Amit Karpe, 3M explains how it is challenging the traditional clarification process. Using its expertise and technology platforms, the company is approaching it with a different perspective
Monoclonal antibody manufacturing is a complex process which includes numerous stages. The process consists of cell culture, cell harvest, protein-A capture, virus inactivation, product concentration, sterile filtration and filling. Service providers push for innovation in the processes downstream of protein-A column. The same cannot be said for upstream process.
Triple assets: According to Amit Karpe, 3M, its Emphaze range offers a new platform of efficiency, purity and economics
Clarification process prior to protein-A column consists of conventional methods eg centrifugation. These clarification methods are not always reliable and often difficult to scale-up. They sometimes break down and cause increased down time and production delays. Another pain point is efficiency – these methods offer little or no removal of host cell DNA. Thus, impurities like host cell DNA in the form of chromatin, host cell proteins (HCP) and any microbial contaminants are loaded on to the protein-A column. As a result, the impurities bind to the protein-A column, this non-specific binding takes away the efficiency from the chromatographic column. These impurities are also difficult to get rid of so the cleaning protocol requires the use of harmful chemicals, posing risk to the media in the column but also to the personnel performing the cleaning procedure. This eventually results in column fade and a reduced number of runs of the expensive protein-A column.
At 3M we challenge this traditional clarification process. With our expertise and the 46 3M technology platforms, we are able to approach a problem from different perspectives. The Emphaze range offers a new platform of efficiency, purity and economics and has led us to create an exciting product called Emphaze AEX Hybrid Purifier. The anionic exchange (AEX) part of the new Emphaze AEX Hybrid Purifier offers chromatographic purification with its four layers of Q functional non-woven hydrogel media. Hybrid nature of the product refers to the constitution of the product; it is a novel product which combines chromatographic separation along with a downstream 0.2 micron membrane filter. The hybrid purifier has been designed from the ground up; we translated the industry needs to deliver this next generation purifying device.
Emphaze AEX Hybrid Purifier is able to reduce host cell DNA by 4 log reduction value (LRV) which translates to 99.99% reduction. HCP reduction of up to 35%, Bioburden reduction of 6 LRV which corresponds to 99.9999% reduction. This product has the potential to replace centrifugation, which is cumbersome and not always reliable. When used in conjunction with a depth filter Emphaze AEX Hybrid Purifier can offer unsurpassed quality of fluid to load on protein-A column.
As the majority of host cell DNA is removed prior to protein-A column, the latter is free to do its main function: capture mAbs. We have encouraging results which show an increase in its performance. Because there is no large amount of DNA/chromatin attached to the column, the cleaning protocols can use less concentrated chemicals post use. This helps to extend protein-A column’s life, another benefit of the new 3M hybrid purifier.
As Emphaze AEX Hybrid Purifier provides early purification, it opens new avenues to downscale existing processes post protein-A columns you use. We have seen AEX column being made redundant in certain cases!
We have launched purifiers ready for R&D, pilot scale and full production scale. Our team of application engineers are ready to work with you and provide you all the necessary information and products to set-up process trials optimised for your needs.