APIs vary in potency depending on their level of concentration, and the huge variations in what can be classified as a highly potent or a traditional API poses challenges when it comes to understanding their individual handling requirements.
Highly potent APIs (HPAPIs) elicit a more targeted and measurable therapeutic effect in lower concentrations compared to traditional APIs. This enhances the efficacy of the finished drug and allows for smaller dosage sizing, potentially reducing the incidence and severity of adverse side effects in patients.
Examples of HPAPIs include:
- Sex hormones and steroids, which can pose a significant risk to the health and wellbeing of handlers if improperly contained
- Drugs with high toxicity, classified as having an occupational exposure limit at or below 10μg/m3 of air as an eight-hour time-weighted average
- High selectivity drugs that are formulated to affect a single organ or system, which can bind to specific receptors or enzymes, impacting their function and having the potential to cause cancers
- Newly discovered ‘novel’ drugs with undetermined potency levels are classified as highly potent until proven otherwise During processing and downstream manufacturing, exposure to these powerful compounds can be hazardous to operating staff, the operating environment, and patients via cross-contamination. Steps must be taken to safeguard line operatives against exposure, or to ensure containment of waste products to prevent potent chemicals entering the environment surrounding the site to jeopardise wildlife or local communities.
Not only must appropriate measures be put in place to ensure adequate containment of these chemicals, but they must also be tailored to the specific nature of the material being processed.
Failure to do so can have significant legal and financial repercussions for drug developers. They could be fined if they are found guilty of failing health and safety or environmental standards, and could suffer long-term reputational damage as well. This could impact on future revenue and business growth, or even affect recruitment and staff retention.
A growing number of new chemical entities (NCEs) entering the drug development pipeline are classified as HPAPIs, making it all the more important to take steps to safeguard employees from exposure to comply with legislative requirements. Increasingly, regulatory authorities in the US and EU are requiring more stringent monitoring of levels of HPAPI in the air within production facilities. The International Society for Pharmaceutical Engineering’s Standardised Measurement of Equipment Particulate Airborne Concentration guideline stipulates stringent analysis of airborne levels of HPAPIs.
Before developers can begin handling an HPAPI, they must first evaluate and classify its occupational exposure band, or occupational hazard class (OHC), to define the required containment and handling controls.
The required measures vary depending on the level of exposure hazard, but fundamentally, all stages of handling HPAPIs must be carried out in a contained environment. Handlers must implement strict engineering controls to prevent the release of particulates into the atmosphere, and ensure the safe disposal of any waste materials.
Implementing containment measures can lead to additional time and cost as developers must adapt their facilities, train their staff, and invest in the right equipment for safe handling and containment.