Total Organic Carbon (TOC):
Back-to-Basics
Total organic carbon (TOC) and conductivity data are used in various life sciences
applications to confirm purified water chemical purity, and demonstrate equipment
cleanliness, process understanding, and process control.
What is TOC and what are the different methodologies for measuring it?
Total organic carbon and conductivity analysis aids in detecting
chemical impurities in pharmaceutical grade water systems and
process equipment. Using TOC to understand the comprehensive
cleanliness of water and equipment allows manufacturers to
consistently deliver safe, high quality drug products. Many TOC
technologies work by oxidizing organic molecules using UV or
chemical oxidation and measuring the resulting CO2.
When choosing a technology, it’s important to ensure the
technology is fit for purpose and satisfies user and regulatory
requirements for accuracy, precision, specificity, quantitative
data, and other important validation requirements. With
Sievers* Membrane Conductometric detection technology,
you can obtain a true measurement of carbon without the
risk of interfering compounds affecting accuracy. Check if your
instrument discriminates between inorganic carbon that may be
present in the sample and the CO2 generated from the oxidation
of organic molecules in the sample, as required by USP <643>.
Why is TOC important?
TOC and conductivity are metrics that and control. TOC and conductivity data help
manufacturers must monitor to comply facilitate improved process understanding,
with regulations such as USP <643>, USP process control and product quality. TOC
<645>, and other harmonized compendia, data can be used in a variety of applications
but compliance is only the beginning. to increase efficiency and reduce resources
They also allow water users to go beyond with automation. When using accurate and
compliance and achieve optimization reliable technology, TOC is a valuable tool.
Is measuring TOC suitable for all compounds, APIs, excipients and detergents?
Many different compounds can be measured with TOC analysis for cleaning validation and verification,
including APIs, detergents, degradants, and excipients. Robust recovery studies performed during method
development and validation can confirm suitability of TOC for your needs.
Water soluble compounds can be analyzed using TOC analysis with little to no method
variation. Compounds that do not readily solubilize in water can still be detected using
small adjustments such as: agitation, pH, or temperature. With Sievers TOC Analyzers,
consumables, and expertise from Veolia, you can be confident your method development
will go smoothly.
300 00257 EN Rev. A
In cleaning validation, TOC, inorganic carbon and conductivity
viewed together can provide an all-inclusive understanding of
cleanliness.
Rather than looking for a single API, using TOC and conductivity
data together encompasses APIs, detergents, degradants, and
excipients that would otherwise go undetected.
What are the best practices using Sievers instruments for TOC and
conductivity analysis?
■ Sampling can vary from analyst to analyst so extensive training
should be conducted and documented to limit sample variability,
especially when using swabbing techniques for cleaning validation.
It is also important to avoid interfering chemicals that could
contaminate the samples.
■ Choosing consumables that are high quality and appropriate
for the application is critical to accurate TOC and conductivity
measurements. In addition to providing specialty vials and a wide
range of accredited certified reference materials, Veolia provides
customized reference standards for unique applications.
■ Determine a system suitability and verification procedure and
frequency that’s justifiable and risk based. System suitability assesses
relative recovery of two compounds, sucrose and benzoquinone,
and is required to be performed on some frequency which should be
determined internally based on risk of failure.
*Trademark of Veolia; may be registered in one or more countries. ©2023 Veolia. All rights reserved. 300 00257 EN Rev. A
■ Run a single point verification at or near points of interest to verify
accuracy.
■ Establish and validate appropriate flow rates for consistent and
defendable methodology. When analyzing cleaning validation
samples, higher TOC levels are generally expected and therefore, it
is recommended to determine the appropriate amount of chemical
oxidation.
■ When validating TOC methodology, ICH Q2 (R1) should be referenced
for requirements. Similarly, when looking to qualify the instrument
itself, USP <1058> Qualifying Analytical Instruments, should be
referenced for the highest degree of confidence in instrumentation,
methodology, and validation.
Learn how TOC can help improve your process by contacting Veolia
300 00257 EN Rev. A
