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    Endotoxin Removal

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    param540
    This document discusses endotoxins, which are pyrogenic components found in gram-negative bacteria. Endotoxins are lipopolysaccharide aggregates that cause fever when injected into humans and other animals. They can exist in various states of aggregation and are difficult to remove due to their heat and pH stability. The document outlines various endotoxin removal methods like reverse osmosis, ultrafiltration, and sterile-grade membrane filters. It also lists endotoxin limits for different products and solutions for toxic control using size exclusion, charge interaction, and hydrophobic interaction filtration techniques.

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    Endotoxin Removal

    Uploaded by

    param540
    93 views10 pages
    This document discusses endotoxins, which are pyrogenic components found in gram-negative bacteria. Endotoxins are lipopolysaccharide aggregates that cause fever when injected into humans and other animals. They can exist in various states of aggregation and are difficult to remove due to their heat and pH stability. The document outlines various endotoxin removal methods like reverse osmosis, ultrafiltration, and sterile-grade membrane filters. It also lists endotoxin limits for different products and solutions for toxic control using size exclusion, charge interaction, and hydrophobic interaction filtration techniques.

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    This document discusses endotoxins, which are pyrogenic components found in gram-negative bacteria. Endotoxins are lipopolysaccharide aggregates that cause fever when injected into humans and other animals. They can exist in various states of aggregation and are difficult to remove due to their heat and pH stability. The document outlines various endotoxin removal methods like reverse osmosis, ultrafiltration, and sterile-grade membrane filters. It also lists endotoxin limits for different products and solutions for toxic control using size exclusion, charge interaction, and hydrophobic interaction filtration techniques.

    Copyright:

    © All Rights Reserved
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    93 views10 pages

    Endotoxin Removal

    Uploaded by

    param540
    This document discusses endotoxins, which are pyrogenic components found in gram-negative bacteria. Endotoxins are lipopolysaccharide aggregates that cause fever when injected into humans and other animals. They can exist in various states of aggregation and are difficult to remove due to their heat and pH stability. The document outlines various endotoxin removal methods like reverse osmosis, ultrafiltration, and sterile-grade membrane filters. It also lists endotoxin limits for different products and solutions for toxic control using size exclusion, charge interaction, and hydrophobic interaction filtration techniques.

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    ENDOTOXIN REMOVAL

    DEFINITION
    Endotoxin are single most important class of pyrogen
    ie. A substance that causes a fever when injected into
    humans
    and animals.

    Endotoxins are complex aggregates of LPS


    (Lipopolysacchrides) and may contain
    protein material.

    PROPERTIES:
    They show pyrogenicity (so they need to be controlled and

    minimized in any processes involving a parental drug.


    In aqueous solutions endotoxin can exist in various state of
    aggregation
    Whereas individual molecules have M.Ws~ 10-20 KDa
    Aggregation can have M.Ws as high as 1MDa
    Divalent cations, as (Mg, Ca) are found to stabilize the
    aggregation structure LPS
    Whereas detergents structure into subunits
    These endotoxin can easily pass through a 0.2um sterilizing-grade
    membrane filter(ie. Where size exclusion is the sole retention
    mechanism ).
    Traditionally endotoxins have been removed by Reverse Osmosis
    or UF membrane of 10,000 NMWL cut off.

    Causes of Endotoxin Contamination:


    They are continuously shed from the outer membrane
    of viable gram negative bacterial
    Released when bacterial cell dies
    Gram negative bacteria are present in Envirnoment and
    a source of concern in WFI, buffers, and other fluids
    that goes into parental drugs making
    It can be removed by using 0.2 um sterilizing grade
    filter but Endotoxins can still be a concern in WFI
    distribution system as LPS itself is difficult to remove
    or inactivate because it is extremely Heat and pH
    stable.

    Amount of Endotoxin Required to Generate a


    Pyrogenic Reaction

    Amount is on the order 0.1 ng per Kg of body weight.


    [ 0.1ng ~ 1 EU (Endotoxin unit)]

    E.g.. Given typical gram negative bacterium contains


    10-15 g of LPS (0.1 ng would require 105 bacterial cells
    precursor.

    Endotoxin limits for Various Products:


    WFI

    < 0.25 EU/ ml

    LVPs

    < o.5 EU/ml

    Hlb Vaccine

    < 50 EU/ml (< 25 EU/dose)

    Factor IX

    < 0.1 EU/ml ( <5 EU/dose)

    Globulin

    <0.91 EU/ml (< 5 EU/dose

    Solution for Toxic


    Control

    Size Exclusion:
    Family of UF products ie. PelliconTM,
    ProstaicTM, Spirals
    Used for solution where a 10,000 NMWL
    cut off membrane

    Charge Interaction:
    Endotoxins are negatively charged at pH above
    2
    A positive membrane surface can remove
    endotoxin.
    e.g. Charged Durapore membrane surface has a net
    positively charge on its surface
    Note :
    In the presence of competing negative ions, such as in
    buffer filtration, a charged membrane cannot be used
    because its losses its adsorption properties.

    Hydrophobic Interaction:
    Using the hydrophobic interaction of the
    lipid A component of the endotoxin and
    hydrophobic membrane filter, device
    containing hydrophobic Durpore can be
    used for removing endotoxin from buffer
    ions solution.

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