Disclosed is a sustained-release microsphere comprising a physiologically active substance and a biodegradable polymer, which is obtainable from a process which comprises subjecting a w/o/w emulsion or o/w emulsion, wherein said physiologically active substance is in an inner aqueous phase and said biodegradable polymer is in an external oil phase, to an in-water drying method under the following conditions: 1) the amount of microspheres per m<3> of an external aqueous phase is about 0.1 to about 500 kg, 2) the square root of the area (unit: m<2>) of the liquid surface in contact with the gas phase is about 0.2 to about 4.5 per the cube root of the volume (unit: m<3>) of an external aqueous phase, 3) the w/o/w emulsion or o/w emulsion is replaced at the replacement frequency of about 0.01 to about 10 times/minutes, 4) a gas is blown to the w/o/w emulsion or o/w emulsion at the gas transfer rate near the liquid surface of about 0.1 to about 300 m/second, and 5) the gas is replaced at the replacement frequency of not less than about 0.5 times/minutes. The method described increases the rate of solvent removal from microspheres in in-water drying, reducing the amount of solvent in microspheres in a short time.
