Handbook of analytical validation

225 Pages·2012·5.247 MB·English

by  Michael Swartz, Ira S Krull

Handbook of
ANALYTICAL
VALIDATION
© 2012 by Taylor & Francis Group, LLC
© 2012 by Taylor & Francis Group, LLC
Handbook of
ANALYTICAL
VALIDATION
Michael E. Swartz
Ira S. Krull
Boca Raton London New York
CRC Press is an imprint of the
Taylor & Francis Group, an informa business
© 2012 by Taylor & Francis Group, LLC
CRC Press
Taylor & Francis Group
6000 Broken Sound Parkway NW, Suite 300
Boca Raton, FL 33487-2742
© 2012 by Taylor & Francis Group, LLC
CRC Press is an imprint of Taylor & Francis Group, an Informa business
No claim to original U.S. Government works
Version Date: 20120309
International Standard Book Number-13: 978-1-4200-1448-8 (eBook - PDF)
This book contains information obtained from authentic and highly regarded sources. Reasonable
efforts have been made to publish reliable data and information, but the author and publisher cannot
assume responsibility for the validity of all materials or the consequences of their use. The authors and
publishers have attempted to trace the copyright holders of all material reproduced in this publication
and apologize to copyright holders if permission to publish in this form has not been obtained. If any
copyright material has not been acknowledged please write and let us know so we may rectify in any
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Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced,
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For permission to photocopy or use material electronically from this work, please access www.copy-
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tocopy license by the CCC, a separate system of payment has been arranged.
Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are
used only for identification and explanation without intent to infringe.
Visit the Taylor & Francis Web site at
http://www.taylorandfrancis.com
and the CRC Press Web site at
http://www.crcpress.com
© 2012 by Taylor & Francis Group, LLC
CRC Press
Taylor & Francis Group
6000 Broken Sound Parkway NW, Suite 300
Boca Raton, FL 33487-2742
© 2012 by Taylor & Francis Group, LLC
CRC Press is an imprint of Taylor & Francis Group, an Informa business
No claim to original U.S. Government works
Printed in the United States of America on acid-free paper
Version Date: 20120309
International Standard Book Number: 978-0-8247-0689-0 (Hardback)
This book contains information obtained from authentic and highly regarded sources. Reasonable
efforts have been made to publish reliable data and information, but the author and publisher cannot
assume responsibility for the validity of all materials or the consequences of their use. The authors and
publishers have attempted to trace the copyright holders of all material reproduced in this publication
and apologize to copyright holders if permission to publish in this form has not been obtained. If any
copyright material has not been acknowledged please write and let us know so we may rectify in any
future reprint.
Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced,
transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or
hereafter invented, including photocopying, microfilming, and recording, or in any information stor-
age or retrieval system, without written permission from the publishers.
For permission to photocopy or use material electronically from this work, please access www.copy-
right.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222
Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that pro-
vides licenses and registration for a variety of users. For organizations that have been granted a pho-
tocopy license by the CCC, a separate system of payment has been arranged.
Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are
used only for identification and explanation without intent to infringe.
Visit the Taylor & Francis Web site at
http://www.taylorandfrancis.com
and the CRC Press Web site at
http://www.crcpress.com
© 2012 by Taylor & Francis Group, LLC
Contents
Preface ...................................................................................................................xiii
Chapter 1 Introduction to Analytical Method Validation .....................................1
1.1 Introduction ...............................................................................1
1.2 Drug Development Process .......................................................1
1.3 FDA Hierarchy and Organization .............................................3
1.4 International Conference on Harmonization .............................4
1.4.1 Structure of the ICH .....................................................5
1.4.1.1 European Commission of the European
Union (EU) ...................................................6
1.4.1.2 European Federation of Pharmaceutical
Industries and Associations (EFPIA) ...........6
1.4.1.3 Ministry of Health and Welfare, Japan
(MHW) .........................................................6
1.4.1.4 Japan Pharmaceutical Manufacturers
Association (JPMA) ......................................6
1.4.1.5 US Food and Drug Administration (FDA) ...6
1.4.1.6 Pharmaceutical Research and
Manufacturers of America (PhRMA) ..........6
1.4.1.7 Observers ......................................................7
1.4.2 ICH Administration ......................................................7
1.4.3 ICH Harmonization Process ........................................7
1.4.3.1 Step 1 ............................................................7
1.4.3.2 Step 2 ............................................................8
1.4.3.3 Step 3 ............................................................8
1.4.3.4 Step 4 ............................................................8
1.4.3.5 Step 5 ............................................................8
1.4.4 ICH Harmonization Initiatives .....................................8
1.5 AMV Guidance .........................................................................9
1.5.1 Types of Analytical Procedures .................................11
1.5.2 Reference Standards ...................................................11
1.5.3 Certificate of Analysis ................................................11
1.5.4 Characterization of a Reference Standard ..................12
1.5.5 Content and Format for Analytical Methods and
Procedures ..................................................................13
1.5.6 Content and Processing of the Method Validation
Package .......................................................................13
1.5.6.1 Selection and Shipment of Samples ............13
1.5.6.2 Responsibilities ...........................................14
