Page 228 - Assurance of Sterility for Sensitive Combination Products and Materials

Risk to the patient—Quantifying assurance of sterility 207

7.6 Conclusion
This chapter places the quantification of patient risk in perspective across
several industry sectors and in perspective relative to real-world infection
rates in health-care facilities. Terminal sterilization is the preferred approach
to minimizing the risk of infection due to bioburden on health-care prod-
ucts and has served the industry well for decades. Terminally sterilized prod-
uct is packaged before sterilization and, if the packaging is developed and
validated as per ISO 11607-1 and 11607-2, sterility is assured for the life-
time of the product As per ISO 13408-1, if terminal sterilization cannot
be applied due to deleterious effects on product, aseptic processing may be
applied. Aseptic processing has also served the industry well for decades. As
per ISO TS 19930:2017, if terminal sterilization cannot be applied due to
deleterious effects on product, another option can be utilized in addition
to aseptic processing, a risk-based use of alternative SALs (PNSU*s in this
chapter).
−6
The use of a terminal sterilization SAL (PNSU*) of 10 has historically
been deemed necessary, in general, because when attempting to set suitable
microbial limits or standards for medical devices, the industry is faced with
multiple and varied factors impacting safety, and cannot define precisely
what level and types of product bioburden represent a hazard and what is
safe [5]. A view across industry sectors, however, and a risk-based approach
provides a new opportunity to manage risk effectively while creating new
opportunities for new products and technologies.
The use of packaging standards to ensure robust processes to maintain
sterility, and the use of sterilization standards to achieve terminal sterilization
or validated aseptic manufacture of sterile product, has been demonstrated
by history to achieve appropriate controls and consistently sterile product as
intended. This is despite using quantifiable processes and sample sizes which
do not always statistically achieve the intended PNSU*. However, a rigid
implementation of the terminal sterilization expectation of a 1 in a million
PNSU* has unintended consequences. The need to achieve a PNSU* of
−6
10 can limit the development and introduction of new sensitive combi-
nation products, pharmaceutical, or biologic products. The result may be a
reduced benefit to the patient and the inability to address unmet clinical
−4
needs. The use of higher PNSU*s, for example, 10 , however, can main-
tain acceptable risk and provide access to new technologies with minimal
impact to the patient based on the potential of infection from a contami-
nated device. Data and analysis of this chapter demonstrate the added risk