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Description of the incident:

The maximum temperature observed was 28.2C in the Naproxen storage room of the Naproxen
clean room facility of C-Block on 06/01/2015 ,against the allowed limit: - Less than 25C.
Investigation and Conclusion:
Based on the investigation it can be concluded that the probable chances of variation are due to
cooling problem to the coils:
1) Variation in Chilled water flow rate due to damage in utility lines or valve failure.
2) Chilled water not supplied at desired temperature to AHUs.
3) Probable choking of the coils due to corrosion of coils or PHE
Due to this reason temperature was increased to above the specified limit >25C.
Based on Long term stability data (temperature at 252C) of Naproxen Product there is no
impact on the Naproxen product quality due to this high temperature.
Impact assessment: There were no batches executing at the above time of the deviation. Hence
no impact.
Correction:
As an immediate measure brine supply was provided to AHU to control the temperature within
the range. All the operations were resumed after getting the temperature under control.
Corrective action & Preventive action:
Cleaning schedule for VAM Condenser was prepared for every 3 months with reference to
notification 200085486 and CAPA notification No 200097111 and has been implemented.
Temperature & Humidity variation B-Block
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Description of the incident:


The pressures of all the rooms in the Naproxen sodium product blending facility of C- Block
have been observed out of the specified limits from the date(07/01/2015).
Investigation and Conclusion:
Based on the investigation it can be concluded that the probable chances of variation:
1) Variation in Chilled water flow rate due to damage in utility lines or valve failure.
2) Chilled water not supplied at desired temperature to AHUs.
3) Probable choking of the coils due to corrosion of coils or PHE
Due to this reason temperature was increased to above the specified limit >25C.
Based on Long term stability data (temperature at 252C) of Naproxen Product there is no
impact on the Naproxen product quality due to this high temperature.
To promote innovative chemical technologies that reduce or eliminate the use or generation of
hazardous substances in the design, manufacture, and use of chemical products.
Impact assessment: There were no batches executing at the above time of the deviation. Hence
no impact.
Correction:
As an immediate measure brine supply was provided to AHU to control the temperature within
the range. All the operations were resumed after getting the temperature under control.
Corrective action & Preventive action:
Cleaning schedule for VAM Condenser was prepared for every 3 months with reference to
notification 200085486 and CAPA notification No 200097111 and has been implemented.
Temperature & Humidity variation B-Block
000000200104211

If recirculation is used check the recirculation air damper settings.

The resulting room pressure is dependent on the following


parameters:
Size of the room leakage area

Area of the overflow opening

Set ratio of the supply and exhaust air


volume flow
Control accuracy of the volume flow controller and

volume flow difference (supply air - exhaust air)

Running time and possible hysteresis of the


actuators used
If you are following ISPE recommendations for a sterile fill facility you only need 10-15Pa (0.04"wc 0.06"wc) between different room classifications (i.e. ISO 8 to ISO 7).
However, here is an even better question that I need some help with. We have three cascading
rooms that have differentials pressures set at 0.05"wc between each room. Each room's differential
pressure gauge is measuring between atmospheric and the room, such that the analog gauges read
like so:
Room 1 (0.05"wc) <----- Room 2 (0.10"wc) <------Room 3 (0.15"wc)
We do not have a microprocessor controlled system and the rooms are under one HVAC unit. The
room pressures are controlled by mechanical dampers. The arrows above indicate the direction of
airflow. As I stated above the ISPE guideline states that the rooms should have between 0.04"wc 0.06"wc between rooms. Because the gauges are reading to atmospheric, all the gauges vary
slightly (perhaps +/-0.01"wc) due to atmospheric conditions, room heating and cooling, etc.
The million dollar question is: At what setpoints should I set each individual room's differential
pressure Hi and Lo alarm set-point? QA requires a minimum of 0.04"wc between rooms at all times,
engineering/testing has shown anything within 0.01"wc of the setpoint will give nuisance alarms (we
have a 2 minute delay on the alarm), we do not have continuous monitoring of values, and we need
to know when any room is below specification (0.04"wc between rooms).
I can provide more information / clarity, but any immediate best practice out there is definitely
appreciated
First a word of warning - playing around with a live active HVAC system can be dangerous high
pressure will blow out windows and sometimes doors low pressure can cause the whole structure
to collapse inwards with disastrous results for occupiers. This has happened at several pharma
plants.
It is almost standard practice to measure all the room pressures relative to outside ambient. Your
room differential should all be 15pa plus or minus 3. You will go into alarm when doors are opened,
however it is pretty standard to fit delays so that these transients are ignored.
Three rooms in cascade, I hope you dont mean the same air enter one room and leaves that room
to enter another. That would raise quite a problem about the quality of the air.
You dont know whether the pressure drop over the filters is low because of low flow in the system,
or flow leaving the system.
Measure the flow, there are excellent instruments for the job remove one of the plugs (they are
designed into the system for carrying out these tests) in the trunking and insert a sensor tube for a
flow-meter. Measure the flow as it leaves the fan, compare this to the drawing specification (since it
is pharmaceutical it must be validated so there will be drawings available.
If the flow is Low;Check where the AHU draws its air from, it is common to recirculate a percentage of the air. If
recirculation is used check the recirculation air damper settings.

