Examining High-Potency API Manufacturing - Pharmaceutical Technology

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Examining High-Potency API Manufacturing
High-potency manufacturing of active pharmaceutical ingredients is a growing and specialized capability.

Pharmaceutical Technology
Volume 33, Issue 7, pp. 42-46

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

Table I: Examples of technology and equipment in SAFCs high-potency active pharmaceutical ingredient (HPAPI) facilities.
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.

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,


1. D. Bornett, "High-Potency APIs: Containment and Handling Issues," Pharma Ingredients supp., Pharm. Technol. 32 (9), s12–s16 (2008).


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