At-A-Glance: Highly Potent API

The highly potent active pharmaceutical ingredient (HPAPI) market is growing rapidly with no signs of slowing down. But what is it, how is the market changing, and what are the expected trends in this space?

HPAPI is generally defined as:

• A pharmacologically active biological ingredient or intermediate with activity at approximately 150 µg/kg of body weight or below in humans (therapeutic daily dose at or below 10 mg)
• An API or intermediate with an occupational exposure limit (OEL) at or below 1µg/m3 of air as an 8-h time-weighted average
• A pharmacologically active ingredient or intermediate with high selectivity (i.e., ability to bind to specific receptors or inhibit specific enzymes) and/or with the potential to cause cancer, mutations, developmental effects, or reproductive toxicity at low doses
• A novel compound of unknown potency and toxicity

The potency of HPAPIs is characterized by OELs in µg/m3. The lower the value, the more potent the compound and the greater the level of containment required. OELs and related criteria, such as toxicity and carcinogenicity, establish exposure control limits.

Critical Factors for Achieving Appropriate Levels of Containment in HPAPI Manufacturing

• Equipment selection
• Facility design
• Engineering controls
• Operator safety (personal protection equipment, materials handling training, and other measures to prevent operator exposure to hazardous materials)

Shifting HPAPI Approaches
The industry continues to move away from compound classifications— such as beta-lactones, cytotoxics  and other similar classifications to establish control limits— and is now focusing more on data-based acceptable daily exposure (ADE) / permitted daily exposure (PDE) calculations to quantify the toxicity risk for both patients and drug manufacturing operators, with all appropriate controls being based on that data. In short, the trend is to not reject something or draw conclusions based on a compound class.

Alcami relies on certified internal and third-party toxicologists who perform evaluations to establish not only an OEL but also an ADE. In cases of substantial uncertainty and limited information, this analysis also allows us to assign banding to facilitate effective internal communication for managing a particular compound.

HPAPI Market Trends
Currently, approximately 25 percent of drugs in development worldwide are classified as highly potent. This number continues to rise, driven in particular by growth in the oncology market.

The global oncology market was valued at $107 billion in 2015, an increase of 11.5 percent from 2014. The IMS Institute for Healthcare Informatics and Grand View Research estimate that the market for HPAPIs will be valued at $25.86 billion by 2022. The high investment necessary to establish and maintain cost-effective production sites has led many sponsor companies to turn to contract development and manufacturing organizations (CDMOs) like Alcami, with established track records in the successful development, scale-up  and commercialization of highly potent small-molecule APIs and biologic drug substances.

The market for HPAPIs continues to grow at approximately 10 percent per year, primarily due to the development of highly targeted drugs for the treatment of cancer and chronic diseases such as diabetes and heart disease.

Stay tuned for our next HPAPI post titled: Have a Highly Potent API? Here’s What to Consider.

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