Biologics high-potency manufacturing.
SAFC is expanding bacterial and fungal fermentation-derived HPAPI capacity at its Jerusalem facility. The Jerusalem site
has an existing API manufacturing plant using fermentation, and the $29-million expansion will add a new GMP HPAPI fermentation
facility next to the existing plant. Requirements for both containment for HPAPI manufacturing and the scale-up and the purification
of biologics through fermentation had to be factored into the new facility's design and operation.
"From a facility design aspect, one needs to have the ability to use solvents, so the design of blast-proof suites was an
important consideration," says Backer. The scale of production, which will be more than 10 L in a Biosafety Level-2 environment,
requires dedicated suites, airlocks, 100% single-pass air, and exit showers. "Since the facility will operate 4000-L fermenters,
there are appropriate systems and procedures for cleaning and sterilizing of equipment as well as for the transfer of product
and large volumes of liquid," he adds. Biohazard safety cabinets will be used for small-scale operations.
SAFC will seek SafeBridge certification for its HPAPI fermentation facility in Jerusalem, which includes implementation of
operator safety procedures and practices. "For personnel, strict gowning procedures are implemented to protect the employees
that are trained and qualified to perform these operations, including the manufacture of these potent products," says Backer.
"Personnel, materials, and waste flows are kept unidirectional. All of these measures plus strict changeover procedures also
ensures the prevention of cross contamination, which is the heart of GMP." The product becomes more potent as it moves downstream
and is concentrated into a powder stage. At this point, operations occur in isolators, and operators use respirators, similar
to equipment and protection offered in other HPAPI facilities.
A look forward
As in other areas of manufacturing, disposables or flexible containment technologies are becoming important in HPAPI manufacturing.
"The manufacturing of potent products follows a trend in the industry of providing smaller lots and more potent products.
The use of disposable equipment is being employed, where appropriate, though the use of various chemicals and solvents limits
the use for certain HPAPI products. We also use dedicated equipment where appropriate," says Backer. Table I identifies the
facilities in which SAFC uses disposable technologies.
Table I: Examples of technology and equipment in SAFCs high-potency active pharmaceutical ingredient (HPAPI) facilities.
Patricia Van Arnum is a senior editor at Pharmaceutical Technology, 485 Route One South, Bldg F, First Floor, Iselin, NJ 08830 tel. 732.346.3072, firstname.lastname@example.org
1. D. Bornett, "High-Potency APIs: Containment and Handling Issues," Pharma Ingredients supp., Pharm. Technol. 32 (9), s12–s16 (2008).