Specification of Drug Substances and Products

Development and Validation of Analytical Methods

2nd Edition - July 23, 2020
Editors: Christopher M. Riley, Thomas W. Rosanske, George L. Reid
Language: English
Paperback ISBN:
9 7 8 - 0 - 0 8 - 1 0 2 8 2 4 - 7
eBook ISBN:
9 7 8 - 0 - 0 8 - 1 0 2 8 2 5 - 4

Specification of Drug Substances and Products: Development and Validation of Analytical Methods, Second Edition, presents a comprehensive and critical analysis of the requireme… Read more

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Specification of Drug Substances and Products: Development and Validation of Analytical Methods, Second Edition, presents a comprehensive and critical analysis of the requirements and approaches to setting specifications for new pharmaceutical products, with an emphasis on phase-appropriate development, validation of analytical methods, and their application in practice. This thoroughly revised second edition covers topics not covered or not substantially covered in the first edition, including method development and validation in the clinical phase, method transfer, process analytical technology, analytical life cycle management, special challenges with generic drugs, genotoxic impurities, topical products, nasal sprays and inhalation products, and biotechnology products.

The book's authors have been carefully selected as former members of the ICH Expert Working Groups charged with developing the ICH guidelines, and/or subject-matter experts in the industry, academia and in government laboratories.

