Viral filtration is the process used during biopharmaceutical manufacturing to remove or inactivate potential virus contamination from biologics, ensuring the finished product is safe for patient use. Different clearance steps are incorporated during upstream and downstream processing to reduce the risk of viable virus transmission.
Types of Viral filtration Methods
There are several commonly used viral filtration methods during biomanufacturing:
Filtration
Microfiltration and ultrafiltration are effective physical separation methods for removing viruses based on size. Filters with pore sizes smaller than the largest virus particle are able to block viral contamination from passing through. Downstream processing almost always incorporates some type of filtration to capture contaminating viruses.
Nanofiltration and virus retentive filters with extremely small pore sizes near the size of most viral particles provide the highest clearance capacity. Multiple filtrations in series can further improve viral filtration rates. However, these small pore membranes can increase pressure drops and reduce throughput.
Chromatography
Certain chromatographic purification steps like affinity, ion exchange and size exclusion are capable of facilitating Viral Clearance through selective binding interactions. Non-enveloped viruses in particular may be susceptible to clearance through hydrophobic interactions or ionic bonding within the chromatography media. The multiple diffusion and convection mechanisms involved with chromatography contribute to high log reduction values for some viruses.
Solvent/Detergent Treatment
Exposure to chemicals like tri(n-butyl)phosphate and certain detergents is a commonly applied inactivation method for enveloped viruses through disruption of the lipid viral envelope. The treatment specifically targets envelope structures while leaving the therapeutic protein relatively unaffected. It provides broad-spectrum inactivation of many relevant viruses but requires a subsequent purification step to remove the solvents and detergents.
Ph And Temperature Changes
Extremes of pH and heat stress can render some viruses non-infectious by denaturing viral capsid structures or internal proteins. Downstream pasteurization holds product at elevated temperatures for a defined time period to inactivate potential viruses. Likewise, chromatographic steps at extreme pH values may contribute to viral filtration via capsid disruption. However, the product itself must also withstand these harsh conditions without compromising integrity or activity.
Viral Clearance Validation Studies
Regulatory agencies require biopharmaceutical manufacturers to validate the virus safety of their processes. This involves spiking manufacturing runs with relevant model viruses (e.g. prionids, parvoviruses) and accurately quantifying log reduction values achieved by each downstream purification step and the process as a whole.
Typical Viral Filtration Validation Studies Will Involve:
– Selection of appropriate model viruses based on physicochemical properties, process robustness, and potential for manufacturing contamination. Enveloped and non-enveloped viruses are usually represented.
– Spiking clarified or purified process intermediates with high titers of model viruses.
– Subjecting virus-spiked samples to downstream purification steps under normal manufacturing conditions.
– Accurately enumerating infective virus particles before and after each purification unit operation using cell culture-based or PCR-based virus detection assays.
– Calculating the log reduction value (LRV), or magnitude of virus clearance, provided by that single step.
– Multiplying LRV data across multiple steps to quantify the overall virus clearance capacity of the full downstream process.
– Determining whether total virus clearance meets predefined acceptance criteria for ensuring final drug substance safety.
– Periodic revalidation as manufacturing changes occur to ensure continued virus clearance performance.
Together, these characterization studies provide strong evidence that potential viral contaminants would be effectively cleared from the final drug product. They form a key part of ensuring the viral safety of biopharmaceuticals.
Does Viral Clearance Always Succeed? Limits And Challenges
While current purification technologies offer extensive viral filtration most of the time, there are some challenges and limitations:
– Novel or emerging viral threats may have unpredicted biophysical properties that reduce their susceptibility to established clearance methods. Continuous monitoring is required.
– Very high initial virus titers could potentially overwhelm clearance capacity, though careful upstream development aims to prevent this.
– Some non- enveloped viruses like parvoviruses are inherently more resistant to certain methods like solvent/detergent. Alternative strategies may be required.
– Process deviations or manufacturing equipment issues could reduce expected LRV values. Robust validation with safety margins aims to address this.
– Current virus detection technologies may not be sensitive enough to detect very low residual virus levels after high clearance. This represents a detection limit barrier.
Overall though, with multifaceted Viral Clearance approaches and stringent validation practices, the biopharmaceutical has demonstrated an excellent virus safety record to date. Ongoing improvements continue enhancing the margin of viral filtration performance.
This article has outlined the key aspects of viral filtration – the crucial methods, validation studies, and existing challenges involved in ensuring the viral safety of biologic medicines. Rigorous clearance validations paired with ongoing monitoring remain vital for maintaining patient confidence in biopharmaceutical quality and safety.
*Note:
1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
About Author – Ravina Pandya
Ravina Pandya,a content writer, has a strong foothold in the market research industry. She specializes in writing well-researched articles from different industries, including food and beverages, information and technology, healthcare, chemicals and materials, etc. With an MBA in E-commerce, she has expertise in SEO-optimized content that resonates with industry professionals. LinkedIn Profile