Highly potent active pharmaceutical ingredients (HPAPIs) are pharmacologically active substances that exhibit biological activity at extremely low concentrations, such as daily therapeutic dose of <10 mg or an occupational exposure limit (OEL) of < 10 μg/m3 at an eight hour time-weighted average.
Each HPAPIs have specific OEL that must be considered by an institution to guarantee safe handling, as there is a selective process in choosing the most appropriate strategy for containment.
The continuous expansion of the biopharmaceutical market, particularly, the global demand in the field of medical oncology, calls for an increase in the development and conventional drug manufacturing of high potency active pharmaceutical ingredients (HPAPIs).
Antibody drug conjugates (ADCs), which use very toxic molecules specifically targeting cancer cells serve as one example for HPAPIs.
HPAPIs now account for 25% of all drugs produced globally, with some analysts projecting that it will reach a value of $40 billion by 2027.
This projected expansion shows the potential of the market. However, safety and regulations must be followed for successful growth, as HPAPIs are notoriously difficult to handle.
With several major oncological drugs also due to go off patent over the next few years — including Nilotinib in 2024, Pomalidomide in 2025 and Enzalutamide in 2026 — “HPAPI ready” businesses will be free to make bids for their manufacture.
For this reason, it is critical that manufacturers can demonstrate to authorities, such as the EMA or the FDA that they can work with highly potent ingredients safely.
The major problem with this is that human intervention is present at almost every stage of the manufacturing process, thus, increasing the risk for personnel exposure. This could lead to various adverse health effects to all personnel involved; that is why, ensuring the safety of the manufacturing personnel is of high importance. However, addressing this issue should not impede productivity.
In the manufacture of these highly potent compounds, specialized considerations are needed to be deliberated for the facility design, equipment, operation, and safety to achieve the best level of containment of the drug product.
Although the process requirements for HPAPIs are typically no different to less toxic APIs however the toxicity of HPAPIs demands specialized facilities and equipment to ensure the safety of personnel and the environment.
Containment strategies are critical, with a need for state-of-the-art engineering controls, personal protective equipment, rigorous procedures and specialist training. Crosscontamination risks further intensify the complexity of HPAPI handling which require robust cleaning procedures and verification.
- Physicochemical Properties of Drugs
- Contamination Control Strategy (CCS) for Pharmaceutical Industry
- Sourcing of Starting Material in Pharmaceutical Industry
Resource Person: BARBARA PIROLA