A method of ascertaining the bio-safety of an agent is disclosed. The method comprises: (a) contacting the agent with differentiating human pluripotent stem cells; (b) analyzing a level of gene expression of a plurality of genes in the differentiating human pluripotent stem cells, wherein the agent is qualified as being safe if at least one of the following qualification parameters are fulfilled: (i) the agent causes a difference in the level of gene expression below a predetermined number of genes as compared to control differentiating human pluripotent stem cells that have not been contacted with the agent; (ii) the agent causes a difference in gene expression below a predetermined number of tissue-specific genes of a tissue as compared to control differentiating human pluripotent stem cells that have not been contacted with the agent; or (iii) the agent causes a difference in gene expression below a predetermined number of genes involved in fetal development as compared to control differentiating human pluripotent stem cells that have not been contacted with the agent.