Page 257 - Assurance of Sterility for Sensitive Combination Products and Materials

234 Assurance of sterility for sensitive combination products and materials

The choice of an alternative SAL and the support of that choice depend on
risk assessment and the applicable regulatory authority. The document does,
however, provide much guidance associated with options for achieving a
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maximal SAL of 10 . Some of the options presented in the document that
might be pursued in determining whether a product can be sterilized to a
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maximal SAL of 10 include assessment of product design, materials, vali-
dation approaches, sterilization methods, and bioburden reduction. One or
more of these options might allow a sterilization process that can achieve a
−6
maximal SAL of 10 .
A significant inclusion in the document is a flow chart that guides the
user through the process of determining whether a product can be steril-
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ized to a maximal SAL of 10 and, if not, what should be done to support
the selection of an alternative SAL. Risk management is a main theme in
supporting the choice of an alternative SAL and guidance is given for areas
to be addressed, including risk management considerations and risk man-
agement output. In addition, ISO TS 19930 contains a section on Label
Claims that discusses the regulatory requirements that apply for a product
to be labeled sterile and again emphasizes that labeling a product as sterile is
typically subject to national or regional regulations or standards.
The ISO TS 19930 guidance points out that clinical benefit must be
weighed against other technical and logistical factors in order to determine
whether a product can or should be sterilized to a maximal SAL other than
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10 SAL.
9.5.4 Documents pertaining to aseptic processing
and assurance of sterility

The introduction of ISO 13408-1, as well as the decision tree provided in
the EMA guidance on sterilization of medicinal products, clearly indicate
that terminal sterilization is the preferred method of providing assurance of
sterility, and, if terminal sterilization cannot be achieved, aseptic processing
should be used. Terminal sterilization is preferred because it applies a pro-
cess that inactivates microorganisms rather than using procedures that pre-
vent the introduction of microorganisms. Consequently, an active process
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−3
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that ensures a maximal sterility assurance level of 10 , 10 , or 10 could
be considered as an option to using aseptic processing.
9.5.5 ISO 13408 series
The ISO 13408 series of standards specifically addresses aseptic process-
ing and the many requirements associated with that approach to provide