Good morning to all.
Particle count is found out of limit in operation condition inside the filling room and LAF during filling of powder for injection (PFI). The excessive particle is seemed as powder product as the count is within limit during at rest condition.
Would you please suggest how we can conclude it ?
It is understandable that total particle count at the powder dispensing area is higher due to the reason you mentioned.
You should understand the behaviour of the total particle count to establish effective alert/control limits so that you are able to truly know when there is an abnormal situation that is causing additional variability that needs to be controlled. In other words… you must claculate alert/action levels according to the actual variability of your process, which for obvious reasons will be higher than traditional specs.
This should be understood and very well documented though, using a risk approach to the quality of the product and safety of the patient.
Taken from PIC/S Annex 1 (GUIDE TO GOOD MANUFACTURING PRACTICE FOR MEDICINAL PRODUCTS ANNEXES):
9.20 In the case where contaminants are present due to the processes involved and would potentially damage the particle counter or present a hazard (e.g. live organisms, powdery products and radiation hazards), the frequency and strategy employed should be such as to assure the environmental classification both prior to and post exposure to the risk. An increase in viable particle monitoring should be considered to ensure comprehensive monitoring of the process. Additionally, monitoring should be performed during simulated operations. Such operations should be performed at appropriate intervals. The approach should be defined in the CCS
I hope this helps!
The FDA (in its aseptic processing guidance) mentioned a solution for this problem , the solution is increasing the Air velocity of the LAF of aseptic powder filling machine to be larger than the known range (0.36 - 0.54 m/s) , in order to suppress particle generation
You may try this solution
If this solution works with you, you can officially increase this range in your LAF SOP based on the scientific justification mentioned by FDA and based on your qualification results which are to be shown to external auditors in the future -if needed- to scientifically justify this modified range as stated by the new EU Annex 1
FDA guidance on aseptic processing:
“A velocity of 0.45 meters/second (90 feet per minute) has generally been established, with a range of plus or minus 20 percent around the setpoint. Higher velocities may be appropriate in operations generating high levels of particulates.”
Thank you very much sir for your valuable feedback.
Thanks sir for the valuable feedback.
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