High-potency manufacturing is a niche, but specialized area that requires proper facility design, equipment selection, production
processes, and operator knowledge to safely handle and produce highly potent APIs (HPAPIs) and finished drug products containing
HPAPIs. Pharmaceutical Technology conducted an industry roundtable to gain a perspective of these issues. Participating were: Joe Cascone, director of potent
product pharmaceutical development at Metrics; Joe Nettleton, vice-president and director of operations at Cambrex's Charles
City, Iowa, facility; Peter Müller, delegate of the Dishman board and member of the Carbogen Amcis' management team; Theodore
Iliopoulos, chief scientific officer at Euticals; Paul Doherty, chemical engineer, Sigma Black Belt, and plant manager at
Ferro Pfanstiehl Laboratories; and David Bormett director of operations at SAFC.
Facility design and equipment selection
PharmTech: A key challenge in high-potency manufacturing is to maintain the level of containment throughout the manufacturing process.
What are the key considerations in designing a high-potency manufacturing facility and in selecting equipment?
Iliopoulos (Euticals): High-potency containment structures address both cross-contamination requirements targeting patient safety, and at the same
time, worker safety by maintaining occupational exposure limits (OELs) below 10 mcg (Band III) or 10 ng (Band IV) per cubic
meter of air for an eight-hour weighted average. Exposure to just a small quantity of a highly potent HPAPI or highly potent
compound can pose significant health risks.
The challenge in designing a high-potency containment facility is to find the appropriate level of containment that should
manage the exposure risk at a reasonable cost. It also is crucial that the operators and the production staff understand the
need and proper use of engineering controls. Enclosed reactors, centrifuges, dryers, and highly dusty mills are key manufacturing
assets in an API production line and, together with product-transfer systems, are key elements in a high-containment design.
The most crucial issues in selecting the proper equipment are the containment of the process itself. In other words, one must
ensure that no airborne particles are released to the ambient air and that product remains in the process piping used. Equipment
and facility-engineering controls apply to all areas handling such compounds, not just manufacturing. It also refers to process-development
and quality-control laboratories.
Manufacturing chemist in personal protective equipment handling material in fully contained glovebox isolator at SAFC's facility
in Verona, Wisconsin.
Bormett (SAFC): Proper initial design and engineering of a potent-compound handling facility is crucial to achieve the desired levels of
containment. Consideration must be given for containment of the entire process, from weighing and charging of raw materials,
to packaging of the final material. Key facility-design criteria include single-pass heating, ventilation, and air-conditioning
(HVAC) systems, controlled access to areas, airlocks around potent-compound handling rooms for segregated gowning/degowning,
proper room-pressure differentials for containment, degown misting showers, bag-in/bag-out filtration components, sufficient
support utilities (such as supplied air), and proper waste-handling capabilities.