Scaling up lab-size purification processes is inadequate to meet the needs of commercial scale production of today’s large, complex molecules, such as monoclonal antibodies.
“Although the basic principles of chemistry, physics, and engineering remain the same (as with proteins), complex molecules are much larger and their surfaces may be more highly decorated with various chemical structures,” which complicates separation, Alexei Voloshin, global application strategy specialist at 3M, tells GEN.
For example, he says, “The mRNA vaccines that were made during the COVID-19 pandemic used processes that were, essentially, a brute force scaleup of lab processes. While you can make a few vaccines like that, you can’t make hundreds of different vaccines using those processes,” at the quality, consistency, and cost required for widespread commercial acceptance.
Consider the challenge of scaling up using porous beads separation technology. As molecular sizes increase, the products or contaminants often no longer diffuse into the pores. Enlarging beads’ pores, however, effectively reduces the capacity of the purification column, allowing some contaminants to escape. Increasing production quantity 100-fold would require increasing purification capacity 100-fold, “and that’s not very practical at industrial scale,” Voloshin says.
Engineering systems from scratch
To resolve that challenge, 3M is introducing nonwoven, chromatographic purification technology for complex molecules and proteins. “We are engineering systems from scratch,” points out Voloshin, to ensure the chemistry and physics are well-suited. “The diffusion problem doesn’t exist in the world of fiber, so you can sidestep that limitation,” and, therefore, scaleup more easily.
In practice, this is a single-use flow-through chromatographic clarification and polishing technology in which the nonwoven material is encased in a plastic container. Solution flows in, contaminants bind into the material based upon charge, and a purer biopharmaceutical comes out. These systems include the 3M™ Harvest RC and the 3M Polisher ST, and others still in development.
The systems scale from the milliliter quantities used in labs to the tens of thousands of liters needed for commercial production.
Sometimes these nonwoven separation systems simply can be swapped out, one for one. Typically, however, implementation enables other purification steps to be removed. The Harvest RC, for example, offers single-stage clarification, so product can go directly from cell culture, to purification, to sterilizing membrane, eliminating the need for centrifugation and depth filtration.
“The biggest barrier to implementation is changing people’s mindsets,” Voloshin says. “3M supports its customers with the necessary data and expertise to validate this technology to meet regulatory standards.”