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Statistical Design and Analysis of Stability Studies




ISBN 9781584889052
Published May 30, 2007 by Chapman and Hall/CRC
331 Pages - 11 B/W Illustrations

 
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Book Description

The US Food and Drug Administration's Report to the Nation in 2004 and 2005 indicated that one of the top reasons for drug recall was that stability data did not support existing expiration dates. Pharmaceutical companies conduct stability studies to characterize the degradation of drug products and to estimate drug shelf life. Illustrating how stability studies play an important role in drug safety and quality assurance, Statistical Design and Analysis of Stability Studies presents the principles and methodologies in the design and analysis of stability studies.

After introducing the basic concepts of stability testing, the book focuses on short-term stability studies and reviews several methods for estimating drug expiration dating periods. It then compares some commonly employed study designs and discusses both fixed and random batch statistical analyses. Following a chapter on the statistical methods for stability analysis under a linear mixed effects model, the book examines stability analyses with discrete responses, multiple components, and frozen drug products. In addition, the author provides statistical methods for dissolution testing and explores current issues and recent developments in stability studies.

To ensure the safety of consumers, professionals in the field must carry out stability studies to determine the reliability of drug products during their expiration period. This book provides the material necessary for you to perform stability designs and analyses in pharmaceutical research and development.

Table of Contents

INTRODUCTION
Background
Regulatory Requirements
Stability Testing
Practical Issues
Aim and Scope of the Book

ACCELERATED TESTING
Chemical Kinetic Reaction
Statistical Analysis and Prediction
Examinations of Model Assumptions
An Example
Discussion

EXPIRATION DATING PERIOD
Basic Concepts
Shelf-Life Estimation
Other Methods
Concluding Remarks

STABILITY DESIGNS
Basic Design Considerations
Long-Term Stability Designs
Design Selection
Discussion

STABILITY ANALYSIS WITH FIXED BATCHES
Preliminary Test for Batch Similarity
Minimum Approach for Multiple Batches
Multiple Comparison Procedure for Pooling Batches
Example
Discussion

STABILITY ANALYSIS WITH RANDOM BATCHES
Linear Regression with Random Coefficients
Random Batch Effect and Other Fixed Effects
Shelf-Life Estimation with Random Batches
Comparison of Methods for Multiple Batches
Determining Shelf Life Based on the Lower Prediction Bound
Concluding Remarks

STABILITY ANALYSIS WITH A MIXED EFFECTS MODEL
Linear Mixed Effects Model
Restricted Maximum Likelihood Estimation
Restricted Maximum Likelihood Estimation
The EM Algorithm Procedure
Example
Discussion

STABILITY ANALYSIS WITH DISCRETE RESPONSES
Binary Data without Batch-To-Batch Variation
The Case of Random Batches
Testing for Batch-To-Batch Variation
Example
Ordinal Responses
Concluding Remarks

STABILITY ANALYSIS WITH MULTIPLE COMPONENTS
Basic Idea
Models and Assumptions
Shelf-Life Determination
Example
Discussion

STABILITY ANALYSIS WITH FROZEN DRUG PRODUCTS
Two-Phase Stability Study
Stability Data and Model
An Example
Discussion

STABILITY TESTING FOR DISSOLUTION
USP/NF Dissolution Testing
Dissolution Profile Testing
Statistical Methods for Assessing Similarity
Numerical Examples
Concluding Remarks

CURRENT ISSUES AND RECENT DEVELOPMENTS
Scale-Up and Postapproval Changes
Storage Conditions in Different Climatic Zones
Optimal Designs in Stability Studies
Current Issues in Stability Analysis
SAS Programs for Stability Analysis

APPENDIX A: Guidance for Industry
APPENDIX B: SAS Macro Files for STAB System for Stability Analysis

REFERENCES

INDEX

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Author(s)

Biography

Shein-Chung Chow

Reviews

"…This book provides a comprehensive and unified presentation of the principles and methodologies of design and analysis of stability studies. The text is well-written and provides a well-balanced summary of current regulatory perspectives. The primary SAS programs (macros) —comprising STAB—for estimating the expiration dating period of a drug product based on linear regression analysis are listed in the Appendix B and these macros help to reinforce the theory presented in the text. …"
International Statistical Review, 2008

". . . serves as a useful reference for those who are interested in the statistical design and analysis of stability studies in drug research and development. Its clear explanation, plentiful illustrations, moderate mathematical exposition, and inclusion of SAS programming codes make all the materials accessible to most of the applied statisticians working in the biopharmaceutical environment."

– Ying Qing Chen, Fred Hutchinson Cancer Research Center, in JASA, March 2009