(REGIS TECHNOLOGIES)
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By itself, supercritical fluid chromatography (SFC) is a well-known technique in pharmaceutical laboratories. Combined with
chiral separation media, however, the technique can prove to be a powerful tool for reducing early-phase development costs
and time. Although SFC chiral chromatography can be used at a process scale, its most typical application involves separating
50–100 g of materials for toxicology studies during the discovery and preclinical stages (see Figure 1).
Figure 1: Preparative separation using supercritical fluid chromatography.
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Regis Technologies manufactures chiral stationary phases and performs SFC custom separation work using chiral stationary phases
under good manufacturing practices (GMP).
"We work with a lot of companies that are just starting in their own process and looking for drugs to market," says Francis
Mannerino, director of chromatography at Regis Technologies (Morton Grove, IL). "We see compounds in their earliest stage
and a lot of them have difficulties in their purification. If they have a chiral separation built in, we try to marry the
custom synthesis with the separation work or the purification work."
Better business, better science
Figure 2: Scientist using an SFC preparative instrument in the Regis Separations laboratory.
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The method development for SFC chiral chromatography is similar to that for a typical liquid chromatography (LC) technique.
SFC chiral chromatography uses the same columns that are used in LC and the same, readily available stationary phases (see
Figure 2). Only the carrier is different. LC requires the use of 100% solvent, such as hexane–isopropyl alcohol (IPA) mobile
phase. In SFC chiral chromatography, CO2 liquid is the main carrier with a 5–10% cosolvent added with it. Most cosolvents are hexane, IPA, methanol, and ethanol.
About 95% of the separations by LC also can be separated with the SFC chiral method and, in some cases, the resolution can
be improved over traditional LC results.
According to Mannerino, there are two main business advantages of SFC chiral chromatography: separations can be completed
at least five times faster than separations using traditional LC and the technique uses about one-tenth of the amount of solvent,
which reduces process costs and produces less hazardous waste.
"What it comes down to is speed. Getting your drug to toxicology testing faster. If you're going to fail, fail fast. Take
your resources and put them into another project," says Mannerino.
The GMP road
As the first company performing SFC chiral separations under GMP, Regis faced several challenges. "For any new technique,
qualifying for GMP is very trying,"says Mannerino. Fortunately, the company manufactures active pharmaceutical ingredients
and finished-drug products under GMP conditions, so there were quality systems already in place. "We just needed to make the
capability GMP, so it was about 40 or 50 new standard operating procedures, and we customized them for SFC equipment and personnel."
After about 10 months and several dry runs, the company gained GMP qualification. "Our challenge right now on the research
side is improving productivity. There are no precedents, so we are developing different methods such as putting columns in
series and using different phases in series," says Mannerino.
Increasing productivity is crucial for shortening cycle time. SFC separation is a continuous process. Once automated systems
are developed and the technique is optimized, machines can run all day. "If you want a technique for commercial use, you have
to optimize it as much as you can. That's the biggest challenge now:increasing productivity by doing the research," says Mannerino.
