# Continuous synthesis, crystallization, and isolation (CSCI) of an API: process model-controlled enzymatic synthesis of beta-lactam antibiotics

> **NIH FDA U01** · GEORGIA INSTITUTE OF TECHNOLOGY · 2020 · $472,319

## Abstract

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.

## Key facts

- **NIH application ID:** 9982224
- **Project number:** 5U01FD006484-03
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** ANDREAS S BOMMARIUS
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2020
- **Award amount:** $472,319
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982224

## Citation

> US National Institutes of Health, RePORTER application 9982224, Continuous synthesis, crystallization, and isolation (CSCI) of an API: process model-controlled enzymatic synthesis of beta-lactam antibiotics (5U01FD006484-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9982224. Licensed CC0.

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