2018 Volume 8 Issue 2 Pages 123-128
The cellular or tissue based products manufactured from mesenchymal stem cells out of various organs and tissues are being under clinical trials. Upon initiating the trials, the safety of these cell products in humans must be estimated in advance by conducting nonclinical safety studies. To date, several technical guidelines and the guidance on nonclinical safety assessment of the cellular products have been issued by the regulatory agency in Japan. In principle, the assessments of general toxicity, tumorigenicity and potential effects on vital organs (i.e., central nerve, respiratory, cardiovascular system) as well as safety evaluation of impurity exposure need to be carried out before the first clinical trial. Due to the restriction of study plans or interpretation of results caused by the immune response to the human cells in animals, the aims of the studies should be hazard identification rather than determination of NOAEL or estimation safety margin. The studies should also be planned on a case-by-case basis while taking into account the cell source, its character and complexity in the manufacturing process. This article provides the overview of general considerations for planning the study design of general toxicity and tumorigenicity and assessing the safety of central nerve, respiratory organ, cardiovascular system and impurity exposure.
