Strategies for Manufacturing High-Potency APIs Outlined at Recent Conference

Newark, NJ (Sept. 14)- High-containment manufacturing for highly potent active pharmaceutical ingredients (HPAPIs) represents a niche, but a growing niche, in API manufacture. Strategies on serving this sector were discussed at a recent program, “High-Potency Active Ingredients: Realizing the Opportunities,” organized by the Drug, Chemical, and Associated Technologies Association (Robbinsville, NJ, www.dcat.org) in conjunction with Pharmaceutical Technology.

Opportunities in HPAPI Manufacture

Roughly 25% of all emerging new chemical entities (NCEs) are highly potent substances, estimated John Minatelli, senior director of commercial development at Ferro Pfanstiehl Laboratories, Inc. (Waukegan, IL, www.ferro.com), a CRO/CMO providing HPAPI development and manufacturing services to the virtual pharmaceutical sector. Of these emerging clinical NCEs, roughly 60% are novel, highly targeted small molecules, and 40% are proteins, vaccines, or monoclonal antibodies.

Minatelli explained that there is a significant barrier to entry into the HPAPI sector because of the high cost of installing HPAPI facilities because of the significant handling issues associated with highly potent or cytotoxic compounds. Current containment technologies include air entrainment systems, flexible systems, and isolator systems, outlined Hari Fluora, president of Floura LLC.

Categorization and certification for HPAPI manufacture

Cytotoxic drugs, prostaglandins, opiates, and certain hormones may be classified as potent compounds, explained Robert Sussman, managing principal of Eastern operations at SafeBridge Consultants Inc. (Mountain View, CA, www.safebridge.com).

While most manufacturers have specialized handling and containment systems in place for making potent pharmaceutical products, the systems for the categorization of these products vary from company to company. The generally accepted practice within the pharmaceutical industry is to use a categorization or banding system based on the potency or toxicity of the active pharmaceutical ingredients. These performance-based occupational exposure limits (PB-OELs) or hazard categories incorporate four-, five-, or six-band systems. The number of bands is usually based on the number of different containment environments that can be described. The SafeBridge system uses four bands and classifies “potent compounds” (Category 3) as compounds with OELs between 30 ng/m³ and 10 mcg/m³ and highly potent compounds (Category 4), as those with OELs less than 30 ng/m³. 

SafeBridge has also developed a certification program for potent compound manufacturers that provides a third-party assessment of a company's ability to handle potent compounds safely by certifying competency in the occupational health aspects of potent compound manufacturing. This certification may be used by a CMO as proof of its competency in this area to drug innovator companies. It may also be used by a pharmaceutical or biotechnology company to perform a gap analysis or needs assessment for their own manufacturing operations.

Recent examples of high-potency facilities include a retrofit of an API pilot plant by Pfizer, which was outlined by Paul Richards, project and technology engineer at Pfizer, Inc. (New York, NY, www.pfizer.com). The 30-year-old pilot plant with an open floor plan was successfully upgraded in 2001 with contained processing and handling systems to enable the manufacture of potent compounds.