Five costly mistakes pharmaceutical manufacturers make when scaling spray drying from lab to commercial production

Facility design, containment, and cleaning validation decisions can greatly influence a commercial yield and time-to-market.
June 25, 2026
4 min read
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Key Highlights

  • Lab success does not guarantee scale-up success; airflow, heat transfer, and particle behavior change at larger volumes, risking yield loss and process inefficiencies.
  • Safety considerations for organic solvents and explosion hazards demand major infrastructure investments, including fire suppression and inerting systems, to prevent delays and ensure compliance.
  • Fragmented procurement and inadequate specifications can cause costly delays; thorough review and rigorous testing of equipment specifications are essential.
  • Containment must be integrated into the initial design to prevent costly retrofits, delays, and regulatory issues, especially when working with high-potency APIs.
  • Ignoring operational factors like cleaning validation can cause excessive downtime, reducing capacity and increasing costs; early planning improves operational predictability.
Courtesy of Genesis AEC
Scaleup project

Scaling spray drying from lab success to commercial production is one of the most complex transitions in pharmaceutical manufacturing. While early-stage results may appear promising, many organizations underestimate how facility design, safety systems, and day-to-day operations affect performance at scale. These oversights are among the most common spray drying scale-up mistakes and often lead to delays, failed validation efforts, and reduced commercial yield.

It is critical to avoid the following five pitfalls:

1. Falling for the “scale-up illusion” can undermine return on investment

Processes that perform well in a lab environment often struggle 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 does not just impact efficiency; it can severely undermine the return on a large capital investment and threaten the long-term viability of the product.

2. Underestimating infrastructure and safety risks can delay time to market

Courtesy of Genesis AEC
Spray dryer

Processes that perform well in a lab environment often struggle in a 20-foot drying chamber, which can undermine ROI and threaten a product's long-term viability.

Spray drying with organic solvents at scale introduces serious explosion hazards that are not always present during lab testing. Designing equipment and facilities to manage these risks safely requires more than minor upgrades. It often calls for major capital investments in fire and explosion suppression and nitrogen inerting systems, as well as accurate electrical classification and division design for the drying chamber and associated areas, sealed conduits, controlled access, and strict adherence to regulatory standards and operating procedures. Overlooking these factors in the early design phase can lead to hidden costs, late-stage redesigns, and permitting delays that can push product launch back by six to twelve months, with direct impact on revenue and market competitiveness.

3. Fragmented procurement can lead to costly 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). After installation 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 startup delay that could have been prevented by rigorous equipment specifications and a thorough review of submittals.

4. Treating containment as an afterthought can trigger cascading delays

When working with high-potency active pharmaceutical ingredients (APIs), containment must be a core component of pharmaceutical facility design, not a late-stage add-on. Retrofitting equipment with split butterfly valves (SBVs), upgrading material dispensing stations to include isolators, adding floor drains 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 because of space, airflow, and compliance constraints. Mid-project retrofits can trigger cascading delays, budget overruns, and increased regulatory scrutiny. Designing for containment and hazard control from the outset is significantly more cost-effective and supports operator safety, regulatory compliance, and smoother project execution.

5. Ignoring operational friction and cleaning validation can cause excessive downtime

Courtesy of Genesis AEC
Spray dryer

Without appropriate system controls and facility design, cleaning can become a major operational bottleneck at production scale.

Spray-dried powders can be difficult to handle, particularly when formulations have a low glass transition temperature. Without appropriate system controls and facility design, cleaning becomes a major operational bottleneck. Cleaning validation can quickly turn into a prolonged, resource-intensive effort, with equipment sitting idle for days between batches. This downtime reduces production capacity, disrupts scheduling, increases labor costs, and limits a facility’s ability to meet market demand.

A holistic design approach safeguards capital investment and ensures operational predictability

Avoiding these mistakes requires a holistic approach that integrates process knowledge with pharmaceutical facility design expertise. A process-led strategy that addresses solvent handling, containment, cleaning validation, and infrastructure planning early in the project lifecycle helps organizations move beyond simply “building a facility” to protecting commercial yield, ensuring operational predictability, and safeguarding the business case for the product. Success in large-scale spray drying depends on more than the equipment on the floor; it requires cross-disciplinary foresight to understand how today’s technical decisions influence tomorrow’s market performance.

About the Author

Robert Polksy

Robert Polsky is senior process engineer at Genesis AEC, an architecture, engineering and construction management firm specializing in the life sciences industry.

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