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Determine if your bioprocess needs a sterilizing-grade filter, and if so, use these guidelines to select the proper one for your application.
STERILIZING-GRADE FILTRATION PRODUCTS have increasingly diverse applications in the manufacture of biotechnologically derived drugs. These applications include tissue culture media, buffers, cell culture supernatants, additions to the bioreactor and formulation and filling of the products into a final container. Some of the parameters to consider during filter selection are removal rating (i.e., the removal efficiency of the filter for different size organisms or particles), materials of construction, compatibility with pH, wettability and adsorption, as well as membrane and filter construction.
Assessing filtration needs
The first step is to determine if the application requires a sterilizing-grade filter. Traditionally, a sterilizing-grade filter is one that, when challenged with test organism Brevundimonas diminuta (B. diminuta) at a minimum concentration of 107 colony forming units (CFU)/cm^sup 2^ produces a sterile effluent. In Sept. 2004, the Food and Drug Administration issued guidelines for aseptic processing that define a sterilizing-grade filter as one that "when properly validated will remove all microorganisms from a fluid stream, to produce a sterile effluent."
However, there are many process steps for which a bioreduction filter meets process requirements for bioburden control. Many bioreduction filters on the market today have liter reductions in excess of 1 × 10^sup 6^ when challenged with aqueous suspensions of B. diminuta. Against this backdrop, bioreduction filters may be used to protect sensitive downstream processing equipment (such as tangentialflow filtration and chromatography systems), to preserve the sterility of a process stream after cell harvest or clarification filtration, to prevent bacterial contamination of final filters used in intermediate or final biological product streams, and to protect the final sterilizing-grade filter in formulation and filling applications (Figure 1).
Since a bioreactor must be totally protected from bacterial contamination, all fluids and components (e.g., nutrients, pH adjusters and anti-foam agents) added to the vessel require sterile filtration. Although the chromatography and tangential-flow filtration applications may not be sterile processes, the buffers used in these unit operations are typically filtered through sterilizing-grade filters to provide additional bioburden control for the downstream process and prevent release of genetically modified organisms into the downstream processing area. Sterilizing-grade filters are also used for air and...