Pyrogens ultrafiltration

Ultra filtration. This process removes macromolecules, microorganisms, particulate matter, and pyrogens using a thin, selectively permeable membrane. Ultrafiltration caimot remove ions from water and is generally employed as a polishing process. 

Municipal water systems usually contain 5-50 EU/ml of endotoxin. Pharmaceutical waters are treated by ultrafiltration, distillation, or reverse osmosis to separate endotoxin from water.f The principal source of endotoxin is bacteria within a water system in the form of biofilm or colonies entrapped in resin beds, etc. A water system will be contaminated unless there is an ongoing sanitization program. The endotoxin limit for Water for Injection was set at 0.25 EU/ml because it is a critical vehicle and a major source of pyrogens. 

Cross-flow filtration (CFF) also known as tangential flow filtration is not of recent origin. It began with the development of reverse osmosis (RO) more than three decades ago. Industrial RO processes include desalting of sea water and brackish water, and recovery and purification of some fermentation products. The cross-flow membrane filtration technique was next applied to the concentration and fractionation of macromolecules commonly recognized as ultrafiltration (UF) in the late 1960 s. Major UF applications include electrocoat paint recovery, enzyme and protein recovery and pyrogen removal. 

Ultrafiltration is used to remove pyrogens and other microorganisms from high purity water. Pyrogens are lipopolysaccharides (also known as endotoxins) with molecular sizes ranging from 20,000 dalton (-0.005 pm) up to about 200,000 dalton ( 0.1 pm) produced from bacterial cell walls. Pyrogens induce fever when injected into animals or humans and cannot be removed by autoclaving or microfiltration.l H ... 

Typical UF performance for pyrogen removal with a polymeric and ceramic membrane is shown in Table 13. It can be seen that both types of UF membranes can adequately remove pyrogens. The choice of UF membrane (ceramic or polymeric) will depend on operating conditions or other special process requirements. Ceramic membrane ultrafiltration can achieve a 5 log reduction in pyrogen level. These UF membranes have been validated for the production of water meeting the requirements of pyrogen-free water for injection (WFI) standards.f ... 

Table 13. Pyrogen Removal with Ultrafiltration Membranes... 

Muller K. Steam-sterilizable ultrafiltration for pyrogen-free water in pharmaceutical production. Swiss Contam Control 1990 3(4a) 146-148. 

Nelson LL. Removal of pyrogens from parenteral solutions by ultrafiltration. Pharm Technol 1978 ... 

Other applications of ultrafiltration are scattered. Not surprisingly there is a growing market in microelectronics, where smaller and smaller integrated circuits require purer and purer water. There is also a market in pyrogen removal for pharmaceuticals. Ultrafiltration is used to sterilize beer without heating and hence to produce draft beer in cans. Enzyme recovery, gelatin concentration, and juice clarification are possible, but their success depends on specific situations. 

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