Monolithic HPLC Column - Economic Impact

Economic Impact

Though the many advances of HPLC and monoliths are highly visible within the confines of the analytical and pharmaceutical industries, it is unlikely that general society is aware of these developments. Currently, consumers may witness technology developments in the analytical sciences industry in the form of a broader array of available pharmaceutical products of higher purity, advanced forensic testing in criminal trials, better environmental monitoring, and faster returns on clinical tests. In the future, presumably, this may not be the case. As medicine becomes more individualized over time, consumer awareness that something is improving their quality of care seems more likely. The further thought that monoliths or HPLC are involved is unlikely to concern the general public, however.

There are two main cost drivers behind technological change in this industry. Though many different analytical areas use LC, including food and beverage industries, forensics labs, and clinical testing facilities, the largest impetus toward technology developments comes from the research and development and production arms of the pharmaceutical industry. The areas in which high-throughput monolithic column technologies are likely to have the largest economic impact are R&D and downstream processing.

From the Research and Development field comes the desire for more resolved, faster separations from smaller sample quantities. The only phase of drug development under direct control of a pharmaceutical company is the R&D stage. The goal of analytical work is to obtain as much information as possible from the sample. At this stage, high-throughput and analysis of tiny sample quantities are critical. Pharmaceutical companies are looking for tools that will better enable them to measure and predict the efficacy of candidate drugs in shorter times and with less expensive clinical trials. To this end, nano-scale separations, highly automated HPLC equipment, and multi-dimensional chromatography have become influential.

The prevailing method to increase the sensitivity of analytical methods has been multi-dimensional chromatography. This practice uses other analysis techniques in conjunction with liquid chromatography. For example, mass spectrometry (MS) has very much gained in popularity as an on-line analytical technique following HPLC. It is limited, however, in that MS, like nuclear magnetic resonance spectroscopy (NMR) or electrospray ionization techniques (ESI), is only feasible when using very small quantities of solute and solvent; LC-MS is used with nano or capillary scale techniques, but cannot be used in prep-scale. Another tactic for increasing selectivity in multi-dimensional chromatography is to use two columns with different selectivity orthogonally; ie… linking an ion exchange column to a C18 endcapped column. In 2007, Karger reported that, through multi-dimensional chromatography and other techniques, starting with only about 12,000 cells containing 1-4μg of protein, he was able to identify 1867 unique proteins. Of those, Karger can isolate 4 that may be of interest as cervical cancer markers. Today, liquid chromatographers using multi-dimensional LC can isolate compounds at the femtomole (10−15 mole) and attomole (10−18 mole) levels.

After a drug has been approved by the U.S. Food and Drug Administration (FDA), the emphasis at a pharmaceutical company is on getting a product to market. This is where prep or process scale chromatography has a role. In contrast to analytical analysis, preparatory scale chromatography focuses on isolation and purity of compounds. There is a trade-off between the degree of purity of compound and the amount of time required to achieve that purity. Unfortunately, many of the preparatory or process scale solutions used by pharmaceutical companies are proprietary, due to difficulties in patenting a process. Hence, there is not a great deal of literature available. However, some attempts to address the problems of prep scale chromatography include monoliths and simulated moving beds.

A comparison of immunoglobulin protein capture on a conventional column and a monolithic column yields some economically interesting results. If processing times are equivalent, process volumes of IgG, an antibody, are 3,120L for conventional columns versus 5,538L for monolithic columns. This represents a 78% increase in process volume efficiency, while at the same time only a tenth of the media waste volume is generated. Not only is the monolith column more economically prudent when considering the value of product processing times, but, at the same time, less media is used, representing a significant reduction in variable costs.