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Filtration in Pharmaceutical Production

Small molecule drugs, sometimes called active pharmaceutical ingredients (API), are still a vital part of the industry. Filters are used in many applications during API production. They reduce or remove particles and reduce bacteria in process components. Filters protect process solutions from contamination when stored in tanks. Of course, finished product is sterile filtered. If an inert gas is used to replace atmosphere in the containers, it is also sterile filtered. Finally, water used for washing and rinsing containers is also filtered to remove bacteria and prevent contamination.

While biopharmaceuticals have gotten a lot of attention in recent years, APIs are made on a large scale by many global organizations. Several challenges face the industry, including cost control pressures. With the large number of filters used during API production, partnering with a supplier committed to cost-effectiveness is important to your business.

The figure below is a simplified schematic of a basic small molecule chemical process showing the basic filtration steps. The applications are discussed briefly below and in more detail on the applications pages.

These applications are discussed briefly below and in more detail on the applications pages.

Filters in API Production

Clarification & Prefiltration in API Production

Clarification and prefiltration covers a wide range of filtration applications

Removing unwanted particles from the liquid components used to make APIs is only one application. Undissolved powders and solid impurities, for example, may be introduced to the process by product components. Removal of these particles is critical to the quality of the final product.

Particle control targets visible particulates and larger solids carried by a liquid. Clarification removes smaller particles that may be suspended in the liquid and causing a haze. Clarification may also be part of a prefiltration process designed to remove both particles and larger microorganisms to reduce the particle load on the more expensive membrane filters used downstream.

The filters marked "1" in the figure are the possible location of filters for all clarification and prefiltration applications. Only one filter housing is shown in this diagram, though multiple filter stages may be used in liquid streams with large particle loads.

Clarification and prefiltration is 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 efficacy of the critical downstream membrane filters is the most important goal of prefiltration.
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Bioburden Control

Removing at least some of the organisms that might be in the stream may be part of the prefiltration process. As described above, the final filters (see Sterilizing Filtration 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 figure are in place to reduce the amount of bacteria and prevent premature fouling of the final, sterilizing filters. Bioburden reduction filters are usually membrane-based filter with pore sizes of 0.45μm to 0.80μm. This filter captures the bulk of the microorganisms, though not all.

The new High Capacity PES Membrane cartridge filters and capsule filters are examples of filters for bioburden control. Visit our Products page for more information.
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Sterilizing Filtration

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.
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Tank Vent & Process Gas Filters

Normal atmosphere may or may not be allowed to contact product components or the final product during storage. If oxygen will cause oxidation of components or support the growth of potential bacteria, then a process gas may be pumped into the process tanks. 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.

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.

Filters (housings marked "3") assure that no bacteria are carried into the tanks or containers by the air or process gas. In most facilities, hydrophobic 0.22μm membrane filters are used to make sure all bacteria are removed.

The sizing of the filter system is critical. Tanks are often not designed to withstand vacuum conditions. In such cases, a very small amount of negative pressure can implode a tank. Restricting air or gas flow into the tank as it is emptied will result in negative pressure, 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. Another alternative is to install tanks that are rated to withstand vacuum.
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To estimate the number of filters you will need for your application, use our unique sizing tools.

Critical Process Filtration will provide Validation assistance. Click here to download a brochure outlining those services.