In vitro methods for immunotoxicology, cellular toxicology, efficacy markers and ADME parameters

Experience and competence

Our experts have collectively more than 50 years of experience in drug development and are well versed in appropriate safety assessment legislations, allowing them to assist you in moving your project further on the value chain. 

Our tests are based on regulatory requirements and international guidelines and practices but we are flexible in providing tailor-made test models according to your specific requirements. 

Project support and risk mitigation

Our in vitro laboratory provides expert assistance in assessment, prediction and/or interpretation of  toxicological effects in the immune system and various organs (e.g liver and kidney), as well as providing essential ADME parameters. Since computer-based (in silico) and GLP certified in vivo capabilities are also operating within our facilities, your project will automatically have access to these areas of expertise and test systems when you contact us. For example, an effect demonstrated during in vitro testing can be further investigated in vivo and again followed-up by ex vivo verifications in the in vitro laboratory. Further, data from in vitro experimentation can also be fed into various in silico tools for enhancing their predictive capacity. All data derived within your project is thus handled within the same unit and data integration and problem-solving activities can proceed without you as the customer losing time in forwarding information between different contract laboratories.

As well as providing experimental data in vitro, each project is supported by extensive ability to rationalise data in terms of potential mechanism(s) of toxicity, and translatability between species. We also help you to interpret regulatory requirements and guidelines from government agencies (ICH, EMA, FDA, OECD), to ensure that the choice of models is fit for purpose for your project from a regulatory perspective.

Tests

We test both low molecular weight and biological drug candidates, as well as industrial chemicals and the test models deliver both functional- and quantitative data. GLP is available upon request. Examples of the “off the shelf” tests we perform are clustered below under various areas of toxicity:

Immunotoxicology and immunological effects

Test systems related to both innate and acquired immunity are included in our offer and provide, for example, cytokine measurements, antibody measurements, immune phenotyping, detection of memory cells, lymphocyte activation, phagocytosis, oxidative burst, NK cell activity, T-cell dependent antibody-response (in vivo trials included), histamine release, ADCC, CDC and prediction of immunogenicity (in silico testing included). Other test models can be ordered as desired. Fit for purpose efficacy models for drugs can also be designed, depending on therapeutic target.

Liver toxicology

We can offer testing/screening of drug candidates for potential mitochondrial toxicity and hepatotoxicity in the state of the art Glu/Gal HepG2 method used by big Pharma. We can also offer assays in frozen or fresh human hepatocytes. These in vitro methods are recommended if the substance has previously given a positive prediction for hepatotoxicity potential from in silico methods, which are also available in-house. In our in vivo studies, we can perform histopathological evaluation on the liver and also monitor the development of liver damage by studying plasma biomarkers which include both traditional markers such as ALT  in combination with newly validated markers such as GLDH, CSF1R, miR-122  and  HMGB1.

ADME

We can measure plasma protein binding and perform metabolic stability studies in microsomes from relevant species. We also offer intellectual support in evaluating ADME data and integrating these in risk predictions and risk assessments.

Other

• Cholesterol efflux
• PCR-testing
• Hybridization ELISA