Integration of Less-Formal Risk Assessment Tools into Change Control - Pharmaceutical Technology

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PharmTech Europe

Integration of Less-Formal Risk Assessment Tools into Change Control
Managing risk in biopharmaceutical operations is of utmost importance for patient protection.

Pharmaceutical Technology
Volume 36, Issue 10, pp. 80-84

Comparison matrix

The CM is a less-formal risk tool used to compare two different states in an effort to understand what the differences mean from a risk-based perspective. The primary objective of the CM is to determine if, overall, the change will lead to more or less risk exposure for the process or system. The CM is particularly helpful when making "go/no-go" decisions regarding individual change requests.

The process for the CM is as follows:

1. Identify critical parameters for the system under review.

2. Populate the CM with details for each critical parameter, for both the current and proposed states.

3. Determine what the differences between the current and proposed states mean from a risk-based perspective (i.e., the change to overall risk profile for each critical parameter).

4. Evaluate whether changes to overall risk profile are acceptable.

Table I: Comparison matrix: hypothetical scale-up of saline solution.
A hypothetical change request, for example, related to scaling up the production of saline solution may identify the following attributes as critical parameters: bioburden specifications, environmental exposure, vessel type, and vessel capacity. Once the CM is populated with details on how the current and proposed states fulfill each of these critical parameters, the potential impact of each change on the overall risk profile is assessed (see Table I). This assessment must take into consideration the nature (i.e., types of risk or potential failures), the gravity (i.e., frequency or severity of a failure), and the pervasiveness (i.e., where the failure might occur or what downstream impact it might have) of each risk.

The overall risk profile may be increased if the proposed change increases variability, reduces reproducibility or robustness, introduces a variable that is not well understood (such as a new technology), or cannot be quantified. Conversely, the exposure to overall risk may be reduced if the change decreases variability, improves reproducibility or robustness, or upgrades an element of the system in a way that is well-understood and controlled. Overall risk may remain the same if the change does not affect that particular critical parameter or if it is proven or expected to be equivalent to the current system. As with any risk assessment, available data should be cited as justification for the conclusions drawn.

The final step in the CM process is to assess whether the change is acceptable from a risk-based perspective. In general, the proposed change is acceptable if the overall risk profile has not changed or has been reduced for the majority of critical parameters. If the overall risk profile, however, has increased for the majority of critical parameters that were assessed, the proposed change should not be accepted until additional analyses are conducted or risk mitigation measures are pursued.

To continue the hypothetical example in Table I, the overall reduction of the risk profile suggests that it is appropriate to move forward with this change. The critical parameter surrounding the introduction of a new product-contact material, however, increases risk and should be examined more thoroughly.

Although the CM illustrates whether a given change should be pursued, individual risks associated with the proposed state (change) are not thoroughly explored through this tool. These individual risks are best assessed through another less-formal tool, the risk estimation matrix (REM).


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