The Viscosity Reduction Platform: Viscosity Reducing Excipients For Improvement Of Filtration Processes

By Stefan Braun, Jennifer J. Widera, and Tobias Rosenkranz

In the preparation of highly concentrated protein formulations for subcutaneous injection, protein viscosity is a major challenge. The Viscosity Reduction Platform (VRP) possesses technical features and benefits for formulations. However, the difficulties associated with highly viscous solutions extend beyond drug administration to patients; these solutions can also impose technical limitations in the manufacturing process.

When advanced downstream processing (DSP) methods are utilized, the challenge of highly viscous proteins intensifies as a higher protein concentration can promote protein interactions that may ultimately lead to high viscosity. Consequently, the resulting reduced flux rates due to higher flow resistance may cause protein gelation and membrane fouling.

In the production of highly concentrated monoclonal antibodies (mAbs), critical challenges include reducing processing time, footprint, and aggregate formation. Tangential flow filtration (TFF) is commonly employed for the final formulation step to exchange the process buffer for the formulation buffer (diafiltration), remove small molecular impurities, and concentrate the protein to the desired final concentration. The sizing of the unit operation and overall process economics depend on the mass transfer/permeate flux during concentration and diafiltration steps.

Here, we evaluate the effect of excipients in the Viscosity Reduction Platform on ultrafiltration processes used to produce a highly concentrated mAb formulation. This work demonstrates two filtration methods.