Analytical chemistry : an introduction to pharmaceutical GMP laboratory /
edited by Kim Huynh-Ba.
- 1 online resource (xxx, 386 pages) ; illustrations.
Includes bibliographical references and index.
Cover
Title Page
Copyright Page
Contents
Einstein Quotation
Preface
About the Editor
Biographies of Contributing Authors
Editorial Notes
Acknowledgments
Chapter 1 Drug Regulations and the Pharmaceutical Laboratories
1.1 Introduction
1.2 Food and Drug Administration: Roles and Its Regulations
1.2.1 Code of Federation Regulations
1.2.2 FDA Guidance Documents
1.2.3 FDA Manual of Policies and Procedures
1.3 International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and Its Role
1.3.1 ICH Background
1.3.2 ICH Structure
1.3.3 ICH Organization
1.3.4 ICH Topics
1.4 Pharmaceutical Analysis
1.4.1 Analytical Testing
1.4.2 Interaction of the Analytical Development Department and Other Functional Areas
1.4.3 Drug Development Process
1.5 Summary
List of Abbreviations
References
Chapter 2 Good Manufacturing Practices (GMPs) and the Quality Systems
2.1 Introduction to Good Manufacturing Practices
2.2 Objectives of GMPs
2.2.1 Definitions
2.2.2 Organization of 21 CFR Regulations
2.3 Personnel Qualification and Responsibilities - Subpart B
2.3.1 Responsibilities of the Quality Control Unit
2.3.2 Personnel Qualifications and Responsibilities
2.4 Equipment - Subpart D
2.4.1 Metrology Functions
2.4.2 Qualification Phases
2.5 Laboratory Controls
2.5.1 General Requirements
2.5.2 Testing and Release for Distribution
2.5.3 Stability Program
2.5.4 Retention Program
2.6 Records and Reports
2.7 Pharmaceutical Quality
2.7.1 Quality Manual
2.7.2 Quality Risk Management
2.7.3 Product Quality Review
2.7.4 Pharmaceutical Quality Systems
List of Abbreviations
References
Chapter 3 Analytical Techniques Used in the GMP Laboratory
3.1 Introduction
3.2 Definitions. 3.2.1 Raw Data and Analytical Data
3.2.2 Analyses
3.2.3 Analytical Documents
3.3 Basic Laboratory Procedures
3.3.1 Balances
3.3.2 Volumetric Glassware
3.3.3 Potentiometry (Ion-Selective Electrode) and pH Test
3.3.4 The Density Test
3.3.5 The Friability Test
3.3.6 The Hardness Test
3.3.7 The Titration Test
3.3.8 The Karl Fischer Titration-Water Determination
3.3.9 Loss on Drying
3.3.10 Residue on Ignition/Sulfated Ash
3.3.11 Thermo Gravimetric Analysis
3.3.12 Differential Scanning Calorimetry
3.3.13 The Disintegration Test
3.3.14 Particulate Matter
3.3.15 Osmolality
3.4 Chromatography
3.4.1 High-Performance Liquid Chromatography
3.4.2 Ultra-High-Pressure Liquid Chromatography
3.4.3 Detectors of Liquid Chromatography
3.4.4 System Suitability Tests for Chromatographic Methods
3.4.5 Maintenance of HPLC and UHPLC
3.4.6 Gas Chromatography
3.4.7 Thin-Layer Chromatography
3.4.8 Bio-Pharmaceutical Separations
3.5 Spectroscopic Sciences
3.5.1 Ultraviolet-Visible
3.5.2 Infrared-Absorption
3.5.3 Mass Spectroscopy
3.5.4 Atomic Absorption, Inductively Coupled Plasma, Inductively Coupled Plasma/Mass Spectrometry, and Inductively Coupled Plasma/Optical Emission Spectrometry
