RT Journal Article
SR Electronic
T1 Bioprocess: Robustness with Respect to Mycoplasma Species
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP 201
OP 212
DO 10.5731/pdajpst.2018.009613
VO 74
IS 2
A1 Talia Faison
A1 Julie Wang
A1 Sarah Johnson
A1 Matthew Brown
A1 Meng-Jung Chiang
A1 Sherri Dolan
A1 Carl Breuning
A1 Sai Rashmika Velugula-Yellela
A1 Scott Lute
A1 Erica J. Fratz-Berilla
A1 Kurt Brorson
YR 2020
UL http://journal.pda.org/content/74/2/201.abstract
AB Capture bioprocessing unit operations were previously shown to clear or kill several log10 of a model mycoplasma Acholeplasma laidlawii in lab-scale spike/removal studies. Here, we confirm this observation with two additional mollicute species relevant to biotechnology products for human use: Mycoplasma orale and Mycoplasma arginini. Clearance of M. orale and M. arginini from protein A column purification was similar to that seen with A. laidlawii, though some between cycle carryover was evident, especially for M. orale. 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 M. arginini though detectable levels of M. orale remained. A small-scale model of a commercial low-pH hold step did inactivate live M. orale, but this inactivation required a lower pH set point and occurred with slower kinetics than previously seen with A. laidlawii. Additionally, ultraviolet-C irradiation was shown to be effective for A. laidlawii and M. orale inactivation whereas virus-retentive filters for upstream and downstream processes, as expected, cleared A. laidlawii. These data argue that M. orale and M. arginini overall would be largely cleared by early bioprocessing steps as shown previously for A. laidlawii, and that barrier technologies can effectively reduce the risk from media components. For some unit operations, M. orale and M. arginini 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.