Filters and Filtration:

A Review of Mechanisms That Impact Cost, Product Quality and Patient Safety

Filtration is a widely used unit operation in the pharmaceutical industry. Filtration is used for clarification purpose (clarification filtration) and/or to sterilize solution using sterilizing grade filter membranes (0.2 µ or smaller pore size filters). Filtration is of great importance in injectable/parenteral formulations where control of visible and sub-visible particulate matter and sterility are of prime importance and a mandate. Mainly filters can be categorized into depth and membrane filters, the former is prone to particle generation and can contaminate the product thus these filters cannot be used as means of sterilization whereas the later one is best suitable for sterile filtration of parenteral dosage forms [1]. Filtration of parenteral products ensures removal of particulate matter and can be used either for clarification or for sterilization purposes. The choice of the filter for the intended purpose needs to be done judiciously since the choice of filter may influence the quality of the product being filtered i.e., constituents of the product may get adsorbed, filters may shed particles or may cause
leachables to get into the product under certain conditions which is highly undesirable [2]. Other sources of particulate matter includes silicone oil, rubber, plastic, and cotton etc. Great care needs to be taken to reduce or remove particle shedding/formation during clarification or sterile filtration since these particles will remain in the final
product thus impacting product quality, administration of such a product containing particulate matter to patients can have adverse effects such as infusion phlebitis, pulmonary artery granulomata and coronary vasoconstriction and immunogenic reactions causing toxic effects [2, 3]. Similarly, leachables from the filter components could cause undesirable toxicity when administered to patients. Filtration as a Source of Particulate Contamination A product that needs to be administered parenterally should be free from any microbial and or particulate contamination that may cause infections and related complications. Thus, the unit operation of filtration is becoming a necessity and different types of filters and filter types can be used depending on the application. However, such filter choices if not carefully made could sometimes become a source of contamination rather removal and may cause several complications associated due to such particulate matter triggering untoward reactions in the body by virtue of its size or nature. In the case of protein solutions, aggregation is a major concern and needs to be handled appropriately during filtration since filter components including filter membranes may shed the particles into the protein solutions leading to protein aggregation.