1.6 Validation Process ...................................................................15
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vi Contents
1.6.1 Software Validation ....................................................17
1.6.2 Analytical Instrument Qualification ..........................17
1.6.3 System Suitability .......................................................18
1.7 Training ...................................................................................18
1.8 Conclusion ...............................................................................20
References ..........................................................................................20
Chapter 2 Analytical Instrument Qualification ..................................................23
2.1 Introduction .............................................................................23
2.2 Components of Data Quality ...................................................23
2.3 AIQ Process .............................................................................24
2.3.1 Design Qualification...................................................24
2.3.2 Installation Qualification (IQ) ....................................25
2.3.3 Operational Qualification (OQ) .................................26
2.3.3.1 HPLC Pump Flow Rate Accuracy ..............27
2.3.3.2 Gradient Accuracy ......................................28
2.3.3.3 Injector Accuracy........................................28
2.3.3.4 Column Oven and Auto Sampler
Temperature ................................................29
2.3.3.5 UV Detector Wavelength Accuracy
and Linearity...............................................30
2.3.4 Performance Qualification (PQ) ................................30
2.3.5 Preventative Maintenance and Repairs ......................32
2.4 Roles and Responsibilities .......................................................34
2.5 Software Validation and Change Control ................................34
2.6 AIQ Documentation ................................................................34
2.7 Instrument Categories .............................................................35
2.8 Conclusion ...............................................................................36
References ..........................................................................................36
Chapter 3 HPLC Method Development and Optimization with Validation
in Mind ...............................................................................................37
3.1 Introduction .............................................................................37
3.2 HPLC Method Development Approaches ...............................37
3.3 Method Goals ..........................................................................38
3.4 HPLC Method Development Instrumentation ........................39
3.4.1 HPLC Systems for Column and Method Scouting ....44
3.4.2 Automated HPLC Method Development Systems .....47
3.4.3 UHPLC in Method Development Systems .................49
3.4.4 Solvent Management ..................................................50
3.4.5 Sample Management ..................................................51
3.4.6 Detection ....................................................................51
3.4.7 Column Module ..........................................................55
3.4.8 Columns for Method Development ............................56
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Contents vii
3.4.9 Mobile Phase Considerations .....................................57
3.5 Method Optimization ..............................................................58
3.6 Summary .................................................................................59
References ..........................................................................................59
Chapter 4 Method Validation Basics ..................................................................61
4.1 Introduction .............................................................................61
4.2 Method Validation Guidelines .................................................61
4.3 Terms and Definitions .............................................................62
4.3.1 Accuracy .....................................................................63
4.3.2 Precision .....................................................................65
4.3.2.1 Repeatability ...............................................65
4.3.2.2 Intermediate Precision ................................65
4.3.2.3 Reproducibility ...........................................66
4.3.2.4 Ruggedness .................................................67
4.3.3 Specificity ...................................................................68
4.3.4 Detection Limit ..........................................................70
4.3.5 Quantitation Limit ......................................................71
4.3.6 Linearity and Range ...................................................73
4.3.7 Robustness ..................................................................74
4.4 Validation according to Method Type .....................................75
4.5 Documentation ........................................................................75
4.5.1 Validation Protocol .....................................................75
4.5.2 Test Method ................................................................76
4.5.3 Validation Report .......................................................77
4.6 Summary .................................................................................78
References ..........................................................................................78
Chapter 5 Robustness and System Suitability .....................................................81
5.1 Introduction .............................................................................81
5.2 Robustness Studies for Method Validation .............................81
5.3 Robustness Study Experimental Design..................................83
5.3.1 Screening Designs ......................................................83
5.3.1.1 Full Factorial Designs .................................84
5.3.1.2 Fractional Factorial Designs .......................84
5.3.1.3 Plackett–Burman Designs ..........................86
5.3.2 Determining the Factors, Measuring the Results .......86
5.4 Analyzing the Results ..............................................................89
5.5 Documentation and Reporting ................................................90
5.6 System Suitability Tests ...........................................................91
5.7 System Suitability Standards ...................................................92
