Demystify Simulated Moving Bed (SMB) for Chromatography: Productivity vs. Connectivity

The Truth About Simulated Moving Bed (SMB) Chromatography: Productivity Myth

In the bioprocessing world, “productivity” is a prized metric. Naturally, any technology claiming to increase productivity gets attention. One example? Simulated Moving Bed (SMB) chromatography for bioprocessing.

Some suppliers promote SMB systems as tools to boost the productivity of chromatography in downstream purification. It’s a sexy claim. But it’s also deeply misleading. Let’s break it down and clarify what SMB actually does — and does not — for chromatography process.

What Really is SMB

SMB is not new. It’s a derivative of Moving Bed (MB) and Fluidized Bed technologies used for decades — particularly in the petrochemical industry. The MB systems allow solid phase (like chromatography resin) to move continuously in a loop in the opposite direction of liquid (or gas) phases while the periodical elements are performed at different sections of the loop. The idea is to maintain the system in a steady state where the feed, elution, wash, and regeneration zones are continuously refreshed.

In bioprocessing, while some tried to use cyclones or hollow fibers as the media for carrying the moving bed, a true moving bed setup isn't technologically available. A packed bed is however usually necessary for required purification performance. So we simulate it with SMB. In SMB, the resin is packed in a series of columns, and rather than moving the resin, we rotate the flow paths — making it work as if the bed is moving. Hence the name.

Continuous Operation ≠ Increased Productivity

SMB translates a periodical chromatography process into a continuous chromatography process. But here’s what SMB does not do:

It doesn’t magically increase the productivity of your chromatography step.

Productivity in chromatography is defined as:

Product Yield / (Resin Mass × Time)

This is a function of resin binding capacity, flow rate, and cycle time. If your total resin mass stays the same and the chromatogram profile doesn’t change, then no matter how many columns or how clever your switching logic is, the productivity stays the same.

You’re just slicing the same pie differently.

Where the Confusion Comes From

So why do SMBs claim increased productivity?

Instead of using total resin mass, some SMB vendors only count the resin in the smallest unit or single column, which is misleading. When you run a traditional batch chromatography step with 20 L of resin in a single column, and an SMB setup uses 4 columns of 5 L each, the total resin is still 20 L. Just spread out.

Some'll show higher cycles per column or faster switching times and claim “higher productivity.” But that’s only true if you ignore the full resin inventory. This is not a fair comparison.

So What Is SMB Good For

SMB isn’t useless — far from it. It’s actually a useful architecture for enabling connectivity in bioprocessing. Its real strengths lie in:

• Better synchronization with continuous upstream or downstream steps

• Consistent product quality under steady-state operation

If your goal is to run a continuous DSP line with minimal interruptions and better flow-through, SMB is a possible option. SMB is however not the only option. There are many other flow schemes that will be able to translate a periodical process into a steady-state constant flow process as SMB does. In fact level 3.1 process intensification (PI) requires connectivity from a process step such as chromatography step but not necessarily an SMB.

If your goal is to increase the amount of product you get per gram of resin per hour, SMB doesn’t help. That’s a matter of chemistry, flow physics, and column dynamics, not fancy flow paths.

Bottom Line

SMB is an engineering workaround — a very smart one — that simulates moving bed systems for bioprocesses where true fluidized or moving bed columns aren’t viable. It enables process continuity. But it doesn’t make chromatography inherently more productive.

Productivity is tied to the resin's performance, binding capacity, flow rate, and cycle efficiency — not how you wire the flow paths.

So let’s use SMB for what it’s good at. What will really increase productivity in process intensification is the connectivity resulted from the steady state processes which reduces the overall processing cycle time when other steps are connected. If there are no connected steps, SMB does not increase productivity.