Page 119 - Assurance of Sterility for Sensitive Combination Products and Materials

Package/container closures 103

performance and stability testing. Aspects related to SBS sterility need to
be validated, however, there are elements of the design that can be verified
by checking that design outputs meet design inputs. Key elements include
the qualification of materials including aspects of biocompatibility, package
dimensions, position of the device in the packaging, and the presence of the
label as specified.

5.3.4.1 Material qualifications, chemical, and biological compatibility
ISO 11607-1:2006—Section 5.5 addresses the physical, chemical, environ-
mental, and biological requirements of materials used in the manufacture of
SBSs. Many of these requirements are guaranteed by suppliers of preformed
SBSs. Manufacturers may have to assess certain specific properties them-
selves for material qualification during the qualification of their suppliers or
for routine incoming quality control to satisfy quality management system,
respectively, regulatory requirements.
5.3.4.2 Microbial barrier properties
Porous materials used for SBSs allow the sterilization gases to enter and
exit the package while preventing the ingress of microorganisms based on a
defined porosity. ISO 11607-1 requires that microbial barrier properties are
evaluated to be adequate, without further indication about what “adequate”
means. As a horizontal standard, ISO 11607 “Packaging for terminally sterilized
medical devices” applies to a wide range of different sterile barrier solutions,
which could be small or very large, and which could be used in very dif-
ferent environments and conditions over shelf lives ranging from months
to decades. This evaluation will be dependent on the specific application,
the targeted environment, the analysis of risks, and the specific regulatory
requirements. The new upcoming European MDR [67] requires risks to be
“acceptable” and “compatible with a high level of protection of health and safety,
taking into account the generally acknowledged state of the art.” It requires also to
eliminate or to reduce as far as possible the risk of infection to patients and
to design to “prevent microbial contamination of the device or its content such as
specimens or fluids.”

5.3.4.3 Biological compatibility and toxicological attributes
It is a regulatory requirement to demonstrate the compatibility between
the sterilized device and the impacted biological tissues of the patient. This
includes the impact of the packaging in contact with the device. Plasticizers,
additives, impurities, residues of polymer catalysts, endotoxins, adhesives,
inks, and particulates that transfer can impact the safety of the device or