Whilst an in vivo bioassay method may be available, identifying a cell line that responds to a particular monoclonal antibody target or to the antibody itself, in both a specific and reproducible manner, can often be a hurdle in the development of a cell based potency assay. This can prove to be a significant challenge in the development of monoclonal antibodies that target PBMCs as the responsiveness can be very low with huge differences between donors and lots. A cost and time effective alternative to screening a wide range of possible cell lines can be the generation of reporter cell line that has been genetically modified to contain the antibody target and a reporter gene which will switch on when the monocloncal binds to its target. This approach has been accepted by the regulatory agencies and provided that the mechanism of action of the bioassay closely mimics the in vivo mechanism of action of the drug, the use of reporter gene bioassays can prove to be highly valuable.
BioOutsource has successfully created a number of reporter cell lines, and has developed potency assays that have successfully been used in bioassay validation and lot release. Typically, a number of double-stable clones are generated and screened for responsiveness from which a single clone is selected. A GMP cell bank will then be prepared which will undergo suitable characterization for use within a GMP environment including certification of sterility and freedom from mycoplasma and viability assessments. The cell bank will also be certified for a defined number of passages, with sequencing and copy number established.