Inside Your Process Mixing: How CFD De-Risks Scale-Up And Optimizes Manufacturing

Scaling up and transferring biopharmaceutical processes is rarely straightforward. Subtle changes in vessel geometry, feed strategy, or agitation can result in costly delays, repeat runs, or regulatory setbacks.

What if you could see exactly what was happening inside your tank, line, or bed?

That’s where Computational Fluid Dynamics (CFD) comes in. By creating a powerful digital model of your equipment, CFD shows precisely how materials move, mix, and transfer heat and mass. This unique insight provides the foundation for predictable product introductions, robust tech transfers, and optimized manufacturing processes, allowing you to make informed decisions before scaling up or transferring your process.  

Revealing Flow Dynamics for Measurable Improvements 

Many transfer and scale-up challenges are hidden inside the equipment itself. Issues such as poor blend times, dead zones, gas maldistribution, or unexpected heat spots can derail a campaign, but are invisible to the naked eye. 

CFD makes these hidden dynamics visible. The result is not just a picture, but specific, actionable recommendations—like adjusting agitation rates, sparging strategies, or nozzle placement—that translate into measurable improvements at the plant level. 

Real-World Impact: Example Project Outcomes 

Our engineers at APC are experts in the analysis and visualization of simulation outputs and helping clients harness data to optimize their process. Our CFD-driven project outcomes speak for themselves: 

• Reduced Experimentation: Dissolution modeling narrowed the design space, reducing wet runs by ~60% and shaving 10 days off decision timelines

• Robust Tech Transfer: Simulation-based equivalence criteria for a lab-to-plant transfer enabled first-pass success and reduced the project timeline significantly

• Process Optimization: An updated agitation and jacket strategy for a photo-reactor eliminated hot spots, delivering an 8% increase in conversion with ~15% lower energy use

• Regulatory Support (QbD/PAT): An FT-IR + CFD meso-mixing study produced a new feed profile that cut PPQ preparation time by ~25% with zero repeat runs required

• Improved Safety: For a sensitive inactivation step, mixing analysis confirmed uniform exposure, reducing hold time by ~20% while validating process safety

• Enhanced Bioreactor Performance: CFD-guided adjustments increased effective kLa by ~25%, hitting oxygen transfer targets across two different scales on the first attempt

Applications Across the Manufacturing Landscape 

CFD is a versatile tool that helps troubleshoot and optimize a wide range of unit operations. It is particularly valuable when you are moving processes to different equipment, scaling sensitive mixing steps, or troubleshooting unexpected deviations. 

We use CFD and DEM (Discrete Element Method for powders) to diagnose critical issues in: 

• Mixing & Blending: Eliminating dead zones, stratification, and feed maldistribution in stirred tanks (STRs) and single-use bags (SUBs)

• Bioreactors & Gas Transfer: Addressing kLa limits, gas hold-up, shear hot spots, and ensuring uniform oxygen/CO₂ transfer

• Filtration & Chromatography: Preventing flow maldistribution, early fouling, channeling, and peak distortion in columns and filter cassettes

• Crystallization: Controlling supersaturation, improving circulation, and preventing PSD drift and fouling

• Powder Handling (DEM): Solving issues like rat-holing, arching, and segregation in hoppers, feeders, and granulators

• Clean-in-Place (CIP): Identifying coverage gaps and trapped volumes to optimize cleaning time and resource usage

A Smarter Path to Scale-Up and Tech Transfer 

Whether you’re scaling a sensitive process or transferring it across facilities, CFD provides a defensible, data-rich foundation for your digital CMC strategy. It supports QbD, PAT, and regulatory compliance by delivering clear, evidence-backed settings and ranges that withstand audits and ensure process robustness.