USP <643> Total Organic Carbon

USP <643> outlines the method for measuring Total Organic Carbon (TOC) in water used for pharmaceutical purposes. TOC is an indirect measure of organic molecules present in water, quantified as carbon. These organic molecules can originate from the source water, purification and distribution system materials, or biofilm growth within the system. The standard provides guidance on qualifying analytical technologies for TOC measurement and interpreting instrument results for use as a limit test. USP <643> differentiates between limit tests for bulk water, like Purified Water, Water for Injection (WFI) or Water for Hemodialysis at a TOC level of 0.50 mg/L and for sterile water like Sterile Water for Injection, Sterile Purified Water, Sterile Water for Irrigation or Sterile Water for Inhalation at TOC levels depending on the storage container size ranging from 8.00 to 48.00 mg/L.

The primary parameter measured in the USP <643> method is the concentration of organic carbon in water. This is achieved by oxidizing organic molecules in the water sample to produce carbon dioxide (CO₂), which is then measured. The TOC value is obtained by either subtracting the inorganic carbon (IC) from the total carbon (TC) or by purging the IC from the sample before oxidation. The method ensures that the measured TOC reflects the organic content accurately by discriminating between inorganic and organic carbon.The USP <643> method is crucial for several reasons:

1. Quality Control: TOC measurement is essential for ensuring the quality of pharmaceutical bulk water and sterile water. High levels of organic carbon can indicate contamination, which could affect the safety and efficacy of pharmaceutical products.
2. Process Monitoring: TOC serves as a process control attribute, helping to monitor the performance of water purification and distribution systems. Consistent TOC levels indicate that the system is functioning correctly and efficiently.
3. Regulatory Compliance: Adhering to USP <643> ensures compliance with regulatory standards, which is vital for pharmaceutical manufacturers. Non-compliance can lead to product recalls, legal issues, and damage to the company's reputation.
4. Versatility: The method allows for both online and laboratory testing, providing flexibility in monitoring and ensuring water quality. This adaptability is beneficial for continuous monitoring and periodic quality checks. The method is widely used for TOC cleaning validation.

In summary, USP <643> is a comprehensive standard that provides a reliable method for measuring TOC in pharmaceutical water. By ensuring accurate and consistent TOC measurements, it plays a critical role in maintaining the quality and safety of pharmaceutical products as well as the cleanliness of production equipment.

With more than 30 years of experience in TOC analysis Analytik Jena offers customized solutions and expertise for the pharmaceutical industry. With the multi N/C x300 series, we offer a range of high-quality and reliable TOC analyzers following either the high-temperature catalytic oxidation or the UV/wet-chemical sample digestion principle combined with sensitive and selective CO₂ quantification by NDIR (non-dispersive infrared) detection principle. The devices not only meet the requirements of USP <643>, they also fulfill the requirements of EP 2.2.44, JP 2.59 and KP. They also come along with full FDA 21 CFR Part 11 and data integrity compliance.

Sources

• Norm USP <643> Total Organic Carbon