The future of United States industrial growth resides in the establishment of biotechnology as a new pillar of industrial domestic manufacturing, thus enabling delivery of robust supply chains and revolutionary products such as materials, pharmaceuticals, food, energy. Traditional centralized manufacturing of the past is brittle, prone to disruption, and unable to deliver new products that leverage unique attributes of biology. Today, there exists the opportunity to develop the science, infrastructure, and workforce to establish the BioNETWORK to advance domestic distributed biomanufacturing, strengthen U.S.-based supply chain intermediaries, provide workforce development for underserved communities, and achieve our own global independence and viability in biomanufacturing. Implementing the BioNETWORK to create an end-to-end distributed biomanufacturing platform will fulfill the Executive Order on Advancing Biotechnology and Biomanufacturing Innovation and White House Office of Science and Technology Policy (OSTP) Bold Goals for U.S. Biotechnology and Biomanufacturing.
Challenge and Opportunity
Biotechnology harnesses the power of biology to create new services and products, and the economic activity derived from biotechnology and biomanufacturing is referred to as the bioeconomy. Today, biomanufacturing and most other traditional non-biomanufacturing is centralized. Traditional manufacturing is brittle, does not enhance national economic impact or best use national raw materials/resources, and does not maximize innovation enabled by the unique workforce distributed across the United States. Moreover, in this era of supply chain disruptions due to international competition, climate change, and pandemic-sized threats (both known and unknown), centralized approaches that constitute a single point of attack/failure and necessarily restricted, localized economic impact are themselves a huge risk. While federal government support for biotechnology has increased with recent executive orders and policy papers, the overarching concepts are broad, do not provide actionable steps for the private sector to respond to, and do not provide the proper organization and goals that would drive outcomes of real manufacturing, resulting in processes or products that directly impact consumers. A new program must be developed with clear milestones and deliverables to address the main challenges of biomanufacturing. Centralized biomanufacturing is less secure and does not deliver on the full potential of biotechnology because it is:
- Reliant on a narrow set of feedstocks and reagents that are not local, introducing supply chain vulnerabilities that can halt bioproduction in its earliest steps of manufacturing.
- Inflexible for determining the most effective, stable, scalable, and safe methods of biomanufacturing needed for multiple products in large facilities.
- Serial in scheduling, which introduces large delays in production and limits capacity and product diversity.
- Bespoke and not easily replicated when it comes to selection and design of microbial strains, cell free systems, and sequences of known function outside of the facility that made them. Scale-up and reproducibility of biomanufacturing products are limited.
- Creating waste streams because circular economies are not leveraged.
- Vulnerable to personnel shortages due to shifting economic, health, or other circumstances related to undertraining of a biotechnology specialized workforce.
Single point failures in centralized manufacturing are a root cause of product disruptions and are highlighted by current events. The COVID-19 pandemic revealed that point failures in the workforce or raw materials created disruptions in the centralized manufacturing, and availability of hand sanitizers, rubber gloves, masks, basic medicines, and active pharmaceutical ingredients impacted every American. International conflict with China and other adversarial countries has also created vulnerabilities in the sole source access to rare earth metals used in electronics, batteries, and displays, driving the need for alternate options for manufacturing that do not rely on single points of supply. To offset this situation, the United States has access to workforce, raw materials, and waste streams geographically distributed across the country that can be harnessed by biomanufacturing to produce both health and industrial products needed by U.S. consumers. However, currently there are only limited distributed manufacturing infrastructure development efforts to locally process those raw materials, leaving societal, economic, and unrealized national security risks on the table. Nation-scale parallel production in multiple facilities is needed to robustly create products to meet consumer demand in health, industrial, energy, and food markets.
The BioNETWORK inverts the problem of a traditional centralized biomanufacturing facility and expertise paradigm by delivering a decentralized, resilient network enabling members to rapidly access manufacturing facilities, expertise, and data repositories, as needed and wherever they reside within the system, by integrating the substantial existing U.S. bioindustrial capabilities and resources to maximize nationwide outcomes. The BioNETWORK should be constructed as an aggregate of industrial, academic, financial, and nonprofit entities, organized in six regionally-aligned nodes (see figure below for notional regional distribution) of biomanufacturing infrastructure that together form a hub network that cultivates collaboration, rapid technology advances, and workforce development in underserved communities. The BioNETWORK’s fundamental design and construction aligns with the need for new regional technology development initiatives that expand the geographical distribution of innovative activity in the U.S., as stated in the CHIPS and Science Act. The BioNETWORK acts as the physical and information layer of manufacturing innovation, generating market forces, and leveraging ubiquitous data capture and feedback loops to accelerate innovation and scale-up necessary for full-scale production of novel biomaterials, polymers, small molecules, or microbes themselves. As a secure network, BioNETWORK serves as the physical and virtual backbone of the constituent biomanufacturing entities and their customers, providing unified, distributed manufacturing facilities, digital infrastructure to securely and efficiently exchange information/datasets, and enabling automated process development. Together the nodes function in an integrated way to adaptively solve biotechnology infrastructure challenges as well as load balancing supply chain constraints in real-time depending on the need. This includes automated infrastructure provisioning of small, medium, or large biomanufacturing facilities, supply of regional raw materials, customization of process flow across the network, allocation of labor, and optimization of the economic effectiveness. The BioNETWORK also supports the implementation of a national, multi-tenant cloud lab and enables a systematic assessment of supply chain capabilities/vulnerabilities for biomanufacturing.
Plan of Action
Congress should appropriate funding for an interagency coordination office co-chaired by the OSTP and the Department of Commerce (DOC) and provide $500 million to the DOC, Department of Energy (DOE), and Department of Defense (DOD) to initiate the BioNETWORK and use its structure to fulfill economic goals and create industrial growth opportunities within its three themes:
- Provide alternative supply chain pathways via biotechnologies and biomanufacturing to promote economic security. Leverage BioNETWORK R&D opportunities to develop innovative biomanufacturing pathways that could address supply chain bottlenecks for critical drugs, chemicals, and other materials.
- Explore distributed biomanufacturing innovation to enhance supply chain resilience. Leverage BioNETWORK R&D efforts to advance flexible and adaptive biomanufacturing platforms to mitigate the effects of supply chain disruptions.
- Address standards and data infrastructure to support biotechnology and biomanufacturing commercialization and trade. Leverage BioNETWORK R&D needed to enable data interoperability across the network to enable scale-up and increase global competitiveness.
To achieve these goals, the policy Plan of Action includes the following steps:
1. Congress should appropriate $10 million to establish an interagency coordination office within OSTP that is co-chaired by the DOC. This fulfills the White House Executive Order and CHIPs and Science mandates for better interagency coordination among the DOE, DOC, DOD, National Institute of Standards and Technology (NIST), and the National Science Foundation (NSF).
2. Congress should then appropriate $500 million to DOC and DOE to fund a biomanufacturing moonshot that includes creating the pilot network of three nodes to form the BioNETWORK in regions of the U.S. within six months of receiving funding. This funding should be managed by the interagency coordination office in collaboration with a not-for-profit organization whose mission is to build, deploy, and manage the BioNETWORK together with the federal entities. The role of the not-for-profit is to ensure that a trusted, unbiased partner (not influenced by outside entities) is involved, such that the interests of the taxpayer, U.S. government, and commercial sectors are all represented in the most beneficial way possible. The mission should include education, workforce development, safety/security, and sustainment as core principles, such that the BioNETWORK can stand alone once established. The new work to build the network should also synergize with the foundational science of the NSF and the national security focus of DOD biotechnology programs.
3. Continued investment of an additional $500 million should be appropriated by Congress to create economic incentives to sustain and transition the BioNETWORK from public funding to full commercial operation. This step requires evaluation of concrete go/no-go milestones and deliverables to ensure on-time, on-budget operations have been met. The interagency coordination office should work with DOC, DOE, DOD, and other agencies to leverage these incentives and create other opportunities to promote the BioNETWORK so that it does not require public funding to keep itself sustainable and can obtain private funding.
Create a Pilot Network of Three Nodes
To accelerate beyond current biomanufacturing programs and efforts, the first three nodes of the BioNETWORK should be constructed in three new disparate geographic regions (i.e., East, Midwest, West, or other locations with relevant feedstocks, workforce, or component infrastructure) to show the networking capabilities for distributed manufacturing. The scale of funding required to design, construct, and deploy the first three nodes is $500 million. The initiation and construction of the BioNETWORK should commence within six months. The DOE should lead the initiation and deployment of the technical construction of the BioNETWORK through Theme 2 of their Biomanufacturing goals, which “seeks alternative processes to produce chemicals and materials from renewable biomass and intermediate feedstocks by developing low-carbon-intensity product pathways and promoting a circular economy for materials.” Each node should create regional partnerships that have four entities (a physical manufacturing facility, a cell programming entity, an academic research and development entity, and a workforce/resource entity). All four entities will contain both physical facilities such as industrial fermentation and wet lab space, as well as the workforce needed to run them. On top of the pilot nodes, a science and technology/engineering integrator of the system should be identified to coordinate the effort and lead security/safety efforts for the physical network. Construction of the initial BioNETWORK should be completed within two years.
Achievement of the BioNETWORK goals requires the design plan to:
- Leverage and use regional feedstocks and reagents across the U.S. as inputs to bioproduction to create robustness in the earliest steps of manufacturing.
- Automate the integrated use of small, intermediate, and large-scale biomanufacturing facilities so that they are effective, stable, scalable, and safe for biomanufacturing demand.
- Parallelize scheduling of infrastructure and resources to minimize delays in production and maximize capacity and product diversity.
- Incorporate methods for replication when it comes to selection and design of microbial strains, cell free systems, and sequences of known function.
- Reuse waste streams to create circular economies.
- Include infrastructure biomanufacturing standards from NIST.
The BioNETWORK construction milestones should fulfill the White House OSTP bold goals through new capabilities delivered via distributed manufacturing infrastructure:
- Networked data for distributed biomanufacturing—“establishing a Data Initiative to ensure that high-quality, wide-ranging, easily accessible, and secure biological data sets can drive breakthroughs for the U.S. bioeconomy.”
- Domestic distributed biomanufacturing infrastructure—“expanding domestic capacity to manufacture all the biotechnology products we invent in the United States and support a resilient supply chain.”
- Local hubs for workforce development—“growing training and education opportunities for the biotechnology and biomanufacturing workforce of the future.”
Full Network: Plan for Sustainability
Congress and executive branch agencies establish economic incentives for commercial entities, state/local governments, and consumers of bioindustrial manufacturing products to create commercialization pathways that enhance local economies while also supporting the national network. These include tax credits, tax breaks, low interest loans, and underwritten loans as a starting point. To facilitate tech transition, unique lab-to-market mechanisms and proven tools to address market failure and applied technologies gaps should be used in conjunction with those in the Inflation Reduction Act. This includes prize and challenge competitions, market shaping procurement or loan programs, and streamlined funding of open, cross-disciplinary research, and funding at the state and local levels.
