Suez Total Organic Carbon - March 2020 - 12

application note

recovery of complex compounds with TOC:
cleaning agents
introduction
The goal of any cleaning validation program is to reduce the
opportunity for product contamination or compound carryover that
may be present on production equipment. The validation of this
type of process must prove that the cleaning process consistently
removes product residue, process soils, potential contaminants, and
excipients. It must also remove any degradants from cleaning agents
and the cleaning agents themselves.
Aqueous cleaning agents come in two forms, alkaline or acid, and are
considered one of the four primary cleaning parameters of a cleaning
process. The critical parameters of cleaning are often referred to
as time, action, concentration, and temperature (TACT)- where
the cleaning agent's primary function is to create a "degradation"
environment of all the process or product soils. Because of the
degradation of these materials, the most common industry practice is
to use Total Organic Carbon (TOC) as the analytical method to indicate
removal of these compounds and the cleaning agents. Cleaning
agents typically contain a very small amount of carbon (anywhere
between 5-10%).
This application note investigates the appropriate steps to recover
a complex compound like alkaline cleaning agents and can be used
as a template for feasibility testing or method validation elements as
discussed in ICH Q2(R1).

TOC analysis for cleaning validation
Alkaline cleaning agents have been used to clean production
equipment in the pharmaceutical, biopharmaceutical, cosmetic,
medical device, dietary supplement, dairy, and food and beverage
industries for decades. TOC analysis is a reliable measurement tool
to measure and control how well the cleaning parameters (TACT) are
performing. More specifically, TOC analysis may be used to measure
the amount of organic residue that alkaline cleaning agents can leave
behind on the surfaces of the equipment that are being cleaned.
Analytical technologies used to measure TOC share the objective
of completely oxidizing the organic molecules in a sample to

carbon dioxide (CO2), measuring the resultant CO2 concentration
and expressing this response as carbon concentration. A variety of
laboratory and online technologies are available to measure TOC.

Sievers* TOC technology
The unique Sievers Membrane Conductometric detection method
has proven to be an extremely reliable technique for measuring
TOC. The Sievers technology uses a gas-permeable membrane
that selectively passes only the CO2 produced from the oxidation
of organics. By preventing compounds such as acids, bases, and
halogenated compounds from interfering with the measurement of
CO2 from oxidation, the Membrane Conductometric method delivers
unmatched sensitivity, selectivity, stability, accuracy, and precision.

preparation of cleaning agent test standards
To test the recovery of alkaline cleaning agents with Sievers TOC
Analyzers, stock solutions were created at various concentrations
from 300 ppb C to 5 ppm C. This was done following recommendations
of ICH Q2(R1) which emphasizes analyzing at least five concentrations
for a linearity test and determining accuracy and precision during
method validation.
100 ppm C stock solution: Approximately 1.5 g of the alkaline cleaning
agent was weighed into a cleaned, rinsed, and dried 500-mL glass
volumetric flask. The cleaning agent was diluted to volume in the
flask with low-TOC water (<50 ppb C). The MSDS of this cleaning agent
indicated that it contained 3% carbon, and the molecular weight of
the cleaning agent was 500 g. The conversion factors provided an
accurate stock solution of 100 ppb C. This stock solution was used for
5 ppm C, 3 ppm C, and 1 ppm C spikes.
10 ppm C stock solution: The 100 ppm C stock solution was then diluted
by a factor of 10 to prepare the 10 ppm C stock solution for lower
concentrations for the study. This was done by weighing approximately
10 g of the 100 ppm C stock solution into a 100-mL volumetric flask.
The solution was then diluted to volume in the flask with low-TOC
water for the spikes of 500 ppb C and 300 ppb C.
*Trademark of SUEZ; may be registered in one or more countries.

12
Suez Total Organic Carbon - March 2020

Table of Contents for the Digital Edition of Suez Total Organic Carbon - March 2020
