Mark Melville, Ph.D., senior director of bioprocess development at EPIRUS Biopharmaceuticals, notes that two main avenues to cell-line development are open to virtual companies like EPIRUS.
The more traditional approach involves working with a company that builds cell lines from the ground up using a suitable expression system and host cell line, followed by conventional screening. For biosimilars, EPIRUS’ specialty, quality endpoints would be brought into the development process as early as feasible.
The second strategy, which has become more common since the advent of biosimilars, is to in-license cell lines optimized for the expression of specific biosimilars, for example trastuzumab (Herceptin) or bevacizumab (Avastin).
In-licensing cells significantly has the potential to shorten development times. “But there are tradeoffs,” Dr. Melville cautions. “If you’re going that way you don’t have a wide range of cell lines to select from. By comparison, when working from scratch the sponsor can influence and shape development all along the way. In-licensing may save time, but it adds risk.”
The risk is that, in a new set of hands, the cell line may not meet productivity or quality goals. “These vendors will provide cells, but they cannot guarantee success—that you’ll have an approvable biosimilars if you use their product,” Dr. Melville says. “There are many steps between receiving cells and achieving a commercial process.”
An interesting analogy might be purchasing a component or ingredient for a gourmet dinner rather than making it from scratch. An inexperienced cook probably has a higher expectation of success going this route, but professional chefs know the result will be perfect if they control every “unit operation” in preparing that meal. In other words, companies inexperienced with cell-line development are probably better off in-licensing.
For the in-licensing scenario the risk of not reaching specified quality attributes is a lot more serious than for not achieving viable productivity. “It’s not difficult to achieve commercially viable titers,” Dr. Melville explains. Quality, particularly for biosimilars developers, involves hitting a narrow target of physico-chemical similarity with the innovator drug. Factors such as culture method and medium, feed strategies, and purification all affect quality. Companies that in-license must still perform significant development on these components of a successful process. Furthermore, the analytical methods that originally qualified product-specific cells may be inadequate for demonstrating biosimilarity to regulators.
Dr. Melville is not at liberty to divulge his company’s strategy with respect to sourcing cell-line development services. He did say, however, that most established biomanufacturers tend to keep as much control as possible over cell-line development, except for “selective” cases that make good business sense.