Consider the likelihood or probability or occurrence of harm:

Various approaches may be employed to estimate probabilities of hazardous situations in assessing risk, including, but not limited to:

• use of relevant historical and real-world data;
• prediction of probabilities of risk using analytical or simulation techniques;
• reliability estimates;
• production data; or
• use of expert judgment.

The use of multiple approaches may be considered as this might serve to increase confidence in the results. Where uncertainty exists around these estimates, it may be useful to consider a qualitative approach to risk probability analysis. If it’s determined that the likelihood of a harm occurring due to a device change is negligible, then that change is unlikely to require submission of a new 510(k). If it cannot be determined that a harm’s likelihood is negligible, or the probability cannot be determined at all, then the below factors should also be considered.

Consider the severity of harm:

• New risks – If a device change creates a new risk that did not exist for the original device and the new risk cannot be determined to be negligible, it is likely that the change could significantly affect the device’s safety or effectiveness, and submission of a new 510(k) is likely required. An exception is a device change where the pre-mitigation risk level (the risk level before any risk mitigations or controls are accounted for or product specifications are set) associated with the new risk is considered to be acceptable.
• Changes in risk acceptability – If a device change positively or negatively changes the pre-defined acceptability level (e.g., tolerable, acceptable, insignificant) of an individual risk based on the risk-based assessment, either before or after risk mitigation or control, it is likely that the change could significantly affect the device’s safety or effectiveness, and submission of a new 510(k) is likely required.
• Changes in risk score – In cases where there is no risk acceptability change for an affected risk, a major change to the severity score may still suggest potential significant impact to safety, depending on how the manufacturer determines their risk scores and defines risk acceptability. These types of changes will be very dependent on how a manufacturer conducts risk management and defines risk scores and risk acceptability.
• Duration – Some device features expose patients and/or users to temporary, minor harm; some can cause repeated but reversible harm; others can cause permanent, debilitating injury.

Consider the device effectiveness:

Although ISO 14971 defines risk in terms of device harms and their effects on safety, it is important to note that whether submission of a new 510(k) is required depends on whether the change could significantly affect the safety or effectiveness of the device. Therefore, manufacturers should also consider the possible effects a device change may have on device effectiveness. As with safety risks, the manufacturer should consider the probability and severity (i.e., magnitude) of impacts to device effectiveness.

In considering a device change’s effects on device effectiveness, manufacturers should understand the criticality of the device feature being modified to the safe and effective use of the device. Certain features are more critical than others. Note that labeling changes, which affect user actions, can be critical as well.

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