Application of Total Organic Carbon Analysis to Cleaning Validation

Abstract

Cleaning validation is the process of assuring that cleaning procedures effectively remove residue from manufacturing equipment/facilities below a predetermined level This is necessary to assure the quality of future products using the equipment, to prevent cross-contamination and as a GMP requirement. Currently, cleaning validation samples are measured using HPLC or spectrophotometric methods of analysis which are often time consuming and subject to a number of interferences. Total Organic Carbon (TOC) analysis is a new method which has previously only been applied to measurement of carbon residues on production surfaces for biopharmaceuticals.^§ We have applied the TOC analysis method to a number of traditional pharmaceutical products including antibiotics, steroids, and antinauseants in addition to biopharmaceuticals. The method offers extremely low detection capability (ppm and ppb), rapid sample analysis time and therefore quick turn-around of production equipment and facilities. TOC analysis is also applicable to on-line analysis. The method allows the measurement of extraneous materials such as process intermediates, cleaning agents, and protein materials not possible by other methods.