Page 116 - Assurance of Sterility for Sensitive Combination Products and Materials

100 Assurance of sterility for sensitive combination products and materials

validate those tests, scientists and regulators concluded that integrity testing
of seals and closures and separate microbial barrier testing of porous mate-
rials is significantly more reliable [49, 50].
Tallentire and Sinclair developed a fundamental understanding of the
penetration of particulates in narrow channels. By correlating particu-
lates and spores, they concluded, that microbial barrier performance can
be predicted when testing with particles instead of spores [51, 52]. This
created the basis for the development of ASTM F2638 [53]. Herman
and Larsen gave an excellent overview on these developments [54]. After
the method was recognized by the FDA in 2013 [55], DuPont used it
extensively for equivalence testing comparing data of “transition” Tyvek
produced on the newer manufacturing lines and” legacy” Tyvek pro-
duced on the older manufacturing lines within the framework of the
medical packaging transition project. The method is accepted by many
authorities such as Health Canada, notified bodies in Europe, CFDA in
China, and others.
Research in whole package testing is still active, despite the issues de-
scribed above to validate these methods (see Dunkelberg et al. [56–58] or
Severin et al. [59]). Current research explores the challenges of microbial
ingress testing from aerosolization. The goal of this research is to arrive at
a barrier method that allows the user to control the other variables such as
pressure, humidity, and temperature. This ability allows the user to design
experiments to qualify their packaging systems under ‘real-life’ conditions.
The main challenge to this research is the variation of the input variables
such as specific organisms, as well as process variables such as microbial
growth and recovery. While variability is an issue, the inability to detect
critical size holes continues to be the main issue for validation. With new
technologies, research will probably continue, however, these methods will
likely remain fundamental research tools rather than useful tests for packag-
ing validation purposes.

5.3.3.4 Seal strength test methods
Seal strength is a critical quality attribute for the validation and control of
sealing processes. Meeting a defined mechanical strength of seals can be
important for compatibility with sterilization processes, and is certainly im-
portant for a package being able to withstand the stresses of transport and
handling. Two test methods are mainly used in the industry, ASTM F88 [60]
and according to the annex D in EN 868-5 [61] which will also refer to
ASTM F88 in its new version (Fig. 5.6 and Table 5.6).