5 Costly Mistakes Companies Make When Scaling Spray Drying

Scaling spray drying from lab success to commercial production is one of the most complex and high-risk transitions in pharmaceutical manufacturing. While early-stage results may appear promising, many companies underestimate how facility design, safety systems, and operational realities impact performance at scale. These oversights are among the most common spray drying scale-up mistakes, often leading to costly delays, failed validation efforts, and diminished project ROI.

It’s critical to avoid these five pitfalls:

1. Falling for the “Scale-Up Illusion”

Processes that perform well in a lab environment often fail in a 20-foot drying chamber, where airflow, heat transfer, slurry homogeneity, and particle behavior introduce new challenges such as wall sticking, agglomeration, atomizer or nozzle clogging, and out-of-parameter particle size distribution. The result is often a significant drop in commercial yield. A 20% loss in yield at scale doesn’t just impact efficiency; it can severely undermine the return on a $50 million investment, turning a viable process into a financial liability.

2. Underestimating Infrastructure and Safety Risks

Spray drying with organic solvents at scale introduces serious explosion hazards that are not always present during lab testing. Designing equipment to safely manage these risks requires more than minor upgrades. It requires major capital investments in fire and explosion suppression and nitrogen inerting systems, as well as ensuring accurate electrical classification and division design of the chamber and components exterior to the chamber, a sealed conduit, controlled access to the area, and strict adherence to regulatory standards and the SOP. Overlooking these in the early design phase can lead to hidden costs, late-stage redesigns, and permitting delays that can push product launch by six to twelve months, impacting both revenue and market competitiveness.

3. Fragmented Procurement and Specification Gaps

One recent example of a foreseeable delay involved a secondary dryer purchased for final drying of a spray dried product. The factory built the dryer to the explosion-proof design specification and conducted a witnessed factory acceptance test (FAT). The dryer was delivered and installed in a Class I Division 2 room adjacent to the spray dryer. A third party executing the site acceptance test (SAT) discovered that the electrical components within the secondary dryer control cabinet were not rated for Class I Division 2 service. This caused a significant start-up delay that could have been prevented by a rigorous specification of the equipment and a thorough review of the submittals.

4. Treating Containment as an After-Thought

Particularly when working with high-potency APIs, containment must be a core component of pharmaceutical facility design. Retrofitting equipment with split butterfly valves (SBV), upgrading material dispensing stations to include isolators, adding a floor drain for contained process waste, or finding space for additional gowning and airlocks in an existing spray drying operation is not only expensive but often impractical due to space, airflow, and compliance constraints. Mid-project retrofits can trigger cascading delays, budget overruns, and increased regulatory scrutiny. Designing for containment and hazard from the outset is significantly more cost-effective and ensures operator safety, regulatory compliance, and smoother project execution.

5. Ignoring Operational Friction and Cleaning Validation

Spray-dried powders can be notoriously sticky, particularly when dealing with formulations with a low glass transition temperature. Without proper system controls and facility design, cleaning becomes a major bottleneck. Cleaning validation can quickly turn into a “validation nightmare,” where equipment sits idle for days between batches. This downtime not only reduces production capacity but also disrupts scheduling, increases labor costs, and limits a facility’s ability to meet market demand.

The Path Forward: Integrated Design

Ultimately, avoiding these mistakes requires a holistic approach that integrates process knowledge with pharmaceutical facility design expertise. At Genesis AEC, we advocate for a process-led strategy that addresses solvent handling, containment, cleaning validation, and infrastructure planning early in the project lifecycle.

By integrating these critical elements early on, companies do more than just build a facility. They protect commercial yield, ensure operational predictability, and safeguard project ROI.

Success in large-scale spray drying depends on more than the equipment on the floor; it requires the cross-disciplinary foresight to see how today’s technical decisions dictate tomorrow’s market performance. Partner with Genesis AEC to eliminate costly setbacks and ensure your product reaches the patient on time and within budget.