Destin A. LeBlanc

Cleaning Validation Technologies

Technical Consulting Services

1ST QUARTER 2002

Can Total Organic Carbon (TOC) be an acceptable method for detecting residues of contaminants in evaluating cleaning effectiveness? 

Yes. Since the publication of the inspection guide on cleaning validation in 1993, a number of studies have been published to demonstrate the adequacy of TOC in measuring contaminant residues.

We think TOC or TC can be an acceptable method for monitoring residues routinely and for cleaning validation. But in order for TOC to be functionally suitable, it should first be established that a substantial amount of the contaminating material(s) is organic and contains carbon that can be oxidized under TOC test conditions. This is not a trivial exercise because we know that some organic compounds can not be reliably detected using TOC.

TOC use may be justified for direct surface sample testing as well as indirect (rinse water) sample testing. In either case, because TOC does not identify or distinguish among different compounds containing oxidizable carbon, any detected carbon is to be attributed to the target compound(s) for comparing with the established limit. Thus, a firm should limit 'background' carbon (i.e., carbon from sources other than the contaminant being removed) as much as possible. The established limit - or the amount of residue detected for comparison to the spec - should correct for the target material's composition of carbon. As for any method, recovery studies are necessary. If TOC samples are being held for long periods of time before analysis, a firm should verify the impact of sample holding time on accuracy and limit of quantitation.

References:

- 21 CFR 211.67: Equipment cleaning and maintenance.

- USP 25, <643> Total Organic Carbon

- Guide to Inspections of Cleaning Validation, 1993