Qualification of equipment and utilities.
The EU PQR requires a review of "The qualification status of relevant equipment and utilities, e.g., HVAC, water, compressed
gases, etc." While the concept of ensuring that equipment and utilities continue to operate in a qualified state is CGMP in
both the EU and US, there is no specific FDA PAR or Q7A PQR requirement to include such a review. This review requirement
appears to be another example in which EU authorities are tapping into a current practice being performed under other systems
and are now requiring that it be covered in the PQR. For example, a firm may presently control the initial equipment qualification
via a master plan, and any need to requalify equipment through the change-control and deviation progams and trend results
from the maintenance and calibration programs. One criterion that is often applied when reviewing the essential requirements
to support a change is whether equipment requalification, in whole or part, is required. A deviation investigation may also
lead to questions about equipment qualification status following an equipment fault or other discrepancy. The preventive maintenance
and calibration programs should have been developed in conjunction with equipment qualification (as indicated in the FDA's
1987 validation guideline) and, therefore, directly support the qualified state of equipment in the absence of significant
The underlying theme of the equipment and utilities qualification review in the EU PQR is not to require duplicate information
or lists, or the performance of redundant work. The GMP principle is to demonstrate that equipment and utilities remain in
their qualified state. The review and trending of relevant information on the robustness of related systems (e.g., change
control, deviations, preventive maintenance, and calibration) that are responsible for ensuring equipment and utilities qualification
status is one means of satisfying this section of the EU PQR. The CGMP has long required responsible individuals to review
information to ensure that systems are functioning and outputs meet acceptance criteria. This is a fundamental principle of
system control. Companies should leverage the information that they are currently capturing to demonstrate that equipment
and utilities qualification is under control. The modular approach may be applied by consolidating, summarizing, and/or referencing
key data from relevant systems to provide internal assurance that equipment and utilities qualification, across a product
type, meets the requirements of the EU PQR.
Appropriateness of specifications.
The FDA PAR requires a review to determine the need to make changes in product specifications. The EU PQR requires a review
for the appropriateness of product as well as starting material specifications. The EU uses the term starting materials to include all raw materials (i.e., any substance used in the production of a medicinal product but excluding packaging materials).
The review of starting materials is not specified in the FDA PAR requirements or in the Q7A PQR. In addition to reviewing
the appropriateness of the starting material specifications, the EU PQR also requires a more general review of the starting
materials and packaging materials. (The EU definition for packaging materials includes any materials used in the packaging of a medicinal product, excluding any outer packaging used for transport or shipping
and printed packaging materials.) The EU industry requested the removal of the requirement to include starting and packaging
materials in the PQR or the revision of the wording so as to allow a risk-based review based on materials that are "deemed
to be critical to the product or where issues have occurred"(14). These industry recommendations were not incorporated exactly
into the final version of the EC GMP for PQR, but a concession was made to limit the review of starting and packaging materials
to those "especially from new sources." The requirements for this section may also be fulfilled using the modular approach
by taking data and information currently being gathered and reported from systems such as change control, laboratory information
management, materials receipt and inventory, and deviation management. This information can be summarized and reviewed as
a collective "module" for starting materials or packaging materials. Any trends or issues can then be discussed with corrective
and preventive actions highlighted for product types or individual products. The PQR should include a specific section within
the review for "new source" materials where data and information for this subset of materials are given focused attention.
Recommendations for selecting review areas and items.
As discussed under the section on the objectives of the PAR/PQR, the areas and items for the PAR/PQR should be selected only
when they fulfill one or more of the specified objectives for the respective PAR/PQR.