Donnan effect and diafiltration optimization: Considerations for final formulation UFDF steps of monoclonal antibodies

The goal of a formulation TFF process is to bring the product to its final concentration and to perform a buffer exchange so as to achieve the target product formulation. Eight to ten diavolumes is a standard recommendation an acceptable buffer exchange in a typical final formulation UFDF process. This recommendation comes from the theory that during the DF process, buffer excipients will flow freely through the UF membrane, having an R (retention) value of 0. Given this assumption at 10 diavolumes, 99.995% of the original buffer would be removed from the system; this percentage is considered an acceptable exchange by industry standards. The following study details how the Donnan effect affects the R value of a system (i.e. the removal of excipients), changing the number of diavolumes required to perform a complete exchange. It was observed in this study that if the MAb and buffer excipient(s) that is being removed are oppositely charged, the R value will increase. The higher the R values the more diavolumes will be required to achieve an acceptable exchange. Conversely if the MAb and buffer (excipient) that is being removed are congruently charged, the R value will be negative and less diavolumes will be required. Furthermore, the study showed that the concentration at which the DF is performed also affects the R value since a higher concentration increases electrostatic interaction between the mAb and charged excipients. Using knowledge about the Donnan effect and how it can affect buffer removal, better recommendations can be made for formulation TFF. These new recommendations could make the process more efficient and/or accurate.