OSD
Navigating high potency OSD manufacturing
As therapies become increasingly targeted, high potency APIs (HPAPIs) are becoming a central feature of modern development pipelines. Their ability to deliver therapeutic effect at very low doses brings clear clinical advantages, but it also increases the demands placed on manufacturing, particularly for oral solid dose (OSD) products where containment, process design and facility controls must work seamlessly.
Working with high potency compounds requires facilities, processes and controls designed specifically for safe handling and consistent performance. For many organisations, this makes the choice of CDMO partner critical. Understanding the fundamentals of high potency OSD manufacturing helps teams identify the level of expertise, infrastructure and operational discipline needed to support these products effectively.
Why high potency calls for a specialised approach
HPAPIs demand a higher level of control than conventional molecules. Even extremely low levels of exposure can be significant, meaning containment, cleanliness and cross-contamination management are essential. Regulatory expectations reflect this, with clear OEL definitions, validated cleaning approaches and comprehensive risk assessments forming part of the foundation for compliant manufacture.
These requirements influence every stage of production, and high potency OSD should not be managed through standard approaches. When the right capabilities are not in place, projects often encounter avoidable delays, additional investigations or challenges during scale-up.
The role of containment
Containment is frequently interpreted as a single engineering solution, yet effective high potency manufacturing depends on a system built across several layers.
- The first layer focuses on how the API is handled: isolators, closed transfer systems and engineered solutions that minimise the potential for powder escape.
- The second layer sits within the facility itself. Airflow design, pressure cascades, airlocks and controlled movement of personnel and materials create a safe and predictable working environment.
- The third layer comprises the operational routines that support long-term performance, including training, hygiene monitoring, validated cleaning and defined waste-handling processes.
When these layers operate together, they provide the foundation for safe, controlled and reproducible manufacture.
Process design and facility planning: What often gets overlooked
High potency OSD production places additional emphasis on process and facility design. How material is dispensed, transferred and sampled can influence exposure profiles and process reproducibility. Solutions such as split-butterfly valves, closed transfer systems and dry granulation are often used to strengthen containment and support stable performance, particularly when APIs are sensitive to moisture or heat.
Maintenance, changeovers and cleaning require similar levels of attention, as these activities can present elevated exposure risks if not supported by appropriate engineering controls and defined workflows.
Facility layout underpins these considerations. Segregated HVAC, pressure zoning, dedicated waste routes and clear material and personnel flows are essential for maintaining containment and enabling efficient scale-up.
Tech-transfer: Ensuring continuity, process understanding and speed to market
Tech-transfer is a pivotal stage in the progression of any high potency programme. It is the point where process knowledge, containment strategy and manufacturing conditions must align to ensure a controlled transition from development through to commercial execution.
A complete potency profile, OELs, PDEs, formulation details and critical process parameters, forms the basis for assessing containment requirements and guiding the receiving environment’s preparation. Data driven tools strengthen this work further. By applying statistical modelling and simulation, it becomes possible to explore how a process behaves before scale-up begins. This approach reduces the number of test cycles needed, limits API consumption and provides a clearer understanding of the operating window required for robust, repeatable performance.
Recipharm’s predictive, proprietary tool ReciPredict™, supports this by modelling material behaviour and identifying the parameters that influence process stability and quality outcomes. With fewer iterations and improved insight, programmes can progress toward clinical manufacture with greater predictability and reduced risk of deviation during transfer. A well structured tech-transfer framework therefore supports both continuity and speed, helping ensure that high-potency processes perform as expected across each scale.
Quality and regulatory expertise as a foundation for high-potency work
High potency OSD programmes benefit from partners with stable quality systems and mature regulatory foundations. Facilities operating under established FDA and EMA approvals, supported by consistent right-first-time and on-time performance, create an environment where complex products can move forward with fewer interruptions. Managing high potency also extends beyond the manufacturing floor. Quality control laboratories require the same level of containment thinking, with tailored facility design and procedures that prevent cross-contamination and meet the expectations of regulatory agencies.
Global networks add another layer of stability. When sites follow harmonised development and tech-transfer procedures, supported by coordinated project governance, programmes benefit from a consistent way of working across locations. Local execution, combined with access to broader specialist expertise, helps maintain alignment and continuity from early development through commercial supply.
These elements together form a reliable operational base for the long term manufacture of high potency OSD products.
Looking ahead: What pharma teams should keep in mind
High potency compounds will continue to expand across therapeutic areas, and manufacturing strategies are evolving to support this shift. Automation is reducing operator interaction, digital tools are improving process understanding and facilities are exploring more energy-efficient containment solutions.
As these products continue to grow in complexity and volume, the focus will remain on predictable, well controlled manufacturing environments supported by strong containment systems, structured tech-transfer and stable quality foundations promising safety or compliance.
