Steam sterilization, membrane

Zirconia membranes on carbon supports were originally developed by Union Carbide. Ultrafiltration membranes are commercially available now under trade names like Ucarsep and Carbosep. Their outstanding quality is their high chemical resistance which allows steam sterilization and cleaning procedures in the pH range 0-14 at temperatures up to 80°C. These systems consist of a sintered carbon tube with an ultrafiltration layer of a metallic oxide, usually zirconia. Typical tube dimensions are 10 mm (outer diameter) with a wall thickness of 2 mm (Gerster and Veyre 1985). 

Aseptic Lltration is necessary for parenteral formulations. Because both lipids and the structure of liposomes are unstable at high temperatures, conventional terminal steam sterilization is not suitable for liposome formulations. Thus, the membrane aseptic Lltration is the most reliable method for sterilizing liposome formulations. Since the possibility exists for the membrane being defective, it is advisable to test the integrity of the assembled unit by carrying out a bubble-point test. This test... 

The lyophilized drug nanosuspensions can be transferred to a hnal dry oral dosage form such as tablets or reconstituted prior to administration. Drug nanosuspensions can be directly used as parenteral products. A shelf life of up to three years was shown for selected nanosuspensions. Sterilization can be achieved by aseptic processing of previously sterilized components, membrane filtration for particles sufficiently small or for drugs that can withstand it, steam sterilization, or y-irradiation. 

Pharmaceutical products can be sterilized by steam sterilization, dry-heat sterilization, filtration sterilization, gas sterilization, and ionizing-radiation sterilization. The USP provides monographs and standards for biological indicators required to test the validity of the sterilization process. These products must also be tested for pyrogens—fever-producing substances that arise from microbial contamination most likely thought to be endotoxins or lipopolysaccharide in the bacterial outer cell membrane. 

PTFE membranes are highly hydrophobic and, therefore, are used as air filters. Air filters have to be highly hydrophobic to avoid water blockage due to moisture or condensate, especially after steam sterilization of these filters. Water blockage could be detrimental, if the filter is, for example, used in a tank venting application to overcome condensation vacuum of a non-vacuum resistant tank. If the filter would not allow a free flow of air into the tank, it may implode. Therefore, vent filters for this application have to be chosen and sized with care. PTFE membranes are also highly mechanical and thermal resistant, which is required, because such filters are used over several... 

Nanosuspensions can be sterilized for parenteral use by using conventional steam sterilization in an autoclave, y-irradiation, or membrane microfiltration in certain situations. 

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. 

Polyolefins. Low density polyethylene and polypropylene have been developed as sheet and hollow fiber mlcroporous membranes, respectively, for use In plasmapheresis. Polyethylene Is made porous by stretching the annealed film ( ), while polypropylene la made porous by coextruding hollow fibers with a leachable plasticizer. Neither membrane has been prepared with small pore dimensions suitable for protein rejection. These polyolefin membranes are characterized by good chemical stability, but require special surfactant treatments to make them wettable. Their low deformation temperature precludes the use of steam sterilization. Because they are extruded without the usual antl-oxldants and stabilizers, their stability la lower than Injection molding formulations of the same polymer. 

Steam sterilization of medical devices Is used In Japan. It has the advantage of facilitating removal of water soluble residues left after membrane manufacturing, but requires that the device be shipped filled with water. Steam sterilization appears to alter the pore structure of hydrophobic membranes, despite the fact that their glass transition temperatures may be quite high, for example, the permeability of polysulfone membranes Is altered above 70°C. Literature Cited... 

Figure 19. Iri situ steam sterilization of the membrane ultrafiltration system.

Batch times can range from 12 to 22 hours depending on the desired final concentration and the required number of diafiltration volumes. At the end of a batch run, membranes are chemically cleaned. Cleaning may take up to 3 hours and involve the use of an alkaline or acidic solution, or both, with a final sanitization step (e.g., 200 ppm NaOCI solution, a dilute solution of sodium bisulphite or a bactericide/fungicide). In some cases, steam sterilization may be performed at the end of each run especially when using inorganic membrane filters. 

Table 12 shows the typical LRV values obtained using a polymeric and ceramic microfilter. Sterile filtration requires 100% bacteria retention by the membrane, whereas in many industrial bacteria removal applications the presence of a small quantity of bacteria in the filtrate may be acceptable. For example, drinking water obtained by microfiltration may contain nominal counts of bacteria in the filtrate which is then treated with a disinfectant such as chlorine or ozone. The use of ceramic filters may allow the user to combine the sterile filtration with steam sterilization in a single operation. This process can be repeated many times without changing filters due to their long service life (5 years or longer). 

In selecting a membrane material, its pH compatibility and wettability should be considered. Some hydrophobic membranes require prewetting with a low-surface-tension solvent such as alcohol, whereas cartridges containing membranes are often presterilized using gamma irradiation. Such filter systems do not require assembly and steam sterilization. 

Therefore, membrane filters which can be autoclaved or steam sterilized are... 

The excellent sorption capacity of the hypercrosslinked mesoporous poly-DVB with respect to selective removal of P2M from its mixtures with albumin and other semm proteins, combined with superior hemocompat-ibility of the beads surface modified with poly(N-vinyl)pyrrolidone, justified the manufacturing of an experimental batch of the material for initial clinical studies. The polymer was named BetaSorb (RenalTech International, USA) and was used in 300 mL cylindrical polysrdfone devices that were steam-sterilized and filled with normal saline containing 1000 lU heparin. The device was placed in line with the dialysis circuit, upstream of the dialyzer, in order to not affect the pressure drop across the dialyzer membrane. The blood flow was maintained at the customary value of 400 mL/ min, again the optimal flow rate for the dialyzer. The complete setup of the combined hemoperfusion-hemodialysis treatment [361] is displayed in Fig. 15.2. 

Sterilizability is of essential importance when the pol5mier is used in medical applications. Steam sterilization is preferred over chemical sterilization and radiation sterilization. Steam sterilization consists of a treatment of the membrane with superheated steam of >110°C for 30 min. Steam sterilizable membranes include poly(ether imide), PES and poly-(vinylidene fluoride). 

Aucella, F Vigilante, M Gatta, G Grandone, E Colaizzo, D Margaglione, M Modoni, S Stallone, C. Effects of ethylene oxide and steam sterilization on dialysis-induced C5Tokine release by cuprophan membrane. Artificial Organs, 2002, 26, 543-547. 

All media and feeds are prepared in dedicated media preparation tanks. During transfer to the respective cleaned and steam-sterilized receiving bioreactors or feed tanks, the final formulated culture medium or feed is sterihzed through membrane filtration. Filter sterilization is preferred over heat sterilization due to heat sensitivity of some components. A few smaller volume feeds are held in and supplied from disposable bags. 

Carbon membranes have the ability to be back flushed, steam sterilized or autoclaved [2],... 

Currently used polymers in nephrology have to satisfy many needs. These requirements differ according to both, technical production and clinical application. Polymers for dialysis membranes should be suitable for a reproducible membrane manufacturing, allow an easy sterilization and show long term stability, at least along the time line of the expiry date of the final product. As an example for blood compatibility, steam sterilization for dialyzers represents now the most widely technique for dialyzers (Fig. 13.10). 

Commercially available ceramic membranes, with narrow pore size distributions, exhibit properties not shown by polymeric membranes. For example, they can be used at significantly higher temperatures, have better structural stability, can withstand harsher chemical environments, are not subject to microbiological attack and can be backflushed, steam sterilized or autoclaved [62],... 

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