Table of contents for Statistical design and analysis of stability studies / Shein-Chung Chow.

Bibliographic record and links to related information available from the Library of Congress catalog.

Note: Contents data are machine generated based on pre-publication provided by the publisher. Contents may have variations from the printed book or be incomplete or contain other coding.


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Contents
1 Introduction 3
1.1 Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.2 Regulatory Requirements . . . . . . . . . . . . . . . . . . . . . . 5
1.3 Stability Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
1.4 Practical Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
1.5 Aim and Scope of the Book . . . . . . . . . . . . . . . . . . . . . 25
2 Accelerated Testing 27
2.1 Chemical Kinetic Reaction . . . . . . . . . . . . . . . . . . . . . . 28
2.2 Statistical Analysis and Prediction . . . . . . . . . . . . . . . . . 32
2.3 Examinations of Model Assumptions . . . . . . . . . . . . . . . . 41
2.4 An Example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
2.5 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
3 Expiration Dating Period 51
3.1 Basic Concepts . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
3.2 Shelf-life Estimation . . . . . . . . . . . . . . . . . . . . . . . . . 53
3.3 Other Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
3.4 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . 67
4 Stability Designs 69
4.1 Basic Design Considerations . . . . . . . . . . . . . . . . . . . . . 70
4.2 Long-term Stability Designs . . . . . . . . . . . . . . . . . . . . . 77
4.3 Design Selection . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
4.4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
5 Stability Analysis with Fixed Batches 93
5.1 Preliminary Test for Batch Similarity . . . . . . . . . . . . . . . . 94
5.2 Minimum Approach for Multiple Batches . . . . . . . . . . . . . 99
5.3 Multiple Comparison Procedure for Pooling Batches . . . . . . . 103
5.4 An Example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
5.5 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
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iv CONTENTS
6 Stability Analysis with Random Batches 113
6.1 Linear Regression with Random Coefficients . . . . . . . . . . . . 114
6.2 Random Batch Effect and Other Fixed Effects . . . . . . . . . . 115
6.3 Shelf-Life Estimation with Random Batches . . . . . . . . . . . . 125
6.4 Comparison of Methods for Multiple Batches . . . . . . . . . . . 139
6.5 Determining Shelf-Life Based on Lower Prediction Bound . . . . 145
6.6 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . 148
7 Stability Analysis with Mixed Effects Model 151
7.1 Linear Mixed Effects Model . . . . . . . . . . . . . . . . . . . . . 152
7.2 Restricted Maximum Likelihood Estimation . . . . . . . . . . . . 152
7.3 Restricted Maximum Likelihood Estimation . . . . . . . . . . . . 153
7.4 EM Algorithm Procedure . . . . . . . . . . . . . . . . . . . . . . 154
7.5 An example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
7.6 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159
8 Stability Analysis with Discrete Responses 161
8.1 Binary Data Without Batch-To-Batch Variation . . . . . . . . . 162
8.2 The Case of Random Batches . . . . . . . . . . . . . . . . . . . . 163
8.3 Testing for Batch-To-Batch Variation . . . . . . . . . . . . . . . . 166
8.4 An Example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168
8.5 Ordinal Responses . . . . . . . . . . . . . . . . . . . . . . . . . . 168
8.6 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . 170
9 Stability Analysis with Multiple Components 173
9.1 Basic Idea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
9.2 Models and Assumptions . . . . . . . . . . . . . . . . . . . . . . 174
9.3 Shelf-Life Determination . . . . . . . . . . . . . . . . . . . . . . . 175
9.4 An Example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
9.5 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
10 Stability Analysis with Frozen Drug Products 179
10.1 Two-phase Stability Study . . . . . . . . . . . . . . . . . . . . . . 180
10.2 Stability Data and Model . . . . . . . . . . . . . . . . . . . . . . 181
10.3 An Example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186
10.4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187
11 Stability Testing for Dissolution 189
11.1 USP/NF Dissolution Testing . . . . . . . . . . . . . . . . . . . . 190
11.2 Dissolution Profile Testing . . . . . . . . . . . . . . . . . . . . . . 196
11.3 Statistical Methods for Assessment of Similarity . . . . . . . . . 202
11.4 Numerical Examples . . . . . . . . . . . . . . . . . . . . . . . . . 210
11.5 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . 211
CONTENTS v
12 Current Issues and Recent Development 213
12.1 Scale-Up and Post-Approval Changes . . . . . . . . . . . . . . . . 214
12.2 Storage Conditions with Different Climatic Zones . . . . . . . . . 217
12.3 Optimal Designs in Stability Studies . . . . . . . . . . . . . . . . 222
12.4 Current Issues in Stability Analysis . . . . . . . . . . . . . . . . . 227
12.5 SAS Programs for Stability Analysis . . . . . . . . . . . . . . . . 231

Library of Congress Subject Headings for this publication:

Drug stability.
Drugs -- Research -- Statistical methods.
Drug Stability.
Research Design.
Pharmaceutical Preparations -- standards.
Statistics -- methods.