Fig 1.
Overview of the three antibody formats commonly used in serum-based antivenoms.
IgG is the entire native immunoglobulin G, whereas the formats F(ab)2 and Fab are obtained by enzymatic cleavage in the hinge region with pepsin or papain, respectively.
Fig 2.
Overview of the three different antibody manufacturing process strategies: In the fed-batch process, nutrients for the CHO cells are supplied for a complete cultivation process followed by harvest and purification of the entire batch by single-batch chromatography.
In the continuous perfusion process, cells are retained while the growth medium containing the antibodies is continuously substituted with fresh medium in a perfusion reactor. The used media undergoes simulated moving bed chromatography (SMBC), where the chromatographic processes are conducted in a continuous process as described in [22]. In the hybrid process, cultivation is performed in a fed-batch reactor followed by SMBC instead of single-batch chromatography.
Fig 3.
Schematic representation of two different strategies for recombinant expression of antibody mixtures.
A) Mixing of batches: Antibodies are produced by monoclonal expression in different bioreactors, followed by individual purification, after which they are mixed to yield the final oligoclonal antivenom product. B) Oligoclonal expression: Antibodies are produced by oligoclonal expression in one bioreactor containing different cell lines. Purification can then be performed on the mix of antibodies, providing the final oligoclonal antivenom.
Fig 4.
Estimation of Cost of Goods Manufactured (COGM) per gram for oligoclonal antibody production at different scales of production for three different manufacturing strategies, Fed-batch, hybrid, and continuous perfusion (all using chromatography as purification method, see Fig 2), based on cost estimates from [25,31].
Fig 5.
Estimation of Cost of Goods Manufactured (COGM) per snakebite treatment for oligoclonal antibody production at a production scale of 500 kgAPI for three different manufacturing strategies: Fed-batch, hybrid, and continuous perfusion.
A) Cost estimated based numbers from [31], employing SMBC as purification method for the hybrid and continuous perfusion processes. B) Cost estimated based numbers from [20], employing continuous caprylic acid precipitation as purification method for the hybrid and continuous perfusion processes instead of continuous SMBC. API: Active Pharmaceutical Ingredient. FDP: Final Drug Product.