Biological materials are used in the production of several biopharmaceutical medicines, such as mAbs and plasma factors. This increases the possibility of bacteria, mycobacteria, infectious spongiform encephalopathy (TSE) pathogens, and viruses being accidentally introduced into the production process and contaminating the product. In addition to comprehensive testing during the production process, it is required to demonstrate that the manufacturing process is capable of removing any foreign influences.
In order to build innovative procedures for biopharmaceutical drug manufacture, numerous complementary and established virus removal steps must be introduced into the manufacturing process to inactivate and/or remove possible viral contamination. Alfa Chemistry's orthogonal technology can inactivate and/or eliminate foreign viruses from the final medicine, improving its viral safety.
Alfa Chemistry Biotechnology Integrated Solution
Different but complementary technologies work together to limit the danger of viral contamination reaching the final therapeutic product in the orthogonal approach to virus safety in bioprocessing. Under specific situations, this could involve retention procedures (such as viral filtration), adsorption processes (such as chromatography), and inactivation processes (such as low pH). When synthesizing therapeutic proteins derived from biological materials, some international regulatory organizations need at least two orthogonal virus elimination processes. In batch or continuous processing mode, Alfa Chemistry can provide technology for three orthogonal step alternatives.
Virus Filtration
Membrane barriers are used in virus filtering to keep virus particles contained. It's a size-based virus elimination technology that employs a specifically engineered polymer membrane to trap virus particles on the membrane's surface and pores. The log reduction value (LRV) and throughput are usually the most important performance indicators. Many interaction factors, such as viral load, protein concentration, and the presence of contaminants, can impact these values. As a result, selecting and verifying a virus filter that fits the predicted range of conditions is critical.
Alfa Chemistry has created products that are simple to use and dependable to handle a variety of issues. SV4 and DV20 filters are best for plasma processing requirements in conventional process design areas; for mAb processing requirements, a combination of Prime and Protect filters can give the best solution under varied conditions. Both alternatives include a cartridge that can be used in a typical processing line and a capsule that can be used with a pre-sterilized disposable manifold.
Virus Inactivation
In order to inactivate viral contamination, the biological process fluid must be exposed to circumstances that denature viral proteins rather than active components. The use of low pH or the inclusion of detergents are the two most prevalent ways of inactivation in the manufacturing of biological treatments. Inactivation using a detergent is more common in plasma processing, but inactivation with a low pH is more common in mAb processing. It is normally kept at a low pH of 3.5 for 1 hour and is effective against enveloped viruses in this situation.
Alfa Chemistry has developed a virus inactivation method for small batch or continuous biological processing. The system employs two parallel mixers and recirculation loops that operate simultaneously and alternately, with one group involved in the low pH viral inactivation step and the other with the biological process fluid. The system is designed to process eluent from an upstream continuous capture chromatography step.
Viral Clearance Using Anion Exchange Membranes
Anion exchange (AEX) adsorbents or membranes can be utilized in negative ion or flow-through mode under the right ionic strength circumstances. This is done to get rid of any virus infection on the membrane's surface. Membrane chromatography equipment is ideal for this type of polishing stage because of its plug-and-play nature.
Anion exchange membrane capsules, which are often utilized at the end of a series of chromatographic stages, can assist lower host cell protein (HCP) and DNA contamination levels while also providing an orthogonal way to eliminate viruses. Viral elimination capsules from Alfa Chemistry are particularly effective in this regard and have been successfully employed as part of an orthogonal virus safety strategy in a variety of industrial processes.