Validation Risk Assessment - What's Involved

Validation risk assessment is a structured & documented approach to assessing risks in a validation system. It can be used to identify testing/ information gaps in development and hence determines if further work is required.

For example, when executing process validation (PV) batches, executing extremes of all process parameter ranges may lead to escalation of permutations and hence an impractical number of full scale production runs. A centre-line approach (run three batches at centre of all ranges) may be used once risk assessment determines there is already adequate data available to safely determine effects on process of running process at extremes of ranges. This data may be available from studies in lab or in manufacturing facility e.g. mixing and hold studies.

Failure Mode Effects and Criticality Analysis (FMECA)

A FMECA is central to the risk assessment and is carried out on each individual part of the process. This will list the following for each activity:

• Function - what is this specific activity aiming to achieve
• Failure analysis - what signifies a failure and how it happens
• Effects of failure - list effects of failure listed above on product/ process
• Causes of failure - specify, with as much detail as is available, which process parameter caused failure
• Risk analysis - read section below
• Potential risk mitigations - if risk priority is high this requires mitigations that will result in revised risk priority of low
• Revised risk priority - level risk priority will become post completion of risk mitigations

A separate mitigation tracker document is then generated. This will remain in draft form until mitigations are closed out and no further amendments are required to this document.

Risk Analysis

Risk analysis should be conducted via cross functional team meetings covering the following four criteria:

• Probability - the likelihood that a failure will occur in the process. This parameter is rated on a scale as follows:

1. Low - unlikely to occur during the lifetime of the system

2. Medium - likely to occur sometime during the lifetime of the system

3. High - will occur several times during the lifetime of the system

• Severity - severity of the effect of each failure on the process. This parameter is rated on a scale as follows:

1. Low - expected to have a minor impact

2. Medium - expected to have a moderate impact

3. High - expected to have a very significant negative impact

• Risk Class - the risk class is estimated on the likelihood of occurrence and the impact of the event
• Likelihood of Detection - likelihood of detecting the failure before impact to the process

1. Low - detection of fault is unlikely

2. Medium - detection of fault is perceived to be reasonably likely

3. High - detection of fault is perceived to be highly likely

Risk Priority

The risk priority is estimated on the likelihood of detection in conjunction with the risk class and can be used to define the priority for further mitigating risks. Following implementation of mitigations, the revised risk priority should be low in order to proceed with that activity in the process.

Most important in this assessment are risk priority at medium. Since it is not low potential risk mitigations are required. Execution of this agreed risk mitigation results in a revised risk priority of Low. This means no further work is required on this parameter prior to actual validation runs.