No Shortcuts to the Top: A Digest Special Report on Scale-up in Industrial Biotechnology

Like climbing major summits in the Himalayas, it’s tougher than it looks, and it looks purity darn tough. Scale-up in industrial biotechnology, that is — not for the faint-hearted.

How do the masters of scale-up get it done? For starters, with “no shortcuts to the top”.

Veteran Everest mountaineer Ed Viesturs probably said it best when he noted that there were a hundred ways to reach base camp, but “no shortcuts to the top”.

In climbing Annapurna, the 8901-meter monster of the Himalayas, he wrote:

We were so consumed with the climb…In this once in a lifetime push, all I wanted to do was keep moving upward. Committed to the task at hand, neither Veikka nor I paused to take a single photo on the way up. In the cold and the wind, trying to do so would have been to invite frostbite. It seemed too much of a distraction even to swallow my energy gel or take a drink of water, let along get out the radio for a call to base camp. Both Veikka and I needed to stay completely focused in the moment. Yet, unable to keep Paula’s anxiety out of my mind, I tried to send a thought to her through some kind of telepathy, winging my plea twelve thousand miles around the globe: Be flexible, babe, you know that eight hours was only a guess, you now it can take longer.”

Gemo or Lemon: You have the power to choose, in the path you select to scale-up

We’ve seen a number of scale-up troubles in industrial biotechnology over the years. Most recently, at KiOR, but also at Gevo, Amyris, and INEOS Bio among others — many of them signature projects in the sector, whose delays and difficulties have made it tougher on newer companies looking for scale-up finance.

What makes the difference between the project that succeeds and the project that fails, or flags?

Earlier this month at the BIO World Congress on Industrial Biotechnology in Philadelphia, five leaders gathered in a session titled “Successfully Scaling Up Industrial Fermentations of Chemicals and Fuels,” to look at those very factors.

In terms of experience — these are heavyweights. Genomatica’s Jeff Lievense on “1,4-Butanediol: A Case Study in Rapid Commercialization”; Amyris’ Chuck Kraft on “Launching a Business with New Products, Process, Plant, Geography”; Reverdia’s Marcel Lubben on “Succesfully Scaling Up Industrial Fermentation of Biosuccinium”; Novozymes’ Mike Hess on “Top Lessons Learned in Delivering Innovation to our Customers”; and POET’s John Evans on “From Bench to Commercial: the POET Experience.”

10 Key Lessons?

1. No skipping or skimping of steps – pilot, demo, commercial.
2. Collaboration and feedback is key.
3. Technology scale-up and market pull go hand in hand, for technical as well as commercial reasons.
4. Understand the real “disaster risk” factors like flawed utilities, compressed schedule, rushed commissioning or inadequate aseptic design.
5. Strain development and adequate local testing is key, for fermentation technology.
6. Pilot where you will operate.
7. Changing technology horses in midstream can be a nightmare.
8. Strong mathematical and economic modeling is a must; data must be comparable.
9. Avoid after-thought approach to safety, regulatory, utilities.
10. Get the most experienced team you can find.

Excerpts from the slides

Genomatica’s Jeff Lievense on “1,4-Butanediol: A Case Study in Rapid Commercialization”

Amyris’ Chuck Kraft on “Launching a Business with New Products, Process, Plant, Geography”

Reverdia’s Marcel Lubben on “Succesfully Scaling Up Industrial Fermentation of Biosuccinium”

Novozymes’ Mike Hess on “Top Lessons Learned in Delivering Innovation to our Customers”

POET’s John Evans on “From Bench to Commercial: the POET Experience.”

The complete slides.

Genomatica’s Jeff Lievense on “1,4-Butanediol: A Case Study in Rapid Commercialization”

Amyris’ Chuck Kraft on “Launching a Business with New Products, Process, Plant, Geography”

Reverdia’s Marcel Lubben on “Succesfully Scaling Up Industrial Fermentation of Biosuccinium”

Novozymes’ Mike Hess on “Top Lessons Learned in Delivering Innovation to our Customers”

POET’s John Evans on “From Bench to Commercial: the POET Experience.”