Potency, precision & partnership: Advancing HPAPI development and manufacture
Mario Di Giacomo, managing director of Farmabios, discusses how containment and science underpin HPAPI programmes
Twenty years ago, manufacturing a highly potent API( HPAPI) at commercial scale was a niche specialism, relevant only to a narrow band of cytotoxic oncology drugs. Now, the convergence of targeted cancer therapies, antibody-drug conjugates( ADCs) and precision medicine has placed HPAPIs at the forefront of drug development pipelines worldwide.
A substantial and growing share of new molecular entities currently in development carries a highpotency classification, and the clinical expansion of ADCs, now approved across multiple oncology indications and under investigation in autoimmune disease, has drawn considerable attention to how their payloads— among the most potent synthetic compounds in clinical use— can be manufactured safely and at scale. 1
This is not a straightforward question. HPAPIs sit at the intersection of demanding chemistry, strict occupational safety requirements and rigorous regulatory oversight. The infrastructure needed to manufacture them— contained reaction environments, validated transfer systems, independent air handling and trace analytical methods— requires both significant capital investment and sustained operational expertise.
For most drug developers, the question is not simply where a
The Farmabios site at Gropello
compound can be manufactured, but how risk is managed across the lifecycle of a programme. Earlyphase priorities— speed of route validation, flexibility in development and access to analytical data— shift as projects approach registration, where reproducibility, documentation and inspection readiness become dominant concerns.
OELs & OEBs
The choice of manufacturing partner therefore becomes less about fixed capability and more about how well those shifting requirements are understood and anticipated. A framework for managing potency begins with occupational exposure limits( OELs) and occupational exposure bands( OEBs).
Any discussion of HPAPI manufacturing starts with the question of how potency is defined and measured in an occupational context, because this determines not only how a compound can be handled, but where and how quickly it can be developed and scaled. The regulatory basis for this within the EU is grounded in the concept of the acceptable daily exposure( ADE), defined by the EMA as the dose of a substance unlikely to cause adverse
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