PROCESS LIFECYCLE VALIDATION - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 209

For each of these items, further evaluation of the controls is required. Addi-
tional corrective and preventative actions may be implemented on the basis of
these evaluations. When a new product is being introduced to the facility, it
will be evaluated against the approved RA to determine if additional incremental
controls need to be considered.
8.9 CONTINUED PROCESS VERIFICATION
Assurance that validated processes continue to perform as originally validated
is achieved through IPCs, testing against in-process limits and product speci-
fications, change control, ongoing process monitoring, annual product reviews,
and ongoing risk management. Ongoing process monitoring and review should
be performed to assure that processes are operating in the validated state and
confirms initial decisions on PPQ acceptance criteria. The monitoring strategy
should be documented (e.g., parameter monitoring, SPC).
Various changes that occur during a manufacturing process lifetime include
normal process variability over time, changes in equipment and control system,
and process improvement. Trending of process monitoring data at established
intervals is useful in the ongoing evaluation of the process. Statistical analy-
sis and trending of the data should be applied to alert any undesirable process
behavior. Where no significant changes have been made and process monitoring
or continuous verification confirms that cumulative changes have not impacted the
validated state of the system or process, and that they are consistently producing
results or the product meeting its specification, then there is no need for pro-
cess revalidation, unless explicitly required by regulatory authorities. Changes
to processes, raw materials, specifications, methods, procedures, labeling, and
packaging systems must be evaluated per approved change control procedure.
RAs and other actions that support the implementation of a change should also
be documented and approved.
The evaluation of process changes can determine the significance of the change
and define the necessary supporting validation study requirements and any poten-
tial requirements for regulatory reporting. Validation of changes may require a
repetition of studies originally used to validate the process or new studies to
test specific aspects of a change. An evaluation of the potential impact of a
change on that unit operation, as well as potentially impacted steps downstream
of that unit operation, is made to determine the scope of required validation.
When evaluating the potential impact of a change, the associated risks for the
parameters that impact product quality should be reexamined. Revisiting the RA
should include all parameters that may impact product quality, not just those
identified earlier as CPPs. While overall it may appear that no quality impact is
likely, some aspects of a change can alter the potential risk of deviation, perhaps
leading to a different conclusion of whether a parameter should be classified or
reclassified as a CPP. See Chapter 13 for details on QRM application in change
control.