A new public-private partnership could coordinate across multiple efforts to ensure they drive toward rapid technology deployment and integration. This includes implementing a convertible debt plan that rewards BioNETWORK members with equity after reaching key milestones, providing an opportunity for discounted buyout by other investors during rounds of funding, and working with the federal government to design market-shaping mechanisms such as advance market commitments to guarantee purchase of a bioproduction company’s spec-meeting product.
Additionally, the BioNETWORK should be required to expand the repertoire of domestic renewable raw materials into a suite of high-demand, industry-ready products as prescribed in the DOC’s goals in biomanufacturing. This will ensure all regions have support for commercial goods and can automatically assess domestic supply chain capabilities and vulnerabilities, and are provided compensatory remediation on demand. The full BioNETWORK consists of six nodes—aligned to each of the major geographic regions and/or EDA regions in the United States—which have unique raw materials, workforce, infrastructure, and consumption of products that contribute to supporting the overall network functionality. The full BioNETWORK should be active within five years of project initiation and be evaluated against phased milestones throughout.
Networked solutions are resilient and enduring. A single factory is at risk of transfer to foreign ownership, closure, or obsolescence. The BioNETWORK creates connectivity among distributed biomanufacturing physical infrastructure to form a network with a robust domestic value chain. Today’s biomanufacturing investments suffer from the need to vertically integrate due to lack of flexible capacity across the value chain, which raises capital requirements and overall risk. The BioNETWORK drives horizontal integration through the network nodes via new infrastructure, connecting physical infrastructure of the nodes within the system. The result is a multi-sided marketplace for biotechnology innovation, products, and commercialization.
The federal government should initiate a new program and select performers within the next six months to begin the research, development, and construction of the first three nodes of the BioNETWORK. Taking action to establish the BioNETWORK ensures that the United States has the necessary physical and virtual infrastructure to grow the bioeconomy and its international leadership in biotechnology. The BioNETWORK creates new job opportunities for people across the country where training in biotechnology expands the skill sets of people with broad-spectrum applicability from trades to advanced degrees. The BioNETWORK drives circular economies where raw materials from rural and urban centers enter the network and are transformed into high-value products such as advanced materials, pharmaceuticals, food, and energy. The BioNETWORK protects U.S. supply chain resiliency through distributed manufacturing and links regional development into a national capability to establish biomanufacturing as a pillar of economic and technological growth for today and into the 22nd century.
Establishment of the BioNETWORK scales, connects, and networks the impact of a hub and tailors it to the needs of bioindustrial manufacturing, which requires regional feedstocks and integration of small-, intermediate-, and large-scale industrial fermentation facilities scattered across the United States to form an end-to-end distributed biomanufacturing platform. Similar to the goals of the EDA hub program, the BioNETWORK will accelerate regional economic activity, workforce development, and re-establishment of domestic manufacturing. Leveraging activity of the EDA and NSF Biofoundries program is an opportunity for coordination across the interagency.
Retrofitting existing small-, intermediate-, and large-scale biomanufacturing facilities/plants is necessary to construct the connected BioNETWORK. This includes new/modified fermentation equipment, scale-up and purification hardware, software/communications for networking, transportation, load-balancing, and security infrastructure.
Clear, measurable intermediate milestones and deliverables are required to ensure that the BioNETWORK is on track. Every three months, key performance metrics and indicators should be used to demonstrate technical functionality. Planned economic and workforce targets should be established every year and tracked for performance. Adjustments to the technical and business plans should be implemented if needed to ensure the overarching goals are achieved.
A major outcome of the BioNETWORK program is that biomanufacturing in the United States becomes on par with the other traditional pillars of manufacturing such as chemicals, food, and electronics. Workforce retraining to support this industry leads to new high-paying jobs as well as new consumer product sectors and markets with new avenues for economic growth. Failure to deploy the BioNETWORK leaves the United States vulnerable to supply chain disruption, little to no growth in manufacturing, and out competition by China and other peer nations that are investing in and growing biotechnology.
Secondary milestones include key performance indicators, including increased capacity, decrease in production time, robustness (more up time vs. down time), cheaper costs, better use of regional raw materials, etc.
September should be considered National Bioeconomy Month. This past September marked the one year anniversary of the 2022 Presidential Executive order on Advancing Biotechnology and Biomanufacturing Innovation for a Sustainable, Safe, and Secure American Bioeconomy (affectionately known as the Bioeconomy EO). SynBioBeta celebrated the occasion by organizing a Bioeconomy Product Showcase on Capitol Hill that highlighted many different companies within the bioeconomy and proudly boasted bipartisan support in attendance. FAS wrapped up the month by hosting a Bioeconomy & Biomanufacturing Hill Day and Dinner on September 28th, 2023. We brought in some of our subject matter experts to talk in-depth about their Day One Memos and other contributions with key members of Congress.
Highlights Hill Day & Dinner
- Workforce development for the bioeconomy was a hot topic. Our subject matter experts pointed to the need for workers that have interdisciplinary skill sets that include both bio and engineering or bio and computer science. Support for interdisciplinary fellowships (like the Department of Energy Computational Science Graduate Fellowship) could help fill this need. Robust training is needed at all levels of biomanufacturing processes, and could include internships, apprenticeships, and associates and bachelors degree programs.
- To create supply chain resiliency and be competitive with other nations in the global bioeconomy, it is imperative to reduce costs of producing inputs needed for biomanufacturing (e.g., amino acids for biopharma), and to produce these inputs within the U.S. Our current reliance on other countries, like China, for these materials makes our bioeconomy fragile and susceptible to disruptions.
- A successful U.S. bioeconomy needs a strategic framework that unites the different agencies working on different aspects of the bioeconomy, including investments (e.g., EDA Tech Hubs, DoD Biomanufacturing Strategy, and NSF BioFoundries) and regulatory oversight. Both the Bioeconomy EO and the CHIPS and Science Act of 2022 called for the creation of a coordinating office housed in the Office of Science and Technology Policy (OSTP), but there has been no movement to create this coordinating office.
- The bioeconomy also needs appropriate financing. Many startups face the challenge that funding from venture capital firms requires a fast turnaround time for a return on investment (typically 3-5 years). Due to the nature of the products that are produced, many biotech companies are unable to demonstrate their value so quickly. In addition, scaling from a laboratory benchtop to industrial-scale biomanufacturing is expensive and is seen as too risky for typical bank loans. For the bioeconomy to be economically viable, it will need financial measures (potentially, tax incentives, credits, or other financial programs) to support biomanufacturing so that companies can have a chance to show they are viable and valuable.
- To capture the economic value of the bioeconomy and the impact of investments in this sector, appropriate metrics and measurements are needed. In March of 2023, the Bureau of Economic Analysis (BEA) published a feasibility report that indicated that it would be difficult to measure all aspects of the bioeconomy due to a lack of consensus definition, but a satellite account could be created to track aspects of the bioeconomy. However, in order for the BEA to create this type of account, Congress would need to appropriate the funds and direct the BEA to do so.
- Executive branch agencies are working towards a prosperous and resilient bioeconomy that is competitive at the global level, but these agencies can only do so much without Congressional champions on the Hill to keep fighting and funding the programs needed to achieve this.
Next Year is Critical for the Bioeconomy
In a short timespan, several federal agencies have pushed the needle forward in terms of the U.S. bioeconomy, however there is no shortage of work left in order to achieve a “Sustainable, Safe, and Secure” bioeconomy. For the next year, we would like to see an updated definition of the U.S. bioeconomy that accounts and specifies sectors that are and are not part of the bioeconomy and takes sustainability as its main priority. In addition, the National Institute of Standards and Technology (NIST) should update the Bioeconomy Lexicon and prioritize setting standards for biomanufacturing that utilizes a sector to sector approach instead of an overarching standards approach to ensure that innovation is not stifled by standards that do not allow for the flexibility needed in the biotech space.
Additionally, it will be vital for the federal government to enact a true framework for the U.S. bioeconomy by creating a coordinating office housed in OSTP that works with the various federal agencies focused on the bioeconomy and provide support to publish the reports directed by the Bioeconomy EO on time. Furthermore, in order to achieve products, goods, and services that are sustainable, secure, and safe, it will be essential for the coordinating office to gather public opinions in order to help shape and influence our bioeconomy.
Increased congressional involvement is also necessary to address key challenges the bioeconomy currently faces, such as the inability to measure the bioeconomy and the challenge that companies within the bioeconomy face (such as incomplete knowledge on processes relating to creating a startup, scaling goods and serves, and navigating the regulatory system). The BEA should be directed by Congress to create a satellite account to measure the U.S. bioeconomy and Congress should mandate a public-private driven landscape analysis on the current financial situation of the U.S. bioeconomy in order to be able to identify the gaps in financing the sector currently faces.
There is no doubt that the bioeconomy has potential to grow, but it needs a solid framework to stand upon. Implementing some or all of these ideas will not only lead to a prosperous bioeconomy, but it will also create one that is resilient, sustainable, and secure.
The U.S. bioeconomy has been surging forward, charged by the Presidential Executive Order 14081 and the CHIPS and Science Act. However, there are many difficult challenges that lay ahead for the U.S. bioeconomy, including for U.S. biomanufacturing capabilities. U.S. biomanufacturing has been grappling with issues in fermentation capacity including challenges related to scale-up, inconsistent supply chains, and downstream processing. While the U.S. government works on shoring up these roadblocks, it will be important to bring industry perspectives into the conversation to craft solutions that not only addresses the current set of issues but looks to mitigate challenges that may arise in the future.
To get a better understanding of industry perspectives on the U.S. bioeconomy and the U.S. biomanufacturing sector, the Federation of American Scientists interviewed Dr. Sarah Richardson, the CEO of MicroByre. MicroByre is a climate-focused biotech startup that specializes in providing specialized bacteria based on the specific fermentation needs of its clients. Dr. Richardson received her B.S. in biology from the University of Maryland in 2004 and a Ph.D. in human genetics and molecular biology from Johns Hopkins University School of Medicine in 2011. Her extensive training in computational and molecular biology has given her a unique perspective regarding emerging technologies enabled by synthetic biology.
FAS: The U.S. Government is focused on increasing fermentation capacity, including scale-up, and creating a resilient supply chain. In your opinion, are there specific areas in the supply chain and in scale-up that need more attention?
Dr. Sarah Richardson: The pandemic had such an impact on supply chains that everyone is reevaluating the centralization of critical manufacturing. The United States got the CHIPS and Science Act to invest in domestic semiconductor manufacturing. The voting public realized that almost every need they had required circuits. Shortages in pharmaceuticals are slowly raising awareness of chemical and biomedical manufacturing vulnerabilities as well. The public has even less insight into vulnerabilities in industrial biomanufacturing, so it is important that our elected officials are proactive with things like Executive Order 14081.
When we talk about supply chains we usually mean the sourcing and transfer of raw, intermediate, and finished materials — the flow of goods. We achieve robustness by having alternative suppliers, stockpiles, and exacting resource management. For biomanufacturing, an oft raised supply chain concern is feedstock. I can and will expound on this, but securing a supply of corn sugar is not the right long-term play here. Shoring up corn sugar supplies will not have a meaningful impact on industrial biomanufacturing and should be prioritized in that light.
