In recent years, advancements in oncological research have fueled a surge in demand for highly potent active pharmaceutical ingredients (HPAPIs). So much so that the HPAPI market is estimated to reach USD 31.5 billion by 2029.

Thousands of HPAPIs are currently in development that promise lower dose requirements, enhanced efficacy, improved patient compliance, and fewer side effects. 

Manufacturing these drug products involves expert specialization and careful consideration to ensure that GMP regulations for drug submissions are met, the risk of exposure for CDMO-related personnel is reduced, and every effort is made to prevent cross-contamination.

In Issue 35 of The Altascientist, we explore the intricacies and critical considerations for the safe and compliant manufacture of highly potent drugs, in particular HPAPIs, which include:

• categorization of HPAPI potency;
• classification of exposure potential;
• appropriate containment strategies;
• engineering controls and waste management practices; and
• global regulatory requirements.

What Defines High Potency for an API?

The classification for what constitutes high potency for an API varies depending on the source. However, it is generally defined by one or more of the following: biological activity at approximately 150 μg/kg of body weight or below in humans; hormones; certain steroids; novel compounds with unknown toxicity or potency including biological activity; occupational exposure limits (OELs) at or below 10 μg/m of air as an eight-hour time-weighted average; high selectivity and/or with and potential to cause cancer, mutations, development effects, or reproductive toxicity at low doses. New APIs undergo robust evaluation to determine their classification level for safe handling procedures and clearance limits.

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In Issue 33 of The Altascientist, we explore how a comprehensive, end-to-end integrated approach to drug development for central nervous system (CNS) therapeutics can take you seamlessly from lead candidate selection to market. 

Engaging at the outset with a fully integrated and experienced drug development partner can ensure safety, with timely data sharing at every step of the drug development plan, and facilitate agile, flexible decision-making and planning.

With detailed case studies, study considerations, and more, this Issue covers:

• preclinical safety and toxicity testing,
• formulation and manufacturing,
• early-phase clinical trials, and
• bioanalysis.

the cns drug development landscape

The different parts of the nervous system, including the brain and spinal cord (i.e., central nervous system – CNS) and the peripheral nervous system, are important drug targets for many serious diseases affecting human health. As the body’s processing center, the CNS is responsible for all functions of our bodies, including thoughts, emotions, memories, and behaviors.

According to Fortune Business Insights, the global CNS market is projected to grow from $89.02 billion in 2021 to $166.53 billion in 2028, at a compound annual growth rate (CAGR) of 9.4%. This growth is driven primarily by the rising demand for age-related neurodegenerative treatments due to the increasing global population over the age of 65, the growing potential of psychedelic therapies in treating conditions like PTSD and psychosis, and CNS-active drugs proving increasingly effective across various areas, such as acute and chronic pain, brain diseases, and autoimmune disorders. 

“The successful delivery of drugs targeting the treatment of CNS conditions is challenged by the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BSCFB), which protect the CNS from intrusion by harmful substances. Large molecules are less able to penetrate the blood/brain barrier to deliver therapeutic results and thus most CNS-active drugs are small molecules.”   — The Altascientist, Issue 33, pg. 2.

SPECIALIZED ASSESSMENTS AND STUDIES

Unsurprisingly, drugs working on the CNS are subject to stringent regulatory requirements, and specialized safety assessments are often mandated. To confirm CNS activity without safety concerns, dedicated nonclinical and early-phase clinical studies, with relevant endpoints and biomarkers and supporting bioanalysis, are needed, and drug manufacturing must be carefully managed via rigorous handling and production processes. 

“Specialized assessments in nerve conduction are sometimes performed in CNS drug development, depending on the specifics of the new molecular entities. These key assays, performed in NHPs, can be included in preclinical safety and toxicology programs to assess the peripheral neuropathy (PN) liability of a new drug.” — The Altascientist, Issue 33 pg. 5.

The many advancements in developing CNS-active drugs have been hampered by higher failure rates compared to drug discovery in most other therapeutic domains. Identifying CNS experts with a well-established record of conducting rigorous, high-quality research can assure the effective management of challenges and reduce the risks of delaying or failing to advance promising drug candidates.

Explore all issues of The Altascientist in our Resource Center. And don’t forget to subscribe to “The Altascientist: Audiobooks” on Spotify, Apple Podcasts,  or wherever you get your audio content.