Protein A is a naturally occurring polypeptide present on the surface of Staphylococcus aureus bacteria. In nature, it binds to glycoproteins and antibodies helping the organism adhere to surfaces and evade the immune response of an infected host. The biopharmaceutical industry has harnessed this ability of Protein A to bind selected targets to capture therapeutic proteins from the process stream in biomanufacturing operations.
Protein A plays an important role in the production of the majority of biopharmaceuticals on the market.
Computational modeling can help make preparation for a key downstream processing step easier, faster, and cheaper, according to the team behind new protein A-focused research.
Protein A plays an important role in the production of the majority of biopharmaceuticals on the market, says Simon Caserman, PhD, from Slovenia’s National Institute of Chemistry.
“Protein A chromatography enables highly efficient capture of IgG products from bioprocess fluids with a relatively small amount of remaining impurities in a single step. This makes it the most important purification step in downstream monoclonal antibody production processes,” he explains.
Protein A is a naturally occurring polypeptide present on the surface of Staphylococcus aureus bacteria. In nature, it binds to glycoproteins and antibodies helping the organism adhere to surfaces and evade the immune response of an infected host. The biopharmaceutical industry has harnessed this ability to bind selected targets to capture therapeutic proteins from the process stream.
“Recombinantly produced Protein A is immobilized on a chromatography resin designed to achieve a high density of IgG-specific binding sites, low binding affinity for impurities, and low leaching of Protein A from the resin” Caserman says. “For industrial use, Protein A has been optimized to achieve suitable technological properties, such as stability.”
Model behavior
The challenge for biopharmaceutical users is that Protein A is expensive. According to one report, the median cost per liter is $12,000 while a separate 2020 study suggests it is in the $15,000 to $16,000 range.
As a result, industry is keen to ensure Protein A is used as efficiently as possible, points out Caserman, who outlines a model-based chromatography column loading optimization strategy in a paper published this month.
“Modeling can replace trial-and-error in initial screening. If a model can be shown to simulate the process well, a variety of process conditions can be performed in silico. Clearly, modeling can do the job in a fraction of the time and at a fraction of the cost, making evaluation worthwhile even for strategies whose outcome is difficult to predict,” according to Caserman
To demonstrate the approach, the team built a model using data provided by resin manufacturers combined with information generated from laboratory assessments of resin performance under selected conditions.
The model was used to develop optimised Protein A chromatography column loading strategies which resulted in improved capture performance without any additional investment in new equipment, materials, or energy.
“Increased productivity leads to lower amount of affinity resin demanded to process a given amount of crude harvest or to reduce the processing time,” he says. “With a new loading strategy, less expensive affinity resins may also become an effective alternative.”
