The Answer to Solving Biopharma Production Bottlenecks Might Be In Our Kitchens

Cost, scalability, environmental impact, and a shortage of bioreactors continue to be persistent challenges in biomanufacturing. These factors have arguably impeded the growth of biotech and created an “abyss” in bioproduction—and I say “abyss” because an infrastructure “gap” doesn’t accurately capture the magnitude of the challenge.

For many, the easy answer is to say, “Build more biomanufacturing facilities.” But a biomanufacturing facility for biologics, on average, takes approximately three years to build, over $500M, and its scale is limited by the number of steel tanks that are available. Further, steel tanks can only support a limited number of engineering organisms that themselves have limitations.

Unfortunately, the biopharma industry has settled into an inertia that leads to immense reliance on steel tank bioreactors. What if the limitations were taken off? What if the pharma industry did not need steel tanks at all for bioproduction?

Today, three organisms (or systems)—E.coli, yeast (primarily Pichia pastoris), and Chinese Hamster Ovary (CHO) cells—produce the overwhelming majority of the world’s recombinant protein supply in steel tanks.

E.coli has been a mainstay in the field of biology for over a century because it is easy to find and simple to work with. The field of yeast genetics developed along a similar timeline. CHO cells, which were first developed in the mid-20^th century, grow fast and have good viability, which led to their prominence as a model organism in labs around the world.

Twenty years later, not much has changed. Despite tremendous advances in genetic engineering tools, the vast majority of protein biologics are produced in these same three organisms. This perpetuates the same challenges and limitations indefinitely, including high costs and adverse effects on the environment due to the reliance on steel tank bioreactors.

Why is the pharma industry still focused on using the same three organisms for biomanufacturing the world’s proteins when it doesn’t need to?

Imagine starting to rethink biomanufacturing from first principles. Knowing what the industry knows today, how would biomanufacturing be engineered differently? Think about the types of features that would make for the best biomanufacturing platform. It is reasonable to contend that the system would have the following characteristics:

• A highly amenable genome and the tools to engineer it
• The ability to produce high complexity proteins
• Simple infrastructure (low capital expenditure)
• Lower energy and operating costs
• Massive scalability
• Continuous production with high resilience

Any system that requires bioreactors is highly unlikely to satisfy these characteristics. To improve biomanufacturing, pharmaceutical companies need to think beyond the confines of the steel tank bioreactor.

Considering the alternative

The answer comes from what many people may consider an unlikely option for bioproduction. A tiny but mighty organism that has significant potential to replace the steel tank bioreactor and massively scale protein production—the fruit fly.

Drosophila melanogaster, otherwise known as the common fruit fly, has been studied for over a century in genetics and human development. Its rich scientific legacy has contributed to six Nobel Prizes, and fruit flies have often been described as the go-to model organism for biological and genetic research.

This research provides the foundation for fruit flies as a biomanufacturing platform. Fruit flies can be genetically modified to produce crucial recombinant proteins. Stable, high-yield protein expression in fruit flies allows plateaus in cost and scalability to be broken because the system doesn’t rely on complex infrastructure.

It also allows for modularity in upstream production, which facilitates controlled, linear scaling, as opposed to massive step-wise jumps in scale that are typically utilized in bioreactor systems (ex. 1 liter tank to 100 liter tank to 1,000 liter tank). This offers more flexibility and control over production quantities. In addition, it allows for fully continuous production (i.e., biomass can be harvested every single day). This, coupled to the resilience of insect populations over cell culture, makes for a robust, antifragile production system.

Insects are some of the most efficient bio-converters on the planet, massively reducing the energy costs associated with biomanufacturing. Fruit flies, in particular, have low energy requirements and develop best at near room temperature. Insects’ efficiency at converting inputs into biomass is unparalleled. In fact, insects make up over half of the global terrestrial biomass.

It has already been demonstrated that a fly strain can be scaled from 0 to 120 metric tons of biomass production per day in less than 60 days with minimal capital expenditure.

Low-cost infrastructure, modularity, continuous production, and efficient bioconversion are factors that make insect expression systems highly scalable. Couple these factors to the well-stocked genetic toolkit of Drosophila melanogaster, and a new future of pharmaceutical production takes shape, with massive implications on bioengineering.

The way forward

Shifting to the use of fruit flies as a viable alternative to steel tank-based “bioreactors” presents a bevy of benefits for biopharma production: speeding up deployment, scaling capacity, making manufacturing more economical, and reducing the negative impact on the environment.

Human ingenuity has shown the potential of using biology as a vehicle to create a more sustainable future. Synthetic biology is no longer just a “nice to have.” It’s a necessary piece in the fight against the climate crisis. Relying on steel tank bioreactors is the past, not the future. Change is urgently needed.

The solution to the challenges of biomanufacturing may have been right under our noses (and in our kitchens) the whole time.

Matt Anderson-Baron is the Co-founder and CEO of Future Fields.