Biomanufacturing efforts are different from the long standing production of consumer goods in that they are heavily tied to a scientific vendor market. As we scale to production, part of our supply chain is a lot of sterile plastic disposable consumables. We compete with biomedical sectors for those, for personal protective equipment, and for other appliances. This supply chain issue squeezed not just biomanufacturing, but scientific research in general.
We need something that isn’t always thought of as part of the supply chain: specialized infrastructural hardware. This may not be manufactured domestically. Access to scale up fermentation vessels is already squeezed. The other problem is that no matter where you build them, these vessels are designed for the deployment of canonical feedstocks and yeasts. Addressing the manufacturing locale would offer us the chance to innovate in vessel and process design and support the kinds of novel fermentations on alternate feedstocks that are needed to advance industrial biomanufacturing. There are righteous calls for the construction of new pilot plants. We should make sure that we take the opportunity to build for the right future.
One of the indisputable strengths of biomanufacturing is the potential for decentralization! Look at microbrewing: fermentation can happen anywhere without country-spanning feedstock pipelines. As we onboard overlooked feedstocks, it may only be practical to leverage them if some fermentation happens locally. As we look at supply chains and scale up we should model what that might look like for manufacturing, feedstock supply chains, and downstream processing. Not just at a national level, but at regional and local scales as well.
There are a lot of immediate policy needs for the bioeconomy, many of which are outlined in Executive Order 14081. How should these immediate needs be balanced with long-term needs? Is there a trade-off?
Counterintuitively, the most immediate needs will have the most distant payoffs! The tradeoff is that we can’t have every single detail nailed down before work begins. We will have to build tactically for strategic flexibility. Climate change and manufacturing robustness are life or death problems. We need to be open to more creative solutions in funding methods, timeline expectations; in who comes to the table, in who around the table is given the power to affect change, and in messaging! The comfortable, familiar, traditional modes of action and funding have failed to accelerate our response to this crisis.
We have to get started on regulation yesterday, because the only thing that moves slower than technology is policy. We need to agree on meaningful, aggressive, and potentially unflattering metrics to measure progress and compliance. We need to define our terms clearly: what is “bio-based,” does it not have petroleum in it at all? What does “plant-based” mean? What percentage of a product has to be renewable to be labeled so? If it comes from renewable sources but its end-of-life is not circularizable, can we still call it “green”?
We need incentives for innovation and development that do not entrench a comfortable but unproductive status quo. We need to offer stability to innovators by looking ahead and proactively incubating the standards and regulations that will support safety, security, and intellectual property protection. We should evaluate existing standards and practices for inflexibility: if they only support the current technology and a tradition that has failed to deliver change, they will continue to deliver nothing new as a solution.
We need to get on good footing with workforce development, as well. A truly multidisciplinary effort is critical and will take a while to pull off; it takes at least a decade to turn a high school student into a scientist. I only know of one national graduate fellowship that actually requires awardees to train seriously in more than one discipline. Siloing is a major problem in higher education and therefore in biomanufacturing. What passes for “multidisciplinary” is frequently “I am a computer scientist who is not rude to biologists” or “our company has both a chemical division and an AI division.” A cross-discipline “bilingual” workforce is absolutely critical to reuniting the skill sets needed to advance the bioeconomy. Organizations like BioMADE with serious commitments to developing a biomanufacturing workforce cannot effectively address the educational pipeline without significantly more support.
When we emphasize the collection of data — which data are we talking about? Is the data we have collected already a useful jumping off point for what comes next? Are the models relevant for foreseeable changes in technology, regulation, and deployment? For some of it, absolutely not. As every responsible machine learning expert can tell you, data is not something you want to skimp or cheap out on collecting or curating. We have to be deliberate about what we collect, and why. Biases cannot all be avoided, but we have to take a beat to evaluate whether extant models, architecture, and sources are relevant, useful, or adaptable. A data model is as subject to a sunk cost fallacy as anything else. There will be pressure to leverage familiar models and excuses made about the need for speed and the utility of transfer learning. We cannot let volume or nostalgia keep us from taking a sober look at the data and models we currently have, and which ones we actually need to get.
What are the major pain points the biomanufacturing industry is currently facing?
Downstream processing is the work of separating target molecules from the background noise of production. In purely chemical and petrochemical fields, separation processes are well established, extensively characterized, and relatively standardized. This is not the case in industrial biomanufacturing, where upstream flows are arguably more variable and complex than in petrochemicals. Producers on the biomedical side of biomanufacturing who make antibiotics, biologics, and other pharmaceuticals have worked on this problem for a long time. Their products tend to be more expensive and worth specialized handling. The time the field has spent developing the techniques in the urgent pursuit of human health works in their favor for innovation. However, separating fermentation broth from arbitrary commodity molecules is still a major hurdle for a bioindustrial sector already facing so many other simultaneous challenges. Without a robust library of downstream processing methods and a workforce versant in their development and deployment, new industrial products are viewed as significant scaling risks and are funded accordingly.
There is fatigue as well. For the sake of argument, let us peg the onset of the modern era of industrial biomanufacturing to the turn of the latest century. There have been the requisite amount of promises any field must make to build itself into prominence, but there has not been the progress that engenders trust in those or future promises. We have touted synthetic biology as the answer for two and a half decades but our dependence on petroleum for chemicals is as intense as ever. The goodwill we need to shift an entire industry is not a renewable resource. It takes capital, it takes time, and it takes faith that those investments will pay off. But now the chemical companies we need to adopt new solutions have lost some confidence. The policy makers we need to lean into alternative paths and visionary funding are losing trust. If the public from whence government funding ultimately springs descends into skepticism, we may lose our chance to pivot and deliver.
The right investment right now will spell the difference between life and death on this planet for billions of people.
This dangerous dearth of confidence can be addressed by doing something difficult: owning up to it. No one has ever said “oh goody — a chance to do a postmortem!”. But such introspective exercises are critical to making effective changes. A lack of reflection is a tacit vote for the status quo, which is comfortable because we’re rarely punished for a lack of advocacy. We should commission an honest look at the last thirty years — without judgment, without anger, and without the need to reframe disappointing attempts as fractional successes for granting agencies, or position singular successes as broadly representative of progress for egos.
Biomanufacturing is so promising! With proper care and attention it will be incredibly transformative. The right investment right now will spell the difference between life and death on this planet for billions of people. We owe it to ourselves and to science to do it right — which we can only do by acknowledging what we need to change and then truly committing to those changes.
Corn sugar tends to be the most utilized biomass in the bioeconomy. What are the issues the U.S. faces if it continues to rely solely on corn sugar as biomass?
History shows that low-volume, high-margin fine chemicals can be made profitable on corn sugar, but high-volume, low-margin commodity chemicals cannot. Projects that produce fine chemicals and pharmaceuticals see commercial success but suffer from feedstock availability and scaling capacity. Success in high-margin markets encourages people to use the exact same technology to attempt low-margin markets, but then they struggle to reduce costs and improve titers. When a commodity chemical endeavor starts to flag, it can pivot to high-margin markets. This is a pattern we see again and again. As long as corn sugar is the default biomass, it will not change; the United States will not be able to replace petrochemicals with biomanufacturing because the price of corn sugar is too high and cannot be technologically reduced. This pattern is also perpetuated because the yeast we usually ask to do biomanufacturing cannot be made to consume anything but corn sugar. We also struggle to produce arbitrary chemicals in scalable amounts from corn sugar. We are stuck in an unproductive reinforcing spiral.
Even if commodity projects could profit using corn sugar, there is not enough to go around. How much corn sugar would we have to use to replace even a fifth of the volume of petroleum commodity chemicals we currently rely on? How much more land, nitrogen, water, and additional carbon emissions would be needed? Would chemical interests begin to overpower food, medical, and energy interests? What if a pathogen or natural disaster wiped out the corn crop for a year or two? Even if we could succeed at manufacturing commodities with corn sugar alone, locking out alternatives makes the United States supply chain brittle and vulnerable.
Continued reliance on corn sugar slows our technological development and stifles innovation. Specialists approaching manufacturing problems in their domain are necessarily forced to adopt the standards of neighboring domains. A chemical engineer is not going to work on separating a biomass into nutrition sources when no microbiologist is offering an organism to adopt it. A molecular biologist is not going to deploy a specialized metabolic pathway dependent on a nutrition source not found in corn sugar. Equipment vendors are not going to design tools at any scale that stray from a market demand overwhelmingly based on the use of corn sugar. Grantors direct funds with the guidance of universities and industry leaders, who are biased towards corn sugar because that’s what they use to generate quick prototypes and spin out new start up companies.
The result of relying on corn sugar is an entrenched field and consequently we might lose our chance to make a difference. Without introducing low-cost, abundant feedstocks like wastes, we run the risk of disqualifying an entire field of innovation.
What does the U.S. need to do in order for other biomass sources to be utilized beyond corn sugar? Are there ideas (or specific programs) that the U.S. government could supercharge?
Federal agencies must stop funding projects that propose to scale familiar yeasts on corn sugars to produce novel industrial chemicals. We must immediately stop funding biomass conversion projects meant to provide refined sugars to such endeavors. And we must stop any notion of dedicating arable land solely to corn sugar solely for the purposes of biomanufacturing new industrial products. The math does not and will not work out. The United States must stop throwing money and support at such things that seem like they ought to succeed any minute now, even though we have been waiting for that success for 50 years without any meaningful changes in the economic analysis or technology available.
Ironically, we need to take a page from the book that cemented petroleum and car supremacy in this country. We need to do the kind of inglorious, overlooked, and subsequently taken for granted survey of the kind that enabled the Eisenhower Interstate System to be built.
We need to characterize all of the non-corn feedstocks and their economic and microbial ecosystems. We need to know how much of each biomass exists, what it is composed of, and who is compiling where. We need to know what organisms rot it and what they produce from it. We need to make all of that data as freely available as possible to lower the barriers of entry for cross-disciplinary teams of researchers and innovators to design and build the logistical, microbiological, chemical, and mechanical infrastructure necessary. We need to prioritize and leverage the complex biomasses that cannot just be ground into yeast food.
We need to get the lay of the land so – to use the roadway analogy – we know where to pour the asphalt. An example of this sort of effort is the Materials Genome Initiative, which is a crosscutting multi-agency initiative for advancing materials and manufacturing technology. (And which has, to my chagrin, stolen the term “genome” for non-biological purposes.) An even more visible example to the public is a resource like the Plant Hardiness Zone Map that provides a basis for agricultural risk assessment to everyone in the country.
The United States needs to lean into an old strength and fund infrastructure that gives all the relevant specialties the ability to collaborate on truly divergent and innovative biomass efforts. The field of industrial biomanufacturing must make a concerted effort to critically examine a history of failed technical investments, shake off the chains of the status quo, and guide us into true innovation. Infrastructure is not the kind of project that yields an immediate return. If venture capital or philanthropy could do it, they would have already. The United States must flex its unique ability to work on a generational investment timeline; to spend money in the very short term on the right things so as to set everyone up for decades of wildly profitable success — and a safer and more livable planet.
