Page 13 - Assurance of Sterility for Sensitive Combination Products and Materials

Introduction: Sterilization or aseptic processing of single use 3

Contamination rate is used to describe the results of process simulations
in aseptic processing validations.
The definition of SAL is the probability of survival of a single micro-
organism. Microbiological reduction associated with terminal sterilization
processes is expressed by an exponential function. The values of SAL and
PNSU are a negative power to the base 10. All of the terminal sterilization
methods explicitly use the term SAL and this mathematical construct in
the validation scheme. This construct differs from the term PNSU, which is
based on a product being non-sterile, whether due to a single microorgan-
ism or multiple microorganisms.
Typically, the first step in the development of a new product is under-
standing patient needs. Based on this information, an initial product design
is developed, and integral to the product design is the determination of
whether the product can withstand a terminal sterilization process. This
is particularly challenging for combination products because of the need
to use different materials that might not be suitable for traditional over-
kill sterilization processes. Materials such as active electronics, bioresorbable
materials, and biologics are particularly challenging. The option of aseptic
processing can be considered after demonstrating that the product cannot
be terminally sterilized. The regulatory agencies and industries are adapted
to accommodate sterilization challenges of combination products that can-
not be terminally sterilized by developing aseptic processing standards for
solid combination products (e.g., ISO 13408-7). Chapters in this book ex-
plore the options for both terminal sterilization and aseptic processing, as
well as the selection of an alternate SAL for those products that cannot be
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terminally sterilized to an SAL of 10 .
The underpinning behind the development of sterilization modal-
ities, aseptic processing, packaging, and healthcare acquired infection is
the concept of infection risk to the patient. The independent evolution
of the sectors resulted in different methods and vocabulary to quantify
the risk. A fundamental statistical approach is presented to attempt to
bridge these assessments. The goal of the Risk to Patient chapter is to
open the dialog between groups so that informed scientific-based deci-
sions can be made.
Regardless of the method of providing a sterile product—terminal
sterilization or aseptic processing—the primary packaging is required to
maintain the integrity of the sterile claim. Primary packaging is intended
to provide the sterile barrier throughout the product shelf life, including
handling and distribution activities. Packaging for a combination product