A manufacturing process evaluation was conducted especially focusing on the agitation process (emulsifying process) which influences the physicochemical properties of semisolid topical applied pharmaceutical products. Specifically, we did a scale-up study for the manufacturing of a commercial product, an O/W lotion containing 22-oxa-1α,25-dihydroxvitamin D3 (OCT lotion) using different batch sizes of about 1.2 kg, 20 kg, and 200 kg with the same mechanical homo-mixer (homogenizer), and we evaluated the physicochemical properties of OCT lotion, such as emulsion droplet size, viscosity and drug dissolution. As a result, it was found that the most important factors for the scale-up were rotation speed and agitation time. Then, we performed manufacturing process validation for OCT lotion with the same conditions of rotation speed and agitation time with 3 different batch-size homogenizers based on scale-up theory regarding tip-speed, v (m/s), and pass number, η through the turbine slit of the homogenizer, which resulted in the same quality, apart from viscosity. Furthermore, it was speculated that consistent physicochemical properties of each lotion could be achieved on an actual production scale by three batches with the same conditions of total energy to OCT lotion per volume: E (kW・hr/m3). Therefore, it was concluded that the two proposed scale-up methods in the emulsification process with equal rotation speed/agitation time and total energy per volume are effective ways to ensure quality consistency of topically applied semisolid pharmaceutical products such as OCT lotion.