PHARMACEUTICAL PRODUCT MANUFACTURING - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 301

and sensory parameters such as visual observation. ∗ In the CCP example of
drying the equipment, the critical level is the minimum temperature requirement
of 300 ◦ F before the start of the 30-min drying step.
11.3.4.10 Principle 4: Establish A System to Monitor Control at each CCP
CCP monitoring is the act of conducting a planned sequence of observations or
measurements of control parameters to assess whether a CCP is under control and
to produce an accurate record for future use in verification. Monitoring is best
performed as the process occurs with results received at the actual time the control
occurs (i.e. real-time data) to rather than with results that would be produced days
later as would be the case with microbiological laboratory testing. The first steps
to establish monitoring procedures for each CCP would be to identify the best
atline, online, and/or offline systems and observational procedures. Continuous
monitoring is ideal, but when continuous monitoring is not feasible a monitoring
frequency must be determined. The next steps would be to establish procedures
for the operating personnel at each CCP to define the tasks for performing and
recording the monitoring activities and who is responsible for these activities.
General examples of monitoring activities include visual observations or
measurements of temperature or moisture levels. The monitoring frequency,
technique, and documentation are defined in procedures. For the specific CCP
example of drying the equipment, the temperature of the air used to dry the
equipment is monitored. An alarm sounds to indicate that the proper temperature
has been achieved before starting the 30-min drying step. Shortly after the
30-min equipment drying step, the operator monitors the success of the control
step by visually checking for dryness. Monitoring is best performed immediately
following the 30-min drying step to confirm that the allotted drying time
produced the desired results of total dryness and if not, to address the process
failure or any other issues that may have arisen before moving on to the next
process step.
11.3.4.11 Principle 5: Establish the Corrective Actions to be Taken when Moni-
toring Indicates that A Particular CCP is Not Under Control In manufacturing,
deviations will occur. Specific corrective actions must be developed for each
CCP to address the deviation when it occurs and must ensure that the CCP has
been brought under control. A deviation from an established critical level is only
a symptom of a process failure and a thorough investigation into the root cause
of the process failure is required. Regardless of when or how the deviation is
detected, it is important to promptly notify the proper quality and/or production
authorities and to decide whether to temporarily halt operations until the relative
risk of the failure on product quality can be determined and appropriate corrective
measures are taken.
∗ Limits may be set on the basis of results from the design of experiments, historical trends, and
regulatory guidance or compendia standards.