APIs vs. HPAPIs: Key Differences and Manufacturing Challenges

Nowadays, medicines are an essential element of our daily life. Whether dealing with an occasional headache or a common cold, taking medication regularly has become routine. Yet, most of us do not exactly know how the medication we take acts to alleviate our symptoms. The key player in this process is the active pharmaceutical ingredient, or API, present in the drug product; the molecule that acts on the designated chemical pathway of our body and produces the desired physiological effect. This definition is based on functional properties, and it includes many kinds of molecules: hormones, peptides, carbohydrates, nucleotides, antibodies, etc.

Due to its evident relevance, the API field is the focus of numerous research efforts, continuously striving to find a better and more effective molecule to cure a disease or alleviate its symptomatology. As a result, in recent years, a new category of APIs has arisen: HPAPIs or highly potent APIs.

HPAPIs are defined as pharmacologically active ingredients – or intermediates – that show biological activity at a dosage equal to or lower than 150μg/kg of body weight in humans. As this definition indicates, HPAPIs are effective at much smaller doses than other APIs, which increases their efficiency. Additionally, most HPAPIs show a higher precision and selectivity than their predecessors. Altogether, these advantages confer a level of attractiveness to HPAPIs that has placed them on a fast growth track in the global pharmaceutical market. Currently, over 25% of the existent pharmaceutical formulations contain HPAPIs, and they are used for multiple different applications: hormonal drugs for breast cancer, glaucoma treatment, ADCs used for targeted cancer therapy, cardiovascular medication, etc.

However, these benefits come with specific challenges, especially when it comes to their manufacturing process and handling. The fact that they show a biological effect at such low concentrations makes them more hazardous than other APIs. Consequently, the occupational exposure limit (OEL) for these substances is lower than that of regular APIs, which makes their manufacturing and handling more expensive and time consuming. Before the start of a HPAPI project, the toxicology of the molecule must be studied, the personnel must be accordingly trained, and the convenient containment measures must be taken during production, handling and transport to ensure the protection of workers involved in these processes.

In the face of this strict and demanding landscape, it is convenient for HPAPI manufacturers to decrease as much as possible other additional burdens associated with the production process. Here at GRIT, we contribute to the alleviation of these complexities with our Gas-to-Liquid (GTL) solutions, which provide API & HPAPI manufacturers with tailor-made solutions of hazardous gases in organic solvents, and therefore suppress the added challenge of directly handling these gases.

In conclusion, while HPAPIs offer significant advantages of precision and efficacy, their production presents unique challenges that require advanced handling and safety protocols. By integrating innovative solutions such as Gas-To-Liquid (GTL) technology, manufacturers can streamline processes and enhance safety, ultimately contributing to a more efficient pharmaceutical landscape.