What Is Downstream Processing—and Why It Matters
Your product is your profile—and the profile is shaped in DSP.
In the world of biomanufacturing, attention is often focused on upstream processing—on cell engineering, strain selection, and bioreactor productivity. But what’s often overlooked is the stage that actually determines the final product: downstream processing (DSP).
DSP refers to the purification and refinement steps that transform raw fermentation broth into a usable, market-ready product. This includes separation, extraction, filtration, chromatography, and formulation. It’s a complex, multi-step process—each stage introducing potential yield loss, equipment demands, and cost.
And it’s here—not in the bioreactor—where your product’s critical quality attributes (CQAs) are defined. Purity, potency, stability, conformation, and formulation are all shaped in DSP. These characteristics determine whether your product meets regulatory standards, performs consistently, and delivers value in the market.
Despite its central role, DSP is frequently under-invested in during early process development. And this imbalance often shows up later in the form of:
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High cost of goods (COGs): DSP is often the single largest contributor to total production cost due to its many sequential steps, consumable use, and energy demands.
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Cumulative yield loss: Even modest inefficiencies add up. For example, 90% yield across five steps results in only 59% overall recovery. Yield loss is one of the most significant drivers of high COGs.
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Long development cycles and scale-up delays: Poorly optimised DSP increases tech transfer risk and manufacturing complexity.
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Sustainability and compliance challenges: DSP drives the bulk of water, energy, and solvent usage—adding cost, environmental burden, and regulatory pressure.
Something we hear a lot is: “Is DSP really that important?” The answer is unequivocally yes. DSP is not just a set of cleanup steps—it is the balancing act between what upstream processes deliver and what formulation and product teams require. It’s where the final product is actually created, not just isolated.
Decades of focus have gone into bioreactor and cell line optimisation. DSP hasn’t received the same level of investment or innovation, and it shows—DSP is now the bottleneck in many processes, often limiting yield, quality, and economic viability.
Moreover, DSP is a broad and deep discipline. There are many ways to separate and purify biological materials, each with trade-offs. But detailed knowledge of separation science, step interactions, and commercial constraints is hard to come by. Because of this, teams often default to familiar, suboptimal approaches—choosing what’s worked before rather than what’s truly best.
The typical DSP development journey includes:
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Process scoping based on historical knowledge or equipment availability
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Generating material using early, inefficient steps
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Ranging experiments to explore feasible operating conditions
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DoE-based optimisation using scale-down models
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Pilot scale-up and tech transfer
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Process and product characterisation
Each phase introduces delays and risk. When upstream processes change—or when products move into new markets or regulatory regimes—DSP has to be re-evaluated, creating a moving target.
And all of this is underpinned by high material costs, assay delays, hardware limitations, and the ever-present pressure to reduce COGs and environmental impact. These challenges are closely tied to resource-intensive operations, including:
💧 Water usage: Cleaning, buffer preparation, and rinsing consume hundreds of litres per batch.
⚡ Energy usage: Centrifugation, lyophilisation, filtration, and heating/cooling require significant energy.
🧪 Solvent usage: Solvents add to cost, environmental burden, and regulatory complexity.
In short, your product is your profile—and that profile is created in DSP. Ignoring it isn’t just inefficient—it’s risky. Prioritising it, on the other hand, unlocks better yield, lower cost, faster development, and more sustainable biomanufacturing.