The bacterial removal terminal filters need to be in-line steam steriled for the safety production in pharmaceutical industries, because of their different high polymer materials construction, the steam sterilization have to followed such procedures as below strictly, or the filters would be damaged easily.
In-line Steam Sterilization Procedures:
1).Fully close the outlet valve, slightly open the inlet valve to adjust the steam pressure at 0.1-0.13 Mbar.
2).Slightly open the outlet valve and close that valve when steam begins to discharge, holding 30min at pressure 0.1MPa.(Note: Do not fully open the outlet valve, or the mass steam would damage the filter by high temperature)
3). When sterilization line is complete, immediately introduce clear air or N2 into the system, keep the pressure at 0.02 Mpa above the steam pressure.
4). Holding until the temperature is below 100℃, increase the air pressure to cool the filter cartridge.
5). If the filter cartridge is too wet to be flowed through by steam easily , we need to evaporate the water in the filter first at low steam pressure, then increase to the requested pressure for sterilization when the steam release from the outlet valve.
a)Strictly control the steam pressure, keep it at 0.13Mpa when sterilization.
b)Steam used for sterilization should be free from condensation, which would flow through the membrane and damage it by high temperature.
c)Adequate means for condensate drainage should be employed to ensure steam is free from condensate in sterilization.
d)Cooling the filter system is the key step, an ideal way is to close the valves and maintain the pressure to cool naturally, or according to the above step 3. High pressure air and cold water are neither allowed to damage the filter cartridge by out of shape.
e)In sterilization, slowly adjust the outlet valve to control the differential pressure below 0.12Mpa.
f)The integrity test is necessary to assure the filter is undamaged after steam sterilization.
The filters should be confirmed structural integrity before and after use, three methods: bubble point test, diffusion test and water invasion test can be employed according to the GMP. The wetting liquids are standard reagents(water, alcohol, etc) or process liquid.
1.Principle: The integrity test value is detected by statistical method, according to the differences of surface tension or other physical parameters of the different fluids.
2.Detected filter types: Membrane filters(micron<1 um), Bacterial removal membrane filters, Virus removal membrane filters, Hydrophobic air filters
3.Test items: bubble point, diffusion, pressure holding or water invasion test;
Cartridge filter test:
Plate filter test:
5.Integrity testing procedures
a. Wet the filter cartridge or membrane with the appropriate fluid
b. Connect the integrity tester with air source and power source, then link with the filter housing.
c.Start the integrity tester, input test procedure and data;
d. Install the wetted filter cartridge or membrane in the housing, auto detect and decide the results.
6. Notes of Integrity Tester
a. Power:100-240 V, 50/60Hz, 1.6A;
b. Air source requirements: clear, room temperature, dry, oil free compressed air or N2,
c. Air pressure: ＜7000mbar, normally 6000mbar;
d.Operating temperature: 5-40℃;
e.Relative humidity: 20~80%
a. Move carefully;
b.Stable the power voltage;
c. Ensure the quality of air and pressure stability;
d. Keep the instrument clean;
e. Avoid the liquid into the internal instrument;
f. Calibrate the pressure sensor periodically, Consult the instrument supplier;
g. When not use for a long time, place the filter integrity tester in boxes, and store in a dry place.
|Natural hydrophilicity, resist to alkaline liquor and organic solvent, especially Ketone, Ester, Ether||
|Good hydrophilicity, high protein adsorption, not resist to keton, strong acid and alkalines||
|Good hydrophilicity, low protein adsorption, not resist to keton, strong acid and alkalines||
|High flow rate and temperature resistance, good adsorption to colloid, oil and particles.||
|acid and alkali resistant, wear and impact resistant, evenly distributed micropore.||Widely applied in the injection, oral liquids, wine, beverage, water, air filtration, etc|
|High throughput, low protein adsorption, good chemical compatibility and thermostability, high mechanical strength,soluble in polar solvents(Chloroform, Acetone,etc)||
|Resist to strong alkaline, acid and high temperature(-40-260℃), have hydrophobic membrane and hydrophilic membrane||
Below is the time to exchange the filter cartridge, whichever occurs first.
1).The filter cartridge fail to the integrity test.
2).The differential pressure have been above 2 bar.
3).The flow rate couldn’t meet the production request.
4).The validated servicing life have been reached.
The filter cartridge should be well packaged before use(sterile grade filter cartridge need to be vacuum packaged), then store in a cool, clean, dry place, avoid the sunshine, rain, or heat source;
The filter cartridge needs to be flushed and sterile after use, then dip in fresh 5% NaCl solution for short storage or been dried for long storage.
Completely dry the filter cartridge in electric drying oven at 55℃~60 for 24h or longer time, until the filter cartridge quality change less than 1% in 1 h.
|Hydrochloric acid (strong)||NR||LR||R||R||R||NR||R||LR|
|Hydrochloric acid (6N)||NR||--||R||R||R||NR||R||LR|
|Hydrofluoric acid (6N)||NR||---||NR||R||R||NR||--||NR|
|Methyl Ethyl Ketone||LR||--||R||R||R||NR||NR||R|
|Methyl Isobutyl Ketone||LR||NR||R||R||R||NR||NR||LR|
10)This chart is intended only as a reference. R=Resistant, LR= Limited Resistance, NR=Not Resistant, --=Not Testing.