Statistical Design and Analysis of Stability Studies: 1st Edition (Hardback) book cover

Statistical Design and Analysis of Stability Studies

1st Edition

By Shein-Chung Chow

Chapman and Hall/CRC

331 pages | 11 B/W Illus.

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pub: 2007-05-30
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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.

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

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

About the Series

Chapman & Hall/CRC Biostatistics Series

Learn more…

Subject Categories

BISAC Subject Codes/Headings:
MAT029000
MATHEMATICS / Probability & Statistics / General
MED071000
MEDICAL / Pharmacology
MED072000
MEDICAL / Pharmacy