Project Summary Manufacturing of drugs in continuous processes, instead of the traditional batch processing, is envisioned to lead to more consistent product quality, faster ramp-up in times of shortages, such as during outbreaks of pandemics, and less environmental impact of the production plants. We propose to demonstrate the concept of continuous synthesis, crystallization, and isolation (CSCI) on the example of enzyme-catalyzed beta-lactam antibiotics active pharmaceutical ingredient (API) production. Cephalexin and amoxicillin, representative for cephalosporins and penicillins, respectively, will be our target products. As the FDA has issued Guidances regarding precautions against cross-contamination for both penicillins and cephalosporins, redesign of beta-lactam manufacturing plants towards dedicated facilities will be pertinent and advantageous. Key features of our process include employment of i) an established biocatalyst, Pen G acylase, ii) a recently developed improved kinetic model, and iii) reactive crystallization to enhance selectivity and reduce cycle time. We propose to develop novel integrated reactors and separators as well as an overall process model, to support PAT and process control around a chosen operating point. Our design is intended to enable beta-lactam API production in dedicated, compact, less capital-intensive plants, which in turn is envisioned to lead to better access to medicines for patients and ultimately to less expensive drugs.