Developing affordable monoclonal antibodies for LMICs through high performance manufacturing processes and LMIC based...

Monoclonal Antibodies (mAbs) are one of the most effective developments in disease prevention and treatment of the last century. Active treatment and passive immunization with mAbs targeting key antigens represents a promising approach to preventing and mitigating infectious pathogen-caused illness, particularly in Low and Middle-Income Countries (LMICs). While the development of mAbs against infectious disease has lagged behind that of immune disorders and oncology targets, recent efforts against infectious diseases have seen increasing focus with the development of mAbs against RSV, Ebola strains, and SARS-CoV-2, among others. The price for mAb treatment remains out of reach for most patients in middle income countries and nearly all patients in low-income countries. It is therefore clear that a new approach to manufacturing mAbs is needed. Here, high-productivity, high-yield mAb fed-batch production is demonstrated using clonal variants of ZAC-3, a mAb directed against the conserved core/lipid A region of V. cholerae lipopolysaccharide (LPS). We then extrapolate production levels seen in the ZAC-3 fed-batch run data to a continuous manufacturing approach to show a potentially viable path to manufacturing low cost mAbs at commercial scale. The reduction in cost of manufacturing drug substance resulting from the use of a continuous manufacturing process, coupled with high efficacy, and potential for low dose sizes, could give mAbs such as ZAC-3 the potential to be widely used in LMICs. The manufacture of mAbs in an LMIC-based commercial GMP facility should further reduce the cost of manufacturing, aiding in providing low-cost mAbs to patients in LMICs. Taken together, we aim to show that the potential for developing deployable antibody-based interventions to combat unaddressed pediatric diseases and rapid outbreak responses in LMICs is within reach.