[BEBPA 2019] Qualified, Fit-for-Purpose Bioassays for Liraglutide and Exenatide as Frozen Ready-to-Use Cells

[BEBPA 2019] Qualified, Fit-for-Purpose Bioassays for Liraglutide and Exenatide as Frozen Ready-to-Use Cells
File Name/Number:
BEBPA 2019

Year:
2019


With more than 25% of the world’s population diagnosed with type II diabetes and/or metabolic syndrome, the requirement for cost- effective drugs to control patient disease is increasingly urgent. Agonist drugs of the Glucagon-like peptide-1 (GLP-1) receptor, such as Victoza® (Liraglutide) and Byetta® (Exenatide), modulate glucose-induced insulin secretion and have shown excellent results in the clinic. These molecules are highly sought after for biosimilar and biobetter development, however, the existing cell-based assays to support this development are complex and require extensive development time. Here, we describe the development and qualification of ready-to-use (RTU), fit-for-purpose potency bioassays for these two drugs.  Based on the drug’s well-characterized mechanism of action, these bioassays measure production of cyclic AMP (cAMP) in response to activation of the GLP1 receptor with agonist drug. The assay relies on an easy-to-use homogenous protocol for rapid implementation at any lab globally, resulting in a chemiluminescent readout that can be read on any plate reader. The assay was qualified using the marketed innovator molecules through a multi-day qualification
exercise with two analysts. The assays demonstrated high reproducibility, accuracy, and precision, with good linearity over the tested range of 50%-150%. Importantly, these assays have been developed into frozen RTU cells and the data presented here demonstrates the multiple technical and operational advantages of this approach over the traditional continuous culture assays.