Herceptin (trastuzumab) is a humanised monoclonal antibody that binds to the extracellular component of the Her2/neu receptor, a 185-kDa transmembrane oncoprotein that is overexpressed in approximately 20 to 25% of breast cancer patients. The antibody has been designed to express the human Fc-Gamma-1 isotype to increase both Complement Dependent Cytotoxicity (CDC) and Antibody Dependent Cellular Cytoxicity (ADCC) function of the antibody. The Fab-related function of Herceptin (trastuzumab) causes allows binding with high affinity to the extracellular domain of the HER2/neu receptor causing inhibition of cell proliferation and prevention of angiogenesis.
During early development of the Biosimilar, biocomparability studies are performed using the various Herceptin (trastuzumab) bioassays and binding assays to evaluate product generated from different clones or different versions of the manufacturing processes. These studies can be conducted alongside the innovator product as part of a formal comparability investigation to demonstrate equivalence between Herceptin biosimilar and innovator.
Prior to clinical testing a validated potency assay is required for performance of lot release and stability testing. Consistent with the innovators methodology, this method of choice is the BT474 inhibition of proliferation bioassay.