How to achieve late-phage success in complex oral solid dose development

Key takeaways

• Design for ensuring robustness in manufacturability early—Anchor critical quality attributes (CQAs) and scalable controls from development to ensure consistency during tech transfer and validation.
• Leverage predictive and digital tools—Use in silico modeling, simulations, and Design of Experiments (DoE) to anticipate performance and streamline late-phase decisions.
• Balance technology and process strategy—Select the right processing platform, such as the granulation method and manufacturing mode (batch vs. continuous) to align with product complexity and commercial goals.
• Control variability and mitigate risk—Standardize materials, calibration, and containment approaches to prevent revalidation delays or compliance issues, especially for HPAPIs.
• Strengthen resilience through partnerships—Collaborate with a CDMO offering global infrastructure, regulatory expertise, and integrated technical capabilities for seamless scale-up and commercialization.

A promising molecule that is demonstrated to be safe and effective in a range of doses in early development is only the beginning. Late-phase scale-up is where scientific potential meets operational reality, and without the right framework, even the most promising oral solid dosage (OSD) programs risk stalling. At this stage, formulation complexity, process variability, and regulatory scrutiny converge, turning scale-up into a high-stakes endeavor with many variables. The question is no longer whether the product can be made, but whether it can be made reliably and consistently while meeting all the quality specifications at a commercial scale without introducing delays, rework, batch failures, or compliance risk. 

To scale with confidence, teams must align technical expertise with operational strategy, bringing adaptability, foresight, and successful implementation of each step. Where others falter and stall, late-phase scale-up can be done confidently with proper planning and execution.
 

How to build the strategic foundations for late-phase success

Late-phase success begins with designing for manufacturability and anchoring critical quality attributes in scalable controls. Tech transfer functions best as a translation of product intent, rather than a file handoff: development data, analytical methods, and tacit process know-how move with the product so that performance remains consistent and validation proceeds more quickly.

Many organizations gain leverage from platform experience and qualified equipment trains. These elements compress development cycles, stabilize outcomes, and support regulatory confidence. Predictive tools, such as in silico modeling, scale-up simulations, and design of experiments, help teams make earlier decisions with clearer evidence. For example, roller-compaction simulations can reveal equipment compatibility and process behavior before full-scale trials. This approach not only saves time and materials, but catches problems before they can derail a product while minimizing potential hiccups. 

Choosing the right technology to execute successfully  

Execution choices are most concrete when made in the context of commercial constraints. 

• Selecting the right granulation strategy: The choice between wet and dry granulation should be finalized before Phase II to prevent costly revalidation. Each approach offers unique benefits depending on formulation and commercial goals.
• Batch vs. continuous manufacturing: Batch manufacturing simplifies change management and supports flexible demand. Continuous manufacturing improves process control, reduces variability, and tightens feedback loops.
• Utilizing advanced analytical tools: Process analytical technology (PAT) enables real-time quality monitoring and deeper process understanding. This ensures consistency and compliance during large-scale production.
   

How to minimize risks in late-phase scale-up

In late-phase, missteps are rarely isolated. Timeline slips, revalidation, inspection findings, and launch delays are common downstream effects that consume capacity and erode confidence. Programs that reduce these exposures usually emphasize early regulatory alignment among process design, validation strategy, and control frameworks.
 

Handling high-potency APIs (HPAPIs)

Where high-potency APIs (HPAPIs) are involved, layered protection is the norm. Primary containment through hard-engineered barriers and closed transfers sits alongside facility controls and pressure management, with administrative safeguards for access, documentation, and health monitoring. Multidisciplinary coordination of process development, analytics, and tech transfer is necessary to work as a single system in order to scale while maintaining quality. Using prior knowledge and data-driven tools can help anticipate and avert failures and determine when processes and supply chains can absorb variability without sacrificing compliance or quality. Resilient processes and anticipating for risks can turn a volatile late-phase landscape into predictable execution.
 

Partnering for commercial readiness 

The right CDMO partnership turns strategy into sustained performance by anticipating late-phase complexities and solving them without disrupting progress. A capable partner offers:

• Technical expertise across formulation, process engineering, and analytical science, so emerging issues can be diagnosed quickly and corrected decisively rather than escalating into rework or delays
• Global infrastructure for flexible site transfer and continuity, allows materials, processes, and documentation to move smoothly across facilities while maintaining control, continuity, and chain of custody
• Complete understanding of the regulatory expectations for the product to meet global standards and a robust risk assessment (and mitigation) strategy.
• A proven regulatory track record ensures design, validation, and control strategies are aligned early, minimizing inspection risks and avoiding surprises during scale-up
• Specialized containment for HPAPIs and a culture of safety to turn potential obstacles into predictable execution

It is crucial to find the right CDMO that is prepared for all steps towards commercialization. 

Conclusion: Scaling with confidence

 Late-phase OSD scale-up can be a hurdle, but it’s a hurdle that can be prepared. With the right strategy, disciplined tech transfer, and a collaboration model built for resilience, late-stage scale-up and commercial readiness can be met with confidence.