Feasibility\nof Laboratory Equipment-Based Simulation\nMethods to Assess the Impact of Vehicle Transportation on Product\nQuality of mAb Dosing Solutions

Therapeutic monoclonal antibody (mAb) products for intravenous\n(IV) administration generally require aseptic compounding with a commercially\navailable diluent. When the administration site is located away from\nthe preparation site, the prepared dosing solution may need to be\ntransported in a vehicle. The impact of vehicle transportation on\nthe product quality of mAbs needs to be evaluated to define safe handling\nand transportation conditions for dosing solutions. The design and\nexecution of actual vehicle transportation studies require considerable\nresources and time. In this study, we systematically developed three\ndifferent laboratory equipment-based methods that simulate vehicle\ntransportation stresses: orbital shaker (OS), reciprocating shaker\n(RS), and vibration test system (VTS)-based simulation methods. We\nassessed their feasibility by comparing the impact on product quality\ncaused by each simulated method with that caused by actual vehicle\ntransportation. Without residual polysorbate 80 (PS80) in the mAb\ndosing solution, transportation via a cargo van led to a considerable\nincrease in the subvisible particle counts and did not meet the compendial\nspecifications for the light obscuration method. However, the presence\nof as low as 0.0004%w/v (4 ppm) PS80 in the dosing solution stabilized\nthe mAb against vehicle transportation stresses and met the compendial\nspecifications. Vehicle transportation of an IV bag with headspace\nresulted in negligible micro air bubbles and foaming in both PS80-free\nand PS80-containing mAb dosing solutions. These phenomena were found\nto be comparable to the VTS-based simulated method. However, the OS-\nand RS-based simulated methods formed significantly more micro air\nbubbles and foaming in an IV bag with headspace than either actual\nvehicle transportation or the VTS-based simulated method. Despite\nthe higher interfacial stress (micro air bubbles and foaming) in the\ndosing solution created by the OS- and RS-based simulated methods,\n0.0004%w/v (4 ppm) PS80 in the dosing solution was found to be sufficient\nto stabilize the mAb. The study shows that under appropriate simulated\nconditions, the OS-, RS-, and VTS-based simulated methods can be used\nas practical and meaningful models to assess the impact and risk of\nvehicle transportation on the quality of mAb dosing solutions.