RISK-BASED CHANGE CONTROL - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 370

13.6.3 Step 3: List Failure Modes, Effects, and Causes

The potential impact of the proposed change is assessed with respect to failure
events that affect product quality and regulatory compliance. When possible,
the team should refer to failure modes already identified in existing living risk
assessment documents. Where not available, a simple FMEA spreadsheet can be
used such as the following (Table 13.3).
For each identified type of failure that could happen as a result of implementing
the change request, list all failure modes, effects, and causes. For example, one
failure mode for the tablet manufacturing process might be incorrect direction
of rotation for mixer . The effect would be failed content uniformity . A specific
cause could be mixer wired incorrectly after motor change .
Certain reasonable assumptions should be made to keep the hazard analysis
manageable. Controls that already exist and that serve to mitigate the failure
should be listed and included in the measurement for occurrence and detection.
Other assumptions may be globally recognized (and do not need to be restated
each time), for example, that existing quality systems are in place and functional
(deviations, change control, CAPA, calibration, preventive maintenance, etc.).

13.6.4 Step 4: Assign Severity, Occurrence, and Detection Levels to each
Failure Mode

The team should discuss each failure event and assign the appropriate levels to
severity, occurrence, and detection. The level assignment should be based on
objective data whenever possible.

13.6.5 Step 5: Calculate Overall Risk (RPR) for each Failure Mode

Using the assigned levels for severity, occurrence, and detection, calculate the
risk priority ranking (RPR) for each failure event, using an agreed-upon method.
The RPR can either be a number (if numbers were assigned) or a category
(high-medium-low). Table 13.4 provides an example of one method of deter-
mining RPR based on high-medium-low categories.

TABLE 13.3 Sample Risk Assessment Spreadsheet
Process Failure Current Overall Accept Recommended

Step Mode Effect Severity Cause Occurrence Controls Detection Risk Risk? Actions