Nanoparticle drug product production involves many processing steps, including sterilization step to remove bacteria and any nanoparticle aggregates prior to fill-finish. You are designing the final sterilization step, which involves dead-end filtering using a polyethersulfone microfilter cartridge with a pore size of 200 nm and a membrane area of 1000 cm2. The nanoparticle solution has a viscosity of 15 cP. We expect there to be minimal bacteria content (1 ng/L) and low aggregate content (100 ug/L). The average specific resistance of the cake is 3x1016 m/kg. The permeate is directly introduced into vials for the fill-finish step thus requiring a consistent permeate flow rate (ie flux across the membrane) of 50 mL/min
1. For a constant flux operation, the initial pressure drop across the membrane is 3 bar to an upper limit of 5 bar at a constant permeate rate of 50 mL/min. For how long can you run at constant permeate flowrate with a single cartridge?
2. If each vial is filled with 75 ml, how many vials can you fill with one cartridge operating only at constant flux? One vial represents one dose.
3. The price of filter cartridges has more than quadrupled in the last month. To save costs on cartridges, your boss asks you to assess adding a constant pressure stage after the initial constant flux stage. If you run a second stage at the upper limit of 5 bar until the permeate rate drops to 37.5 mL/minute, determine the additional time of operation and the additional cumulative permeate volume for stage 2.
4. For the memo to your boss, prepare plots of cumulative permeate volume in mL and permeate flux in mL/min- cm2 as functions of time (hr) for each stage - stage 1 constant flux and stage 2 constant pressure. Label the stages on the plot.