How to Design a Biomanufacturing Process for Success

May 20, 2025

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by Noah Helman (Industrial Microbes/Biofuels Digest) ... 78% of consumers consider environmental sustainability important, and aspire to lead more sustainable lives, which is why sustainable products are growing at a rate 2.7 times faster than non-sustainable products. While some people are willing to pay more, it’s clear that green products will take over the larger market when they are the same price or lower.

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Advances in biomanufacturing have offered alternatives to traditional fossil fuel-derived chemicals. Many visionary companies have invested brainpower, years of research, and millions of dollars to bring biobased chemicals to market, exploring a variety of technical approaches and business strategies. Some have succeeded and others have failed – what differentiates the best approaches from those that haven’t gotten to market?

Industry veterans, like me and our team at iMicrobes, have learned that cost-competitiveness is the key to accelerating this transformation. We’re actively shaping biomanufacturing processes to achieve reliability, scalability, and crucially, price parity with petroleum-based incumbents. To avoid the pitfalls of the past, we have studied these historical examples. Here’s what we found.

Why some biomanufacturing processes thrive—and others fail

Everyone knows that biomanufactured medicines can create successful businesses, largely because of their incredible pricing power. Most people doubt that bulk chemicals can compete in the market when you have to achieve very large scale production and hit low price points–but that’s not actually true. There are proven examples of large-scale fermentation-based products in the market in the $1500/MT – $3000/MT range today. The promise of using industrial biotechnology for environmentally-friendly chemical manufacturing is clear. But why have some projects thrived while others faltered? Success hinges on two critical factors:

Feedstock economics:

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Efficient purification:

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The lesson is that controlling costs in the industrial biotechnology industry depends on the design choices we make that enable simplified downstream separations and purification.

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Bringing biotechnology to commodity chemicals: Lessons from experience

The pitfalls of past biotechnology efforts underline the importance of strategic design choices. Our founding team learned firsthand at LS9 how promising technologies falter when they can’t win on economics. Cost competitiveness isn’t just beneficial—it’s essential.

Our techno-economic modeling approach confirmed that our P3HP process fulfills crucial criteria for success:

Cost competitiveness: Matches or beats current petrochemical costs
Carbon efficiency: Significantly reduces emissions and provides a net-zero pathway
Technical feasibility: Proven biological and chemical methods combined strategically
Feedstock flexibility: Ethanol availability and future carbon-negative potential from waste-derived and recycled sources

Initial market adoption and strategic scale-up

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A cost-driven future for industrial biomanufacturing

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Is This Built to Last? A Systems-Based Toolkit for Evaluating iMicrobes’ Biomanufacturing Strategy (Biofuels Digest)

Excerpt from Biofuels Digest: ... Noah Helman’s take on iMicrobes highlights an economy-minded, scale-conscious approach to metabolic engineering. It’s a story not of grandiose breakthroughs, but of methodical focus—feedstock, product, purification. For readers used to hand-waving futurism in synthetic biology, it’s a refreshingly grounded view.

We agree. But I also want to test how far that clarity goes when read through a different kind of lens—not just one focused on financial realism or technology readiness, but on system structure and adaptive design.

Why? The traditional lens doesn’t always capture the strength or weakness of a technology. Too often, there are surprises. Many people were surprised by the closure of Fulcrum Bioenergy, and many people will be surprised to learn that Enerkem has filed for Chapter 11 reorganization, and Global Clean Energy Holdings, too, in recent days.

Why are we surprised? Probably because the lenses we apply — whether they are modeling success in terms of product, platform, Technical Adoption Models, Technical Readiness Levels, or Internal Rate of Return — are giving us green lights across the board. We need a lens that shows yellow lights and red lights, not just green, and in the right way, at the right time.

The Toolkit Behind the Curtain

The General Theory of Evolutionary Systems and Information (GTESI) is a diagnostic toolkit for analyzing persistence. In a world of dazzling demos and imploding startups, GTESI asks a sharper question: is this thing built to last?

