Validation & Compliance: Using Risk Analysis in Process Validation - - BioPharm International

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Validation & Compliance: Using Risk Analysis in Process Validation


BioPharm International
Volume 20, Issue 2

Steps for Conducting an FMEA

Executing an FMEA is a highly structured process, and the basic steps for execution are listed in Table 1. The first two steps are "Scope Definition" and "Defining Problem of Interest." This work, which is common to all risk assessments, is completed in the initiation of the risk management process. The next step is to define the scales that will determine relative risk and ultimately provide a mechanism to prioritize work, or, in the context of this case study, to determine whether a system should be included in the process validation protocol. The impact or relative risk is measured using the product of three different scales: severity, occurrence, and detection:8

  • Severity measures the consequence of the failure, should it occur.
  • Occurrence describes the likelihood or frequency of failure.
  • Detection is the ability to measure or recognize the potential failure before the consequence is observed.

FMEA scales. FMEA scales typically are developed using a 10-point scale. Ideally, the scales are populated with information from the actual process such as process alarm logs, historical investigations, or actual process performance data. If these data are not available, the scales must be populated with descriptions that remove as much subjectivity as possible.

Another aspect of developing the scale is selecting the numerical values. Whether the team defines a scale using all 10 values of a ten-point scale, or only a subset of the values, depends on the level of resolution needed to make appropriate risk-based decisions at the end of the exercise. When the scales are qualitative—in other words, when there are no historical data to describe the observed failure rates—it can be difficult to develop descriptions for all 10 values. The spacing is only relative, so a one-unit difference in a scale value is not as important as agreement that a value of 5 indicates more severe consequences or more frequent occurrence than an item assigned a value of 4. Finally, with text descriptions for every value in the 10-point scale, it can be difficult to provide sufficient descriptions to clearly distinguish each value from the next. This could slow the team down with excessive discussion about a one-unit difference in the assigned scale value.


Table 2. Severity, occurrence, and detection scales used to populate the FMEA
The three scales for this process validation FMEA were developed using a conventional 10-point scale with four different levels (Table 2). By selecting an even number of levels, a mid-point to the scale is eliminated, thus forcing the team away from the center of the scale.

For the case study, the severity scale was designed to describe the consequences related to product quality, as defined by actions resulting from exceeding limits of relative importance. The consequences are at their greatest when there is the potential to compromise patient safety. Therefore, the highest severity rating (10), which was assigned the most serious consequence (a rejected lot), and the lowest severity rating (1), had no consequences because there was no quality impact and no investigation would be required.

The occurrence scale was based on the percentage of time the failure mode was expected to occur. The highest value (10) had a high likelihood of occurrence and the lowest value (1) had a low possibility of occurrence.

The detection scale was defined by the ability to detect each of the failure modes or the effect of the failure before it actually occurred. For the detection scale, the reverse logic is used. If a potential failure mode is easy to detect or has a very high likelihood of detection, the value of the detection scale is low. The converse is true for failure modes or their effects that are difficult or impossible to detect. These modes receive a high value on the detection scale. The detection scale for this process validation FMEA had a high value of 10 ("impossible to detect before the next process step") to the lowest value of 1 ("almost certain to detect the failure before the next process step").


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