Page 185 - Assurance of Sterility for Sensitive Combination Products and Materials

Risk to the patient—Quantifying assurance of sterility 167

through the analysis of the four illustrative cases provided, a good overview
of the conclusions is provided in Section 7.3.6.
This risk analysis is put in perspective relative to ‘real-world’ infection
rates (health-care facility infection rates, as seen in Chapter 5) in Section 7.4.
Importantly, in none of these four representative analyses does the quanti-
fiable aspect of the respective standard alone provide product sterility as-
surance; assurance of sterility results from compliance to all aspects of the
standard. However, it is helpful to see exactly what the statistically quanti-
fiable aspects of the standards say and do not say about the probability of a
non-sterile unit*, PNSU*. This analysis is particularly helpful as alternative
SALs are likely to be considered more broadly in the terminal sterilization
industry with the publication in 2017 of ISO TS 19930 Guidance on as-
pects of a risk-based approach to assuring sterility of terminally sterilized, single-use
health-care product that is unable to withstand processing to achieve maximally a
−6
sterility assurance level of 10 (see Chapter 9). Patient risk acceptability from
potential sterility assurance risks are assessed in Section 7.5, and conclusions
drawn in Section 7.6.

7.1 Risk concepts applied to sterility assurance
The risk standard ISO14971, Medical Devices—Application of Risk Management
to Medical Devices, provides an excellent framework to evaluate the risk to
the patient. It provides medical device manufacturers with a framework to
systematically manage risks to patients, health-care providers (HCP’s) and
caregivers associated with the use of health-care products. Sterilization de-
serves special consideration given the potential for harm that could impact,
in some cases, large numbers of products or patients. Specifically, the stan-
dard describes a process through which the medical device manufacturer
can identify and mitigate risks. The key steps in the process are described
in Table 7.1.
In Step 1, risk acceptability is a planned activity where acceptable risk
levels are defined prior to device design based on desired clinical perfor-
mance and safety. As per ISO 14971, sterilization risks are deemed acceptable
when managed in accordance with standards such as those to be analyzed
in this chapter, as given in Table 7.4. In Step 2, risks such as ‘inadequate
sterilization’ are identified along with potential causes. Each risk is ana-
lyzed using the risk evaluation criteria to establish its Risk Level. In Step 3,