3.5.5 Nuclear Magnetic Resonance Spectroscopy
3.5.6 X-ray Absorption and X-ray Emission Spectrometry
3.6 Uniformity of Dosage Units
3.6.1 Weight Variation
3.6.2 Acceptance Criteria per USP <
905>
3.7 Elemental Analysis
3.8 Appearance
3.9 Visual Inspection
3.10 Microbiological Testing
3.10.1 Microbial Limits
3.10.2 Sterility
3.10.3 Bacterial Endotoxins
3.10.4 Antimicrobial Effectiveness Testing
3.11 Summary
References
Chapter 4 Control Strategies for Pharmaceutical Development
4.1 Introduction
4.2 Quality-by-Design Concept. 4.3 Risk Management
4.3.1 Risk Assessment
4.3.2 Risk Control
4.4 Establishing Specifications
4.4.1 What Is the Specification?
4.4.2 Typical Tests Included in the Specification of a Small Molecule Drug
4.4.3 Typical Tests Included in the Specification of Biological Drugs
4.4.4 Considerations of Setting Acceptance Criteria
4.5 Design of Experiments
4.5.1 Common Terms
4.5.2 Conducting the Study
4.5.3 Results Interpretation
4.5.4 Summary
4.6 Common Statistical Analysis
4.6.1 Mean, Standard Deviation (SD), and Relative Standard Deviation (RSD)
4.6.2 Confidence Interval
4.6.3 Statistical Significance (t-Test)
4.6.4 Outlier Detection
4.7 Summary
List of Abbreviations
References
Chapter 5 Development and Validation of Analytical Procedures
5.1 Introduction
5.2 Method Development
5.2.1 Development of Physical, Chemical, and Microbiological Procedures
5.3 Qualification, Validation, and Verification
5.3.1 Qualification
5.3.2 Validation
5.3.3 Verification
5.3.4 Frequency of Study
5.4 Validation Parameters
5.4.1 Accuracy
5.4.2 Precision
5.4.3 Specificity
5.4.4 Quantitation and Detection Limits (QL and DL)
5.4.5 Linearity
5.4.6 Range
5.4.7 Robustness
5.4.8 System Suitability Tests (SST)
5.4.9 Stability of Samples During Analysis
5.4.10 Tie the Pieces Together
5.5 Validation for Physical, Chemical, Biotechnological, and Microbiological Procedures
5.6 Validation of In-process, Environmental, Release, and Stability Procedures
5.6.1 In-process Procedures
5.6.2 Environmental Procedures
5.6.3 Release and Stability Procedures
5.7 Other Procedures
5.7.1 Process Analytical Technology (PAT)
5.7.2 Parametric Release and Real-time Release
5.8 Validation of Procedures in Continuous and Batch Manufacturing
5.9 Summary. List of Abbreviations
References
Chapter 6 Transfer of Analytical Procedures
6.1 Introduction
6.2 Purpose of Method Transfer
6.3 Transfer Options
6.3.1 Method Transfer Plan
6.3.2 Comparative Testing
6.3.3 Co-validation
6.3.4 Extended Validation or Partial Validation
6.3.5 Transfer Waiver
6.4 Method Transfer Process
6.4.1 Preparation Phase
6.4.2 Gap Analysis
6.4.3 Method Training Phase
6.4.4 Method Qualification Phase
6.5 Transfer Protocol
6.5.1 Content of a Transfer Protocol
6.5.2 Objectives/Scope
6.5.3 Roles and Responsibilities
6.5.4 Assessment of Receiving Lab
6.5.5 Materials, Facilities, and Instrumentation
6.5.6 Analyst Training
6.5.7 Qualification Procedure
6.5.8 Acceptance Criteria
6.5.9 Protocol Amendment and Deviation
6.6 Method Transfer Report
6.6.1 Objectives
6.6.2 Data Evaluation
6.6.3 Conclusion of Transfer Report
6.6.4 Analytical Transfer File
6.7 Related Documents
6.8 Handling Transfer Failures
6.9 Transfer to a Contract Lab
6.10 Transfer to an International Site
6.11 Summary
References
Chapter 7 Dissolution Testing in the Pharmaceutical Laboratory
7.1 Introduction
7.2 Regulatory and Compendial Role in Dissolution Testing
7.3 Theory
7.4 Equipment Operation and Sources of Error
