**New Stem Cell Models**

**Chapter 8**

**Human Pluripotent Stem Cell Applications in Drug**

Various drugs are being introduced into market for generating beneficial therapeutic effects in humans. The pharmaceutical industry invests about \$1.5 billion over the time period of 10-15 years to take a candidate drug from primary screen to market. Unfortunately, many drugs are withdrawn due to side effects associated with off-and on-target toxicity [1]. For example, as many as nine out of ten promising candidates beginning clinical phase I will not achieve marketing approval [2] and only 20% of agents that show efficacy against cardiovascular diseases in preclinical development are licensed after demonstrating sufficient efficacy in phase III testing [3]. The success rate in anticancer drug development process is with 5% of licensed agents even lower. Off-target cardiac toxicity is the most common cause of regulatory delay in approval and market withdrawal of newly developed pharmaceuticals [4, 5]. Druginduced sudden cardiac death and ventricular arrhythmia caused the withdrawal of more drugs in recent years than any other adverse drug reaction. Moreover, over 100 non-cardiac drugs are suspected to be of high-risk and carry cardiovascular-related black box warnings [6]. Similar considerations are raised concerning arrhythmia and toxicity induced by environ‐ mental factors, including industrial chemicals, food additives, cosmetics, and others, as outlined in the European REACH initiative (Registration, Evaluation, Authorization and

Current drug safety evaluation processes that are required for regulatory purposes mostly rely on animal studies and immortalized cell-based assays due to lack of suitable human in vitro cell systems. In Europe, almost 10 million vertebrate animals are used annually for research. Although highly predictive assays involving whole heart or slice preparations and in vivo animal testing remain the standard for preclinical safety pharmacology, this extensive use of

> © 2014 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**Discovery and Toxicology – An overview**

Shiva Prasad Potta, Tomo Šarić, Michael Heke, Harinath Bahudhanapati and Jürgen Hescheler

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/58485

Restriction of Chemical substances).

**1. Introduction**
