Bioprocessing operations face the threat that bacteriophages (viruses that infect bacteria) will infect the cell cultures used to manufacture biotherapeutic proteins in bioreactors. Contamination with bacteriophages, also known as phages, may completely paralyze an operation and even cause a shortage of a biopharmaceutical. Marcin Los, Ph.D., started Phage Consultants to help companies fight and prevent phages from attacking their microbial fermentation systems.
While completing his doctoral studies, Dr. Los published several scientific papers about phages in industrial microbial systems. Researchers at biotechnology companies who read his papers contacted him for help with phage contamination problems. This inspired him to start Phage Consultants in 2007.
The experts at Phage Consultants assist bioprocessing facilities worldwide. About 70% of their clients manufacture biopharmaceuticals or secondary metabolites, such as antibiotics, and 30% are industrial biotechnology firms, such as food, enzyme, and chemical manufacturers. Sometimes a client sends samples from fermentation or a production strain to Poland for analysis, and the problem can be solved remotely. More often, the company’s scientists travel to a customer’s facility to track down the culprit and find solutions.
Phages infect bacterial cells, but not human cells, so contaminated products generally are not a threat to people. However, a phage infection can devastate a biomanufacturing production schedule. Phage infections release proteins that cause foaming and may even clog filters, resulting in the buildup of pressure in bioreactors.
This can lead to leakage and equipment damage, which spreads phages. Just one milliliter of a bacterial fermentation culture can be infected with up to 1013 phages, and spillage of a few milliliters can severely contaminate an entire facility. In the worst cases, production may be forced to shut down, and a biotherapeutic may become unavailable to sell for several months.
Both upstream and downstream bioprocesses can be infected with phages. Phages are nanosized and readily pass through filters used to sterilize process solutions. Media, buffers, induction agents, vitamin mixes, and trace minerals that are fed into bioreactors are all capable of introducing a phage if not properly treated. Particularly worrisome are raw materials generated by bacterial fermentation, such as amino acids and antibiotics.