Reliable Osmolality Testing Of High Concentration mAb Formulations

By Kristeena Wright, Laura Chinn, Kendal Studd, Samantha Heidlebaugh, Cianna Cooper, Cameron Bardliving, Nancy Perlmutter

Osmolality testing has several unique and essential applications throughout bioprocessing, and new use cases are constantly emerging. As the field of biologics manufacturing matures, osmometers and other analytical devices must keep up and even offer new options to remain valuable. The osmolality of monoclonal antibody (mAb) formulations is typically determined using freezing point depression or vapor pressure osmometers. The wider use of subcutaneous injections; an injection that requires less volume but increased concentration to alleviate patient pain and increase patient compliance has led to a trend in increasing mAb concentrations. This higher concentration, however, can pose analytical issues. Due to much higher viscosities being seen in drug formulations; it is critical to have an instrument that will measure concentration with optimal performance. Although freezing point depression osmometers are the gold standard osmometry method, the previously mentioned higher viscosity samples may signify an issue for older technologies. This would have meant the “go-to” method may have been vapor pressure, even though from a usability and data integrity standpoint, this was not preferred. In response to this, Advanced Instruments has developed a new, intelligent freezing point depression technology that is aimed specifically at these hard to measure drug products. This paper details an evaluation of the OsmoTECH® XT (freezing point) and Vapro® 5600 (vapor pressure) osmometers as a means of measuring concentrated protein formulations. In general, mean osmolality values were similar across a range of saline and monoclonal antibody concentrations. Key differentiations were observed in the accuracy of the salt standard measurements and the variance of the mAb measurements, both of which were preferable on the OsmoTECH XT. In addition, the OsmoTECH XT has key advantages in terms of usability and advanced data integrity features that facilitate implementation into GMP workflows.