Artificial Intelligence (AI) has gained momentum in the last 6 months and has become impossible to ignore. The ease of use of these new tools, such as AI-driven text and image generators, have driven significant discussion on the appropriate use of AI. Congress has also started digging into AI governance. Discussion has focused on a wide range of social consequences of AI, including biosecurity risks that could arise. To develop an overarching framework that includes addressing bio-related risks, it will be crucial for Congress, different federal agencies, and various non-governmental AI stakeholders to work together.
Bio Has Already Been Utilizing AI For Decades
Artificial intelligence has a long history in the life sciences. The principles are not new. Turing developed the idea in the 50’s and, by the turn of the century, bioinformaticians (data scientists for biological data) were already using AI in genome analysis. One focus of AI tools for biology has been on proteins. Nearly every known function in your body relies on proteins, and their 3-dimensional shapes determine their functions. Predicting the shape of a protein has long been a critical challenge. In 2020, Alphabet’s DeepMind published AlphaFold 2 as an AI-enabled software tool capable of doing just that. While not perfect, scientists have been able to use it and related tools to predict the shape of proteins faster and even to create new proteins optimized for specific applications. Of course, the applications of AI in biotechnology extends beyond proteins. Medical researchers have taken advantage of AI to identify new biomarkers and leverage AI to improve diagnostic tests. Industrial biotechnology researchers are exploring the use of AI to optimize biomanufacturing processes to improve yield. In other natural sciences, AI can even drive entire courses of experiments with minimal human input, with biological labs in development. Unfortunately, these same tools and capabilities could also be misused to cause harm by actors trying to develop toxins, pathogens, and other potential bio risks.
Proposed Bio x AI Solutions Are Incomplete
Congress is looking for ways to reduce AI risks, beginning with social implications such as disinformation, employment decision making, and other areas encountered by the general public. These are excellent starting points and echo some concerns abroad. Some Congressional action has also called for sweeping studies, new regulatory commissions, or broadly scoped risk management frameworks (see the AI Risk Management Framework developed by NIST). While some recently proposed bills address AI concerns in healthcare, there have been few solutions for reducing risks specifically related to intersections of AI with biosciences and biotechnology.
The Biden Administration recently reached agreements with leaders in the development of AI models to implement risk mitigation measures, including ones related to biosecurity. However, all of the current oversight mechanisms for AI models are voluntary, which has generated discussion on how to provide incentives and whether a stronger approach is needed. As the availability of AI models increases and models specific to biosciences and biotechnology become more sophisticated, this question about how to establish enforceable rules and appropriate degrees of accountability while minimizing collateral impact on innovation will become more urgent.
Approaches to governance for AI’s intersections with biology must also be tailored to the needs of the scientific community. As AI-enabled biodesign tools drive understanding and innovation, they will also decrease hurdles for malicious actors seeking to do harm. At the same time, data sharing, collaboration, and transparency have long been critical to advances in biosciences. Restricting AI model development or access to data, models, or model outputs without hampering legitimate research and development will be challenging. Implementing guardrails for these tools should be done carefully and with a solid understanding of how they are used and how they might be misused. Key questions for oversight of AI in bio include:
- How can we implement oversight on current and future bio-related tools that utilize AI enabled technologies (e.g., AlphaFold2, etc) in order to mitigate biosecurity risks associated with the technology while advancing R&D innovation?
- Are there other ways to reduce the potential for misuse with these technologies?
- AI model training requires an immense amount of data and AI models for biology will require many types of datasets specific to biology (e.g., protein structure databases, genomic sequence databases, etc). How should we address the need for scientists to generate and have access to a wide range of datasets in order to train bio-related AI tools while also balancing the potential for misuse of that data?
- How can bio-related AI or ML tools be applied to improve biosecurity more broadly?
- Into the future, advances in biosciences and biotechnology are likely to become more automated (e.g., with AI-enabled self-driving labs). How can we best ensure that these capabilities are not misused?
Now, While the Policy Window is Open
Recently, the National Defense Authorization Act for Fiscal Year 2022 created the bipartisan, intergovernmental National Security Commission on Emerging Biotechnology. The NSCEB has been tasked with creating an interim report by the end of 2023 and a final policy recommendation report by the end of 2024 with recommendations for Congressional action. One of the areas they are looking into is the intersection of AI and biosciences, specifically how AI technology can enable innovation in the biosciences and biotechnologies while mitigating risks.
The current attention on AI and the upcoming interim report to Congress by the NSCEB provide an important policy window and acts as a call to action that requires stakeholder input in order to create governance and policy recommendations that enable innovation while mitigating risks. If you are an AI or bio expert within academia, the biotech industry, an AI lab, or other non-governmental organization and are interested in contributing policy ideas, we have just launched our Bio x AI Policy Development Sprint here. Timely, well considered policy recommendations that address the key questions listed above will lead to the best possible implementation of AI in biosciences and biotechnology.
The bioeconomy touches nearly every function of the U.S. government. The products of the bioeconomy compete in an international marketplace and include medicines, foods, fuels, materials, and novel solutions to broad challenges including climate and sustainability. The infrastructure, tools, and capabilities that drive the bioeconomy must be safeguarded to maintain U.S. leadership and to protect against misuse. The vast scale of these issues requires a cross-governmental approach that draws on input and engagement with industry, academia, nongovernmental organizations, and other stakeholders across the bioeconomy.
To achieve a durable and strategic interagency approach to the bioeconomy, the Office of Science and Technology Policy (OSTP) should establish and Congress should fund a Bioeconomy Initiative Coordination Office (BICO) to coordinate strategic U.S. government investments in the bioeconomy; facilitate efficient oversight and commercialization of biotechnology products; safeguard biotechnology infrastructure, tools and capabilities; and serve as a focal point for government engagement with nongovernmental partners and experts.
Challenge and Opportunity
Executive Order 14081, “Establishing a National Biomanufacturing and Biotechnology Initiative,” was released in September 2022. Since then, OSTP has worked to coordinate this Initiative and has made significant progress with the March 2023 release of “Bold Goals for Biotechnology and Biomanufacturing,” which describes how government agencies will support and benefit from investments in the bioeconomy; an implementation plan is forthcoming. EO 14081 also initiated interagency efforts to better measure and track the bioeconomy, prepare the regulatory system for future biotechnology products, and establish a Biosafety and Biosecurity Innovation Initiative. Although these efforts are laudable, we need a more strategic, longer-term, and outward-facing approach to ensure that the United States remains the world leader in biomanufacturing and biotechnology development. Expert reports over several years, including those from the National Academies, support the formation of strategic coordinating body within the U.S. government that focuses on the bioeconomy and more strategic planning for its investments in these areas.
The CHIPS and Science Act of 2022 provides a critical opportunity for improved interagency coordination. Division B, Title IV calls for the formation of a National Engineering Biology Research and Development Initiative coordinated by an interagency committee, co-chaired by OSTP, and supported by an Initiative Coordination Office (ICO) with a director and full-time staff. This bill stipulates that this coordination office should:
- Serve as “the point of contact on Federal engineering biology activities for government organizations, academia, industry, professional societies, State governments, interested citizen groups, and others to exchange technical and programmatic information”;
- Oversee “interagency coordination of the Initiative”; and
- Promote “access to, and early application of, the technologies, innovations, and expertise derived from Initiative activities to agency missions and systems across the Federal Government, and to United States industry, including startup companies.”
A recent bipartisan letter from Congressman Jake Auchincloss of Massachusetts confirms Congress’s intent that the ICO described in the legislation incorporate the Initiative as described in Executive Order 14081.
An ICO focused on the bioeconomy would be analogous to other congressionally mandated National Coordination Offices that drive effective interagency coordination at OSTP, including those for the U.S. Global Change Research Program (USGCRP), the National Nanotechnology Initiative (NNI), and the Networking and Information Technology Research and Development (NITRD) Program. These offices have several features in common, including:
- Support for regular interagency strategic planning and assessment mechanisms, including budget cross-cuts of relevant U.S. government activities;
- A focus on topics related to horizon scanning, technology development, and responsible innovation; and
- Robust outreach and engagement with non-government stakeholders, including industry partners.
Now is the time for OSTP to establish and for Congress to fund a durable and well-staffed Bioeconomy Initiative Coordination Office (BICO) that leads ongoing, strategic, interagency coordination across the government to support the bioeconomy. The BICO should not replace current interagency committees and processes. Instead, it should coordinate bioeconomy-related efforts that reach across multiple domains, ensure a durable and long-term approach to the bioeconomy, and serve as a focal point and doorway for U.S. government engagement with industry, academia, and other stakeholders.
Plan of Action
OSTP should establish the BICO within the next year. Its focus should be on (1) biomanufacturing, including infrastructure and capacity, pre-competitive industry issues (e.g., standards), and workforce; and (2) development and commercialization of biotechnology products, tools, and capabilities, with a particular focus on those developed for nontherapeutic uses. The interagency committee that drives the BICO should be established under the National Science and Technology Council, should be co-chaired by OSTP and the Department of Commerce, and should include as participants every agency listed in EO 14081, including:
- Department of Agriculture
- Department of Commerce
- Department of Defense
- Department of Energy
- Department of Health and Human Services
- Environmental Protection Agency
- National Economic Council
- National Science Foundation
- National Security Council
- Office of Management and Budget
- Office of Science and Technology Policy
Congress should provide an appropriation of at least $4 million per year to ensure funding for at least six full-time employees (director, lead for strategic planning and assessment, lead for regulation, lead for safeguarding, outreach coordinator, and administrator), plus office expenses, events, outreach, and other costs. Absent a specific appropriation from Congress, the BICO should follow the funding model of other congressionally mandated coordination offices, including the USGCRP and the NITRD Coordination Office: each participating agency would contribute a small percentage of its total expenditures on biomanufacturing and biotechnologies to support the BICO.
The office should be tasked with:
- Coordinating strategic planning for U.S. government investments in the bioeconomy;
- A “single door approach” for the biotechnology regulatory system that product developers can use to efficiently get actionable answers about their products’ regulatory pathways;
- An interagency process focused on safeguarding the bioeconomy by ensuring that infrastructure and supply chains are secure and reducing the risk that biotechnology tools and capabilities are accidentally or deliberately misused; and
- Extensive public outreach and engagement on these topics that includes academia, industry, nongovernmental organizations, and other bioeconomy stakeholders.
