3.1.1 Purification of Biologicals
Membrane filtrations are preferred because of low costs and increased process
performance in case of large-scale productions and thickening of bacterial toxins.
In the direction of keeping production costs, the following two filtration steps are
needed [7]:
1. Fermentation broth is required to be clarified by using microfilterable membranes.
2. Toxins should be concentrated by ultrafiltration.
In comparison to organic membranes, inorganic membranes have high chemical,
mechanical, biological, and thermal resistances. Also, they have a long life, low
membrane friction, and high performance of filtration [14]. Bacterial toxins must be
purified and detoxified by formalin or heat to get toxoid as product. High flux,
regeneration capacity, and along life cycle are needed to reduce necessary membrane
area, which further reduces the overall process costs. Regarding these requirements,
ceramic membranes are well suitable for biologicals. Apart from this membrane
fouling is a major problem.
Stationary phases for purification of big molecules have designed as membranes
and monoliths. Their advantages lie in their ability to be used at high flowrates, while
exceeding the conventional flow rates. Adsorptive and monoliths are disposable and
scalable, which eliminates the needs for cleaning and sterilization. ATMPs
(advanced therapy medicinal products) are upcoming class of biologicals for gene
therapy and tissue paper repair including cancer treatment. All these molecules,
cells, and VLPs (virus-like particles) require extensive purification to meet regulatory standards. Therefore, this membrane-based technology is promising, especially
for its efficiency in downstream processes [14].
3.2 Sterilization
The reagents and compounds, such as antigens, antibodies, enzymes, human plasma
fractions, parenteral drugs, vaccines, and culture medias, are required to be sterilized
in the field of bioprocess engineering. Additionally, these reagents and compounds
are generally heat and pressure sensitive. Therefore, conventional sterilization
methods, such as heat sterilization, are not suitable for their sterilization. Henceforth,
membrane separation technique proves to be the best sterilization solution for such
reagents and compounds. However, the separation and purification indirectly the
sterilization via membrane separation process should be perfect because in case
single microorganism or impurity may spoil the whole compound completely. For
example, if a single microorganism is permeated across the membranes, then
overnight it can grow into thousands. Furthermore, the clinical data shows that
particulate matter present in IV solutions points to severe health risks, such as
clotting resulting in the direct blood vessel blocking or partial arteries occlusion.
Membrane Technology in Bioprocess Engineering
9
Membrane filtrations are preferred because of low costs and increased process
performance in case of large-scale productions and thickening of bacterial toxins.
In the direction of keeping production costs, the following two filtration steps are
needed [7]:
1. Fermentation broth is required to be clarified by using microfilterable membranes.
2. Toxins should be concentrated by ultrafiltration.
In comparison to organic membranes, inorganic membranes have high chemical,
mechanical, biological, and thermal resistances. Also, they have a long life, low
membrane friction, and high performance of filtration [14]. Bacterial toxins must be
purified and detoxified by formalin or heat to get toxoid as product. High flux,
regeneration capacity, and along life cycle are needed to reduce necessary membrane
area, which further reduces the overall process costs. Regarding these requirements,
ceramic membranes are well suitable for biologicals. Apart from this membrane
fouling is a major problem.
Stationary phases for purification of big molecules have designed as membranes
and monoliths. Their advantages lie in their ability to be used at high flowrates, while
exceeding the conventional flow rates. Adsorptive and monoliths are disposable and
scalable, which eliminates the needs for cleaning and sterilization. ATMPs
(advanced therapy medicinal products) are upcoming class of biologicals for gene
therapy and tissue paper repair including cancer treatment. All these molecules,
cells, and VLPs (virus-like particles) require extensive purification to meet regulatory standards. Therefore, this membrane-based technology is promising, especially
for its efficiency in downstream processes [14].
3.2 Sterilization
The reagents and compounds, such as antigens, antibodies, enzymes, human plasma
fractions, parenteral drugs, vaccines, and culture medias, are required to be sterilized
in the field of bioprocess engineering. Additionally, these reagents and compounds
are generally heat and pressure sensitive. Therefore, conventional sterilization
methods, such as heat sterilization, are not suitable for their sterilization. Henceforth,
membrane separation technique proves to be the best sterilization solution for such
reagents and compounds. However, the separation and purification indirectly the
sterilization via membrane separation process should be perfect because in case
single microorganism or impurity may spoil the whole compound completely. For
example, if a single microorganism is permeated across the membranes, then
overnight it can grow into thousands. Furthermore, the clinical data shows that
particulate matter present in IV solutions points to severe health risks, such as
clotting resulting in the direct blood vessel blocking or partial arteries occlusion.
Membrane Technology in Bioprocess Engineering
9