Sterilization microfiltration

Figure 7.18 Flow diagram illustrating the use of microfiltration sterilization filters in a production line used to prepare ampoules of injectable drug solutions...

Among the methods of field-based separations, membrane filtration is one of the most representative, which includes microfiltration, sterile filtration and ultrafiltration. Microfiltration is used for clarification and sterile filtration, and ultrafiltration for protein concentration and buffer exchange. ... 

The microalgae are cultured in bioreactors under solar or artiflcial light in the presence of carbon dioxide and salts. The bioreactors may be closed systems made of polyethylene sleeves rather than open pools. Optimal conditions for pigment production are low to medium light intensity and medium temperatures (20 to 30°C). Pigment extraction is achieved by cell breakage, extraction into water or buffered solution, and centrifugation to separate out the filtrate. The filtrate may then be partly purified and sterilized by microfiltration and spray dried or lyophilized. 

Laboratory Microfiltration membranes have countless laboratory uses, such as recovering biomass, measuring particulates in water, clarifying and sterilizing protein solutions, and so on. There are countless examples for both general chemistry and biology, especially for analytical proc ures. Most of these apphcations are run in dead-end flow, with the membrane replacing a more conventional medium such as filter paper. 

Downstream Processing Microfiltration plays a significant role in downstream processing of fermentation products in the pharmaceutical and bioprocessing industry. Examples are clarification of fermentation broths, sterile filtration, cell recycle in continuous fermentation, harvesting mammahan cells, cell washing, mycelia recovery, lysate recovery, enzyme purification, vaccines, and so forth. 

The concentrated sterilized medium was pumped into the Wavebag with a peristaltic pump through autoclaved silicone tubes. Then distilled water (17.6 L) was pumped in through a disposable, sterile microfiltration capsule. Rocking was started at an angle of 10.5° at 36-37 rpm as well as the temperature regulation, set-point 28 °C. 

Sterilization can be accomplished by several means, including heat, chemicals, radiation (ultraviolet (UV) or y-ray), and microfiltration. Heat is widely used for the sterilization of media and fermentation equipment, while microfiltration, using polymeric microporous membranes, can be performed to sterilize the air and media that might contain heat-sensitive components. Among the various heating methods, moist heat (i.e., steam) is highly effective and very economical for performing the sterilization of fermentation set-ups. 

Microorganisms in liquids and gases can be removed by microfiltration hence, air supplied to aerobic fermenters can be sterilized in this way. Membrane filters are often used for the sterihzation of liquids, such as culture media for fermentation (especially for tissue culture), and also for the removal of microorganisms from various fermentation products, the heating of which should be avoided. 

The advantages and disadvantages of in-line microfiltration and cross-flow filtration are compared in Table 7.2. In general, in-line filtration is preferred as a polishing operation for already clean solutions, for example, to sterilize water... 

The primary market for the disposable cartridge is sterile filtration for the pharmaceutical industry and final point-of-use polishing of ultrapure water for the microelectronics industry. Both industries require very high-quality, particle-free water. The cost of microfiltration compared to the value of the products is small so these markets have driven the microfiltration industry for the past 15 years. 

Microfiltration is used widely in the pharmaceutical industry to produce injectable drug solutions. Regulating agencies require rigid adherence to standard preparation procedures to ensure a consistent, safe, sterile product. Microfiltration removes particles but, more importantly, all viable bacteria, so a 0.22- xm-rated filter is usually used. Because the cost of validating membrane suppliers is substantial, users usually develop long-term relationships with individual suppliers. 

Microfiltration cartridges produced for this market are often sterilized directly after manufacture and again just prior to use. Live steam, autoclaving at 120 °C, or ethylene oxide sterilization may be used, depending on the applications. A flow schematic of an ampoule-filling station (after material by Schleicher and Schuell) is shown in Figure 7.18. 

Cold sterilization of beer using microfiltration was introduced on a commercial scale in 1963. The process was not generally accepted at that time, but has recently become more common. Sterilization of beer and wine is much less stringent than pharmaceutical sterilization. The main objective is to remove yeast cells, which are quite large, so the product is clear and bright. Bacterial removal is also desirable a 106 reduction in bacteria is equivalent to the best depth filters. The industry has found that 1-p.m filters can remove essentially all the yeast as well as provide a 106 reduction in the common bacteria found in beer and wine. Because the cost structure of beer and wine production is very different from that... 

Microfiltration is widely used for the removal of cells and fragments from suspension. It is also used as a method of sterilization of solutions, and has the advantage of high efficiency, simplicity, compactness, and reliability. 

Microfiltration with inorganic membranes is a promising alternative. As early as 1964 porous silver membranes (composed of permanently molecular bonded pure silver particles) in the disk form were commercially available. Silver membranes with a maximum pore diameter of 1.2 pm were tested successfully on the pilot scale for cold sterilization of beer to remove any organisms that can cause spoilage in closed... 

The u% of synthetic polymeric membranes for water purification is now an established technoli. Historically, this developn nt dates to the beginning of this century, when Zsigmondy and Bachmann prepared the first microporous membrane from cellulose esters. SimOar microfiltration membranes are now widely used in applications ranging fiom sterile filtration to fine particle removal. 

Blanpain-Avet P, Fillaudeau L, and Lalande M. Investigation of mechanisms governing membrane fouhng and protein rejection in the sterile microfiltration of beer with an organic membrane. Food Bioprod. Process., 1999 77(C2) 75-89. 

Microfiltration processing for clarification and defatting of cheese whey, for selective separation and concentration of micellar caseins from milk for various purposes, for fractionation of caseins and their peptides, for recovery of native whey proteins from milk, for gentle sterilization of milk to produce extended shelf fife liquid milk and cheese milk, for fractionation of globular milk fat and its components, for the reduction of microorganisms in cheese brine, and for the removal of colloidal particles in membrane cleaning solutions. 

Microfiltration is a technique that allows the differential concentration in the retentate of the feed components that are larger than the average pore diameter of the membrane [8]. Developed as early as 1929 by Sartorius-Werke, in Germany, microfiltration is one of the oldest filtration technologies whose main use was for water and beverage sterilization [9,10]. MF membranes have pore diameter ranging 0.1-10 p.m, which can selectively separate particles with molecular weights >200 kDa based on sieve effect [8,11,12]. 

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

---