7.4.1 Equipment Variables
7.4.2 Media Deaeration
7.4.3 Vibration
7.4.4 Water Bath of Dissolution Equipment
7.4.5 Glass Vessels
7.5 Common Errors of Dissolution Apparatus
7.5.1 USP Apparatus 1 and 2
7.5.2 USP Apparatus 3
7.5.3 USP Apparatus 4
7.5.4 USP Apparatus 5
7.5.5 USP Apparatus 6
7.5.6 USP Apparatus 7
7.6 Dissolution Method Considerations
7.6.1 Sample Introduction
7.6.2 Media Attributes
7.6.3 Observations
7.6.4 Sinkers
7.6.5 Filters
7.6.6 Manual Sampling. 7.6.7 Automation of Dissolution Sampling
7.6.8 Cleaning of Dissolution Equipment
7.7 Method Development
7.7.1 Drug Properties
7.7.2 Dosage Form Properties
7.7.3 Dissolution Profile
7.7.4 Dissolution Media
7.7.5 Medium Volume
7.7.6 Deaeration
7.7.7 Speed
7.7.8 Sinkers
7.7.9 Filtration
7.7.10 Time Points - Immediate Release
7.7.11 Fast Stir or Infinity Point
7.7.12 Time Points for Extended-Release Products
7.8 Poorly Soluble Drugs
7.8.1 Sink Conditions
7.8.2 Apparatus Selection
7.8.3 The Discriminatory Power of the Method
7.9 Setting Specifications
7.10 Harmonization
7.11 Method Validation
7.12 Validation of Product Performance Parameters
7.12.1 Accuracy/Recovery
7.12.2 Selectivity
7.12.3 Solution Stability
7.12.4 Filter
7.12.5 Robustness
7.12.6 Intermediate Precision
7.12.7 Automated Methodology
7.13 Validation of the Analytical Finish
7.14 Method Transfer Considerations
7.14.1 Robustness
7.14.2 Details of the Analytical Method
7.14.3 Other Considerations
7.15 Good Manufacturing Practices (GMP) in the Dissolution Testing Laboratory
7.15.1 Metrology
7.15.2 Notebook Documentation
7.15.3 Equipment Qualification, Validation, and Method Critical Factors
7.15.4 Good Manufacturing Practice Audits
7.15.5 Training
7.16 Summary
Acknowledgment
List of Abbreviations
Chapter 8 Analytical Data and the Documentation System
8.1 Introduction
8.1.1 Types of Documents
8.2 GMP for Records and Reports-Subpart J
8.2.1 General Requirements
8.2.2 Equipment Cleaning and Use Log
8.2.3 Component, Drug Product Container, Closure, and Labeling Records
8.2.4 Master Production and Control Records
8.2.5 Batch Production and Control Records
8.2.6 Production Record Review
8.2.7 Laboratory Records
8.3 Keeping Good Records
"Analytical testing in the pharmaceutical industry is necessary to establish drug quality based on science and regulatory compliance. It requires analysts to acquire a solid understanding of analytical chemistry and also a thorough appreciation of pharmaceutical regulatory requirements to address day-to-day challenges and maintain a compliant state. Pharmaceutical laboratories are operated under Good Manufacturing Practices (GMP), thus a knowledge of this regulations is necessary to perform pharmaceutical testing of drug substance and drug products"--
Kim Huynh-Ba, M.Sc., PMP, FAAPS, is the Chief Executive Officer and Managing Director of Pharmalytik LLC, where she provides consulting and training services to leading pharmaceutical companies and global organizations. She has decades of experience in strategic analytical development, risk management, strategic drug development, and stability sciences. She is an Adjunct Professor at Temple University School of Pharmacy and Illinois Institute of Technology (IIT) teaching GMPs and various regulatory compliance subjects.
9781119680475
Pharmaceutical industry--Quality control.
Analytical chemistry.
Drugs--Testing.
Drug development.
Pharmaceutical chemistry.
Chemistry, Pharmaceutical.
