Total organic carbon (TOC) is an indirect measure of organic molecules present in pharmaceutical waters measured as carbon. Organic molecules are introduced into the water from the source water, from purification and distribution system materials, and from biofilm growing in the system. TOC can also be used as a process control attribute to monitor the performance of unit operations comprising the purification and distribution system. A TOC measurement is not a replacement test for endotoxin or microbiological control. While there can be a qualitative relationship between a food source (TOC) and microbiological activity, there is no direct numerical correlation.

A number of acceptable methods exist for analyzing TOC. This chapter does not endorse, limit, or prevent any technologies from being used, but this chapter provides guidance on how to qualify these analytical technologies for use as well as guidance on how to interpret instrument results for use as a limit test.

Apparatus commonly used to determine TOC in water for pharmaceutical use have in common the objective of oxidizing the organic molecules in the water to produce carbon dioxide followed by the measurement of the amount of carbon dioxide produced. Then the amount of CO2 produced is determined and used to calculate the organic carbon concentration in the water.

All technologies must discriminate between the inorganic carbon, which may be present in the water from sources such as dissolved CO2 and bicarbonate, and the CO2 generated from the oxidation of organic molecules in the sample. The discrimination may be accomplished either by determining the inorganic carbon and subtracting it from the total carbon (total carbon is the sum of organic carbon and inorganic carbon), or by purging inorganic carbon from the sample before oxidation. While purging may entrain organic molecules, such purgeable organic carbon is present in negligible quantities in water for pharmaceutical use.

When testing water for quality control purposes, ensure that the instrument and its data are under appropriate control and that the sampling approaches and locations of both on-line and off-line measurements are representative of the quality of the water used. The nature of the water production, distribution, and use should be considered when selecting either on-line or off-line measurement.