On-line high-performance liquid chromatography for monitoring fermentation processes for penicillin production

Abstract

The control and regulation of a fermentation process requires accurate and reliable on-line measurements of media components, often over long periods of time. As an alternative to wet chemical and enzymatic methods, high-performance liquid chromatography (h.p.l.c.) can be used. In addition to the product, penicillin V, important by-products and degradation products, as well as the precursor, phenoxyacetic acid, are determined. This makes it possible to control the precursor feed and to establish the optimal harvest time. Moreover, contamination can be detected at an early stage. Control of the precursor feed is desirable because the phenoxyacetic acid represents about 10% of the production costs and because higher concentrations could be toxic. The sterile sample flow is removed from the reactor by a microfiltration probe and drawn through the injection loop of an h.p.l.c. valve. Three analyses per hour can be done, and selected data from a computing integrator are fed to a process computer. The system works reliably for 300 h without requiring further calibration. © 1986.