otherwise likelihood to lose license or to compromise patient safety or

because out of product specifications

of batches or

of step duration

Incapable of measurement and

No checks and

No indication of error and

Not detectable coincidentally

because license or patient safety is in jeopardy or

because of risk of not meeting specs

of batches or

of step duration

Detectable coincidentally only or

Error indications recognized <50% of cases

Potential severe effect on product quality/efficacy or safety or

Loss of complete batch without any rework options

of batches or

of step duration

Occasional manual checks only or

Detectable only indirectly (indications without direct correlation)

Potential moderate effect on product quality/efficacy or safety or

Significant loss of overall yield (≥50%)

of batches or

of step duration

Parameter is manually checked routinely by onsite operator and

No automated system, no automated alarm

Potential minor effect on product quality/efficacy or safety or

Moderate loss of overall yield (≥20%)

of batches or

of step duration

Parameter is manually double checked in batch record and

Failure is detectable only after affected process step is completed

No influence on product quality/efficacy or safety expected and

Minor loss of overall yield (<20%)

of batches or

of step duration

Parameter is manually double checked in batch record and

Failure is detectable before affected process step is completed

No influence on product quality/efficacy or safety expected and

Negligible loss of yield

of batches or

of step duration

Parameter is monitored by a single alarm controlled system or

Manual input parameter is automatically checked

Definitely no impact on product quality/efficacy or safety and

Negligible loss of yield

of batches or

of step duration

Two or more redundant parameters checked by any combination of automated and/or manual controls (input and/or output parameters)

Definitely no impact on product quality/efficacy or safety and

No yield loss but other consequences

of batches or

of step duration

Parameter is monitored by two or more redundant systems and

Two or more of these systems are alarm controlled

Definitely no impact on product quality/efficacy or safety and

Only negligible consequences

Never occurred and

Implausible (but not impossible)

Failure is always immediately obvious to onsite operator