This book focuses on analytical similarity assessment in biosimilar product development following the FDA's recommended stepwise approach for obtaining totality-of-the-evidence for approval of biosimilar products. It covers concepts such as the tiered approach for assessment of similarity of critical quality attributes in the manufacturing process of biosimilar products, models/methods like the statistical model for classification of critical quality attributes, equivalence tests for critical quality attributes in Tier 1 and the corresponding sample size requirements, current issues, and recent developments in analytical similarity assessment.

Author

Shein-Chung Chow, Ph.D, is currently an Associate Director at Office of

Biostatistics, Center for Drug Evaluation and Research, United States Food

and Drug Administration (FDA). Prior to joining FDA, Dr. Chow was a

Professor at Duke University School of Medicine, Durham, NC. He was

also a special government employee (SGE) appointed by the FDA as an

Advisory Committee member and statistical advisor to the FDA. Prior to

that, Dr. Chow also held various positions in the pharmaceutical industry

such as Vice President at Millennium, Cambridge, MA, Executive Director at

Covance, Princeton, NJ, and Director and Department Head at Bristol-Myers

Squibb, Plainsboro, NJ. Dr. Chow is the Editor-in-Chief of the Journal of

Biopharmaceutical Statistics and the Editor-in-Chief of the Biostatistics Book Series

at Chapman and Hall/CRC Press, Taylor & Francis Group. He was elected

Fellow of the American Statistical Association and an elected member of the

ISI (International Statistical Institute). Dr. Chow is the author or co-author of

over 300 methodology papers and 29 books including Designs and Analysis

Design and Analysis of Clinical Trials, and Quantitative Methods for Traditional

Chinese Medicine Development.

1. Introduction

Background

Past Experience for In Vitro Bioequivalence Testing

Analytical Similarity Assessment

Scientific Factors and practical issues

Aim and Scope of the Book

2. Regulatory Approval Pathway of Biosimilar Products

Introduction

Regulatory requirements

Analytical Studies for Functional/Structural Characterization

Global harmonization

Concluding remarks

3. CMC Requirements

Introduction

CMC Development

Manufacturing Process Validation

Quality Control and Assurance

Stability Analysis

Concluding Remarks

4. Assay Development and Process Validation

Introduction

Regulatory Requirements

Analytical Method Validation

Analysis of Validation Data

Evaluation of Reliability, Repeatability, and Reproducibility

Concluding remarks

5. Critical Quality Attributes

Introduction

Identification of CQAs

Classification of CQAs

Concluding Remarks

6. FDA Tiered Approach for Analytical Assessment

Background

Stepwise Approach

Tier Equivalence Test

Other tiered approaches

Some Practical Considerations

Concluding Remarks

7. Sample Size Requirement

Introduction

Traditional Approach

FDA's Current Thinking and Recommendation

Sample Size Requirement

Numerical Studies

Concluding remarks

8. Multiple References

Background

Method of Pairwise Comparisons

Simultaneous Confidence Interval

Reference Product Change

Concluding remarks

9. Extrapolation Across Indications

Introduction

An Example

Development of Sensitivity Index

Assessment of Sensitivity Index

Statistical Inference of Extrapolation

Concluding Remarks

10. Case Studies - FDA Submissions

FDA Abbreviated Licensure Pathway

Sponsor's Strategy for Regulatory Submission

Avastin Biosimilar Regulatory Submission

Herceptin Biosimilar Regulatory Submission

Concluding Remarks

11. Practical and Challenging Issues

Introduction

Hypotheses versus Confidence Interval Approach

Totality-of-the-evidence

Inconsistencies Between Tired Approaches

Individual bioequivalence

Commonly Asked Questions from the Sponsors

Concluding Remarks

12. Recent Development

Introduction

Comparing Means versus Comparing Variances

Switching Design

Non-Medical Switching

FDA guidance on Analytical Similarity Assessment

Concluding Remarks