Cost-effective toxicity screening early on!

1 October 2019

For a successful drug development project, it is of the importance to detect potential safety risks rather earlier than later. Early screening for in vitro toxicity under non-GLP conditions is a cost-efficient way to manage the risk for safety-related failures. Importantly, the screening assays are optimised to consume minimal amounts of compound.

The majority of safety-related drug withdrawals are caused by liver- or cardiotoxicity and hence it is a far-sighted approach to test for these properties early. To support this, we offer hepatotoxicity evaluation by analysing cultured primary hepatocytes for cell death (lactate dehydrogenase, dead cell specific protease activity or DNA binding dye) and cell viability (ATP content). We can include measurement of NCE stability during the assay to confirm the actual assay concentration since in hepatocytes, significant metabolism of the NCE may occur. Even MetID can be performed to identify the major metabolites formed in the assay.

In hepatotoxicity, the prominent mechanistic failure many times relates to mitochondrial impairment. We offer the Glu/Gal assay to detect susceptibility to mitochondrial toxicants in HepG2 cells. The assay measures mitochondrial dysfunction as ATP measurement in parallel to cytotoxicity. In addition, BSEP transporter inhibition can be evaluated with inside-out membrane vesicles.

New assay available – in vitro hemolysis!

We have set up an in vitro hemolysis assay to detect a form of hematologic toxicity. In hemolysis blood erythrocytes disrupt, which leads to hemoglobin release to plasma. Drugs and their metabolites may cause direct or immunological, delayed hemolysis. According to FDA, it is of importance to detect the hemolytic potential of formulation excipients used for i.v. administration. This assay can detect the direct hemolysis as %, and rate of hemolysis may be determined if desired.

In addition to these, we have assays for screening genotoxicity (AMES and MNT) and cardiotoxicity (hERG) in our in vitro toxicology services portfolio.

Please don’t hesitate to contact us for more information on our in vitro toxicology services for safety screening!