Monoclonal antibodies are being widely used for the treatment of various diseases. Microparticle formation in high-concentration protein solutions is a major problem during the manufacture of therapeutic monoclonal antibodies, because aggregation leads to fouling of aseptic filters and may lead to an immunogenic reaction in patients. We found that stirring using a traditional bottom-magnetic type stirrer results in extensive and sustained formation of 500-nm diameter protein microparticles arising from shear stress on protein molecules. The antibody solution stirred for only 5 min using this type of stirrer exhibited significant fouling of aseptic filter membranes. In contrast, a top-entering type stirrer did not lead to the formation of microparticles, and the solution did not exhibit membrane fouling even after 30 min of stirring. We conclude that a top-entering type stirrer is more suited for the manufacture of concentrated therapeutic monoclonal antibody solutions.