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10.6 SMB Accepted for Manufacturing 281

10.6 SMB Accepted for Manufacturing

10.6.1 Practical Implications for Manufacturing

SMB is now accepted as a real production tool. For instance, the Belgium pharma-
ceutical company U.C.B. Pharma announced recently the use of SMB for perform-
ing multi-ton scale purification of an enantiopure drug substance. The concept of
large-scale purification of enantiomers using chromatographic techniques has
moved from a dream to a reality within the last few years.
A major advantage of SMB technology compared to the cost of stereoselective
synthesis is that manufacture of a racemic drug substance has already been proven
to be straightforward, inexpensive, and less time-consuming. Coupling non-stereos-
elective synthesis with an SMB process is an economical way to produce both enan-
tiomers with high purity and recovery. The main object for any pharmaceutical man-
ufacturer is the rapid delivery of enantiopure drugs to market.
The interests of SMB for performing large-scale separations of enantiopure drugs
has been recognized (very short development time, extremely high probability of
success, and attractive purification cost) [68]. Several pharmaceutical and fine chem-
ical companies have already developed SMB processes. However, because of strong
confidentiality constraints, public information is limited, and some of the major
announcements are summarized below:

DAICEL announcement: Daicel has announced an investment in a SMB pro-
duction plant with columns of 100 mm i.d. to be installed in their facilities at Arai
(Japan). This plant produces hundreds of kg per year for a drug currently manu-
factured by Nissan Chemicals (Japan Chemical Week, December 4, 1997).
UCB announcement: UCB Pharma (Belgium) announced in 1997 its decision to
install a SMB made of columns of 45 cm i.d. in order to perform large-scale man-
ufacturing for a promising new class of drugs. UCB decided to replace a classical
chemical process used in the pharmaceutical industry by SMB technology.
AEROJET: AEROJET (California) has announced in 1999 its decision to invest
in a SMB system using columns of 80 cm in diameter.

10.7 Conclusions

The evolution of FDA policies continues to be a significant driving force on the
global pharmaceutical market. Several pharmaceutical firms have made new discov-
eries while evaluating enantiopure drugs originally discovered and marketed as race-
mates by others. These pharmaceutical firms have merged, or other companies have
appropriated portfolios of patents based on chiral switches. Thus, the FDA contin-