CLEANING PROCESS DESIGN AND DEVELOPMENT
Consistent with a life-cycle approach, a cleaning validation program should include the design of the cleaning process before
its implementation in a manufacturing facility. A key to cleaning-process design is an understanding of the cleaning process
itself, including critical quality attributes (CQAs) related to the outcome of the cleaning process, as well as critical process
parameters (CPPs) of the cleaning process itself. The Technical Report discusses in detail the understanding of the various
steps in a cleaning process. Table II illustrates considerations relating to CQAs and CPPs for cleaning processes. Table III
illustrates considerations relating to cleaning-process design.
The four principal cleaning-input parameters for each step are sometimes referred to as time, action, concentration, and temperature
(TACT). These four parameters can vary, but in a controlled cleaning process they are typically fixed. The exception is when
principles of process analytical technology are used for process control. These parameters are also interrelated. For example,
a cleaning process may be effective at a high temperature for a short time, and may be equally effective at a low temperature
and a long time. The effect of these parameters on soil removal should be determined, with acceptable ranges established as
part of the design and development effort. As the cleaning process is designed and developed, other issues, such as the appropriate
residue-acceptance criteria and how to sample and analyze residue, should be considered.
In addition, as part of the design and development effort, personnel should consider the various materials of construction
used in biotech manufacturing. Laboratory evaluations of cleaning-solution compatibility (e.g., concentration, time, and temperature)
and surfaces can be performed under simulated cleaning conditions. Differences between the cleaning of soils on those same
surfaces also can be evaluated in the laboratory under simulated cleaning conditions.
These experiments enable employees to make determinations related to cleanability, such as comparing the equipment's materials
of construction, comparing various soils for a given surface, and comparing various cleaning conditions (e.g., concentration
of the cleaning agent, time, and temperature). Worst-case conditions (e.g., cleaning conditions less stringent than what is
expected in the manufacturing equipment) may be employed in these laboratory evaluations. The outcome of these studies can
be analyzed to create the design space for cleaning. The performance of the cleaning process in the laboratory is then verified
by conducting experiments in the pilot-plant or scale-up equipment. Adjustments to cleaning conditions may be made during
the scale-up process based on plant experience and laboratory development studies.