Evaluation of the financial impact of continuous chromatography in the production of biologics

Abstract

The primary goal of this internship is to explore the financial impact of changing one or more of the downstream chromatography steps involved in the purification of a complex biologic molecule from a batch process to a continuous one. This is particularly relevant, as biologics represent the fastest growing segment of the human therapeutics market, and, consequently, have become a major component of most large pharmaceutical companies, such as Novartis.' Specifically, I examined the Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) system, a continuous chromatography unit produced by ChromaCon, in the first part of the internship.2 By collecting and analyzing data from previous experiments done with this technology, I was able to estimate the potential benefits in the production process of Biologic X. Then, after evaluating the current cost structure of this molecule, I determined the reduction in COGS associated with the successful implementation of MCSGP. In the second part of the internship, I examined the downstream purification of another, more complicated molecule. I studied each individual step, and then modeled each one as if it were continuous. For the chromatography steps, I applied either the MCSGP, or another continuous technology developed by Novasep, the BioSC process. Other key steps, such as the specific enzymatic reactions that are currently done in large batch reactors, were also modeled as continuous processes. I was able to show that with the MCSGP technology, the COGS of the drug substance (DS) of Biologic X could be decreased by 25%, with a resulting eNPV of savings of >$25M. Furthermore, I determined that: 1) MCSGP has a significant developmental risk, but it has considerable cost savings because it can increase product yields, and 2) BioSC has less developmental risk, and it can significantly decrease costs of high throughput products that require large amounts of expensive resins and buffers. There are clearly significant benefits to be gained from continuous chromatography technologies. One must weigh the developmental risks with the financial benefits, keeping in consideration the regulatory implications of changing manufacturing methods. The end result of this work will hopefully translate into higher margins and profits for Sandoz Biopharmaceuticals.