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When applied to companies like iMicrobes, GTESI becomes less of a prediction machine and more of an X-ray. We’re not here to issue verdicts—we’re here to illuminate pressure points, pattern strength, and possible failure modes.

To do this, GTESI uses four core metrics:

IPR: Inverse Persistence Ratio — “Value without memory.” ...
SCD: Symbolic Compression Divergence — “When your story breaks from your system.” ...
TRFI: Trust Ritual Failure Index — “Rituals keep systems sane. ...
EED: Entropy Export Deficit — “Adaptation stalls, pressure builds.” ...

What the iMicrobes Post Gets Right (and we affirm)

iMicrobes’ strategy emphasizes precision, focus, and bounded ambition. It avoids the hype trap and aligns narrative with process.

EED: Entropy Export Deficit — “Adaptation stalls, pressure builds.”
In GTESI, entropy isn’t just metaphor — it’s the cost of complexity, the friction of scale, the heat a system has to shed to stay alive. Companies that adapt well export entropy: they shift burdens outward by solving problems, opening new markets, or aligning efficiently with supply chains. iMicrobes is doing that. Its strategy to tune strains not only for feedstock availability (input constraint) but also for customer performance targets (output constraint) is a textbook example of entropy export. They’re matching biological motion to real-world fit — not just producing novelty for novelty’s sake. That’s entropy relief through design, not marketing gloss. And it suggests a low EED: adaptive, directional, unblocked.
TRFI: Trust Ritual Failure Index — “Rituals keep systems sane.”
A strong TRFI score often shows up in the cracks: missed filings, vague metrics, changing roadmaps, or leadership churn. But a low TRFI — a sign of symbolic health — shows up as coherence. In Noah’s piece, iMicrobes signals with clarity: their challenges are named, not dodged; purification burdens are acknowledged, not waved away; and price-performance constraints are built into their model. That kind of clean, ritualized transparency reinforces trust — internally among teams, and externally among investors, partners, and customers. It’s the ceremonial discipline that says: “We’re real. We’re here. And we’re not hiding.” That’s ritual, not just realism.

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Where GTESI Expands the Insight

GTESI helps us see beyond current momentum into systemic structure.

Purification and Separation: An Entropy Pressure Point\.
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IPR: Inverse Persistence Ratio — “Value without memory.”
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Right now, iMicrobes looks well-aligned: pilot data, design experience, and clear customer signals are holding pace with the story. But if buzz outruns memory — say, with valuations or media hype growing faster than the operational base — IPR climbs. It’s a warning of symbolic overinflation. For iMicrobes, keeping IPR low will matter more if attention spikes.
SCD: Symbolic Compression Divergence — “When story breaks from system.”
Right now, the iMicrobes narrative tracks with what’s actually being built. But SCD rises when ambition outpaces structure
TRFI: Trust Ritual Failure Index — “Rituals keep systems sane.”
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iMicrobes shows strong ritual discipline: challenges are named, not dodged; steps are sequential, not scattershot. But as scale builds, scrutiny rises.
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The Bottom Line

Wondrous science, grit, drive, caring beyond caring, long hours, cheap feedstock, proven commercial deployment, supportive policymakers, devoted investors, hours of demonstration of robust performance, and ready offtakers standing by to use the product — if having these was enough to produce success, Enerkem would be thriving right now instead of reorganizing its capital structure. Success over the long term, requires more. Companies survive, over the long term, because their internal logic maps to the physics of the world. Now, that doesn’t sound like a one-size-fits-all-answers-are-very-quick-and-here-they-are kind of lensing system.

GTESI isn’t easy, because success is complex, and worth studying. GTESI doesn’t promise easy answers. But it does offer durable tools for founders, investors, and policymakers seeking to understand not just momentum—but endurance.

Through this lens, iMicrobes looks less like a bet and more like a build. The road ahead is long. But the structure is promising. And that may be the most important signal of all READ MORE