eBook: TOC and Microbial Detection Monitoring - 13

Continuous TOC Monitoring for Real-time Release

4. Instrument selection
Continuous on-line TOC measurement for real-time
release of Pharmaceutical Water(s)
Once applicable regulatory requirements have been satisfied, users can access additional guidance into operation
and control of the water system through recommendations
and best practices from third party organizations and
professional journals. These resources promote different
strategies to help ensure end-product safety. Many of the
strategies promoted in these resources rely on a detailed
understanding of how each process application behaves
throughout the manufacturing process.
In order to best follow non-regulatory advice on ensuring
end-product safety, continuous measurement of TOC and
conductivity with the fastest response possible can allow for
the most complete, rapid, and reliable indication of trends,
changes, or upsets within a water system. Full transparency
into the behavior of the water system will provide the highest
level of confidence to the user to maintain process control and
end product quality. Combined with continuous analysis,
advanced features such as change in TOC per hour, peak,
average, and minimum TOC levels offers a data-rich system
to fully enable a quick and easy assessment of the health of
a water system. This will allow the user to anticipate trends
and proactively respond to developing changes.
However, several on-line TOC instruments available today
still utilize a batch measurement technique. In contrast
with continuous analysis, the batch method provides
only a single TOC measurement that persists on the
instrument display and any digital or analog signal outputs until the next measurement cycle is completed,
potentially many minutes later.
During routine, stable, in-specification operation of the
water system, a delay of several minutes may not
significantly limit or restrict reliable process control. However,
at the time of a water system excursion, only a continuous
measurement will provide a complete picture of the event,
including critical diagnostic data such as the precise time
it occurred, rate of change in TOC, duration, and profile of

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METTLER TOLEDO White

Paper

the upset to fully understand the nature of the disruption.
By clearly providing a detailed view of the excursion, a
continuous measurement allows for better characterization of the event, enabling better understanding of possible
causes. In addition, the fast measurement response provided by many continuous analysis instruments gives
rapid indication that an event has occurred so that prompt
corrective action can be taken.
Over the course of several minutes, a batch instrument will
only provide a single delayed measurement. As a result,
these instruments severely risk missing valuable diagnostic information to aid with system fault analysis when a
disruption occurs, which can limit the ability to rapidly and
accurately identify the cause. For example, a short-duration event, such as back-flow contamination from a pointof-use, can be missed entirely.
Complete regulatory compliance for TOC and conductivity
The 6000TOCi Sensor from METTLER TOLEDO Thornton
represents the latest advance in continuous, on-line TOC
measurement. Benefiting from decades of METTLER
TOLEDO's experience in ultrapure water analytics and
more than ten years in TOC instrumentation design, the
6000TOCi integrates new, advanced features to support
real-time release of water. Fully compliant with all major
global pharmacopeias, the 6000TOCi is the ideal solution
for any application where reliability, ease of use, and
real-time release and process control are desired.
Designed for ease of integration into a complete water
system instrumentation platform, the 6000TOCi along with
the M800 Transmitter represent a multi-channel, multiparameter system which simplifies integration of TOC and
conductivity measurements. Simultaneous indication of
both TOC and conductivity (provided by the conductivity
sensors in the 6000TOCi) means the 6000TOCi and M800
address two of the regulated compendial parameters for
bulk pharmaceutical water measurements, while still supporting additional TOC sensors or the use of other analytical
measurements such as dissolved ozone.

eBook: TOC and Microbial Detection Monitoring

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