Suez Total Organic Carbon - March 2020 - 19

The vast majority of online TOC instruments employ conductivity
as a means to measure carbon. Sievers TOC Analyzers, such as
the Sievers M9, are carbon analyzers, wherein a gas-permeable
membrane separates interfering compounds from CO2 to allow for
accurate measurement of carbon. This technology instills confidence
in the accuracy and precision of the measurement.
Sensors work by measuring conductivity pre-oxidation and postoxidation. While many TOC instruments measure conductivity preand post-oxidation in some manner, sensors measure the resultant
conductivity without any level of discrimination against interfering
ions. The difference in conductivity is attributed to TOC, even though
other species (not carbon) may be contributing to the measurement.
This leads to over- or under-reporting when interfering substances,
often present in cleaning processes, are in the sample (Figure 1).

the SUEZ solution
Together, total organic carbon, inorganic carbon, and conductivity
provide a comprehensive understanding of a cleaning process. These
three attributes can be assessed collectively to optimize, troubleshoot,
or investigate out-of-specification (OOS) results. Once control ranges
of each attribute are established from validated data, departure
from process control or specification can be quickly identified and
corrected. Data can be used together to determine possible root
cause as shown in Figure 2.

Figure 2. Collectively TOC, inorganic carbon, and conductivity
improve detection of out-of-trend results as well as focusing root
cause investigations.
Figure 1. APIs, degradants, cleaning agents, or excipients could also
be present in a rinse sample. Molecules bonded to organic carbon
molecules are also subject to oxidation.
With sensor technology, not only is there a risk of false reporting,
but sensors can present compliance and efficiency concerns when
attempting calibration, qualification, or maintenance. For example,
sensor methods cannot be validated per ICH Q2 (R1) when attempting
to demonstrate linearity and specificity. Analytical method validation
is a critical component needed to use data for cGMP release.
Calibration, system suitability, and maintenance can be lengthy
processes, requiring attachments or even shipment of an instrument
to the manufacturer. Sievers M9 maintenance, calibration, and system
suitability are entirely self-contained with field support for onsite
validation, maintenance, and troubleshooting activities.
The Sievers M9 reports validated and accurate TOC data in addition
to simultaneously quantifying inorganic carbon and conductivity.
Having data on these three quality attributes offers a robust view into
a cleaning process.

To demonstrate M9 integration and communication with a CleanIn-Place (CIP) skid for real-time, online analysis and data reporting,
a Sievers M9 Portable TOC Analyzer was integrated with a CIP skid
in SUEZ's UltraFlow 45 CIP Skid in SUEZ's Analytical Instruments
development laboratory in Boulder, Colorado (Figure 3).
Flow, pressure, timing, and cleaning methods were adjusted to mimic
common cleaning processes used by manufacturers. The resulting
solutions address complex sampling logistics that companies face.
Whether they are time, volume, or pressure constraints, the Sievers
M9 can be successfully integrated and automated with SUEZ kits
for either pressurized sampling or non-pressurized sampling. It is
also important to note that the M9 Portable Analyzer is the same
technology as the M9 Laboratory Analyzer. When moving from lab
analysis to online, like-for-like M9 technology streamlines the method
transfer process and eliminates the need for a full method validation.

mitigating contamination
Following sample analysis, it is important to consider the risk of
microbial contamination in the sample flow path and take measures

Suez Total Organic Carbon - March 2020

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