HIGH POTENCY APIS
As programmes progress towards late-stage clinical development and Process Performance Qualification( PPQ) activities, early planning for commercial transition also becomes increasingly important. Close coordination between development and commercial teams can help ensure continuity as programmes move from clinical supply into longterm commercial manufacturing.
Conclusion
As accelerated development pathways continue to shape oncology and rare disease programmes, the management of HPAPIs is becoming increasingly complex. While specialist containment technologies and manufacturing capabilities remain essential, successful programme delivery also depends on effective project management, operational flexibility and close collaboration among all stakeholders involved in development and commercialisation. ●
References: 1: American Association for Cancer Research( AACR), Oncology Drug Approvals & New Molecular Entities( NMEs). 2: D. T. Michaeli, T. Michaeli, S. Albers et al., Eur. J. Health Econ., 2024, 25, 979 – 997. https:// doi. org / 10.1007 / s10198-023-01639-x
Rabiaâ Berkous
PROJECT MANAGER – DEVELOPMENT PROGRAMMES
CARBOGEN AMCIS AG k + 41 58 909 0488 J rabiaa. berkous @ carbogen-amcis. com j www. carbogen-amcis. com
Case study: Managing a long-term HPAPI development programme
A programme for the development of a Category 4 + HPAPI for a rare disease indication over a six-year period began in 2020. The compound was assessed and the most appropriate site for process and analytical development and manufacturing activities was selected, based on projected volumes and containment requirements.
At that stage, a Phase II clinical study in patients with tumours was already underway and a GMP batch was required within a short timeframe to support progression into Phase III studies. This required rapid process familiarisation, process optimisation and analytical method validation before GMP manufacturing activities could begin in 2021.
The initial development activities progressed smoothly, enabling the required timelines to be achieved. In 2023, the drug received both orphan drug and fast track designations, along with approval to proceed to Phase III studies using the selected dose confirmed during the Phase IIb study.
Additional process and analytical development activities were then performed to improve process robustness and manufacturing efficiency in preparation for future validation requirements, alongside the manufacture of an additional GMP batch supporting Phase III activities. In parallel, discussions continued on planning for future registration and validation batches ahead of NDA submission and commercialisation.
In early 2024, the programme was transferred to another biotech based in a different country. The new owner introduced significantly more aggressive timelines, requiring a rapid reassessment of priorities and close coordination across all partners in the programme. To support the revised strategy and objectives, several activities had to be carried out in parallel across multiple manufacturing sites, including:
• Manufacture of three additional GMP batches for registration activities
• Failure Mode & Effects Analysis( FMEA) studies
• Proven Acceptable Range( PAR) studies
• Analytical method validation activities
• Preparation & execution of the PPQ campaign
Some activities also required adjustments in response to issues identified elsewhere in the wider manufacturing network, including changes to the regulatory starting materials, additional GMP steps managed at different CDMOs and the impact on analytical method validations.
This required rapid reassessment of priorities and timelines, together with close collaboration between all stakeholders to maintain progress and support the revised registration strategy. Between 2024 and 2026, regular meetings and on-site visits were held to review progress, manage operational constraints and maintain alignment across the teams involved. The activities were completed successfully in Q1 2026.
NDA submission activities are currently underway and transition to specific activities for the commercial phase has started in parallel, with the objective of anticipating a commercial supply agreement for the next production upon FDA approval( review of the NDA is expected within a 60-day timeframe). Throughout, regular communication, operational flexibility and close collaboration between stakeholders were essential to supporting delivery against accelerated timelines.
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