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