Performance Qualification versus Process Validation

Robustness is the ability of a process to consistently produce the same product while
remaining unaffected by small variations in the process. It is possible to have a repeatable
process and not have a robust process, but it is unlikely to have a robust process that is
not repeatable.
One approach to evaluating robustness of a process is to evaluate challenge conditions
during a separate PQ study. In this approach, challenging the validity of the Normal
Operating Range limits is considered Performance Qualification (PQ). This
type of PQ is considered 􀂵worst-case􀂶 or 􀂵most appropriate challenge􀂶 of the parameter
limits.
The number of PQ batches may vary depending on the number and range of critical
parameters to be qualified.
Another (more common) approach is to obtain information on challenge conditions
during process development. The PQ or process development studies are then followed
by Process Validation (PV). In the PV, all process parameters are set to target and
typically 3 consecutive batches are produced to satisfy the requirement for
reproducibility.
The ranges of the critical process parameters must be defined. They may be defined
either during performance qualification or during process development.
Example 1 (PQ for a process)
It has been demonstrated in the pilot plant that lubricant blending for 7 minutes leads to
acceptable product. Seven minutes is chosen as the target lubricant blend time for the
regulatory filing. The production blender with an automated timer is qualified for +/-15
seconds (0.25 minute) and 7 minutes is target blend time. In the PQ, blend time should be
qualified at times above and below the target (e.g. 5 and 9 minutes). Then, in PV, the
three validation lots would be manufactured at target (NOR range would be 6.75 -7.25
minutes).
The PQ has confirmed the limits and the PV have been performed in triplicate at target.
Therefore, data has been obtained demonstrating the robustness of the NOR/regulatory
range and reproducibility of the process.
Example 2 (PQ for a system)
A reactor is controlled by an automated DCS (distributed control system) that is a direct
impact system as defined in the project plan. During OQ portions of the DCS and the
reactor are tested individually. The Performance Qualification (PQ) portion of the system
qualification is defined to execute critical functional testing to demonstrate that the
systems perform reproducibly in the normal manufacturing environment. This would
typically include using water and/or solvent runs in the reactor while evaluating the SOPs
(Standard Operating Procedures). The PV of product processes in the reactor will follow
the successful reactor PQ.