Bioprocess: Robustness with Respect to Mycoplasma Species.

Capture bioprocessing unit operations were previously shown to clear or kill several log of a model mycoplasma in lab-scale spike/removal studies. Here, we confirm this observation with two additional mollicute species relevant to biotechnology products for human use: and Clearance of and from protein A column purification was similar to that seen with , though some between cycle carryover was evident, especially for However, on-resin growth studies for all three species revealed that residual mycoplasma in a column slowly die off over time rather than expanding further. Solvent/detergent exposure completely inactivated though detectable levels of remained. A small-scale model of a commercial low-pH hold step did inactivate live , but this inactivation required a lower pH set point and occurred with slower kinetics than previously seen with Additionally, ultraviolet-C irradiation was shown to be effective for and inactivation whereas virus-retentive filters for upstream and downstream processes, as expected, cleared These data argue that and overall would be largely cleared by early bioprocessing steps as shown previously for and that barrier technologies can effectively reduce the risk from media components. For some unit operations, and may be hardier, and require more stringent processing or equipment cleaning conditions to assure effective mycoplasma reduction. By exploring how some of the failure modes in commercial antibody manufacturing processes can still eliminate mycoplasma burden, we demonstrate that required best practices assure biotechnology products will be safe for patients.