The increasing global incidence of cancer underscores the urgent need for more effective and targeted treatments. Highly potent active pharmaceutical ingredients (HPAPIs) offer significant potential, providing therapies that specifically target cancer cells while minimising side effects. This article explores the advantages and challenges associated with HPAPIs, including their precise targeting capabilities and reduced toxicity. Here, Lucas Sauer-Jones, Vice President and General Manager at Veranova, discusses the role of contract development and manufacturing organisations (CDMOs) in addressing production challenges, emphasising the importance of advanced analytical techniques, regulatory compliance, and safety measures.
Potency and Processing: How CDMOs Can Rise to the Challenge of HPAPI Development
Highly potent APIs(HPAPIs) have grown in popularity over the last decade and are increasingly enabling innovators to develop targeted, low-dose therapies for patients who need them the most.
These compounds, known for their significant biological effects at very low concentrations, offer immense potential for treating various diseases, including cancer, autoimmune disorders, diabetes and more conditions. However, the journey from molecule to market for an HPAPI is complex, requiring specialised expertise and infrastructure. Therefore, it is crucial to explore how the industry can navigate these challenges to effectively scale up the development and manufacture of these vital therapeutics.
Highly Potent and Highly Valuable
Today, nearly 60% of approved oncology drugs involve HPAPIs. Their success lies in their ability to kill cells at low doses, reducing side effects and maintaining efficacy over longer durations, which decreases the need for frequent administration. HPAPIs are valuable not only as standalone therapies but also as components in advanced treatments like antibody-drug conjugates (ADCs). These ADCs target tumour cells precisely and are sometimes described as “silver bullets” due to their ability to minimise damage to healthy cells. This precision has enabled the use of more toxic payloads that were previously deemed too dangerous, offering breakthrough therapies for cancer patients.
What is a HPAPI?
While there is no universal definition for an HPAPI, these molecules are commonly categorised based on control banding strategies, particularly occupational exposure limits (OELs). OELs represent the upper limit on the acceptable concentration of an API in workplace air. Thus, the lower the OEL limit, the higher the potency, which demands rigorous containment and controls. Typically, compounds with OELs less than 10 μg/m³ are classed as highly potent. When working with highly potent molecules, ensuring the safety of workers and the environment is the primary challenge. Handling these potent compounds requires substantial planning and expertise. Even minute quantities can pose significant health risks, necessitating effective containment strategies such as closed systems, isolators, and high-efficiency particulate air (HEPA) filtration. Production line design must minimise operator exposure and ensure safe handling throughout development.