5.8 System Suitability Protocol .....................................................93
5.9 Method Adjustments to Meet System Suitability
Requirements ...........................................................................94
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viii Contents
5.9.1 pH Adjustments ..........................................................96
5.9.2 Column Length, Diameter, and Particle Size
Adjustments: Scaling the Separation ..........................96
5.10 Conclusion ...............................................................................98
References ..........................................................................................99
Chapter 6 Setting Specifications and Investigating Out-of-Specification
Results ..............................................................................................101
6.1 Introduction ...........................................................................101
6.2 Guidance for Setting Specifications ......................................101
6.3 General Concepts for Developing and Setting
Specifications .........................................................................102
6.3.1 Limited Data Available at Filing ..............................102
6.3.2 Periodic or Skip Testing ...........................................103
6.3.3 Release versus Shelf-Life Acceptance Criteria ........103
6.3.4 In-Process Tests ........................................................103
6.3.5 Parametric Release ...................................................103
6.3.6 Pharmacopeial Tests .................................................103
6.4 Universal Tests/Criteria .........................................................104
6.5 Specific Tests/Criteria: New Drug Substances ......................104
6.5.1 Physicochemical Properties .....................................104
6.5.2 Particle Size ..............................................................104
6.5.3 Polymorphic Forms ..................................................104
6.5.4 Chiral-Drug Substance .............................................105
6.5.5 Chiral-Drug Product ................................................105
6.5.6 Water Content ...........................................................105
6.5.7 Inorganic Impurities .................................................105
6.5.8 Microbial Limits ......................................................106
6.6 Specific Tests/Criteria: New Solid Oral Drug Products ........106
6.6.1 Dissolution ................................................................106
6.6.2 Disintegration ...........................................................106
6.6.3 Hardness/Friability ...................................................106
6.6.4 Uniformity of Dosage Units .....................................107
6.7 Specific Tests/Criteria: New Oral Liquid Drug Products ......107
6.8 Specific Tests/Criteria: Parenteral Drug Products .................107
6.9 Decision Trees .......................................................................108
6.10 OOS Background ...................................................................108
6.11 Preventing OOS Results ........................................................111
6.12 Identifying and Assessing OOS Test Results ........................111
6.13 Investigating OOS Test Results .............................................113
6.13.1 General Investigative Principles ...............................113
6.13.2 Laboratory Phase of an Investigation .......................113
6.13.2.1 Assignable Cause ......................................114
6.13.2.2 No Assignable Cause/Retest .....................115
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Contents ix
6.13.2.3 No Assignable Cause/Result Is
Confirmed .................................................115
6.13.3 Retesting ...................................................................115
6.13.4 Resampling ...............................................................115
6.13.5 Averaging (Resampling Testing Data) .....................116
6.13.6 Outlier Tests .............................................................116
6.14 Concluding the OOS Investigation ........................................116
6.15 Conclusion .............................................................................117
References ........................................................................................117
Chapter 7 Validation by Type of Method ..........................................................119
7.1 Introduction ...........................................................................119
7.1.1 Category I Methods ..................................................119
7.1.2 Category II Methods ................................................120
7.1.3 Category III Methods ...............................................121
7.1.4 Category IV Methods ...............................................121
7.2 Validation of Impurity Methods ............................................121
7.2.1 Classification of Impurities ......................................122
7.2.2 Impurity Method Validation Documentation ...........124
7.2.2.1 Reporting Impurity Content of API
Batches ......................................................124
7.2.3 Specificity in Impurity Methods ..............................125
7.2.4 Accuracy in Impurity Methods ................................126
7.3 Stability Indicating Method ...................................................126
7.3.1 Developing and Validating SIMS .............................127
7.3.1.1 Generating the Sample..............................127
7.3.1.2 Developing the LC Method ......................128
7.3.1.3 Manipulating Chromatographic
Selectivity during Method Development ..129
7.3.1.4 Evaluating Specificity during SIM
Development .............................................131
7.3.1.5 New Technology for SIM Development ...134
7.3.2 SIM Validation .........................................................135
7.4 Developing and Validating Dissolution Procedures ..............135
7.4.1 Qualification and Calibration ...................................136
7.4.2 Dissolution Procedure Development ........................137
7.4.2.1 Dissolution Medium .................................137
7.4.2.2 Dissolution Apparatus ..............................138
7.4.2.3 Dissolution Study Design .........................139
7.4.2.4 Assaying the Results .................................140
7.4.3 Dissolution Procedure Validation ............................141
7.4.3.1 Specificity/Placebo Interference ...............141
7.4.3.2 Linearity and Range .................................142
7.4.3.3 Accuracy and Recovery ............................142
© 2012 by Taylor & Francis Group, LLC