Cross-Flow Filtration 331 7.5 Production of Pyrogen-free Water Distillation was used in the past to producehigh purity water. Distilled water is free from inorganic salts but may contain low-boiling organics Water purity or quality can be measured by several analytical test methods The most common water quality measure is its electrical resistance. Pure water resistivity is about 18 M-ohms. a triple distilled water typically shows a resistivity of only about 3 M-ohms. Today the combination of UF, RO, ion exchange and activated carbon is capable of producing 18 M-ohms water 181 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 um)up to about 200,000 dalton(0. 1 um) produced from bacterial cell walls Pyrogens induce fever when injected into animals or humans and cannot be removed by autoclaving or microfiltration. (62 The lipopolysaccharide molecule is thermally unstable and destruction requires exposure to temperatures 250C and higher. Endotoxins can be removed using the principle of molecular size exclusion by reverse osmosis (ROorultrafiltration. Reverse osmosis can be used but may cause retention of certain non-pyrogenic parenteral solutions (63)Ultrafiltration,on theother hand, with a 10,000 MwCo membrane can effectively remove pyrogens along with other microorganisms (not removed by prior separation tech- niques)without retaining salts Typical UF performance for pyrogen removal with a polymeric and ceramic membrane is shown in Table 13. It can be seen that both types ofUF 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(WFD standards. [64Cross-Flow Filtration 331 7.5 Production of Pyrogen-free Water Distillation was used in the past to produce high purity water. Distilled water is free from inorganic salts but may contain low-boiling organics. Water purity or quality can be measured by several analytical test methods. The most common water quality measure is its electrical resistance. Pure water resistivity is about 18 Mshms. A triple distilled watertypically shows a resistivity of only about 3 M-ohms. Today the combination of UF, RO, ion exchange and activated carbon is capable of producing 18 Mshms water.[8] Ultrafiltration is used to remove pyrogens and other microorganisms from high purity water. Pyrogens are lipopolysaccharides (also known as endotoxins) withmolecular 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.['1[62] The lipopolysaccharide molecule is thermally unstable and destruction requires exposure to temperatures 25OOC and higher. Endotoxins can be removed using the principle of molecular size exclusion by reverse osmosis (RO) or ultrafiltration. Reverse osmosis can be used but may cause retention of low molecular weight salts which is highly undesirable in the preparation of certain non-pyrogenic parenteral solutions. [631 Ultrafiltration, on the other hand, with a 10,000 MWCO membrane can effectively remove pyrogens along with other microorganisms (not removed by prior separation tech￾niques) without retaining salts. 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.[64]