Page 23 - Application Handbook - TOC

Sum parameter – Total Organic Carbon
TOC –Determination in cleaning
validation - swab method
SCA-130-203
Cleaning validation substantiates the
effectiveness of a cleaning process and
ensures that no residues remain on the
surfaces of the production equipment. For the
detection of contaminations, validated
analytical methods must be used that are
sensitive enough to determine the defined
acceptable residue level. In general, residue
limits of 10 ppm or 1/1000 of the usual
therapeutic dose of an active substance are
used as acceptance criteria.
■ Cleaning methods: Clean out of Place
For COP cleaning, the entire production
system must be disassembled and the
components must be cleaned individually.
This procedure is very time consuming and
labor intensive. Due to the individual
cleaning, this procedure cannot be
standardized. Advantages are, however, the
low investment costs of the system and the
possibility of visual inspection.
■ Sampling and analysis
In COP cleaning, the wiping method (swab) is
used for sampling of visible residues. These
include coatings, crusts, material deposited in
corners and edges, and especially poorly
soluble substances. The swab can be
extracted in a solvent and the extracted
solution is subsequently analyzed. If water is
used for extraction, TOC analysis is suitable
for subsequent analysis. Alternatively, the
swab can also be measured directly (using a
carbon-free swab) using a TOC solid-sample
module.
■ Measuring system for the swab test
The modular design of Shimadzu’s TOC-L
series now enables the additional
determination of the swabs using the same
instrument. For this purpose, a solid-sample
module (SSM-5000A) was connected to the
main instrument, either a TOC-L series
combustion system or the wet-chemical
model of the TOC-V series.
For TC determination, the swab is placed in a
ceramic boat and transferred into the oven,
which is heated to 900 °C.