Electronic books.
RS189 / .H89 2022
615/.19
QV 25
Includes bibliographical references and index.
Cover
Title Page
Copyright Page
Contents
Einstein Quotation
Preface
About the Editor
Biographies of Contributing Authors
Editorial Notes
Acknowledgments
Chapter 1 Drug Regulations and the Pharmaceutical Laboratories
1.1 Introduction
1.2 Food and Drug Administration: Roles and Its Regulations
1.2.1 Code of Federation Regulations
1.2.2 FDA Guidance Documents
1.2.3 FDA Manual of Policies and Procedures
1.3 International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and Its Role
1.3.1 ICH Background
1.3.2 ICH Structure
1.3.3 ICH Organization
1.3.4 ICH Topics
1.4 Pharmaceutical Analysis
1.4.1 Analytical Testing
1.4.2 Interaction of the Analytical Development Department and Other Functional Areas
1.4.3 Drug Development Process
1.5 Summary
List of Abbreviations
References
Chapter 2 Good Manufacturing Practices (GMPs) and the Quality Systems
2.1 Introduction to Good Manufacturing Practices
2.2 Objectives of GMPs
2.2.1 Definitions
2.2.2 Organization of 21 CFR Regulations
2.3 Personnel Qualification and Responsibilities - Subpart B
2.3.1 Responsibilities of the Quality Control Unit
2.3.2 Personnel Qualifications and Responsibilities
2.4 Equipment - Subpart D
2.4.1 Metrology Functions
2.4.2 Qualification Phases
2.5 Laboratory Controls
2.5.1 General Requirements
2.5.2 Testing and Release for Distribution
2.5.3 Stability Program
2.5.4 Retention Program
2.6 Records and Reports
2.7 Pharmaceutical Quality
2.7.1 Quality Manual
2.7.2 Quality Risk Management
2.7.3 Product Quality Review
2.7.4 Pharmaceutical Quality Systems
List of Abbreviations
References
Chapter 3 Analytical Techniques Used in the GMP Laboratory
3.1 Introduction
3.2 Definitions. 3.2.1 Raw Data and Analytical Data
3.2.2 Analyses
3.2.3 Analytical Documents
3.3 Basic Laboratory Procedures
3.3.1 Balances
3.3.2 Volumetric Glassware
3.3.3 Potentiometry (Ion-Selective Electrode) and pH Test
3.3.4 The Density Test
3.3.5 The Friability Test
3.3.6 The Hardness Test
3.3.7 The Titration Test
3.3.8 The Karl Fischer Titration-Water Determination
3.3.9 Loss on Drying
3.3.10 Residue on Ignition/Sulfated Ash
3.3.11 Thermo Gravimetric Analysis
3.3.12 Differential Scanning Calorimetry
3.3.13 The Disintegration Test
3.3.14 Particulate Matter
3.3.15 Osmolality
3.4 Chromatography
3.4.1 High-Performance Liquid Chromatography
3.4.2 Ultra-High-Pressure Liquid Chromatography
3.4.3 Detectors of Liquid Chromatography
3.4.4 System Suitability Tests for Chromatographic Methods
3.4.5 Maintenance of HPLC and UHPLC
3.4.6 Gas Chromatography
3.4.7 Thin-Layer Chromatography
3.4.8 Bio-Pharmaceutical Separations
3.5 Spectroscopic Sciences
3.5.1 Ultraviolet-Visible
3.5.2 Infrared-Absorption
3.5.3 Mass Spectroscopy
3.5.4 Atomic Absorption, Inductively Coupled Plasma, Inductively Coupled Plasma/Mass Spectrometry, and Inductively Coupled Plasma/Optical Emission Spectrometry
