Ultrafiltration/diafiltration (UF/DF) is the preferred method for biotherapeutics concentration and buffer exchange. Diafiltration is a serial concentration-dilution process that is used to clear out process chemicals such as glycols, in downstream process. During diafiltration, the concentration of undesired species decays exponentially with the number of diavolumes. In the absence of species retention (sieving coefficient of 1), it takes about 7 diavolumes for 99.9% clearance under ideal conditions.<br/>This presentation is focused on a case study for a protein purification process where diafiltration is utilized to purify the protein against an undesired glycol chemical that was introduced to the process for stability purposes. The glycol clears out by the end of 13 diavolumes but then reappears in the product after recovery from tangential flow filtration skid leading to an elevated level of glycol in the final drug substance (FDS). The variability in the residual glycol concentration in the FDS and lack of desired trending in manufacturing data have led to further investigations to gain fundamental understanding and ultimately better control of this phenomenon.  The at-scale investigations in addition to a wide variety of lab-scale studies suggest that some glycol is bound to the membrane during ultrafiltration which then, releases during the recirculation and recovery. There is strong evidence that this rebounding behavior is affected by hydrophobic interactions between the glycol and ultrafiltration membrane. Several studies on determining characteristics such as concentration polarization effect are ongoing to better understand this phenomenon in order to better control it.

Glycol clearance anomaly during ultrafiltration/diafiltration

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.