During TFF process development for mAbs that require high protein concentration liquid formulations, Donnan Effect of buffer excipients, such as acetate and histidine, must be considered to ensure desired pH and excipient concentrations are achieved. A potential approach to address the Donnan Effect is to replace conventional buffered solution with buffer-free solution for diafiltration. The target excipient concentration is then achieved by spiking. This study evaluated the feasibility of diafiltering two mAbs (IgG1 and IgG4) into buffer-free solution at high protein concentration (≥ 200 mg/mL) using TFF. The study included evaluating the effects on protein attributes (viscosity, pH, and aggregation), as well as TFF operating parameters (TMP, retentate and permeate flow rate). In addition, the stability and self-buffering capacity of the mAbs at high protein concentration in buffer-free solution were evaluated up to 7 days at 2-8<sup>o</sup>C. The results supported the buffer-free solution approach for one of the mAbs tested, and that it was feasible to implement using TFF. The results also suggested that this approach was not feasible for another mAb due to precipitation in buffer-free solution.

Feasibility of formulating a highly concentrated monoclonal antibody (mAb) into a buffer-free solution using tangential flow filtration (TFF)

253rd National Meeting (2017)

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