Pharmaceutical Stress Testing

Stress testing is the main tool that is used to predict stability problems,
; s" Q6 J* }" a0 f+ T1 t" @develop analytical methods, and identify degradation products/pathways.
, H+ ~3 J+ V" Y$ ~4 N% S- \Since there are no detailed regulatory guidelines that direct how stress testing
4 N/ |5 M+ d4 ]7 l# F! gis to be done, nor has there ever been a text/reference book on the
subject, stress testing has evolved into an artful science that is highly dependent
9 H5 g! w4 ~3 A  m6 zon the experience of the company or the individuals directing the studies. This
book provides readers with a single source reference that benchmarks the
$ L* B) z. t: ?- \current best practices of experienced pharmaceutical scientists/researchers.
Questions like ‘‘How hot, how long, what conditions are appropriate?’’ and
topics such as mass balance, photostability, oxidative susceptibility, and the
# h( t; W5 \% X, g$ b  b5 vchemistry of drug degradation are addressed in an objective, detailed scientific
1 E: s# ?4 u6 H3 l! [7 o+ w" Imanner, with ample references to relevant guidances and the scientific literature.
$ @  r' O# v0 R! S4 s- ?! S' cCompiling a book to be used as a scientific reference for the topic of
pharmaceutical stress testing was a daunting task. Stress testing, as it relates
2 y' k) {. Y5 g; ?% Zto traditional small molecule pharmaceuticals, is very broad and scientifically
complex. Thus, this book seeks to be a practical and scientific guide
4 f8 q4 |  n- a* dwhich will, hopefully, stimulate new ideas and further development of the
science.
This undertaking is done with some trepidation, since I realize that discussion
, N3 m7 q, g1 s) l8 Qof this topic could lead to attempts to formalize or standardize (i.e.,
' M( }% `) V9 c9 t) Tregulatory standardization) an area of pharmaceutical science that relies on
: K, V3 |! A5 `' K0 v; I- F1 Pscientific expertise and flexibility. Each new drug compound, formulation,
/ ?2 [: w4 a+ Jroute of administration, delivery device, etc. has the potential to present
% Z# z% G+ ]' i$ A, Y& }) gunique challenges and unanticipated problems, and should be approached
# r* ^9 I; x& v8 o- Rwith such a mindset. The pharmaceutical researcher must be free to design
and develop new ways to predict and measure stability-related issues
9 Q$ O* X. V5 c# Tthrough stress testing. Nonetheless, it is hoped that this book will provide
a useful and practical scientific guide that is a welcome addition to the
library of many pharmaceutical scientists. I am confident that the ‘‘artful
science’’ of stress testing will evolve beyond what is represented in this book
as other scientists further the science and fill in topics that are poorly covered
or missing.