How Do CDMOs Scale High-Concentration Biologic Formulations?

Ryan Swanson, PhD, director of process development, Lifecore Biomedical, connected with PharmTech to discuss the formulation challenges behind high-concentration biologic drug products.

One of the biggest hurdles in early development is conserving material, says Swanson, who specializes in the development and aseptic fill-finish of sterile injectable products, including complex, highly viscous formulations, at Lifecore.

Generating both a biologic's drug substance and drug product is expensive and time-consuming, which pushes developers toward surrogate molecules and small-scale experiments designed to translate to an eventual GMP-scale process. Product hold-up must also be scrutinized at every step to minimize losses as a high-concentration process is designed.

Biologics also carry sensitivities that small molecules do not, including susceptibility to shear and temperature, Swanson, who was previously at Bristol Myers Squibb, told PharmTech. As concentration rises toward a solubility limit, some technologies now shift a biologic into a suspension format to keep pushing that boundary higher. But that shift adds complexity. "The trade-off is that it's a sterile injectable, and the sterility assurance activities for a sterile injectable suspension product are far more complex than they are for a non-suspension product," Swanson says. Because biologics generally cannot withstand terminal sterilization without damaging their critical quality attributes, the sterile boundary has to move upstream of forming the suspension, adding downstream unit operations behind that boundary.