Figure 1 Definition of PQ
A PQ is almost always established for a group of multiple differing components which are linked or interconnected into an overarching system. This is illustrated in Figure 2 using a filling line as an example.
The responsibility for performing the PQ almost always lies with the pharmaceutical manufacturing company. In most cases equipment from different suppliers are linked together and subject to PQ as a complete plant or line. As a consequence, the documentation required for the PQ must be generated by the pharmaceutical manufacturer.
Figure 6.G-2 Example of a plant configuration for PQ
In general, it can be said: Production plants which can only yield the required performance as an interacting system are to be subjected to a PQ together. Whether it is possible to forgo a separate PQ for the system if appropriate tests are performed during the OQ, is to be decided on a case-by-case basis.
Acceptance criteria are defined and the performance tests are performed in the same manner as for an OQ. The purpose is to demonstrate that the specific line/plant meets the predefined requirements for the process.
It is important to know that the product specifications utilized for the PQ are not necessarily the specifications of a medicinal product and (may) be based on different specifications. In practice, since it is common for various different medicinal products to be manufactured with the same equipment, appropriate test descriptions should be aligned in advance which reflect these processes. During the PQ it is common practice to perform the tests using placebo batches, i.e. without active ingredients.
Tests performed to define operating parameters can also be included in the PQ. This can include qualification batches or technical trials, for example, which are necessary to define the process control strategy.
PQ tests are often performed using water, which has become entrenched in the term wet run. Wet runs can provide insight into how all of the components interact, and it is possible to test system behavior at upper and lower control ranges as well as to simulate partial loads economically. It must be assessed, however, if water adequately simulates the product properties.
It is possible to forgo the PQ if the essential aspects such as performance, interaction of components and worst case conditions are covered by the Process Validation (PV).
PQ is performed after conclusion of OQ for the impacted technical system. This requires a documented release for PQ or a comparable statement in the qualification report. Should it be necessary to make changes during the PQ, these are to be captured in the change control management system and assessed regarding their impact to the qualified status.
Execution of the PQ is usually scheduled before the Process Validation or, as applicable, before the Cleaning Validation. The PQ is often set up as a link between qualification and validation, and it is performed as the first phase of the Process Validation. This is permitted but must be documented in a traceable manner. The decision regarding the character of these tests is up to the company individually.
Handing over the system to Operations needs to be planned as part of the project management, since this is when the responsibility for the equipment is transferred to the operating department. This is most often completed before Process Validation. In some situations, the hand-over is performed earlier, i.e. before the PQ.
The sequence of the qualification activities and project phases are shown in Figure 3.
Figure 3 Performance Qualification in the course of the project
The FDA guideline on Process Validation established in 2011 the new term Process Performance Qualification (PPQ). A PPQ is defined there as follows:
“The PPQ combines the actual facility, utilities, equipment (each now qualified), and the trained personnel with the commercial manufacturing process, control procedures, and components to produce commercial batches. A successful PPQ will confirm the process design and demonstrate that the commercial manufacturing process performs as expected.”
According to the FDA, a PPQ provides the conclusive evidence prior to the start of Continued Process Verification. The concepts derived from this school of thought have not been standardized yet and are handled differently in practice by different organizations.