Online NVPC Qualification updated

Online Non-Viable Particle count monitoring:
 Non- viable particle count monitoring in Grade-A & B areas shall be done continuously
in static and dynamic conditions using online particle counters.
 Initially during qualification of the system, extensive monitoring of the room using offline
particle counter at different critical locations has to perform. From the extensive monitoring
worst case locations has to shortlist for placement of sensors for regular monitoring.
 Justification for selection of the particular location and locations Layout along with Operation
and calibration SOP has to prepare before starting monitoring.
 After satisfactory Commissioning, Installation & Operational qualification of Online NVPC
machine by vendor Performance qualification will be started by continuously monitoring the
locations for desired period and trend data along with actual data will be filed under P.Q
 Unlike offline particle counter online particle counter sampling will be done continuously
and at regular print intervals the data will be saved.
 Sampling will be done in 1m3 or 1ft3.
1 m3 = 35.3 ft3 or 1000lt’s = 36min sampling
1ft3 = 0.028m3 or 28.3lt’s = 1min sampling
 Practical experimentation demonstrates that tubing lengths over 2 m should not be used
whenever the quantification of 5.0μm particles is required. Providing they maintain at least a
tube diameter 4 radius.
 Cumulative Particle count at the end of 36min for 0.5µ & 5.0µ size is considered for action,
alert limits.
 Trend data for a particular period shall be attached with raw data for easy understanding.
 In Liquid injectables it’s not difficult to monitor the area during operation condition because
the particles generated during filling will be in limit only, but in Dry powder injectables it is
very difficult to monitor the filling area in operation condition, because the powder particles
may travel a distance and cause excursions in monitoring.
 The EU GMP Annex 1 Regulations:
Clean rooms and clean air devices should be routinely monitored in operation and the
monitoring locations based on a formal risk analysis study and the results obtained during the
classification of rooms and/or clean air devices.
 For Grade A zones, particle monitoring should be undertaken for the full duration of critical
processing, including equipment assembly, except where justified by contaminants in the
process that would damage the particle counter or present a hazard, e.g. live organisms and
radiological hazards. In such cases monitoring during routine equipment set up operations
should be undertaken prior to exposure to the risk. Monitoring during simulated operations
should also be performed. The Grade A zone should be monitored at such a frequency and with
suitable sample size that all interventions, transient events and any system deterioration would
be captured and alarms triggered if alert limits are exceeded. It is accepted that it may not
always be possible to demonstrate low levels of ≥5.0μm particles at the point of fill when
filling is in progress, due to the generation of particles or droplets from the product itself.
 Except where justified by contaminants in the process that would damage the particle counter
or present a hazard, e.g. live organisms and radiological hazards. In such cases monitoring
during routine equipment set up operations should be undertaken prior to exposure to the risk.
Monitoring during simulated operations should also be performed.
 The FDA has a similar philosophy: Some operations can generate high levels of product (e.g.,
powder) particles that, by their nature, do not pose a risk of product contamination. It may not,
in these cases, be feasible to measure air quality within the one-foot distance and still
differentiate background levels of particles from air contaminants. In these instances, air can be
sampled in a manner that, to the extent possible, characterizes the true level of extrinsic particle
contamination to which the product is exposed. Initial qualification of the area under dynamic
conditions without the actual filling function provides some baseline information on the nonproduct particle generation of the operation.
 As per regulatory guidelines it is clear that during operation condition the sensors very close to
particles generation location shall be disabled by proving acceptance results before and after
the activity. If possible during sensor disable time monitoring using offline particle counter is
recommendable.
 In other cases the sensor height can be increased and continue monitoring during operation
condition also.