Statistical Design Anal Stab Stud

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.

INTRODUCTIONBackgroundRegulatory RequirementsStability TestingPractical IssuesAim and Scope of the BookACCELERATED TESTING Chemical Kinetic ReactionStatistical Analysis and Prediction Examinations of Model Assumptions An ExampleDiscussionEXPIRATION DATING PERIOD Basic Concepts Shelf-Life EstimationOther Methods Concluding RemarksSTABILITY DESIGNS Basic Design ConsiderationsLong-Term Stability DesignsDesign SelectionDiscussionSTABILITY ANALYSIS WITH FIXED BATCHES Preliminary Test for Batch SimilarityMinimum Approach for Multiple BatchesMultiple Comparison Procedure for Pooling Batches ExampleDiscussionSTABILITY ANALYSIS WITH RANDOM BATCHESLinear 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 RemarksSTABILITY ANALYSIS WITH A MIXED EFFECTS MODEL Linear Mixed Effects ModelRestricted Maximum Likelihood Estimation Restricted Maximum Likelihood EstimationThe EM Algorithm ProcedureExampleDiscussionSTABILITY ANALYSIS WITH DISCRETE RESPONSES Binary Data without Batch-To-Batch Variation The Case of Random BatchesTesting for Batch-To-Batch VariationExampleOrdinal ResponsesConcluding Remarks STABILITY ANALYSIS WITH MULTIPLE COMPONENTS Basic IdeaModels and Assumptions Shelf-Life DeterminationExampleDiscussionSTABILITY ANALYSIS WITH FROZEN DRUG PRODUCTSTwo-Phase Stability Study Stability Data and ModelAn Example DiscussionSTABILITY TESTING FOR DISSOLUTION USP/NF Dissolution TestingDissolution Profile TestingStatistical Methods for Assessing Similarity Numerical ExamplesConcluding RemarksCURRENT ISSUES AND RECENT DEVELOPMENTSScale-Up and Postapproval ChangesStorage Conditions in Different Climatic ZonesOptimal Designs in Stability Studies Current Issues in Stability AnalysisSAS Programs for Stability AnalysisAPPENDIX A: Guidance for IndustryAPPENDIX B: SAS Macro Files for STAB System for Stability Analysis REFERENCESINDEX