Analytical similarity assessment in biosimilar product development

Description

Cover......Page 1 Half Title......Page 2 Title Page......Page 4 Copyright Page......Page 5 Table of Contents......Page 6 Preface ......Page 12 Author ......Page 14 1.1 Background ......Page 16 1.2 Past Experience for In Vitro Bioequivalence Testing ......Page 19 Emitted dose uniformity, priming, priming/re-priming, and tail-off profile ......Page 20 Droplet size distribution ......Page 21 1.2.2 Bioequivalence Limit ......Page 22 Non-comparative analysis ......Page 23 Non-profile Analysis ......Page 24 Profile Analysis ......Page 26 1.2.4 Sample Size Requirement ......Page 27 1.3.1 Tier 1 Equivalence Test ......Page 28 1.3.2 Tier 2 Quality Range Approach ......Page 29 1.4.1 Fundamental Similarity Assumption ......Page 31 1.4.2 Primary Assumptions for Tiered Approach ......Page 33 1.4.3 Fixed Approach for Margin Selection ......Page 34 1.4.4 Inconsistent Test Results between Tiered Approaches ......Page 35 1.4.6 Relationship between Similarity Limit and Variability ......Page 36 1.4.7 Regulator’s Current Thinking on Scientific Input ......Page 37 1.4.8 A Proposed Unified Tiered Approach ......Page 38 Criteria for biosimilarity ......Page 40 1.4.10 Remarks ......Page 41 1.5 Aim and Scope of the Book ......Page 42 2.1 Introduction ......Page 44 2.2.1 World Health Organization (WHO) ......Page 46 2.2.2 European Union (EU) ......Page 49 2.2.3 North America (United States of America and Canada) ......Page 51 2.2.4 Asian Pacific Region (Japan, South Korea, and China) ......Page 54 2.2.5 Debatable Issues in Regulatory Requirements ......Page 55 2.3 Analytical Studies for Structural/Functional Characteristics ......Page 60 2.4 Global Harmonization ......Page 63 2.5 Conclusion Remarks ......Page 66 3.1 Introduction ......Page 68 3.2.1 Fermentation and Purification Process ......Page 69 3.2.2 Drug Substance and Product Characterization ......Page 70 3.2.3 Reference Standards and Container Closure System ......Page 72 3.3.1 Manufacturing Process ......Page 73 3.3.2 Process Validation ......Page 76 3.3.3 Practical Issues ......Page 77 3.4.1 General Principles ......Page 78 3.4.2 Quality by Design ......Page 79 3.5 Stability Analysis ......Page 84 3.6 Concluding Remarks ......Page 90 4.1 Introduction ......Page 92 4.2.1 FDA Guidance on Analytical Procedures and Methods Validation ......Page 93 4.2.2 ICH Guidance on Assay Validation ......Page 95 4.2.3 United States Pharmacopeia and National Formulary (USP/NF) ......Page 96 4.3.2 Study Design ......Page 97 4.3.3 Choice of Validation Performance Characteristics ......Page 99 4.3.4 Acceptance Criteria ......Page 100 4.4.1 Assessment of Accuracy, Linearity, and Specificity ......Page 101 4.4.2 The Assessment of Assay Parameters Related to Variability ......Page 106 4.5 Evaluation of Reliability, Repeatability, and Reproducibility ......Page 110 4.5.1 Study Design and Statistical Model ......Page 111 4.5.3 Sample Size for Comparing Variabilities ......Page 113 4.5.4 An Example ......Page 115 4.6 Concluding Remarks ......Page 117 5.1 Background ......Page 120 5.2.1 Link between CQAs and Clinical Outcomes ......Page 121 5.2.2 Statistical Design and Methods ......Page 122 5.3 Stepwise Approach for Demonstrating Biosimilarity ......Page 127 5.4 Tier Assignment for Critical Quality Attributes ......Page 128 5.4.2 Statistical Model ......Page 129 An Example – For the two measures proposed in the Section 5.3.2, p1 is based on the absolute difference between y and ŷ. To test the hypothesis H0: p1 ≤ p0 versus Hα: p1 > p0 or the given α, p0, the set of data (xi, yi) and the selected observation (x0, y......Page 136 5.4.3 Validity of the Translational Model ......Page 137 5.4.4 Two-Way Translational Process ......Page 138 5.4.5 Remarks ......Page 139 5.5 Concluding Remarks ......Page 140 6.1 Background ......Page 142 6.2 Stepwise Approach for Demonstrating