Overcoming challenges for the production of a novel engineered mAb
Introduction
Tracing back 30 years with the licensing of the first monoclonal antibody (mAb) for clinical use, the development of mAb-based drug products is well established in the biopharmaceutical industry1. However, as our understanding of the role antibodies play within our natural immune responses continues to advance, along with genetic engineering techniques, novel antibody products that have been specifically designed or engineered to target a particular disease will rise2.
These drug products are inherently more complex and may require significant development and manufacturing optimization to produce efficacious and safe products for clinical and commercial use.
Why did the customer approach Enzene?
A customer approached Enzene Biosciences to help overcome an upstream batch bottleneck for their human-engineered mAb product, which currently was not viable for more than 10 days.
In addition, no established purification steps were in place. The development of an effective manufacturing method was made harder by the instability of the mAb product.
Enzene’s approach
Enzene started by completing several screens to identify the best clone and media to obtain the optimum yield and quality. A 2L batch was used initially for proof of concept before the clone, media, and process were optimized and finalized.
The cell bank was then fully characterized to take the batch to GMP and the 50L reactor was moved to research and development. Here, installation qualification (IQ), operational qualification (OQ), and performance qualification were completed in 10 days.
In parallel, seed generation and required material procurement were done for the 50L batch to save time.
Outcomes
Achieved in only 5 months, the manufacturing process was scaled from proof of concept (250mL) to large scale (50L), producing 55g of drug substance from the 50L bioreactor.
Therefore the bottleneck was overcome and Enzene delivered an efficient process to the customer that could be used to deliver treatments for clinical or commercial applications.
1 Liu, J.K.H. (2014) ‘The history of monoclonal antibody development – progress, remaining challenges and future innovations’, Annals of Medicine & Surgery, 3(4), pp. 113–116. doi:10.1016/j.amsu.2014.09.001.
2 Stone, C.A., Spiller, B.W. and Smith, S.A. (2023) ‘Engineering therapeutic monoclonal antibodies’, Journal of Allergy and Clinical Immunology [Preprint]. doi:10.1016/j.jaci.2023.11.018.
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