Page 187 - Assurance of Sterility for Sensitive Combination Products and Materials

Risk to the patient—Quantifying assurance of sterility 169

A core concept of ISO 14971 is that medical devices may cause harm if
a root cause, which is typically triggered by a sequence of events, occurs and
thereby exposes the patient or user to harm. Thus, evaluating risk requires
the user to estimate the likelihood of the sequence of events, that is, causes
of harm, and the magnitude or seriousness of the harm. Risk mitigation can
be achieved in two ways: (1) reduce the probability of the event, for exam-
ple, sterilization failure, or (2) reduce the severity of the harm. Reducing
the harm entails changing the way in which the device fails such that the
potential harm is reduced. In the case of a sterilization failure, there is no
opportunity to change the potential harm, infection. The focus must be on
reducing the likelihood of causes to reach an acceptable risk level. The user
can then make decisions on the acceptability of individual risks and the
overall residual risk for a medical device.
As manufacturers apply sterilization standards such as those to be used
in this chapter (see Table 7.4) and others to control risk, they may discover
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that achieving a PNSU* of 10 is detrimental to the device itself based on
the materials used in the design. A well-established alternative to the manu-
facturer is aseptic processing, as discussed in Chapter 4. In addition, a newly
clarified option for the manufacturer is the use of an alternative SAL as per
ISO TS 19930:2017. This guidance document provides a new regulatory
paradigm that frames requisite risk assessment to be completed prior to uti-
lizing alternative SALs in the scenario that terminal sterilization cannot be
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achieved at an SAL of 10 (see Chapter 9). Increasing the SAL, for example,
−4
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providing a 10 SAL vs a 10 SAL, for a device can mitigate device perfor-
mance or safety issues due to the sterilization process, but as would be ana-
lyzed in Step 4 increases the risk of infection. Thus, the manufacturer must
use the risk management process to assess the higher risk of infection against
the patient benefits resulting from the change in sterilization methods.
This discussion related to patient risk will be picked-up again in
Section 7.4 after foundational statistical concepts are discussed. Grounding
patient risk discussion in the statistics of quantifiable aspects of sterility as-
surance ensures a focus on the patient and patient risk, as opposed to pe-
ripheral issues or legacy paradigms in any given industry sector [4].

7.2 Statistical concepts applied to sterility assurance

Statistical calculations are frequently required to turn data into evidence
that supports the safety and efficiency of a process or device. The claim
that a process provides a PNSU* below a specified level may be true but