To maintain U.S. leadership in the bioeconomy, the federal government has made significant investments in biomanufacturing and biotechnology development over many years, and EO 14081 provided an important step toward a more strategic approach to these investments. However, we need a more robust and ongoing structure that incorporates opportunities for assessment of the rapidly changing bioeconomy and iteration of planning activities. The BICO should coordinate a strategic approach that includes:
- A strategic planning process with regular updates (e.g., every three years) to revisit goals, assess progress, and renew commitments;
- Budget cross-cuts, published annually, that track U.S. government investments in the bioeconomy; and
- A National Bioeconomy Assessment that incorporates advances in biotechnology products, tools, and capabilities; biomanufacturing infrastructure and workforce; and trends in public and private investment. Because the bioeconomy is rapidly changing, this assessment should incorporate a Living Evidence approach that identifies and incorporates relevant updates as they arise.
To generate an accurate National Bioeconomy Assessment and ensure that it captures updated, relevant information, the BICO should actively seek external stakeholder input and engagement that includes academia, industry, manufacturing institutes (such as BioMADE or NIIMBL), state and local governments, nongovernmental organizations, and others. In addition to informing federal investment in the bioeconomy, this ongoing assessment will be valuable for other activities within the BICO by providing insight into the types of novel products that regulators might expect to see and highlighting priority topics for outreach and engagement on safeguarding biotechnology tools and capabilities. If a Living Evidence approach is not feasible, then National Bioeconomy Assessments could be generated in a more traditional format, with publication of updated assessments at regular intervals (e.g., every three years, offset from the strategic planning publication cycle).
A “Single Door Approach” for the Biotechnology Regulatory System
For the bioeconomy to flourish, the biotechnology regulatory system must allow low-risk products to be developed and marketed quickly and efficiently. At the same time, regulatory oversight is essential to identify and limit risks to human health and the environment. The BICO should establish and support a “single door approach” for the biotechnology regulatory system to reduce ambiguities and uncertainties in the system and to better prepare the regulatory agencies for future products. (See FAQs for more information.)
An effective single door approach requires robust interagency coordination that includes OSTP and high-level decision makers from each of the primary regulatory agencies: Environmental Protection Agency (EPA), Food and Drug Administration (FDA), and U.S. Department of Agriculture (USDA). Future biotechnology products will include a wide range of applications in the environment, so governmental entities responsible for environmental protection should also be included in this interagency process, including U.S. Fish and Wildlife Service, the National Marine Fisheries Service, and the Council on Environmental Quality. These groups have rarely engaged on issues related to the use of genetically engineered organisms in the environment but should prepare for this type of decision-making. Representation in this interagency process should include lawyers from the Offices of the General Counsel of EPA, FDA, and USDA who can work together within a reasonable time frame (e.g., three months) to determine which agency should lead when novel products arise. To support this single door approach, the BICO should:
- Work with the regulatory agencies to establish a method or portal through which product developers can submit information and requests about their products;
- Facilitate interagency meetings and discussion, including with product developers, as needed;
- Track submissions and timelines, work to address bottlenecks to decision-making, and maintain accountability by publishing summaries of decision-making efficiency; and
- Conduct outreach to relevant product developers and industry groups, including a website, to raise awareness and provide information about the regulatory system.
When possible and as experience is gained, the BICO should work with the agencies to distill generalizable principles or summaries of decisions to provide guidance to product developers and the broader bioeconomy on how different types of products are likely to be regulated.
Safeguarding the Bioeconomy
As the bioeconomy grows, the United States must ensure that its investments are protected and that biotechnology tools and capabilities are not accidentally or intentionally misused. In addition to coordinating discussions among U.S. government agencies on these topics, a key role for the BICO will be to conduct outreach and engagement with the broader bioeconomy community. There are several areas where outreach, particularly to industry partners, will be critical to maintaining U.S. competitiveness and leadership in the bioeconomy. Many industry standards and practices are not well-established, and there are opportunities for the federal government to work with industry partners to protect U.S. assets and keep biomanufacturing and biotechnology development securely within the United States. The BICO, in collaboration with the National Security Council, should facilitate engagement on topics such as:
- Supplies and capabilities that create key bottlenecks for U.S. companies;
- Industry best practices for securing biomanufacturing infrastructure from cyberattacks;
- Industry best practices that enable secure sharing of materials and data between partnering companies or entities, including legal approaches (e.g., contracting and subcontracting arrangements) and technical solutions such as developing standards for APIs (application programming interfaces); and
- How to navigate venture capital interest and investment from other countries, including China, which is particularly difficult for smaller companies and start-ups.
Safeguarding the bioeconomy also requires a process to better understand the potential for accidental or deliberate misuse of biotechnology tools, services, and capabilities to cause harm, and to support development of resources and best practices to reduce these risks. The BICO should develop an engagement strategy that includes opportunities for public discussion of risks related to misuse and strategies to reduce those risks; a publicly accessible portal for experts outside the government to raise concerns or suggest topics for further scrutiny; and a protected venue in which companies can securely share more sensitive information about business products, interactions, or practices. The BICO will maximize the benefit of this forum by conducting outreach and raising awareness of these opportunities, particularly by targeting industry partners.
Currently, the U.S. government does not have a venue or forum for multi-stakeholder engagement on risks related to potential misuse of biotechnology tools and capabilities. As the bioeconomy grows, a wide range of tools and capabilities will be developed to make biology easier to engineer, including many enabled by artificial intelligence. Accidental or deliberate misuse of these rapidly expanding capabilities could pose risks that will be difficult to anticipate and mitigate. By establishing a process for ongoing and robust engagement to better understand and manage these risks, the BICO can help address these biosecurity needs.
By establishing the BICO as a focal point for coordination among the interagency community and outreach to the broader bioeconomy, OSTP can ensure a long-term and robust U.S. government commitment to biomanufacturing and biotechnology. This commitment includes a strategic approach to investments that can be tracked over time, improvements to the regulatory system that will enable safe and useful products to be more easily commercialized, and activities and engagement to better safeguard advances in the bioeconomy. With appropriate funding, the BICO will form the foundation for a true cross-governmental approach that will ensure U.S. leadership and competitiveness and will ultimately enable the bioeconomy to flourish.
Because OSTP is part of the Executive Office of the President, there is a risk that establishing the BICO at OSTP will make it vulnerable to changes in funding or priorities, particularly during presidential transitions. However, there are several reasons for the BICO to be at OSTP. A critical factor is that the CHIPS and Science Act names OSTP as co-chair for the interagency engineering biology initiative that is described in the Act. Executive Order 14081 also names OSTP as a key point of coordination for U.S. government activities on the bioeconomy. Some aspects of the bioeconomy, particularly the regulation of biotechnology, have been coordinated by OSTP for decades. Furthermore, OSTP plays a key role in multiple science- and technology-rich initiatives that are supported by Coordination Offices, including the USGCRP, NITRD, and NNI.
If it is not feasible for OSTP to establish the BICO, coordination could be established by lead agencies that are committed to supporting the bioeconomy. A model for this type of coordination is the Wildland Fire Leadership Council, which is established by a Memorandum of Understanding among the Secretary of the Interior, Secretary of Agriculture, Secretary of Defense, and Secretary of Homeland Security. However, to capture the full scope of coordination that is needed for the bioeconomy, this approach may require negotiation of multiple MOUs among different sets of government agencies.
Currently, the U.S. government regulates biotechnology products based on the Coordinated Framework for the Regulation of Biotechnology, established in 1986 and most recently updated in 2017. Under this system, agencies regulate biotechnology products based on their product-based authorities (e.g., drugs are regulated by FDA; pesticides are regulated by EPA). However, there are gaps, ambiguities, and uncertainties in the regulatory system that will be compounded by the accelerating pace of biotechnology development, expanding range of applications, and potential novelty of new products. Often, developers of novel products struggle to determine which agency (FDA, EPA, or USDA) has primary responsibility for regulation of their product and can receive conflicting information from the agencies over the course of months or years. Several reports, including from the National Academies and from PCAST, have called for improved interagency coordination and a single door approach to the regulatory system that would enable product developers to contact a single entity within the U.S. government and receive an actionable answer about their product’s regulatory path. Importantly, this approach will not require changes to the underlying statutes that define regulatory authorities or to the regulations that define how these authorities are applied. Instead, it calls for efficient decision-making among the agencies to decide which agency will take the lead for novel products as they arise.
To use the single door approach, product developers would submit basic information about their products for the regulatory agencies to consider. At its simplest, this portal could be a submission system similar to that used by the federal government when requesting information from the public through regulations.gov (though product developer submissions would not be released publicly). A more secure system could be modeled on the Case Management System used for companies to share documents with the Committee on Foreign Investment in the U.S.
A more robust interagency process could also drive efforts to better harmonize regulatory approaches across agencies. For example, in 2017 the National Academies recommended ways the agencies could streamline oversight of familiar and low-risk products while focusing resources on products that are novel or require more complex risk assessments. The BICO should facilitate coordination on these topics, including progress agencies have made since 2017, lessons learned, and opportunities for improvements. The BICO should also conduct horizon scanning activities (e.g., as part of its National Bioeconomy Assessment or in public meetings focused on specific product types) so that regulators can best anticipate novel products and prepare for future decision-making. Expert groups, including PCAST, have also identified a need for training of regulators and opportunities for engagement between regulators and the broader bioeconomy; the BICO will be well-positioned to coordinate these activities.
DNA synthesis is one type of biotechnology for which the risks of misuse are well described, frameworks for reducing risk are already being developed and applied (including the 2010 HHS Screening Framework Guidance and efforts toward international harmonization), and best practices among responsible companies are established. An interagency process to update the Screening Framework Guidance is nearing completion; this process would have benefited from additional opportunities for engagement between the U.S. government and the DNA synthesis industry. The BICO should provide a forum for this type of engagement in support of future policy development.
The U.S. government is currently focused on advancing the U.S. bioeconomy while simultaneously figuring out how to both measure and standardize. But this can only be accomplished if the U.S. tackles questions that it has yet to address: What does ‘bioeconomy’ actually mean?, What sectors does the bioeconomy include?, and What is the role of sustainability in the U.S. bioeconomy?
There is no doubt that the widespread effort of corralling different government agencies together to focus on the U.S bioeconomy is a massive win for the nation, but it remains to be seen if enough stakeholders are being tapped into these conversations. The bioeconomy is currently a large and vague grouping that encompasses a lot of different sectors, industries, and areas. Are the groups that have thought about natural capital accounting being consulted when thinking about the role of bioecology in the bioeconomy? Does it make sense to include the groups that have thought about sustainability for years into the conversation of the U.S. bioeconomy? Currently, conversations around the state of the U.S. bioeconomy are very insular, conducted by a select few people within a few industries and the U.S. government. But, in reality, the bioeconomy encompasses a much larger, and a much more diverse group of people than what is currently being considered. For the U.S. bioeconomy to prosper and boom, the U.S. needs to land on a single, working definition of the bioeconomy while considering the role of sustainability in order to be competitive at the global scale.
A recent Office of Science and Technology Policy report has outlined a “broad vision for the U.S. bioeconomy and what can be achieved with concerted action from industry, academia, nonprofits, the Federal Government and other organizations.” However, setting goals for the bioeconomy does not necessarily mean it will go in any strategic direction. To accomplish that, the U.S. will need to agree on 1) a definition; 2) how to track and measure the bioeconomy; and 3) creating standards so that analysis between sectors within the bioeconomy, companies, and others can be made to better understand the return on investments that the government is making.
