Bioprocessing of antibody production

For this week’s discussion I selected a review article that discusses bioprocessing of antibody production. Monoclonal antibodies (mAbs) production has become a very promising market, with a steady and increasing approval rate for global manufacturing. Due to the demand, it has surpassed other therapeutics such as recombinant protein (Yang et al., 2019). Although there are different operating modes in the bioprocessing of mAbs, for the purpose of this discussion I will focus on conventional batch processing and continuous processing of mAbs. Batch processing and continuous processing, which are involved in the production of mAbs, both require a host cell to express the protein of interest (mAbs). There are various host cells that may be used, and as we learned in previous weeks, the bioprocessing of the product will be greatly impacted by which host cell has been selected (CHO, yeast, E. coli, etc.). However, there are other factors that also weigh heavily to determine profitability for each batch processing and continuous processing of mAbs. For example, in the review article by Yang et al. (2019), they use the COG (Cost of goods) equation which allows biomanufacturers to determine the cost of goods per gram (COG/g) by combining direct costs [labor, materials (media, buffer, and cleaning) and consumables (filters and membranes, resins for chromatography, etc.)], and indirect costs (utilities, construction, engineering) of the process divided by the annual product output. With the output cost, the Monte Carlo analysis can be implemented along with economic analysis software that can determine the variation of parameters and include best, worst, and base case scenarios while considering batch loss and percentage yield loss.

The model building and operational economic analysis of the life cycle and cost of goods in biomanufacturing has shown to improve decision making to determine which process would be suitable for biomanufacturing. In the case of mAbs production, batch and continuous processing were each reviewed, and the analysis concluded that some processes were ideal for specific steps. For example, batch processing using perfusion bioreactors was ideal for inoculation for optimal cell density, whereas this is not used in continuous processing. In contrast, continuous processing involves exchange bioreactors that improve productivity and scalability (Yang et al., 2019). The researchers determined that it could be feasible to change from batch to continuous processing to maintain cell density and overall yield while maintaining production costs at a relative equal value. However, in this hybrid process water consumption would be 85% higher than that of batch processing due to the increase in downstream activities. As different operating modes and hybrid processes are developed and implemented, with the use of model building and software platforms biomanufacturers could potentially identify and determine economic their economic impact.

Although the review does not comment much on US production versus alternative, non-US plant locations, they do mention how from 2008 to 2013 global sales of mAbs grew from ~$39 billion to ~$75 billion and was expected to reach $125 billion by 2020 and $138.6 billion by 2024. Further online searching provided information that the mAbs market hit ~$157 billion last year. The resource from the reading list that was most relevant to this discussion was Bioprocess Design and Economics (Petrides, D., 2000). The textbook provided me with better insight of the process analysis when considering different processing for a given bioproduct from feasibility to market entry including the total plant direct costs and indirect costs.

References:

Fortune Business Insights. (n.d.). Monoclonal antibody therapy market size, share & COVID-19 impact analysis, by type (human mAb, humanized mAb, chimeric mAb, and murine mAb), by application (cancer, autoimmune diseases, and others), by distribution channel (hospital pharmacy retail pharmacy, and online pharmacy), and regional forecast, 2021-2028. https://www.fortunebusinessinsights.com/monoclonal-antibody-therapy-market-102734 Yang, O.,

Qadan, M., &Ierapetritou, M. (2019). Economic Analysis of Batch and Continuous Biopharmaceutical Antibody Production: A Review. Journal of Pharmaceutical Innovation, 14, 1–19. https://doi.org/10.1007/s12247-018-09370-4