Biology Reference
In-Depth Information
CHAPTER
6
Toxicogenomics - A Drug
Dev
elopment Perspec
tive
Yuping Wang
1
, Jurgen Borlak
2
, Weida Tong
1
1
Division of Bioinformatics and Biostatistics, National Center for Toxicological
Research, US Food and Drug Administration, Jefferson, Arkansas
2
Center of Pharmacology and Toxicology, Hannover Medical School, Hannover,
Germany
Disclaimer: The views presented in this article do not necessarily reflect current or future opinion
or policy of the US Food and Drug Administration. Any mention of commercial products is for
clarification and not intended as an endorsement.
6.1 INTRODUCTION
Drug development is a lengthy, complex, and costly process. While the number of new
molecular entities approved for the past 50 years has remained around 20 to 30 per year
[1]
, the
total global spending on research and development (R&D) has doubled since 1996 to over $1.1
trillion
[2]
with an attrition rate of >99%. Only 0.1% of drug candidates that begin pre-clinical
testing ever make it to human testing, and only one in five of these is ever approved for human
usage
[3]
. There are several arguable causes for this trend, including increased regulatory barri-
ers, the rising costs of scientific inquiry, and the lack of proven drug development models that
have successfully and effectively incorporated new technologies such as genomics, bioinfor-
matics, and cheminformatics. Above all, safety concerns continue to be one of the most signifi-
cant causes for drug attrition in both the discovery and development processes
[4-6]
.
It has been estimated that drug safety concerns alone account for approximately 35% to
40% of all drug discontinuations
[7]
. With the high drug attrition rate being due in large part
to the high incidence of adverse effects, there is a huge financial incentive for drug compa-
nies to develop reliable approaches that allow rapid elimination of toxic compounds from
the drug pipelines. Although common side effects of medications are detected and quantified
in the premarket clinical trials, many safety issues cannot be detected until after a drug has
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