Can’t Measure What You Can’t Define
Currently, there are two different approaches that are being considered by the U.S. government to measure the U.S. bioeconomy: changes to the North American Industry Classification System (NAICS) and North American Product Classification System (NAPCS) and the creation of a satellite account within the U.S. Bureau of Economic Analysis. Both these methodologies have hit the same roadblock – there is no encompassing, consensus definition of the bioeconomy.
NAICS and NAPCS codes are designed to capture economic activity by sector and product type, but they are not well suited to capture the economic activity within the bioeconomy because of the many different sectors and products are, in many cases, differentiated more by the process by which they were made than by their final characteristics.
The U.S. Bureau of Economic Analysis (BEA) published a report which discussed the feasibility of measuring the U.S. bioeconomy by creating a bioeconomy satellite account. A satellite account enables the BEA to measure a slice of the economy that is “not easily identifiable under the standard industry classification commonly used to organize U.S. economic statistics, the NAICS.” Ultimately, the report concluded that a satellite account could be technically possible to develop and would complement efforts in the EU and other international organizations, but refining it to accurately measure specific sectors of the bioeconomy was technically infeasible at this time due to a lack of existing data and due to a lack of general consensus on practical definitions.
How does the U.S define the bioeconomy? The 2022 White House Executive Order (EO) on the bioeconomy defines the bioeconomy as “economic activity derived from biotechnology and biomanufacturing”. A follow up brief to the EO created by the Congressional Research Service in 2022 defines the bioeconomy as “the portion of the economy based on products, services, and processes derived from biological resources (e.g., plants and microorganisms).” The National Academies recommended in their 2020 report “Safeguarding the Bioeconomy” that the bioeconomy should be defined as “economic activity that is driven by research and innovation in the life sciences and biotechnology, and that is enabled by technological advances in engineering and in computing and information sciences.” As a result of the 2022 EO on the bioeconomy, the National Institute of Standards and Technology (NIST) created a lexicon around the bioeconomy and defined the bioeconomy as “economic activity derived from the life sciences, particularly in the areas of biotechnology and biomanufacturing, including industries, products, services, and the workforce.” While all these definitions are similar, each definition lacks something a different definition includes, thus resulting in a lack of consensus.
The definitions listed above don’t consider some of the aspects of the bioeconomy that the European vision includes, specifically the idea of sustainability. In 2012 the European Commission defined the bioeconomy as “the production of renewable biological resources and the conversion of these resources and waste streams into value added products, such as food, feed, bio-based products and bioenergy. Its sectors and industries have strong innovation potential due to their use of a wide range of sciences, enabling and industrial technologies, along with local and tacit knowledge.” In 2018 the European Commission updated their definition to “the bioeconomy covers all sectors and systems that rely on biological resources (animals, plants, micro-organisms and derived biomass, including organic waste), their functions and principles. It includes and interlinks: land and marine ecosystems and the services they provide; all primary production sectors that use and produce biological resources (agriculture, forestry, fisheries and aquaculture); and all economic and industrial sectors that use biological resources and processes to produce food, feed, bio-based products, energy and services.” with an emphasis that the “European bioeconomy needs to have sustainability and circularity at its heart.” There is only one U.S.-based definition that includes the concept of sustainability in the definition of the bioeconomy and it is not a U.S. government definition. In April of 2022, Schmidt Futures release a Bioeconomy Task Force Strategy where they introduced the idea of a “circular bioeconomy”, defined as “an economy that forgoes the traditional linear economic model of “take-make-consume-throw away” for one that uses the power of biotechnology, design for bioproduction, and machine learning/artificial intelligence to create and economic system in which waste products serve as inputs to create highly valued products and materials that are used as long as possible, and reused without drawing down limited resources or generating waste that are disposed into the atmosphere, landfills, or rivers, lakes, and oceans.”
Which begs the question, why is there a stark lack of sustainability in the governmental U.S. definition of the bioeconomy?
Inherent Issues within NAICS & NAPCS Codes
Beyond the definition of the bioeconomy, the NAICS and NAPCS codes themselves do not do a good job of classifying the bioeconomy. Companies within the biomanufacturing sector tend to produce many different types of products,which is difficult to capture using a singular NAICS code. Due to NAICS and NAPCS codes are not updated regularly they do not accurately capture emerging or novel products, nor do they currently accurately capture advancements to the field (such as algorithms to predict binding interactions, CRISPR sequence prediction tools, and data sets). Because the industry and product codes are not fit for purpose, it is difficult for companies to determine which codes apply to them. This confusion makes it difficult to collate different bioeconomic activity together across sectors when using NAICS codes alone. It would be beneficial for the U.S Government to update the industry and product codes and to work with these companies in order to re-classify in a more systematic way.
In a recent panel hosted by FAS, experts had some suggestions for updating these classification systems:
- Designing classifications for what companies are doing and not what they are producing; this approach would likely involve developing new NAICS and NAPCS codes.
- Creating a tiered classification system to resolve discrepancies. One example: 1) biology vs not biology; 2) modified genome vs naturally occurring genome; 3) if modified, how was it done (breeding vs. direct modifications vs. engineering).
- Adding a two-digit code to the end of current NAICS codes to differentiate biological products and innovations from other products and innovations that are not biobased.
Standardization within the bioeconomy
The U.S.’s ongoing efforts to standardize critical and emerging technology will greatly impact standardization efforts within the U.S. bioeconomy. However, this is occurring without clear guidance on how the U.S. bioeconomy is defined and how it will be measured. There is no doubt that standardization would give a massive spurt in growth to the nascent bioeconomy sector, and for emerging technologies the return on investment could be upwards of trillions. However, setting priorities for standardization is no easy task. To better understand the complexity behind standards creation and standards setting, FAS hosted a group of expert panelists to discuss these issues.
During these discussions, a few panelists pointed out that Europe’s bioindustrial infrastructure is more appealing for industry than the U.S.’s precisely because they have set standards in place, which in turn leads to higher quality and more advanced facilities. Some areas where standards could greatly benefit the U.S. bioindustrial sector are standards around equipment and sanitary design. Additionally, the U.S. needs to improve its ability to redeploy facilities and standardization can help achieve this.
For consumers and investors, climate sustainability has grown as a prerequisite to doing business. To meet those needs, an increasing number of companies are claiming their products and methods are sustainable, but there are no rules in place to define sustainability. Marketing techniques, like labeling products “carbon smart”, are just that – marketing. There is no standard definition or body governing those labels. Standardization in carbon accounting during the biomanufacturing process would benefit not just the bio sector, but the entire economy, repairing trust amongst consumers.
Public-private partnerships have an opportunity to lead when it comes to adopting standards. However, it would be important to include vendors and large-scale developers, such as companies that provide the starting material or the equipment used and both large-scale fermentation companies and other large contracted manufacturing organizations, in order to create and establish a full value-chain in the bioindustrial sector. The role of research universities in this partnership would need to be evaluated and strengthened in order to facilitate the development of a workforce that has the technical expertise needed in the bioindustrial sector, such as in areas of scale and in technology transfer.
But what can we do right now? The experts we spoke to had a few ideas up their sleeves:
- There are current opportunities for standardization in both upstream (e.g., feedstocks for bioindustrial manufacturing) and downstream processes (e.g., purification and collection of resulting products), however, it will be easier to create standards in the upstream process than the downstream process.
- Communication standards would be greatly beneficial to the sector and could be created by looking at unit-operations and then determining the best way to communicate these processes.
- Standards for data security should be built into the bioindustrial sector, however these standards would need to continue to enable information sharing within the sector.
- Standardization of communicating the capabilities of facilities will be crucial for the bioindustrial sector. Currently, Europe has a better understanding of what their capabilities are and has the workforce trained in different bioindustrial areas to promote quick adaptation and innovation.
- Companies are willing to adopt standards as long as they are not restrictive and do not interfere with a company’s ability to innovate and produce products in a cost-efficient manner.
The work currently being performed to advance the U.S. bioeconomy will quickly stagnate and not lead to any strategic advancement if the U.S. does not address the need for clarity on definitions, measurement, and standards. To achieve this, the U.S. government will need to reach consensus on a working definition – inclusive of sustainability – of the U.S. bioeconomy in order to be competitive at the global scale. Furthermore, the U.S. government should update the NAICS and NAPCS codes so that they better capture the all encompassing entity that is the bioeconomy. Congress should appropriate the creation of a satellite account within the BEA to measure the U.S. bioeconomy. Finally, the U.S. needs to work on creating standards within the different bioeconomy sectors that aid the biomanufacturing and biotechnology pathways in being more streamlined and efficient than what we currently have. Without addressing these initial challenges, no amount of bold goals will lead the U.S. bioeconomy in a strategic direction.
The advancement and commercialization of bioprocesses in the United States is hindered by a lack of suitable and available pilot-scale and manufacturing-scale facilities. This challenge stems in part from our inability to repurpose facilities that are no longer needed due to a lack of standardization and inadequate original design. Historically, most biomanufacturing facilities have been built with a single product in mind and with a focus on delivering a facility as cheaply and quickly as possible. While this might be the best approach for individual private companies, it is not the best approach for the bioeconomy as a whole. The Biden-Harris Administration should establish a program to standardize the construction of biomanufacturing facilities across the United States that also permits facilities to be repurposed for different products in the future.
Through government-incentivized standardization, better biomanufacturing facilities can be built that can be redeployed as needed to meet future market and governmental needs and ultimately solve our nation’s lack of biomanufacturing capacity. This program will help protect U.S. investment in the bioeconomy and accelerate the commercialization of biotechnology. Enforcement of existing construction standards and the establishment of new standards that are strictly adhered to through a series of incentivization programs will establish a world-leading biomanufacturing footprint that increases supply resilience for key products (vaccines, vitamins, nutritional ingredients, enzymes, renewable plastics), reduces reliance on foreign countries, and increases the number of domestic biomanufacturing jobs. Furthermore, improved availability of pilot-scale and manufacturing-scale facilities will accelerate growth in biotechnology across the United States.
This memo details a framework for developing and deploying the necessary standards to enable repurposing of biomanufacturing facilities in the future. A team of 10–12 experts led by the National Institute for Standards and Technology (NIST) should develop these standards. A government-sponsored incentivization program with an estimated cost of $50 million per year would then subsidize the building of new facilities and recognition of participating companies.
Challenge and Opportunity
Currently, the United States faces a shortage in both pilot-scale and manufacturing-scale biomanufacturing facilities that severely hinders product development and commercialization. This challenge is particularly large for the fermentation industry, where new facilities take years to build and require hundreds of millions of dollars in infrastructure investment. Many companies rely on costly foreign assets to advance their technology or delay their commercialization for years as they wait for access to one of the limited contract pilot or manufacturing facilities in the United States.
Why do we have such a shortage of these facilities? It is because numerous facilities have been shut down due to changing market conditions, failed product launches, or bankruptcy. When the facilities were ultimately abandoned and dismantled for scrap, the opportunity to repurpose expensive infrastructure was lost along with them.
