The enzymatic synthesis of beta-lactam semi-synthetic antibiotics has been receiving increasing attention as a green-chemistry alternative for the industrial production of these drugs, because mild reaction conditions may be used. A nonconventional fed-batch reactor is presented here, using a bi-disperse gel matrix for immobilization of the enzyme penicillin G acylase (PGA) [EC 3.5. 1.11]. The catalyst particles are suspended within Taylor-Couette vortices, performing the kinetically controlled synthesis of ampicillin (AMP) from phenylglycine methyl ester (PGME) and 6-aminopenicillanic acid (6-APA). This is a serial-parallel set of reactions, where the desired product (AMP) is the intermediate species, and a high selectivity is essential for the process economics. With this objective, AMP should be precipitated, withdrawing the antibiotic from the liquid phase and reducing its hydrolysis. One key point is to protect the physical integrity of the catalyst within this environment. To avoid damages to the catalyst particle caused by conventional impellers, while preserving a good mixing, Taylor-Couette flow was used. In addition, a convenient biocatalyst matrix was developed, to allow easy separation between the crystals and the enzyme support. A bench-scale (50 mL) Taylor vortex flow reactor (VFR), with a radius ratio of eta= 0.27 and operating in fed-batch mode, was used for proof of the concept. To sustain homogeneous fluidization of the biocatalyst, the VFR operated with a rotational Reynolds number of Re = 5605, within the turbulent Taylor vortices flow region. With this reactorcatalyst ensemble, 100% activity and complete physical integrity of the particles were sustained after 200 h of operation.