No luck there then:Go to the air duct inlet filter or screen, there has to be a filter there to stop rodents and birds entering
the system.
It will not be a HEPA filter it might be a fine mesh screen, but they can get blocked with debris
especially foliage and or ice.
Check the bag inlet filters actually on the AHU are clear.
Satisfied the AHU is not getting starved of air, check the bag filter inlet filters actually on the AHU are
clear progress to the AHU fan speed controller.
There are several ways a design engineer will control the air flow in a system such as yours.
Fit an attenuator (silencer) into the system. The air flow through the attenuator causes a small
pressure drop across the attenuator. A sensor is used to measure this pressure drop. A certain flow
will have a certain pressure drop.
The main AHU fan motor is powered from a solid state inverter. The sensor through a controller can
automatically raise or reduce the frequency from the inverter - which (since motor speed is a function
of supply voltage frequency) increases or reduces the fan speed.
Now as the system ages and the HEPA filters progressively clog up the flow in the system is
reduced the reduced flow is sensed by the attenuator sensor, which causes a signal to be sent to
the fan motor speed controlled, which increase the fan speed to reinstate the flow.
Another way is to have the sensor and the attenuator, but have a motorised airflow control valve. So
in this case the when the sensor senses the HEPA filter are reducing the flow - it opens the air flow
controller valve slightly and allows more pressurized fan air into the system.
Obviously any of a series of faults in this system can cause low fan speed. So you must test this
system to ensure it is not the cause of your problem.
If you still have trouble gives us an email and we will take it further.
Hellow everybody,
I am very much excited with the conversation on this specific topic. Let me take participate with the
group.
The process of achieving required pressure within cleanroom associated with adjucent areas are
called pressure balancing. Its a pure engineering work.
Theoretically the pressure differencial is caused due to bleeding of excess air from a specific room to
its adjucent rooms through clearances.
In an equilibrium condition, the incomming air (X) entering in the cleanroom goes out through raisers
(Y) & the additional amount of air (X-Y) is subjected get bleeded out through clearances. This X-Y
amount of air is resposible for pressure diffrencial.
So, if we want to alter the pressure differencial, all we need to increase/decrease the bleed air
quantity. This can be done by following ways:
(1) Increase the cfm of incomming air (enhancement of blower capacity).
(2) Reduce the return air damper opening.
(3) Reduce the clearances (e.g. door clearances, plugging the leakages, etc.)
(4) Reduce the pressure diffrencials of the adjucent rooms by the one of the above methods.
But one thing we should keep in mind that in 1st case, changing the inlet air cfm means significant
change in room air changes which is not desirable due to design considerations.
So, the later two options are more handy.
Hope I am able to make some sense, plz reply.

200097111 and has been implemented.


P00011677
Temperature & Humidity variation B-Block
200104211