Most U.S. biomanufacturing facilities are built to produce a specific product, making it difficult to repurpose them for alternative products. Due to strict financing and tight timelines for commercialization, companies often build the minimally viable facility, ultimately resulting in a facility with niche characteristics specific to their specific process and that has a low likelihood of being repurposed. When the facility is no longer needed for its original purpose—due to changes in market demand or financial challenges—it is very unlikely to be purchased by another organization.
This challenge is not unique to the biomanufacturing industry. In fact, even in the highly established automotive industry, less than half of its manufacturing facilities are repurposed. The rate of repurposing biomanufacturing facilities is much lower, given the lower level of standardization. Furthermore, nearly 30% of currently running biomanufacturing facilities have some idle capacity that could be repurposed. This is disappointing considering that many of these biomanufacturing facilities have similar upstream operations involving a seed bioreactor (a small bioreactor to be used as inoculum for a larger vessel) to initiate fermentation followed by a production reactor and then harvest tanks. Downstream processing operations are less similar across facilities and typically represent far less than half the capital required to build a new facility.
The United States has been a hot spot for biotech investment, with many startups and many commercial successes. We also have a robust supply of corn dextrose (a critical input for most industrial fermentation), reasonable energy costs, and the engineering infrastructure to build world-class biomanufacturing facilities providing advantages over many foreign locations. Our existing biomanufacturing footprint is already substantial, with hundreds of biomanufacturing facilities across the country at a variety of scales, but the design of these facilities lacks the standardization needed to meet the current and future needs of our biomanufacturing industry. There have been some success stories of facilities being repurposed, such as the one used by Gevo for the production of bio-butanol in Minnesota or the Freedom Pines facility in Georgia repurposed by LanzaTech.
However, there are numerous stories of facilities that were unable to be repurposed, such as the INEOS facility that was shuttered in India River, Florida. Repurposing these facilities is challenging for two primary reasons:
- A lack of forethought that the facility could be repurposed in the future (i.e., no space for additional equipment, equipment difficult to modify, materials of construction that do not have broad range of process compatibility).
- A lack of standardization in the detailed design (materials of construction, valve arrangements, pipe sloping, etc.) that prevents processes with higher aseptic requirements (lower contamination rates) from being implemented.
In order to increase the rate at which our biomanufacturing facilities are repurposed, we need to establish the policies and programs to make all new biomanufacturing facilities sustainable, more reliable, and capable of meeting the future needs of the industry. These policies and associated standards will establish a minimum set of guidelines for construction materials, sterilizability, cleanability, unit operation isolation, mixing, aeration, and process material handling that will enable a broad range of compatibility across many bioprocesses. As a specific example, all fermentors, bioreactors, and harvest tanks should be constructed out of 316L grade stainless steel minimum to ensure that the vast majority of fermentation and cell culture broths could be housed in these vessels without material compatibility concerns. Unfortunately, many of the U.S. biomanufacturing facilities in operation today were constructed with 304 grade stainless steel, which is incompatible with high-salt or high-chloride content broths. Furthermore, all process equipment containing living microorganisms should be designed to aseptic standards, even if the current product is not required to be axenic (absent of foreign microorganisms).
These standards should focus on upstream equipment (fermentors, media preparation tanks, sterilization systems), which are fairly universal across the food, pharma, and industrial biotech industries. While there are some opportunities to apply these standards to downstream process equipment, the downstream unit operations required to manufacture different biotech products vary significantly, making it more challenging to repurpose equipment.
Fortunately, guiding principles covering most factors that need to be addressed have already been developed by experts in the American Society of Mechanical Engineers (ASME), Bioprocess Equipment (BPE), and the International Society for Pharmaceutical Engineering (ISPE). These standards cover the gamut of biomanufacturing specifications: piping, mixing, valves, construction materials, and, in some cases, the design of specific unit operations. Companies are often forced to decide between following best practices in facility design and making tight timelines and budgets.
Following these standards increases capital costs of the associated equipment by 20% to 30%, and can extend construction timelines, preventing companies from adopting the standards even though it directly improves their top or bottom line by improving process reliability. Our biggest gap today is not ability to standardize but rather the incentivization to standardize. If the government provides incentives to adopt these standards, many companies will participate as it is widely recognized that these standards will result in facilities that are more reliable and more flexible for future products.
The National Institute for Standards and Technology (NIST) should initiate a program focused on biomanufacturing standards. The proposed program could be housed or coordinated out of a new office at the NIST—for example, as described in the previously proposed “Bio for America Program Office (BAPO)”—which should collaborate closely with the Office of the Secretary of Commerce and the Under Secretary of Commerce for Standards and Technology, as well as additional government and nongovernmental stakeholders as appropriate. NIST is the appropriate choice because it harbors cross-disciplinary expertise in engineering, and the physical, information, chemical, and biological sciences; is a nonregulatory agency of the U.S. Department of Commerce, whose mission it is “to drive U.S. economic competitiveness, strengthen domestic industry, and spur the growth of quality jobs in all communities across the country”; and is a neutral convener for industry consortia, standards development organizations, federal labs, universities, public workshops, and interlaboratory comparability testing.
Plan of Action
The Biden-Harris Administration should sponsor an initiative to incentivize the standardization that will enables the repurposing of biomanufacturing facilities, resulting in a more integrated and seamless bioeconomy. To do so, Congress should appropriate funds for a program focused on biomanufacturing standards at NIST. This program should:
- Develop a set of design and construction standards that enable facilities to be efficiently repurposed for different products in the future.
- Create, in collaboration with other government agencies, an incentivization program to encourage participation.
- Recognize participating companies with a certification.
- Track the program’s impact by measuring the rate of facility repurposing long-term.
First, the program will need to be funded by Congress and stood up within NIST. The award amounts will vary based on the facility size, but it is estimated that each participating company will receive $6 million on average, leading to a total program cost in the range of $30 million to $50 million per year. While the costs might seem high, the investment is at reduced risk by design, since facilities that adopt the program are better equipped to be repurposed should the original company abandon the facility.
Next, design and building standards would be defined that ensure the highest chance of redeployment along with reliable operation. While relevant standards exist (i.e., ASME BPE Standards), they should be refined and elaborated by an expert panel established by NIST with the purpose of promoting repurposing. The adoption rate of the existing nonmandatory standards is low, particularly outside of the pharma industry. This new NIST program should establish a panel of experts, including industry and government representatives, to fully develop and publish these standards. A panel of 10–12 members could develop these standards in one year’s time. Thereafter, the panel could be assembled regularly to review and update these standards as needed.
Once the standards are published, NIST should launch (and manage) a corresponding incentivization program to attract participation. The program should be designed such that an estimated 50% incremental cost savings would be achieved by adhering to these standards. In other words, the improved infrastructure established by following the standards would not be fully subsidized, but it would be subsidized at the rate of 50%. The NIST program could oversee applicants’ adherence to the new standards and provide awards as appropriate. NIST should also work with other federal government agencies that support development of biomanufacturing capacity (e.g., Department of Energy [DOE], Department of Defense [DoD], and Department of Agriculture [USDA]) to explore financial incentives and funding requirements to support adherence with the standards.
In addition, the government should recognize facilities built to the new standards with a certification that could be used to strengthen business through customer confidence in supply reliability and overall performance. NIST will publish a list of certified facilities annually and will seek opportunities to recognize companies that broadly participate as a way to recognize their adoption of this program. Furthermore, this type of certification could become a prerequisite for receiving funding from other government organizations (i.e., DoE, DoD, USDA) for biomanufacturing-related funding programs.
Last, to measure the program’s success, NIST should track the rate of redeployment of participating facilities. The success rate of redeployment of facilities not participating in the program should also be tracked as a baseline. After 10 years, at least a twofold improvement in redeployment rate would be expected. If this does not occur, the program should be reevaluated and an investigation should be conducted to understand why the participating facilities were not redeployed. If needed, the existing biomanufacturing standards should be adjusted.
Given the large gap in biomanufacturing assets needed to meet our future needs across the United States, it is of paramount importance for the federal government to act soon to standardize our biomanufacturing facilities. This standardization will enable repurposing and will build a stronger bioeconomy. By establishing a program that standardizes the design and construction of biomanufacturing facilities across the country, we can ensure that facilities are built to meet the industry’s long-term needs—securing the supply of critical products and reducing our reliance on foreign countries for biomanufacturing needs. In the long run, it will also spur biotech innovation, since startup companies will need to invest less in biomanufacturing due to the improved availability of manufacturing assets.
A committee will need to be established to create a detailed budget plan; however, rough estimates are as follows: A typical biomanufacturing facility costs between $100 million and $400 million to build, depending on scale and complexity. If the program is designed to support five biomanufacturing facilities per year, and we further assume an average construction cost of $200 million with $40 million of that being equipment that applies to the new standard, a 15% subsidy would result in ~$6 million being awarded to each participating facility. If we assume that following these standards increases the costs of the associated equipment by 30%, the net increase in costs would be from $40 million to $52 million. This 15% subsidy is designed to offset the cost of applying these new standards at roughly a 50 cents on the dollar rate. In addition, there will be some overhead costs to run the program at NIST, but these are expected to be small. Thus, the new program would cost in the range of $30 million to $50 million per year to run, depending on how many companies participate and are awarded on an annual basis.
When they apply for funding, companies will describe the facility to be built and how the funds will be used to make it more flexible for future use. A NIST panel of subject matter experts will evaluate and prioritize nominations, with an emphasis on selecting facilities across different manufacturing sectors: food, pharma, and industrial biotech.
Given that the life of biomanufacturing facilities is on the order of years, it is expected that this program will take several years before a true impact is observed. For this reason, the program evaluation is placed 10 years after launch, by which time it is expected that more than 20 facilities will have participated in the program, and at least a few will have been repurposed during that time.
Keeping the standards general across industries enables repurposing of facilities across different industries. The fact that different standards exist across industries, and are present in some industries but not others, is part of the current challenge in redeploying facilities.
The initial focus is on standardization within the United States. Eventually, standardization on a more global scale can be pursued, which will make it easier for the United States to leverage facilities internationally. However, international standardization presents a whole new set of challenges due to differences in equipment availability and materials of construction.
A number of biomanufactured products require amino acids and growth factors as inputs, but these small molecules and proteins can be very expensive, driving up the costs of biomanufacturing, slowing the expansion of the U.S. bioeconomy, and limiting the use of novel biomedical and synthetically produced agricultural products. Manufacturing costs can be substantially limiting: officials from the National Institutes of Health and the Bill & Melinda Gates Foundation point to the manufacturing costs of antibody drugs as a major bottleneck in developing and distributing treatments for a variety of extant and emerging infectious diseases. To help bring down the costs of these biomanufacturing inputs, the Biden-Harris Administration should allocate federal funding for a Grand Challenge to research and develop reduced-cost manufacturing processes and demonstrate the scalability of these solutions.
