This section of our website is focused on biopharmaceutical processes. If you are producing small molecule drugs using chemical processes, please visit our Pharmaceuticals page.
The figures below are simplified schematics of the upstream and downstream processes and the formulation and filling process for biopharmaceuticals. The applications labeled are discussed briefly below the figure and in more detail on the applications pages.
Filters in Biopharmaceutical Production - Upstream Processes
Filters in Biopharmaceutical Production - Downsteam Processes
Filters in Biopharmaceutical Production - Formulation & Filling
Particles in the feedstocks, media, buffers and mixed solutions can interfere with downstream operations. Particles can be undissolved powder nutrients, crystals formed during a mixing process or particles that enter the system with raw materials. Of course, even the microorganisms or used in the production of biopharmaceuticals, or their fragments, are particulates to be controlled.
In general, particle control targets larger solids carried in the fluid stream, usually particles larger than 1 to 3 microns. Control of smaller particles, often referred to as clarification, removes particles suspended in the stream that may cause a haze. Clarification may also be part of a prefiltration process designed to remove both particles and larger microorganisms to protect more expensive and critical membrane filters used downstream.
The filters marked "1" in the figures above are the possible location of filters for particle control and clarification applications. Only one filter housing is shown in the figures, though multiple filter stages may be used in liquid streams with large particle loads.
Particle control and clarification are often performed using depth filtration media, with the filters trapping progressively smaller particles in the layers of media. Some applications will use membrane based filters to capture both small particles and larger microorganisms. Again, protecting the critical downstream processes or membrane filters are the most important goals of this filter step.
Removing at least some of the organisms that might be in the stream may be part of the prefiltration process. As described above, sterilizing filters (see below) must be protected from premature fouling by an excess of particles or bacteria. Bioburden Control filters are designed into the system to remove most, but not all bacteria. The sterilizing filters are then able to perform their function for an entire batch of product without fouling and causing undue difficulties with batch processing.
The housings marked "2" in the figures are in place to reduce the amount of bacteria and prevent contamination of downstream processes and premature fouling of the final, sterilizing filters. Bioburden control filters are usually membrane-based filter with pore sizes of 0.45μm to 0.80μm. This filter captures the bulk of the organisms, though not all.
When bacteria must be removed, before final packaging or to protect an intermediate process, this filter is chosen to remove whatever bacteria may be present in the product.
Filters used for this final filtration step are almost always membrane filters with an effective pore size of 0.22μm or 0.10μm with the pore size chosen based on the organisms that have been identified in the customer’s system. Sterilizing filters are integrity tested before and after use to assure that the filter has been installed properly and has not been damaged in any way.
As a tank is filled or emptied, the air inside has to escape or outside air has to enter the tank to replace the volume of liquid removed. Because the air around the tank contains airborne particles and bacteria, a vent filter (housing 4 in the figures) is used to block those contaminants from entering the tank.
If normal atmosphere will cause oxidation of components or support the growth of potential bacteria, then a process gas may be pumped into the process tanks instead of normal atmosphere. The gas could be nitrogen, argon, carbon dioxide or a combination. As the tanks are filled or emptied, the process gas “blanket” is either forced out or pumped in. to prevent contaminants in the gas from harming product quality, sterilizing filters in the same locations as the normal vent filters (housings marked 4) are used to block any bacteria and other particles in the gas from reaching the stored liquid.
Process air or gas is also used to support fermentation (housing 5 in the upstream processes figure). Similarly, as the final product is packaged, process gas may be injected into the container to make sure that there is little to no oxygen that can contact the product and create the potential for oxidation. As with the tanks, nitrogen, argon or carbon dioxide or a combination may be used. A sterilizing filter (housing 5 in the formulation and filling figure) is used to prevent final product contamination.
Vent Filter System Sizing
The sizing of the vent filter system is critical. Tanks are not always designed to withstand vacuum conditions. In such cases, a very small amount of negative pressure (vacuum) can implode a tank. Restricting air or gas flow into the tank as it is emptied will result in a partial vacuum, so the system must be designed to allow the free flow of air or gas. Tanks should also be equipped with rupture discs, vacuum switches or other mechanisms to prevent tank collapse if a vacuum condition is accidentally created. Visit our Technical page for access to a vent filter system sizing calculator.
To estimate the number of filters you will need for your application, use our unique sizing tools.