TOC (Total Organic Carbon) Testing − Essential to Quality Manufacturing of Pharmaceutical, Nutraceutical, and Cosmetics Products

All pharmaceutical, nutraceutical, or cosmetics manufacturers can benefit from Total Organic Carbon (TOC) testing which should be considered an essential part to ensuring the quality of your product manufacturing process.  Here we discuss proper TOC testing and will also reference the appropriate USP (United States Pharmacopeia) standards for conducting such testing.

What is TOC testing?

The element most essential to just about any manufacturing process is water. Traditionally, TOC testing has had a long history of being used as a method to measure water quality for the drinking water purification process. For example, increasing levels of the amount of Natural Organic Matter (NOM) has been shown to increase the levels of carcinogens in processed drinking water which TOC testing detects quite well.  However, beyond drinking water, the quality of the water you use in manufacturing will dramatically affect the quality of a pharmaceutical, nutraceutical or cosmetics products you are producing.  Therefore, TOC is the total amount of carbon bound in an organic compound and is used as a non-specific indicator of water quality or cleanliness in your product manufacturing process.  In addition to the USP, (with specific reference to USP General Chapter <643>), the EP (European Pharmacopeia) and JP (Japanese Pharmacopeia) also recognized TOC as a required test for purified water as well as for WFI or (Water For Injection). As the USP states: “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 proceed control attribute to monitor the performance of unit operations comprising the purification and distribution system.”  At NJ Labs we have also noticed that customers will ask us to perform TOC testing for measuring low Total Carbon Content <500 ppb in a production batch; measuring organic molecules or contaminants; or finally for cleaning validations.

What is TOC sampling & how is the test performed?

The determination of TOC involves sampling, oxidizing organic carbon in that sample, and detecting the oxidized carbon result in units of mass of carbon per volume of the sample.   There are several methods of oxidizing samples that can be used, depending upon the nature and concentration of TOC being measured, analytical requirements and the instruments being used for the TOC analysis.  Such methods include:

• High temperature combustion measured by non-dispersive infrared absorption (NDIR)
• High temperature catalytic oxidation with a platinum catalyst followed by NDIR
• Thermo-chemical oxidation
• Photo-chemical oxidation with UV and a chemical oxidizer
• Photo-oxidation via UV light or with the use of a catalyst

The sampling methods above describe the methods in which TOC testing can be performed.  In practice, the actual test formula is to subtract the IC (Inorganic Carbon) from the total carbon in the sample.

Studies have shown and our experience at NJ Labs concurs that the photo-oxidation method via UV light is the most reliable and accurate method for performing TOC tests and determining TOC levels.

What is a TOC Analyzer?

Total organic carbon analyzers measure the amount of organic, inorganic, or total carbon in water samples.  This works by oxidizing the organic compound into a form which can be quantified. Oxidizing organic carbon produces CO2, which can then be measured and converted into a TOC value or measurement.   At NJ Labs, we perform TOC analyses using the state-of-the-art Fusion Analyzer from Teledyne Tekmar. This is a modern laboratory instrument designed to determine the carbon content in water and other materials. Using safe and proven Ultra Violet (UV)-promoted persulfate oxidation of carbonaceous material to carbon dioxide followed by Non-Dispersive Infrared (NDIR) detection of the CO2 product, the Fusion is sensitive from 0.2ppbC – 4,000ppmC. Varieties of carbon can be independently determined by selecting a pre-defined instrument method. These include: Total Carbon (TC), Inorganic Carbon (IC), Total Organic Carbon (TOC), and Non-Purgeable Organic Carbon (NPOC). The Fusion is a state-of-the-art analytical instrument designed to detect, with accuracy, carbon down to the ppt level. It uses a UV oxidation reactor, which is a relatively new technology that allows a degree of sensitivity previously unattainable.

Conclusion on TOC Testing for the Pharmaceutical Industry

TOC testing is essential in the pharmaceutical industry for inspection of ultrapure water and evaluation of cleaning effectiveness. TOC has also found wide acceptance in the biotechnology industry to assist in cleaning validation procedures, especially Clean-In-Place (CIP) procedures. NJ Labs follows strict USP set parameters – inbuilt USP specs that we cannot change.

In addition to the many controls we have put in place, our scientists went through extensive training with the manufacturer.  We know the ins and outs of this instrumentation and we have become very familiar with the nuances of precise TOC testing. We are not just operators of this sensitive instrument but have a relationship with it. We are very confident in our performance and our capabilities to measure USP grade level accurately. By ensuring the water is the quality it should be, it will assist in maintaining the integrity of the your products.  In conclusion: The basics of the water used to clean, rinse, as well as to be used in production is very critical to the function of any manufacturer.