POINTS TO CONSIDER FOR COMMISSIONING AND QUALIFICATION OF MANUFACTURING FACILITIES AND EQUIPMENT - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 127

• Stage 2-Process qualification (PQ): During this stage, the process design is
confirmed as being capable of reproducible commercial manufacturing.
• Stage 3-Continued process verification: Ongoing assurance is gained during
routine production that the process remains in a state of control.

Under Stage 2 a. Design of a Facility and Qualification of Utilities and Equip-
ment, the FDA states that “Proper design of a manufacturing facility is required
under part 211, subpart C, of the CGMP regulations on Buildings and Facili-
ties. It is essential that activities performed to assure proper facility design and
commissioning precede PPQ (process performance qualification). Here, the term
qualification refers to activities undertaken to demonstrate that utilities and equip-
ment are suitable for their intended use and perform properly. These activities
necessarily precede manufacturing products at the commercial scale [3].” The
linking of qualification to the GMPs indicates that the FDA considers the func-
tion and the qualification of equipment and facility to have an impact on product
quality. Therefore, decisions made to plan and perform qualification should be
based on risk to product quality.
Figure 7.1 illustrates a three-stage approach to validation similar to the one
discussed in the FDA PV guidance. Qualification steps, which are set between
process design and commercial manufacture, demonstrate and provide confidence
that the process or system design will result in reliable and consistent process
performance and, therefore, product quality.
The FDA PV guidance does not specifically endorse a method for facility and
equipment qualification. However, it is important to show that the equipment,

STAGE 2
Process
Qualification

STAGE 3
Continuous Process
verification

STAGE 1
Process Design

Based on
product quality
and patient
safety

know the
process

know the
variables

have the
confidence

vigilance

5. Monitoring
and
improvement

1. Process
understanding

2. Process
design

3. Process
qualification

4. Commercial
manufacture

Information Management

Critical
Quality
Attribute
Requirements

Parameters,
Variables,
Control
strategy

FAT SAT
Commissioning
Support system Qualification
IQ,OQ, PQ
D.O.E., Statistical sampling plans

Continuous process
verification
Monitoring
Reaction to issues
Process improvement Design Review

Validated Process

Figure 7.1 Three-stage validation approach.