POINTS TO CONSIDER FOR COMMISSIONING AND QUALIFICATION OF MANUFACTURING FACILITIES AND EQUIPMENT - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 170

of facility and equipment must be communicated to those preparing or execut-
ing the qualification protocols. Even noncritical changes to impact systems may
result in deviations, errors, and delays during execution. In some instances, the
changes may not be consistent with process requirements or may not be com-
pliant with regulatory expectations. For this reason, a good engineering change
control system should be in place as early as practical on the project. Changes
should be evaluated as to their potential impact on product quality and process
performance. Where they are found to have an impact, steps should be taken to
mitigate or minimize any adverse affects on product quality or related process
performance.
Chapter 13 presents an in-depth discussion of the use of risk management
for change management and change control. Therefore, this chapter will not
go into detail on methodology. However, care should be taken to address the
effects or unintended consequences of change. Additional risks remaining after
changes are made, sometimes referred to as residual risk , should be evaluated and
reduced to acceptable levels. Once addressed, changes should be communicated
to all parties who will make decisions based on the information related to the
changed system, including those responsible for development of commissioning,
qualification, and validation protocols. Some changes to equipment or process
steps may alter the results of impact assessment, moving items from one category
to another. For example, a process step change that adds a sterile addition to an
upstream compounding procedure may move certain environmental conditions
from indirect or relatively low impact to relatively critical direct impact. Likewise,
a change from an elastic gasket to a more rigid gasket material, coupled with
the need for sterilization may result in the need for additional testing to assure
integrity of the sealed system after steaming.
7.3.21 Failure Investigation
Deviations or discrepancies may be the result of unacceptable study results, inac-
curate information, or poorly executed protocols. Where deviations are the result
of study failures, and investigation should be conducted to determine if and to
what extent the failure has an impact on or represents a risk to product qual-
ity. Corrective actions should be determined and implemented before repeating
the study. Actions should be commensurate with the level of risk the failure or
systems function represents to product quality.
One should avoid repeating studies, without corrective actions, until results
are satisfactory. If the deviation is a result of study execution or testing, then
the study may be repeated. If the deviation is a result of inaccurate information
transfer, then the study may not have to be repeated. In most cases, deviations
should be investigated with the conclusion and subsequent actions documented.
Avoid initiating an investigation with a predetermined conclusion as the objective.
Any corrective actions that affect operating procedures or parameters should be
communicated to the appropriate individuals. Any investigations that involve