Analytical Prowess Powers Efficient CLD Through Data-Driven Decision-Making

By Felix Vega, Aragen Life Sciences

Cell line development (CLD) is a complex endeavor that demands pharmaceutical companies and their partners be mindful, at every step, of cell productivity (titer) and product quality, as well as the eventual cost of goods sold (COGS). Further, biologics development is not always predictable due to the inherent plasticity of the expression systems. Both known and unknown liabilities in the protein sequence can complicate CLD, especially for complex (nontraditional) format biologics.

Stated simply, more complex molecules generally lead to more liabilities. Relevant to complex format biologics, unknown degradation or post-translational modifications can make CLD more difficult, time-consuming, and expensive. Still, disease indications targeted by standard antibodies are low-hanging fruit and are a very competitive field. So, more biopharmas are exploring more complex formats of protein therapeutics (though still largely based on antibody structures), such as an antibody cytokine infusion, or a single-chain Fv antibody fragment.

These more complex molecules are harder to express and have different degradation products because they might be considered “unnatural.” Specifically, the cells are not used to expressing the complex molecules like they would a natural immunoglobulin G (IgG) antibody. So, the cells tend to degrade, the degradation products get into the cell culture supernatant, and those product-related impurities need to be purged before the product proceeds to the clinic and, ultimately, to the market.

Trustworthy analytics enable the flexibility and responsiveness to proceed where the data indicates, pushing clones or cells closer, at each step of CLD, to an environment conducive to a product’s intended quality specifications.