Management likes SFC because carbon dioxide, the primary mobile phase in SFC, is cheaper, uses less energy, is non-flammable, and contributes to positive press about the reduction of organic solvent use and reuse of a greenhouse gas, compared to LC. This technology adoption also portends a future for SFC as a technology useful beyond the laboratory and into the pilot and production plants where it will rival traditional LC and simulated moving bed  (SMB) chromatography.

The increased use of SFC technology stems from the fact that obtaining man-made optically pure chiral compounds is one of the most challenging problems in the drug industry. According to a 2002 study from Penn State's Dana Bauer, "two thirds of the drugs now on the market—for anxiety, indigestion, heartburn, arthritis, AIDS, and allergies, even the big, billion-dollar drugs like Zoloft—are chiral drugs, which means that of their two forms one is good, the other is ineffective or even dangerous." Companies producing flavors and fragrances also face such a challenge, but the FDA requires drug companies to achieve the highest purity possible. The use of a single enantiomer can improve the effectiveness of chiral drugs, reduce the dosage needed, and reduce side effects.

Two schools of thought dominate the debate on how to obtain compounds in high enantiomeric excess. The first is asymmetric synthesis, favored by medicinal chemists and well understood by those at the discovery and process levels. The second school of thought maintains that chromatography (especially SMB technology) can solve the purity challenge. Chromatographers point to the success of H. Lundbeck's single-enantiomer drug Lexapro, which is used by 13 million Americans today.

Despite, or perhaps because of, the success of SMB technology, some industry observers and SFC users call for the application of SFC to meet the pharmaceutical industry's challenge for a cost-effective and environmentally-friendly technology. Merck's Dr. Christopher Welch's article in LC/GC in June 2005 highlighted the advantages of using SFC preparative separations of more than one kilogram using an SFC instrument with a flow rate of 350 gram/minute of carbon dioxide modified with methanol. Furthermore, Regis Technologies' announcement of a GMP-certified separations lab using the same equipment signifies a shift in the industry.

"We ran a separations business unit next to our core synthesis unit years ago but the cost of  solvent, solvent drying/disposal plus the related labor costs forced us to close it down. However, now that we use SFC technology, we can provide a faster turnaround and higher purity GMP material to the customer", said Regis' director of chromatography Francis Mannerino.

A major benefit of SFC is that it is actually a subset of LC, utilizing similar equipment and methodology. Carbon dioxide in the liquid and supercritical phases allows for high flow rates with low back pressures due to its lower viscosity, greater diffusivity, and greater ease of removal at the end of the process relative to water or organic solvents. The high capital cost and lack of robust equipment deterred potential users in the past. I have used multiple types of SFC equipment and can assert that SFC instrument manufacturers have overcome the quality problems of the past. Dr. Lalit Chordia, president and CEO of Thar Technologies states that "the price of SFC equipment is actually going down as more companies buy into the technique to solve their problems.

As a consultant, grandparent, and recent retiree from Pfizer/Pharmacia/Upjohn, SFC still fascinates me. I expect to see applications for SFC in quality control, natural product purification, mass-directed purification of combinatorial libraries, and achiral analyte purification as soon as in the next twelve months. We are only beginning to scratch the surface of potential for this technology. We must make it so, if my grandchildren are to be left with hydrocarbon resources.