ABSTRACT
Stress testing is the main tool that is used to predict stability problems, develop analytical methods, and identify degradation products and pathways. Since there are no detailed regulatory guidelines that describe how to carry out stress testing studies (nor has there been a textbook or reference book devoted to the subject prior to the fi rst edition of this book), stress testing has evolved into an “artful science” that is highly dependent on the experience of the company and of the individuals directing the studies. Questions such as “How hot?”, “How long?”, “What level of humidity?”, “What pH values should be used?”, “What reagents/conditions for oxidative studies should be used?” are faced by every pharmaceutical investigator attempting to carry out stress-testing studies. As will be described in more detail in the section “Historical Context”, this has led to a tremendous variation in stress testing approaches and conditions. An article in 2003 about stress testing (or forced degradation) was even entitled “The Gray Area,” in reference to the vagueness of the current guidelines ( 9 ).
