HIGH POTENCY APIS

OELs challenge and in some cases fall below the current OEB 5 definition.

The industry conversation about whether OEB 5 infrastructure remains adequate for the most potent compounds now in development is a real one and CDMOs whose containment capability is built on isolator technology and engineered systems are better positioned to adapt than those managing potency through procedural controls alone. 4

The second is the evolution of process monitoring. Real-time, in-line measurement of critical process parameters— the process analytical technology( PAT) approach formalised by the FDA in 2004— reduces the frequency and duration of manual sampling steps that represent exposure risk in HPAPI manufacture. 6

Combined with increasing automation of transfer and handling operations, these technologies point towards manufacturing processes in which operator exposure is minimised by design at every stage, not managed retrospectively through protective equipment and procedural discipline.

Conclusion

Successful HPAPI manufacturing ultimately comes down to how well complex risks are anticipated and managed across the lifecycle of a programme. Scientific understanding of potent chemistry, containment infrastructure aligned to the demands of highly active compounds and development methodologies that deliver reproducible, regulatorycompliant processes all play a role, but their value is realised only when they are applied in a way that supports real-world programme needs.

For drug developers, this means avoiding late-stage surprises, maintaining timelines under regulatory pressure and ensuring that

The value of combining process chemistry expertise with appropriate containment infrastructure is most clearly demonstrated through a specific programme that was defined by a fixed regulatory submission window and limited tolerance for process iteration beyond pilot scale.

A speciality pharmaceutical company required registration batches for a Phase IIb oncology compound within a fixed twentymonth window. The existing synthetic route was five steps long, yielded 16 % overall and produced impurity profiles above ICH Q3A thresholds at every step evaluated. In addition, several key reagents presented occupational and environmental risks that could not be managed within the client ' s containment capability.

Farmabios redesigned the route using in silico modelling to identify and remove the hazardous reagents, then applied Design of Experiments( DoE) across the critical process parameters—

processes developed at small scale translate reliably into commercial manufacture. Organisations that have built this alignment over time are typically better equipped to navigate these demands consistently, not just technically, but operationally where it matters most.

For companies seeking a partner for HPAPI programmes, the relevant question is not whether a CDMO has the right equipment but the knowledge about how to use it and what to do when a project does not behave as expected. ●

temperature, stoichiometry and reaction time— of the new synthesis.

Scale-up behaviour was characterised using computational fluid dynamics modelling before any physical pilot-scale work was initiated, compressing the timeline between laboratory and pilot manufacture. Particle engineering was conducted in parallel with route development, using fractional factorial design to define crystallisation conditions that delivered the target particle-size distribution in a form compatible with contained processing.

Three cGMP registration batches, each of 40 kg, were completed within eight months of programme initiation. Overall yield reached 42 %; impurity levels across all steps fell below 0.05 %; and hazardous waste generated per kg of API produced was reduced by 95 % relative to the original route. The programme comfortably met its regulatory submission deadline.

Mario Di Giacomo

MANAGING DIRECTOR

JUL / AUG 2026 SPECCHEMONLINE. COM

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