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10.5 SMB as a Production Tool 275

Choosing the second option, we would increase the flowrates in zones I and
decrease the flowrate in zone IV. Then adjust the flowrates in zones II and III (the
feed flowrate is slightly decreased to improve the margin in these two zones). With
the assistance of the simulation program, we can determine to what degree the
flowrates should be decreased or increased to obtain the target purity.
The final flowrates are determined by replacing the initial set of flowrates:

Q = 567 l h –1 Q = 395 l h –1 Q = 521 l h –1 Q = 400 l h –1
I II III IV
by:
Q = 587 l h –1 Q = 409 l h –1 Q = 519 l h –1 Q = 395 l h –1
I II III IV
which leads to an extract purity of 99.4 % and to a raffinate purity of 99.4 %. The
new flow rates are thus very close from the initial one.

10.5 SMB as a Production Tool

10.5.1 cGMP Compliance

Current Good Manufacturing Practices (cGMP) and compliance are the require-
ments found in the legislation, regulation, and administrative provisions for drug
manufacturing processes. It defines the facilities, equipment, manufacturing pro-
cesses, and packaging of a drug substance or product. It assures that such drug sub-
stance or product meets the requirements as to safety, efficacy, and purity. Under
cGMP, the FDA provides guidelines for the manufacturing, processing, and packag-
ing of all drug substances, which include enantiopure drugs as API. The API or fin-
ished dosage form of the drug is intended to provide pharmacological activity for the
diagnosis, cure, treatment, or prevention of a disease. APIs include substances man-
ufactured by processes such as: chemical synthesis, fermentation, and biotechnology
methods, purification process such as chromatography, and isolation and recovery
from natural products.
The FDA recognizes that at certain early production stages, applying stringent
controls may not be feasible or necessary. The stringency of controls, such as the
extent of written instructions, in-process controls, sampling, testing, monitoring and
documentation, in the manufacture of API’s increase as the process proceeds from
early intermediate stages to final synthesis and purification.

10.5.1.1 Manufacturing and Process Controls

In March of 1998, the FDA announced a draft guidance document for Industry for
the manufacturing, process, or holding of APIs [64]. We shall apply our interpreta-