Page 242 - Assurance of Sterility for Sensitive Combination Products and Materials

218 Assurance of sterility for sensitive combination products and materials

if the natural bioburden is more susceptible to the sterilant than a biolog-
ical indicator. The guidance documents for all sterilization processes (ISO
11135, ISO 11137, ISO 17665, or ISO 20857) have bioburden-based meth-
odologies, but the additional characterization of the natural bioburden pop-
ulation is more resource intensive and costly.
Finally, an alternative option is to sequentially reduce bioburden. This
is especially effective if the bioburden is due to incoming material that is
outside of the immediate control and the sensitive components are added
later in the process. This strategy involves identifying the major sources of
bioburden, isolating those components, and presterilizing. Overall biobur-
den is reduced if the appropriate controls are implemented during the final
product assembly.

8.4.4 Other SAL options

Alternative SAL strategy development requires the documentation of the
systematic assessment outlined in Sections 8.4.1–8.4.3 to demonstrate a
−6
10 SAL was explored and not technically feasible. This assessment, how-
ever, is only half of the equation. The benefits of the device to the patient
also needs to be identified. A meaningful discussion with regulatory bodies
can only occur after both the risks and the benefits are understood.

8.4.4.1 Identifying the risks
−6
The 10 sterility assurance limit is the gold standard. For some difficult
to sterilize products, this may not be achievable. A systematic approached,
such as strategies out lined in Section 7 of ISO/TS 19930:2017, should be
−6
used to demonstrate a 10 SAL could not be achieved.
8.4.4.2 Identifying the benefits
An informed decision requires both the risks and the benefits to be un-
derstood. The product definition along with how it meets unmet patient
needs must be assessed. What is the purpose of the product and what is the
competitive landscape? What is the indication for use and what is the im-
plication if not treated? Does this improve patient outcome or compliance,
and what is the impact of noncompliance? These key questions enable the
risk to be taken in context.

8.5 Conclusion

The development of sterile single use medical products, both devices and
pharmaceuticals, can have a significant impact on the patient’s quality of