Cover image
Title page
Table of Contents
Copyright
Contributors
Part I. Introduction
Chapter 1. Introduction
Chapter 2. General principles and regulatory considerations: specifications and shelf life setting
2.1. Introduction
2.2. Regulatory requirements
2.3. Specification setting process
2.4. Shelf life and retest date
2.5. Release and stability specification
2.6. Reference standards
2.7. Documentation
2.8. Conclusions
Chapter 3. General principles and regulatory considerations: method validation
3.1. Introduction
3.2. Definitions
3.3. Guidelines
3.4. Phase appropriate method validation
3.5. Verification of compendial methods
3.6. Revalidation of methods
3.7. Method remediation
3.8. Conclusions
Chapter 4. Application of quality by design to the development and validation of analytical methods
4.1. Introduction
4.2. Analytical target profile
4.3. Method risk assessment
4.4. Method development and optimization: understanding the method operating space
4.5. Empirical models: design of experiments (screening, modeling, and robustness)
4.6. Approaches using explicit models
4.7. General recommendations on design/analysis of experiments
4.8. Case study—sample extraction method development using a response surface design
4.9. The transition from development to validation
4.10. Knowledge management
4.11. Analytical quality by design throughout the method lifetime
4.12. Conclusions
Chapter 5. Analytical methods in the clinical phase of development
5.1. Introduction
5.2. Regulatory submissions
5.3. Key partnerships
5.4. Overview of chemistry, manufacturing, and controls deliverables
5.5. Methods and testing
5.6. Specifications development
5.7. Method transfer
5.8. Industry responsibilities, federal regulations, and FDA guidances
5.9. Conclusions
Chapter 6. Analytical method transfer
6.1. Introduction
6.2. Method transfer process
6.3. USP General Chapter <1224> transfer of analytical procedures
6.4. Science- and risk-based approaches for transfer of analytical procedures
6.5. Knowledge and risk management approaches
6.6. Regulatory considerations
6.7. Common transfer issues
6.8. Conclusions
Chapter 7. Process analytical technology
7.1. Introduction
7.2. Drivers behind the development and implementation of process analytical technology
7.3. Quantifiable benefits of process analytical technology
7.4. Additional considerations of process analytical technology
7.5. Conclusions and future directions
Part II. Universal tests
Chapter 8. Description and identification
8.1. Introduction
8.2. Description
8.3. Drug substance identification testing
8.4. Drug product identification
8.5. Conclusions
Chapter 9. Assay and impurities: specifications
9.1. Introduction
9.2. Analytical methodology
9.3. Calculations
9.4. Analysis of samples
9.5. Specification of assay and impurities
9.6. Other applications of assay methodology
9.7. Conclusions
Appendix A.9.1: Rules of rounding, significant figures, and use of spreadsheets
Appendix A.9.2: Summary of the “Barr case,” averaging, and outliers
Chapter 10. Assay and impurities: method development as part of analytical life cycle management
10.1. Introduction
10.2. Rational design of analytical methods
10.3. Techniques and mode selection based on physicochemical properties
10.4. Maximizing orthogonality using column screening and mobile phase screening
10.5. Systematic and efficient column and mobile phase screening
10.6. Method optimization and robustness using simulation software
10.7. Enhanced selectivity, peak capacity, orthogonal methods, and two-dimensional chromatography
10.8. Cases studies: examples of systematic method development
10.9. Conclusions
Chapter 11. Assay and impurities: method validation
11.1. Introduction
11.2. Validation of methods for assay, impurities, and related procedures
11.3. Conclusions
Chapter 12. Mutagenic impurities
12.1. Introduction
12.2. Assessment and control as a function of the lifecycle
12.3. Developing control strategies
12.4. Impurities to be considered for mutagenic risk assessment
12.5. Analytical challenges and strategies
12.6. Case study 1—galunisertib
12.7. Case study 2—pazopanib HCl
12.8. Case study 3—N-Nitrosamines in sartans
12.9. Conclusions
Chapter 13. Residual solvents
13.1. Introduction
13.2. Residual solvent classes
13.3. Test articles and supplier management
13.4. Specifications and acceptance criteria
13.5. Analytical methods
13.6. Analytical methods validation
13.7. Conclusions
Chapter 14. Elemental and inorganic impurities
14.1. Scope
14.2. Introduction
14.3. Compliance requirements
14.4. Elemental impurity classification
14.5. Permitted daily exposure limits
14.6. Compliance options
14.7. Preparing the risk assessment
14.8. Analytical techniques
14.9. Method development
14.10. Method validation
14.11. Other compendial methods for inorganic impurities
14.12. Lifecycle management
14.13. Conclusions
Part III. Specific tests: drug substances
Chapter 15. Solid-state characterization—method development and validation
15.1. Introduction
15.2. Conclusions
Chapter 16. Chiral methods
16.1. Introduction
16.2. Implementation of health authority guidelines to chiral drug development
16.3. Chiral liquid chromatography
16.4. Other chiral separation methods
16.5. Nonseparation techniques
16.6. Chiral method validation
16.7. Conclusions
Chapter 17. Water determination
17.1. Introduction
17.2. Loss on drying (LOD)
17.3. Karl Fischer titration (KFT)
17.4. Gas chromatographic methods
17.5. Near-infrared spectroscopy (NIRS)
Part IV. Specific tests: Drug product
Chapter 18. Dissolution
18.1. Introduction
18.2. The dissolution test
18.3. Method development
18.4. Method validation
18.5. Automation
18.6. Sources of error in dissolution testing
18.7. Visual observations
18.8. Performance verification of dissolution equipment
18.9. Regulatory aspects and specifications
18.10. Conclusions
18.11. Bibliography
Chapter 19. Drug release: topical products
19.1. Introduction
19.2. In vitro release test
19.3. Method development
19.4. IVRT method validation
19.5. Common sources of variability in IVRT methods
19.6. Regulatory guidelines
19.7. Conclusions
Chapter 20. Extractables and leachables
20.1. Introduction
20.2. Overview of the study design
20.3. Extraction study
20.4. Extractable analysis
20.5. Leachables study
20.6. Impact of leachables in the drug product above the AET
20.7. Combination medical devices
20.8. Conclusions
Part V. Biotechnology products
Chapter 21. Specification of biotechnology products
21.1. Introduction
21.2. Regulatory considerations
21.3. Specification of drug substance and drug product
21.4. Justification of specification
21.5. Challenges and issues in specification development
21.6. Conclusions
Chapter 22. Biotechnology products: validation of analytical methods
22.1. Introduction
22.2. Method design
22.3. Method validation
22.4. Compendial method verification
22.5. Continuous method usage
22.6. Guidelines
22.7. Conclusions
Part VI. Pharmacopeial methods
Chapter 23. Pharmacopeial methods and tests
23.1. Introduction
23.2. Legal recognition
23.3. Requirements for inclusion in a pharmacopeia24
23.4. Revision process
23.5. Input of regulatory authorities
23.6. Pharmacopeial harmonization
23.7. Content of monographs
23.8. Compendial reference standards
23.9. Conclusions
Part VII. Biological fluids
Chapter 24. Bioanalysis of biological matrix samples using liquid chromatography–tandem mass spectrometry detection
24.1. Introduction
24.2. Technologies for the bioanalysis of biological matrix samples
24.3. Validation of LC-MS bioanalytical methods
24.4. LC-MS bioanalytical methods for proteins
24.5. Conclusion
Index

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health

Specification of Drug Substances and Products

Development and Validation of Analytical Methods

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Christopher M. Riley

Thomas W. Rosanske

George L. Reid