Biosimilarity ......Page 143 6.3 Tier 1 Equivalence Test ......Page 144 6.4.1 Quality Range Approach for Tier 2 ......Page 151 6.4.2 Raw Data and Graphical Comparison for Tier 3 ......Page 154 6.5 Some Practical Considerations ......Page 156 6.6 Concluding Remarks ......Page 160 7.1 Introduction ......Page 162 7.2.1 Power Calculation ......Page 163 7.3.1 FDA’s Current Thinking ......Page 165 7.3.2 FDA’s Recommendation ......Page 168 7.4.1 Chow et al.’s Proposal for Test/Reference Lots Selection ......Page 169 7.4.2 Recent Development ......Page 171 7.5 Numerical Studies ......Page 175 7.6 Concluding Remarks ......Page 179 SAS Codes ......Page 183 8.1 Background ......Page 188 8.2.1 Equivalence Test for Tier 1 CQAs ......Page 189 8.2.2 Pairwise Comparisons with Multiple References ......Page 191 8.2.3 An Example ......Page 192 8.3.1 Assumptions and Statistical Framework ......Page 194 8.3.2 Simultaneous Confidence Interval with the Assumption That  ......Page 196 8.3.3 Simultaneous Confidence Interval without the Assumption of  ......Page 200 8.3.4 An Example ......Page 207 8.4 Reference Product Change ......Page 208 8.4.1 Kang and Chow’s Approach ......Page 209 8.4.2 Criteria for Biosimilarity ......Page 210 8.4.3 Statistical Tests for Biosimilarity ......Page 211 8.4.4 Remarks ......Page 215 8.5 Concluding Remarks ......Page 217 9.1 Introduction ......Page 218 9.2 An Example ......Page 219 9.3 Development of Sensitivity Index ......Page 222 9.4.1 The Case Where ε Is Random and C Is Fixed ......Page 224 9.4.2 The Case Where ε Is Fixed and C Is Random ......Page 226 9.4.3 The Case Where Both ε and C Are Random ......Page 229 9.5 Statistical Inference of Extrapolation ......Page 232 9.5.1 The Case Where ε Is Random and C Is Fixed ......Page 233 9.5.2 The Case Where ε Is Fixed and C Is Random ......Page 235 9.5.3 The Case Where ε and C Are Random ......Page 236 9.5.4 The Confidence Interval of the Effect Size in Original Population ......Page 237 9.5.5 An Example ......Page 238 Appendix ......Page 240 10.1 FDA Abbreviated Licensure Pathway ......Page 244 10.2 Sponsor’s Strategy for Regulatory Submission ......Page 246 10.3 Avastin Biosimilar Regulatory Submission ......Page 248 10.4 Herceptin Biosimilar ......Page 256 10.5 Concluding Remarks ......Page 261 11.1 Introduction ......Page 264 11.2.1 Interval Hypotheses Testing ......Page 265 11.2.2 Confidence Interval Approach ......Page 266 11.2.3 Remarks ......Page 267 11.3.1 Primary Assumptions of Stepwise Approach ......Page 268 11.3.2 Relationships among Analytical, PK/PD, and Clinical Similarity ......Page 269 11.3.3 Practical Issues ......Page 271 11.3.4 Examples ......Page 272 11.3.5 Remarks ......Page 273 11.4.1 In Vitro Bioequivalence Testing versus Analytical Testing ......Page 274 11.4.3 Inconsistencies between Different Tiered Tests ......Page 275 11.5 Individual Bioequivalence ......Page 276 11.6 Commonly Asked Questions from the Sponsors ......Page 278 11.7 Concluding Remarks ......Page 285 12.1 Introduction ......Page 288 12.2 Comparing Means versus Comparing Variances ......Page 289 12.2.2 Similarity Test in Variability ......Page 290 12.3.1 Introduction ......Page 292 12.3.2 Concept and Criteria for Drug Interchangeability ......Page 293 12.3.3 Hybrid Parallel-Crossover Design ......Page 294 12.3.4 Statistical Model and Analysis ......Page 297 12.3.5 Sample Size Requirement ......Page 302 12.4 Non-Medical Switching ......Page 309 12.4.1 Introduction ......Page 310 12.4.2 Approaches for Evaluation of Non-Medical Switch ......Page 311 12.4.3 Clinical Studies ......Page 314 12.4.4.1 Scientific Factors ......Page 317 12.4.4.2 Statistical Considerations ......Page 318 12.4.5 Design and Analysis of Switching Studies ......Page 320 12.5 FDA Draft Guidance on Analytical Similarity Assessment ......Page 321 12.6 Concluding Remarks ......Page 324 References and Further Reading ......Page 326 Index ......Page 336