Tissue cross-reactivity (TCR) studies
Tissue cross reactivity (TCR) is used to identify possible cross reactivity of novel biologicals with the primary aim of reducing the risk associated with first-in-human (FIH) testing. The assessment of potential cross reactivity involves the screening of and using of immunohistochemical staining techniques on frozen tissues.
TCR assessments are performed in accordance with the FDA Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use (1997) and the EMA ICH S6 (R1) Preclinical Safety Evaluation of Biotechnology Derived Pharmaceuticals (2011).
In the assessment, three donors of each tissue are screened for possible "off-target" binding. The results from these studies can also be used to compare staining patterns between human and research model tissues, providing additional justification for the choice of models used to generate other preclinical safety data.