Page 17 - 2_Pharmaceutical industry

Sum parameter – Total Organic Carbon
TOC – Determination according to USP 661.2
Testing of Plastic Packaging Systems and their
Materials of Construction
SCA-130-208
In the pharmaceutical industry plastic
packaging is used in various forms – for
example for intravenous bags, bottles,
cartridges or pre-filled syringes. The
packaging must be tested for suitability for
these uses. It is published in USP 39-NF34,
which will be valid from May 2016.
Besides to the change of the title “Plastic
Packaging Systems and their materials of
Construction”, two new chapters are
established.
This application note is related to the second
chapter 661.2.
■ 661.2 Plastic packaging system
This chapter deals with the required testing of
the final packaging system since packaging
often consists of than one plastic material.
Characterization takes place by identifying
and determining the biocompatibility, general
physicochemical properties and Additives.
The TOC Parameter as an indicator for
extractable organic material is part of the
physio-chemical characteristics that must be
determined.
For testing the packaging system, it is filled
with ultra-pure water, sealed and heated in an
autoclave. The temperature and dwell time
depend in the plastic used. In order to
determine the blank value, ultra-pure water is
poured into a glass flask and heated to the
same temperature. The TOC of both solutions
is determined. The difference between the two
measured TOC values should not exceed
8mg/L.
■ TOC determination in pharmaceutical
application
The TOC determination is performed
according to the USP<643>. This regulation
describes the TOC determination for pure
water, purified water and water for injection. It
does not prescribe any particular oxidation
technique for TOC determination.
The TOC systems, however, must be able to
differentiate between inorganic and organic
carbon. This can be carried out either via
removal of the inorganic carbon (NPOC
method), or via a separate determination
(difference method). The limit of detection for
TOC should be at least 0.05 mg /L. The
applicability of the method must be determined
via a system suitability test.
However, material extracts may have TOC
values that are higher than those of purified
water because of extracted organic
substances.
Thus the TOC analyses performed should
have a limit of detection of 0,2mg/L and should
have a demonstrated linear dynamic range
from 0,2 – 20mg/L.