equipment
and Systems......................................................................................189
Critical Utilities................................................................................189
Clean Rooms and Classified Areas...................................................190
Component Preparation...................................................................192
Product Sterilization and Filtration..................................................194
Filling Equipment and Systems........................................................197
Inspection, Labeling, and Secondary Packaging Systems.................198
Lyophilization...................................................................................198
Material Storage, Handling, and Transport.....................................199
Testing Laboratories.........................................................................199
Additional Parenteral Processes........................................................200
Cleaning Validation..........................................................................200
Computer System Validation............................................................200
Terminal Sterilization.......................................................................200
Container Closure Integrity..............................................................200
Periodic Assessment and Requalification..........................................201
Stage 2b—PPQ or Process Performance Qualification.....................202
Number of Batches...........................................................................202
Conclusion........................................................................................205