By Mike Brewer & Karen Salomon
The need for speed in biologics development is greater than it has ever been. Regardless of the modality or therapeutic class, there are often multiple companies racing to develop, manufacture, and commercialize high-quality products to be the first-in-class therapeutic. However, there are many manufacturing and analytical challenges that a company can face as it strives to be the first to market. Manufacturers must perform a battery of analytical tests to demonstrate the quality, consistency, purity, potency, and safety of products produced in cell-culture. One of these critical tests is quantitation of residual host cell DNA — both during purification and as the product nears final dosage form — to ensure the levels of host cell DNA fall below regulatory guidelines.
Typically, there are three options for manufacturers to achieve their analytical method development and/or testing needs. These options include developing the methodology and tests in-house, engaging a contract development and manufacturing organization (CDMO), or acquiring commercially available solutions. However, developing the capabilities in-house — as opposed to going with a commercially available solution — can pose financial, scientific, and process-related challenges for companies. Ultimately, when making this decision, it is critical manufacturers remain focused on long-term development goals to ensure the chosen strategy does not jeopardize the efficiency of the manufacturing process in addition to the purity and safety of their biological product.
In this article, we illustrate approaches for analytical method development and the challenges that may be encountered, particularly in the development of a quantitative assay for residual host cell DNA.