3.5.5 Nuclear Magnetic Resonance Spectroscopy
3.5.6 X-ray Absorption and X-ray Emission Spectrometry
3.6 Uniformity of Dosage Units
3.6.1 Weight Variation
3.6.2 Acceptance Criteria per USP <
905>
3.7 Elemental Analysis
3.8 Appearance
3.9 Visual Inspection
3.10 Microbiological Testing
3.10.1 Microbial Limits
3.10.2 Sterility
3.10.3 Bacterial Endotoxins
3.10.4 Antimicrobial Effectiveness Testing
3.11 Summary
References
Chapter 4 Control Strategies for Pharmaceutical Development
4.1 Introduction
4.2 Quality-by-Design Concept. 4.3 Risk Management
4.3.1 Risk Assessment
4.3.2 Risk Control
4.4 Establishing Specifications
4.4.1 What Is the Specification?
4.4.2 Typical Tests Included in the Specification of a Small Molecule Drug
4.4.3 Typical Tests Included in the Specification of Biological Drugs
4.4.4 Considerations of Setting Acceptance Criteria
4.5 Design of Experiments
4.5.1 Common Terms
4.5.2 Conducting the Study
4.5.3 Results Interpretation
4.5.4 Summary
4.6 Common Statistical Analysis
4.6.1 Mean, Standard Deviation (SD), and Relative Standard Deviation (RSD)
4.6.2 Confidence Interval
4.6.3 Statistical Significance (t-Test)
4.6.4 Outlier Detection
4.7 Summary
List of Abbreviations
References
Chapter 5 Development and Validation of Analytical Procedures
5.1 Introduction
5.2 Method Development
5.2.1 Development of Physical, Chemical, and Microbiological Procedures
5.3 Qualification, Validation, and Verification
5.3.1 Qualification
5.3.2 Validation
5.3.3 Verification
5.3.4 Frequency of Study
5.4 Validation Parameters
5.4.1 Accuracy
5.4.2 Precision
5.4.3 Specificity
5.4.4 Quantitation and Detection Limits (QL and DL)
5.4.5 Linearity
5.4.6 Range
5.4.7 Robustness
5.4.8 System Suitability Tests (SST)
5.4.9 Stability of Samples During Analysis
5.4.10 Tie the Pieces Together
5.5 Validation for Physical, Chemical, Biotechnological, and Microbiological Procedures
5.6 Validation of In-process, Environmental, Release, and Stability Procedures
5.6.1 In-process Procedures
5.6.2 Environmental Procedures
5.6.3 Release and Stability Procedures
5.7 Other Procedures
5.7.1 Process Analytical Technology (PAT)
5.7.2 Parametric Release and Real-time Release
5.8 Validation of Procedures in Continuous and Batch Manufacturing
5.9 Summary. List of Abbreviations
References
Chapter 6 Transfer of Analytical Procedures
6.1 Introduction
6.2 Purpose of Method Transfer
6.3 Transfer Options
6.3.1 Method Transfer Plan
6.3.2 Comparative Testing
6.3.3 Co-validation
6.3.4 Extended Validation or Partial Validation
6.3.5 Transfer Waiver
6.4 Method Transfer Process
6.4.1 Preparation Phase
6.4.2 Gap Analysis
6.4.3 Method Training Phase
6.4.4 Method Qualification Phase
6.5 Transfer Protocol
6.5.1 Content of a Transfer Protocol
6.5.2 Objectives/Scope
6.5.3 Roles and Responsibilities
6.5.4 Assessment of Receiving Lab
6.5.5 Materials, Facilities, and Instrumentation
6.5.6 Analyst Training
6.5.7 Qualification Procedure
6.5.8 Acceptance Criteria
6.5.9 Protocol Amendment and Deviation
6.6 Method Transfer Report
6.6.1 Objectives
6.6.2 Data Evaluation
6.6.3 Conclusion of Transfer Report
6.6.4 Analytical Transfer File
6.7 Related Documents
6.8 Handling Transfer Failures
6.9 Transfer to a Contract Lab
6.10 Transfer to an International Site
6.11 Summary
References
Chapter 7 Dissolution Testing in the Pharmaceutical Laboratory
7.1 Introduction
7.2 Regulatory and Compendial Role in Dissolution Testing
7.3 Theory
7.4 Equipment Operation and Sources of Error
