Suez Total Organic Carbon - March 2020 - 11

TOC for Compendial Water Testing and Cleaning Validation;
Comparison of Laboratory, At-Line, and Online Analysis
Michelle Neumeyer
Life Sciences Product Applications Specialist

Michelle Neumeyer is the Life Sciences Product Applications Specialist for the Sievers line of analytical instruments at SUEZ.
Previously, Michelle has worked in Quality at Novartis and AstraZeneca, ensuring compliant water systems, test methods and
instrumentation. Michelle has a B.A. from University of Colorado, Boulder in Molecular, Cellular and Developmental Biology.

Total organic carbon (TOC) and conductivity testing are important quality
control measures for ensuring water purity and equipment cleanliness
and can be deployed to accommodate various sampling scenarios and
efficiency needs. TOC and conductivity analysis help manufacturers achieve
compliance to USP <643> and USP <645>, or with process control needs.
While conductivity is traditionally measured with a meter and probe,
advanced TOC technologies can also offer conductivity measurements
simultaneously with TOC analysis. The three common deployments of TOC
technology are laboratory, at-line, and online analysis. When choosing
which strategy and deployment are best for a unique application, consider
the following to ensure you get the most out of the technology.
Laboratory analysis: TOC and conductivity analysis are routine tests that
can be found in most Quality Control (QC) laboratories supporting cGMP
operations. Benchtop TOC analyzers and software are available that allow
users to stack protocols, run system protocols, run large volumes of
samples at a time, manage data, and electronically sign and export data.
Whether the TOC analyzer is being used for cleaning samples or water
monitoring, efficiency is an important factor for most laboratories. For
example, companies can now implement a "lean lab" solution that allows
for simultaneous TOC and conductivity analysis from a single vial. Specialty
vials are used to prevent ionic leaching from the vial surface and to prevent
atmospheric CO2 from dissolving into the sample. Both of these factors
can cause over-reporting of conductivity. Traditional measurement of
conductivity using a meter and probe can also introduce atmospheric CO2
from having an open sample container while the measurement stabilizes.
Meter and probe analysis is a very time-consuming methodology that
requires analysts to test one sample at a time, wait for a stable reading,
and then manually transcribe the data. Simultaneous TOC and conductivity
testing ensures a lean lab and provides confidence in the data and data
integrity while avoiding contamination risks. Whichever laboratory method is
deployed, it is critical to have a properly calibrated and validated instrument
if supporting cGMP operations. With laboratory analysis, it is inevitable that
grab samples must be taken from equipment or purified water points of use.
Additionally, QC laboratory workflow can take time - which is not conducive
to efficient cGMP equipment turnover. With high frequency and high sample
throughput, at-line or online analysis may satisfy the demand for efficiency
gains in a monitoring program.
At-line analysis: At-line analysis can greatly increase process efficiency,
particularly in a cleaning validation program with time constraints. At-line
deployment uses a portable TOC analyzer located directly next to the process
to be monitored. Once the cleaning process is complete, required samples
are taken and can be analyzed almost instantaneously. This deployment is
most successful for cleaning validation samples, particularly swabs, for
monitoring time-critical operations. The laboratory workflow can be slow
and clunky, creating unwanted equipment downtime. Coordinating activities
with QC, sampling, analysis and release of data can leave equipment sitting
idle for periods of time. To turn around equipment faster following cleaning,
at-line analysis allows samples to be taken and immediately analyzed on

a portable TOC analyzer located within reach. From there, swab and rinse
sample results can be generated and reviewed within minutes, avoiding
any delays from the QC workflow and reducing equipment hold times.
At-line monitoring can provide efficiency gains for the right application
in comparison to laboratory analysis. At-line avoids QC workflow and
generates data within minutes following sample collection. For even greater
efficiency, online analysis can enable real-time release of cGMP equipment
and elimination of sampling activities all together. While at-line is a good
fit for many applications, it limits the number of samples to be analyzed
at a given time, which online analysis can overcome. Additionally, taking
grab samples represents a single timepoint. To get multiple timepoints
and a greater understanding of a process, online analysis may be the best
deployment, generating multiple data points over time.
Online analysis: A pain point of cleaning validation is equipment downtime
due to the work involved in sampling and sample analysis, as mentioned
above. While time constraints can be improved upon with at-line deployment,
online deployment facilitates instantaneous data generation and equipment
turnover. Equipment downtime can be reduced from days to minutes with realtime release using data from a TOC analyzer integrated directly onto a CleanIn-Place (CIP) skid. Programmed automation diverts CIP rinse samples from
the skid directly to the analyzer for analysis. The samples are analyzed, and
data are automatically exported to the site data host. Online analysis is gaining
momentum for cleaning validation for efficiency and quality gains, but it has
been steadfast for compendial water testing. Online TOC and conductivity
testing for purified water allows for reduction or elimination of point-of-use
water sampling. Online analysis makes out-of-trend results highly detectable
in real time, thus allowing for preventative and corrective actions. Whether
for cleaning validation or compendial water testing, it is important to consider
like-for-like technology to traditional laboratory analysis when moving to
online analysis. Using the same technology online as is used in established
laboratory methods simplifies the method transfer process. Rather than
executing a full-blown method validation, an equivalency protocol can be
performed to demonstrate suitable methodology from laboratory to online
using the same validated technology.
Whether deploying laboratory, at-line, or online TOC analysis, consider
your goals around efficiency, analytical performance, and data integrity.
Equipment that can provide high accuracy, precision, and data integrity
while offering opportunities to save you time will be the most valuable to
your monitoring programs. While conductivity testing is often performed
in the lab with a meter and probe, advances in analytical testing now
enable conductivity to be measured simultaneously with other parameters
to offer greater automation. TOC and conductivity are important quality
metrics to understand and control the chemical purity of purified water and
cleanliness of equipment. Advances
in technology now allow TOC and
conductivity monitoring to be faster
and more reliable than ever.


Suez Total Organic Carbon - March 2020

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