Phenylacetic acid, a strong acid, was formed from the enzymatic hgdroly sis of penicillin G to 6-amino-penicillanic acid, Because of the difficulty of maintaining the pH constant inside the reactor, the reaction mixture was circulated at a high flow rate between the packed bed reactor and the vessel for adjusting pH, The reactor and the vessel were connected via a pump, When an immobilized enzyme made of compressible fibers was packed in the packed bed reactor, the hydrolytic efficiency of the immobilized enzyme was approximately 9.5, The low efficiency of the immobilized enzyme was assumed to be caused by the aggregation of the immobilized enzyme due to the pressure generated by flow of the reaction mixture, Therefore, the aggregation in the packed bed reactor was analyzed experimentally using Kozeny- Carman’s equation in order to estimate the distribution of the aggregation in the reactor, Furthermore, a new column devised specially to prevent aggregation of the compressible fibrous support was developed, A reaction time required for completing the hydrolysis (98 % of conversion) was adopted to estimate the efficiency of the entire immobilized enzyme packed in the reactor throughout the entire period of reaction, The efficiency of the immobilized enzyme packed in the new column of the reactor was concluded to be increased by approximately 1.8 times, compared with that of conventional packed bed columns.