7.4.1 Equipment Variables
7.4.2 Media Deaeration
7.4.3 Vibration
7.4.4 Water Bath of Dissolution Equipment
7.4.5 Glass Vessels
7.5 Common Errors of Dissolution Apparatus
7.5.1 USP Apparatus 1 and 2
7.5.2 USP Apparatus 3
7.5.3 USP Apparatus 4
7.5.4 USP Apparatus 5
7.5.5 USP Apparatus 6
7.5.6 USP Apparatus 7
7.6 Dissolution Method Considerations
7.6.1 Sample Introduction
7.6.2 Media Attributes
7.6.3 Observations
7.6.4 Sinkers
7.6.5 Filters
7.6.6 Manual Sampling. 7.6.7 Automation of Dissolution Sampling
7.6.8 Cleaning of Dissolution Equipment
7.7 Method Development
7.7.1 Drug Properties
7.7.2 Dosage Form Properties
7.7.3 Dissolution Profile
7.7.4 Dissolution Media
7.7.5 Medium Volume
7.7.6 Deaeration
7.7.7 Speed
7.7.8 Sinkers
7.7.9 Filtration
7.7.10 Time Points - Immediate Release
7.7.11 Fast Stir or Infinity Point
7.7.12 Time Points for Extended-Release Products
7.8 Poorly Soluble Drugs
7.8.1 Sink Conditions
7.8.2 Apparatus Selection
7.8.3 The Discriminatory Power of the Method
7.9 Setting Specifications
7.10 Harmonization
7.11 Method Validation
7.12 Validation of Product Performance Parameters
7.12.1 Accuracy/Recovery
7.12.2 Selectivity
7.12.3 Solution Stability
7.12.4 Filter
7.12.5 Robustness
7.12.6 Intermediate Precision
7.12.7 Automated Methodology
7.13 Validation of the Analytical Finish
7.14 Method Transfer Considerations
7.14.1 Robustness
7.14.2 Details of the Analytical Method
7.14.3 Other Considerations
7.15 Good Manufacturing Practices (GMP) in the Dissolution Testing Laboratory
7.15.1 Metrology
7.15.2 Notebook Documentation
7.15.3 Equipment Qualification, Validation, and Method Critical Factors
7.15.4 Good Manufacturing Practice Audits
7.15.5 Training
7.16 Summary
Acknowledgment
List of Abbreviations
Chapter 8 Analytical Data and the Documentation System
8.1 Introduction
8.1.1 Types of Documents
8.2 GMP for Records and Reports-Subpart J
8.2.1 General Requirements
8.2.2 Equipment Cleaning and Use Log
8.2.3 Component, Drug Product Container, Closure, and Labeling Records
8.2.4 Master Production and Control Records
8.2.5 Batch Production and Control Records
8.2.6 Production Record Review
8.2.7 Laboratory Records
8.3 Keeping Good Records
"Analytical testing in the pharmaceutical industry is necessary to establish drug quality based on science and regulatory compliance. It requires analysts to acquire a solid understanding of analytical chemistry and also a thorough appreciation of pharmaceutical regulatory requirements to address day-to-day challenges and maintain a compliant state. Pharmaceutical laboratories are operated under Good Manufacturing Practices (GMP), thus a knowledge of this regulations is necessary to perform pharmaceutical testing of drug substance and drug products"--
Kim Huynh-Ba, M.Sc., PMP, FAAPS, is the Chief Executive Officer and Managing Director of Pharmalytik LLC, where she provides consulting and training services to leading pharmaceutical companies and global organizations. She has decades of experience in strategic analytical development, risk management, strategic drug development, and stability sciences. She is an Adjunct Professor at Temple University School of Pharmacy and Illinois Institute of Technology (IIT) teaching GMPs and various regulatory compliance subjects.
9781119680475
Pharmaceutical industry--Quality control.
Analytical chemistry.
Drugs--Testing.
Drug development.
Pharmaceutical chemistry.
Chemistry, Pharmaceutical.
Electronic books.
RS189 / .H89 2022
615/.19
QV 25