Filter selection sterile filters

Hydrophobie filters do not come directly into contact with the product, and therefore the standard baeterial retention test alone is generally sufficient validation. However, as hydrophilie filters are in direet contact with the product, additional validation is necessary for eaeh produet type to demonstrate that the filters selected for product sterilization do not affeet the safety, identity, strength, quality, or purity of the drug produet. Qualifieation of hydrophilie filters is also neeessary to demonstrate that the speeifie produet type in eonjunetion with a baeterial ehallenge does not affect the filter effieaey. Validation of filters by means of baeterial retention tests requires special equipment and is often arranged between the filter manufacturer and the BPS operator. 

Store in high concentration of ammonium sulphate (e.g. 4M). Freeze in 50% glycerol, especially suitable for enzymes. Add stabilising agents e.g. glycerol (5-20%), serum albumin (10 mg/ml), ligand (concentration is selected based on the concentration of the active protein). Sterile filter to avoid bacterial growth. 

In the selection of sterilizing filters for compressed air systems (Figure 6.45), the following parameters should be fulfilled as the ... 

Technical report no. 26 from the Parenteral Drug Association [63] identifies the following factors that should be part of selecting and qualifying a filter for use as a product sterilizing fdter ... 

Since all protein formulations are aseptically filled for final sterilization of the product, selection of the membrane filter and its media composition is very important. The chemical nature of the filter membrane and the pH of the protein adsorption16 are perhaps two of the most important parameters to study. 

Membrane filtration application to biopharmaceutical product development is extremely important since sterile protein-peptide products can only be prepared via sterile filtration and gamma radiation steam cannot be used under pressure. There are several excellent works in the field of sterile membrane filtration.34-36 The filter media most often tested for protein formulations with minimum adsorption and maximum compatibility are mixed esters of cellulose acetate, cellulose nitrate, polysulfone, and nylon 66. Membrane filters must be tested for compatibility with the active drug substance and selected for formulations if they have the lowest adsorption and maximum compatibility with the product. 

Figures 5(a) and 5(b) show the simulated breakthrough curves of both total protein and HSV-1 respectively. It should be noticed that the dimensionless time scales in these two figures differ by four orders of magnitude. The breakpoint of HSV-1 is the operating endpoint at which the effluent from the adsorption column can no longer meet the desired sterilization criterion. Since the HSV-1 has a much higher affinity to the bead surface, the breakpoint of HSV-1 appears much later than that of the total protein. To optimize the protein recovery, one should improve the design of the bead surface (better selectivity, higher loading capacity), size, and operating parameters of the filter to further delay the breakpoint of the virus elution. A stochastic approach to model the removal process may be more appropriate in low concentrations of viruses.

The essential method to obtain sterile air, whether packed-bed or cartridge filters are used, is to reduce the humidity of the air after compression so that the filter material always remains dry. The unsterilized compressed air must never reach 100% relative humidity. Larger plants install instrumentation with alarms set at about 85% relative humidity. Careful selection of the cartridge design or the design of packed-bed filters will result in units that can operate in excess of three years without replacement of filter media. If a fiber material is used in a packed-bed type filter, the finer the fiber diameter the shallower the bed depth needs to be for efficient filtration. Other filter media are less common and tend to have special problems and/or shorter life. The bed depth of filters is only 10 to 18 inches for fibers of less than 10 microns. These filters run clean for 2 weeks or longer before being resterilized. 

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