Breaking Barriers: How Kemwell’s Mitigation Strategy Overcomes Viscosity-Induced High-Concentration TFF Challenges

Introduction:

Recent advances in biologics development are primarily focussed on development of high titre producing cell lines to substantiate the requirement of high dosage mAbs which may be as high as 600-700 mg drug per dose. This also brings in the requirement of subcutaneous injectables to alleviate the hassles of IV infusion. Therefore, to achieve both these objectives, substantial work has also been initiated for development of high concentration formulation along with high titre cell lines. One of the biggest challenges for the development of high concentration formulation is increase in viscosity which impact the injection force and patient comfort. As part of purification process flow, the concentration of the protein molecules is achieved by TFF unit operation which is also the unit operation where this challenge is encountered the most. This poster focuses on the strategy to mitigate these challenges and achieve a concentration of >200 mg/mL for mAbs as well as other mammalian recombinant proteins.

Barriers during TFF:

Key Contributors:

Conclusion:

During high-concentration TFF unit operations, pressure drop escalation and gel layer formation on the membrane surface are significant challenges to achieving concentrations >200 mg/mL at the drug substance stage. The strategies discussed in this work effectively mitigate these issues by reducing protein-protein interactions and minimizing gel layer formation on the membrane surface. This results in better displacement and higher recovery during the TFF process. By applying these approaches, consistent concentration >200 mg/mL was successfully achieved at the pilot scale and subsequently scaled up to 2000L at GMP.

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