Virus filtration is a specialized manufacturing process that ensures the safety of liquid products by physically separating viral particles from the stream. This method relies on the significant size difference between microorganisms. Bacteria, typically measuring around 0.2 micrometers (200 nanometers) and larger, are easily removed by standard sterilization filters. Viruses, however, are much smaller, often ranging from 18 to 300 nanometers, requiring filters with extremely fine pores to capture them effectively.
Principles of Viral Removal
The ability of a filter to capture viruses is based on two mechanisms: size exclusion and adsorption. Size exclusion, also known as mechanical sieving, is the foundational mechanism for modern virus filters and provides reliability. This process involves manufacturing a membrane with a highly controlled pore size designed to be smaller than the smallest target virus. This physically blocks the virus from passing through while allowing the therapeutic product to flow freely.
Virus filters are designed with pore sizes in the range of 20 to 70 nanometers to target viruses like parvoviruses (18–26 nm) and retroviruses (80–100 nm). Therapeutic molecules, such as monoclonal antibodies, are typically much smaller (around 12 nanometers) and navigate the pores without being retained. Adsorption, a secondary mechanism, involves electrostatic or hydrophobic interactions between the virus and the filter material. Manufacturers rely on the consistent, predictable physical barrier of size exclusion to meet strict regulatory requirements for patient safety.
Essential Applications in Industry and Medicine
Virus filtration ensures that biopharmaceuticals are free from contamination during the production of modern medicines. This technology is widely used in the purification of biologics, including complex therapeutic proteins like monoclonal antibodies and recombinant proteins. Since these products are often derived from mammalian cell lines, there is a risk of adventitious viruses being present, necessitating this removal step.
Another application involves the processing of blood and plasma products, which carry an inherent risk of contamination from human pathogens. Filtration systems were implemented in this industry following historical public health issues, adding a defense against blood-borne viruses. The technology is also employed in vaccine manufacturing, particularly for products that utilize cell culture processes, to ensure the final product remains pure before administration.
Comparing Filtration Methods
Filtration methods are distinguished by the precision of the membrane pore sizes, which dictates the type of contaminants that can be removed. Nanofiltration and ultrafiltration are the two techniques used for virus removal in biopharmaceutical manufacturing. Nanofiltration membranes feature the smallest pores, typically ranging from 1 to 10 nanometers (0.001 to 0.01 micrometers). These fine pores allow nanofiltration to remove the smallest viruses and some organic molecules while letting water and smaller ions pass through.
Ultrafiltration membranes have slightly larger pores, generally between 1 to 100 nanometers (0.001 and 0.1 micrometers). This range is effective for removing bacteria, colloidal particles, and high molecular weight substances, including many viruses. Specialized virus filters are engineered specifically for virus removal, often using pore sizes between 20 and 70 nanometers. These methods contrast with microfiltration, which uses pores of 0.1 micrometers or larger and is designed to remove bacteria and larger debris but is insufficient for capturing small viruses.
Ensuring Filter Effectiveness
The performance of a virus filter is quantified using the Log Reduction Value (LRV), which determines the filter’s capacity to remove viral contaminants. The LRV is calculated by comparing the initial viral load before filtration to the remaining viral load after the process. A filter with an LRV of 4, for example, indicates that it has reduced the virus concentration by a factor of 10,000, meaning 99.99% of the virus particles were removed.
To validate this performance, manufacturers must conduct viral clearance studies, which are required by regulatory agencies. These studies involve intentionally “spiking” the product stream with a known quantity of non-pathogenic model viruses that represent a worst-case contamination scenario. By measuring the LRV achieved during this scaled-down experiment, the manufacturer proves the filter’s ability to provide a consistent level of viral safety. Achieving sufficient viral clearance often necessitates that the overall purification process includes multiple, distinct virus removal or inactivation steps.