Doxofylline For Injection And PES 0.22?m Microporous Folded Filter Filtration System Verification

Filtration sterilization is a high risk sterilization.It is usually used simultaneously with sterile operation when the product can not tolerate terminal steam sterilization and its conditions in drug production process.It is necessary for the filtration sterilization to be verified.Doxofylline for injection is a freeze dried powder of Doxofylline.In its production,filtration sterilization by PES 0.22?m folded microporous filter is used but not terminal sterilization.The filter must be verified in order to ensure the requirments of relevant laws and regulations and drug quality and safety.In this paper the integrity,chemical compatibility,dissolved-out matter,bacterial challenge and reusability of PES 0.22?m folded microporous filter were verified.Bubble points of the filter wettd by pure water and drug solution respectively were tested.The results showed all bubble points were more than 3.4bar and bubble points relative deviations were within ±10%.These results verified the filter has good structural integrity.Bubble points,pure water flow,membrane thickness and membrane blasting pressure of the filter before and after it was contacted with drug solution at the production conditions(75-80?,9h)were tested.The bubble points were all more than3.4bar and bubble points relative deviations were within ±10%.The relative deviations of pure water flow and membrane blasting pressure were all within ±10%.The membrane thickness was almost not changed.These results verified the filter has good chemical compatibility with drug solution.Ethanol and water solution(10/90,pH2.0±0.1)was used as model reagent.The filter was soaked for 24 and 48 hours with model reagent at the production condition(75-80 ?).Nonvolatile residues(NVR),UV absorption and Fourier transform infrared spectroscopy(FTIR)of dissolved-out matter were tested.The results verified the filter,s dissolved-out matter complied with national standards and it did not have any harmful substances.The filter was complied with quality and safety requirments.The experiments of drug bacteriostasis,rinsing of retention analysis membrane and degermation to Brevundimonas diminuta of the filter were done.The resultsverified the filter has good degerming ability even if the bacterial concentration is more than 107cfu/cm2.Residual drug bacteriostasis,bubble points and degermation to Brevundimonas diminuta of the filter which was used for 9 times in the actual production were tested.The results verified the filter can still remain good structural integrity and degerming ability after it was used for 9 times.The researches in this paper provide very important data for the safety and reliability about application of PES 0.22?m folded microporous filter in the production of Doxofylline injection.