Amino acids are essential but costly inputs for large-scale bioproduction. To reduce these costs, federal funding should be used to incentivize the development of scalable production methods resulting in production costs that are half of current costs. Specifically, the U.S. Department of Agriculture (USDA) and ARPA-H should jointly commit to an initial funding amount of $15 million for 10 research projects in the first year, with a total of $75. million over five years, in Grand Challenge funding for researchers or companies who can develop a scalable process for producing food-grade or pharmaceutical-grade amino acids or growth factors at a fraction of current costs. ARPA-H should also make funding available for test-bed facilities that researchers can use to demonstrate the scalability of their cost-saving production methods.
Scaling up the use of animal cell culture for biosynthetic production will only be economically effective if the costs of amino acids and growth factors are reduced. Reducing the cost of bioproduction of medical and pharmaceutical products like vaccines and antimicrobial peptides, or of animal tissue products like meat or cartilage, would improve the availability and affordability of these products, make innovation and new product development easier and more cost effective, and increase our ability to economically manufacture bioproducts in the United States, reducing our dependence on foreign supply chains.
For a better understanding of the use of amino acids and growth factors in the production of biologics and animal cell-based products, and to accurately forecast supply and demand to ensure a reliable and available supply chain for medical products, the Department of Defense (DoD) and USDA should jointly commission an economic analysis of synthetic manufacturing pathway costs for common bioproducts and include assessments of comparative costs of production for major international competitors.
Challenge and Opportunity
Amino acids are necessary inputs when synthesizing protein and peptide products, including pharmaceutical and healthcare products (e.g., antibodies, insulin) and agricultural products (e.g., synthetic plant and animal proteins for food, collagen, gelatin, insecticidal proteins), but they are very expensive. Amino acids as inputs to cell culture cost approximately $3 to $50 per kg, and growth factors cost $50,000 per gram, meaning that their costs can be half or more of the total production cost.
Biomanufacturing depends on the availability of reagents, small molecules, and bioproducts that are used as raw inputs to the manufacturing process. The production of synthetic bioproducts is limited by the cost and availability of certain reagents, including amino acids and small signaling proteins like hormones and growth factors. These production inputs are used in cell culture to increase yields and production efficiency in the biosynthesis of products such as monoclonal antibodies, synthetic meat, clotting factors, and interferon (proteins that inhibit tumor growth and support immune system function). While some bioproducts can be produced synthetically in plant cells or bacterial cells, some products benefit from production steps in animal cells. One example is glycosylation, a protein-modification process that helps proteins fold into stable structures, which is a much simpler process in animal cells than in bacteria or in cell-free systems. The viruses used in vaccine development are also usually grown in animal cells, though some recombinant vaccines can be made in yeast or insect cells. There are benefits and drawbacks to the use of plant, fungi, bacteria, insect, or animal cells in recombinant bioproduction; animal cells are generally more versatile because they mimic human processes closely and require less engineering than non-animal cells. All cells, whether they are animal, plant or bacteria, require amino acids and various growth factors to survive and function efficiently. While in the future growth factors may no longer be required, amino acids will always be required. Amino acids are the most costly necessary additive on a price per kilogram basis; the most costly of the supporting additives are growth factors.
Growth factors are proteins or steroids that act as signaling molecules that regulate cells’ internal processes, while amino acids are building blocks of proteins that are necessary both for cell function and for producing new proteins within a cell. Cells require supplementation with both growth factors and amino acids because most cells are not capable of producing their own growth factors. Biosynthetic production in animal cells frequently uses growth factors (e.g., TGF, IGF) to increase yield and increase production speed, signaling cells to work faster and make more of a particular compound.
Although pharmaceutical products are expensive, relatively small demand volumes prevent market forces from exerting sufficient cost pressure to spur innovation in their production. The biosynthetic production of pharmaceuticals involves engineering cells to produce large quantities of a molecule, such as a protein or peptide, which can then be isolated, purified, and used in medicine. Peptide therapeutics is a $39 billion global market that includes peptides sold as end products and others used as inputs to the synthesis of other biological compounds. Protein and peptide product precursors, including amino acids and growth factors, represent a substantial cost of production, which is a barrier to low-cost, high-volume biomanufacturing.
For example, the production of antimicrobial peptides, used as therapeutics against antibiotic-resistant bacteria and viruses, is strongly constrained by the cost of chemical inputs. One input alone, guanidine, accounts for more than 25% of the approximately $41,000 per gram production cost of antimicrobial peptides. Reducing the cost of these inputs will have substantial downstream effects on the economics of production. Antimicrobial peptides are currently very expensive to produce, limiting their development as alternatives to antibiotics, despite a growing need for new antibiotics. The U.S. National Action Plan for Combating Antibiotic-Resistant Bacteria (CARB) outlines a coordinated strategy to accelerate the development of new antibiotics and slow the spread of antibiotic resistance. Reducing the cost to produce antimicrobial peptides would support these goals.
The high costs of synthetic production limit the growth of the market for synthetic products. This creates a local equilibrium that is suboptimal for the development of the synthetic biology industry and creates barriers to market entry for synthetic products that could, at scale, address environmental and bioavailability concerns associated with natural sources. The federal government has already indicated an interest in supporting the development of a robust and innovative U.S.-based biomanufacturing center, with the passage of the CHIPS and Science Act and Executive Order 14081 on Advancing Biotechnology and Biomanufacturing Innovation for a Sustainable, Safe, and Secure American Bioeconomy. Reducing the costs of basic inputs to the biomanufacturing process of a range of products addresses this desire to make U.S. biomanufacturing more sustainable. There are other examples of federal investment to reduce the cost of manufacturing inputs, from USDA support for new methods of producing fertilizer, to Food and Drug Administration investment to improve pharmaceutical manufacturing and establish manufacturing R&D centers at universities, to USDA National Institute of Food and Agriculture (NIFA) support for the development of bioplastics and bio-based construction materials. Federal R&D support increases subsequent private research funding and increases the number of new products that recipients develop, a positive measure of innovation.
The effort to reduce biomanufacturing costs is larger than any one company; therefore, it requires a coordinated effort across industry, academia, and government to develop and implement the best solution. The ability to cost-effectively manufacture precursors will directly and indirectly advance all aspects of biomanufacturing. Academia and industry are poised and ready to improve the efficiency and cost of bioproduction but require federal government coordination and support to achieve this essential milestone and to support the development of the newly emerging industry of large-scale synthetic bioproducts.
Developing cost-effective protein and peptide synthesis would remove a substantial barrier to the expansion of synthetic medical and agricultural products, which would address current supply bottlenecks (e.g., blood proteins, antibody drugs) and mounting environmental and political challenges to natural sourcing (e.g., beef, soy protein). Over the past decade, breakthroughs in the manufacturing capability to synthetically produce biological products, like biofuels or the antimalarial drug artemisinin, have failed to reach cost-competitiveness with naturally sourced competitors, despite environmental and supply-chain-related benefits of a synthetic version. The Department of Energy (DoE) and others continue to invest in biofuel and bioproduct development, and additional research innovation may soon bring these products to a cost-competitive threshold. For bioproducts that depend on amino acids and growth factors as inputs, that threshold may be very close. Proof of concept research on growth factor and amino acid production, as well as techno-economic assessments of synthetic meat products, point to precursor amino acids and proteins as being substantial barriers to cost competitiveness of bioproduction—but close to being overcome through technological development. Potential innovators lack support to invest in the development of potentially globally beneficial technologies with uncertain returns.
Reducing the costs of these inputs for the peptide drug and pharmaceutical market could also bring down the costs of synthetic meat, thereby increasing a substantial additional market for low-cost amino acids and growth factors while alleviating the environmental burdens of a growing demand for meat. Israel has demonstrated that there is strong demand for such products and has substantially invested in its synthetic meat sector, which in turn has augmented its overall bioeconomy.
Bringing the cost of synthetic meat from current estimates of $250 per kg to the high end of wholesale meat prices at $10 per kg is infeasible without reducing the cost of growth factors and amino acids as production inputs but would also reduce the water and land usage of meat production by 70% to 95%. Synthetic meat would also alleviate many of the ethical and environmental objections to animal agriculture, reduce food waste, and increase the amount of plant products available for human consumption (currently 77% of agricultural land is used for livestock, meat, and dairy production, and 45% of the world’s crop calories are eaten by livestock).
Bioeconomy initiatives and opportunity
Maintaining U.S. competitiveness and leadership in biomanufacturing and the bioeconomy is a priority for the Biden-Harris Administration, which has led to a national bioeconomy strategy that aims to coordinate federal investment in R&D for biomanufacturing, improve and expand domestic biomanufacturing capacity, and expand market opportunities for biobased products. Reducing the cost and expanding the supply of amino acids and growth factors supports these three objectives by making bioproducts derived from animal cells cheaper and more efficient to produce.
Several directives within President Biden’s National Biotechnology and Biomanufacturing Initiative could apply to the goal of producing cost-effective amino acids and growth factors, but a particular stipulation for the Department of Health and Human Services stands out. The 2022 Executive Order 14081 on Advancing Biotechnology and Biomanufacturing Innovation for a Sustainable, Safe, and Secure American Bioeconomy includes a directive for the Department of Health and Human Services (HHS) to invest $40 million to “expand the role of biomanufacturing for active pharmaceutical ingredients (APIs), antibiotics, and the key starting materials needed to produce essential medications and respond to pandemics.” Protein and peptide product precursors are key starting materials for medical and pharmaceutical products, justifying HHS support for this research challenge.
Congress has also signaled its intent to advance U.S. biotech and biomanufacturing. The CHIPS and Science Act authorizes funding for projects that could scale up the U.S. bioeconomy. Title IV of the Act, on bioeconomy research and development, authorizes financial support for research, test beds for scaling up technologies, and tools to accelerate research. This support could take the form of grants, multi-agency collaborative funding, and Small Business Innovation Research (SBIR) or Small Business Technology Transfer Program (SBTTP) funding.
Biomanufacturing is important for national security and stability, yet much research and development are needed to realize that potential. The abovementioned funding opportunities should be leveraged to support foundational, cross-cutting capabilities to achieve affordable, accessible biomanufactured products, such as the production of essential precursor molecules.
Plan of Action
To provide the catalyst for innovation that will drive down the price of components, federal funding should be made available to organizations developing cost-effective biosynthetic production pathways. Initial funding would be most helpful in the form of research grants as part of a Grand Challenge competition. University researchers have made some proof-of-concept progress in developing cost-effective methods of amino acid synthesis, but the investment required to demonstrate that these methods succeed at scale is currently not provided by the market. The main market for synthetic biomanufacturing inputs like amino acids is pharmaceutical products, which can pass on high production costs to the consumer and are not sufficiently incentivized to drive down the costs of inputs.
Recommendation 1. Provide Grand Challenge funding for reduced-cost scalable production methods for amino acids and growth factors.
The USDA (through the USDA-NIFA Agriculture and Food Research Initiative [AFRI] or through AgARDA if it is funded) and ARPA-H should jointly commit to $15 million for 10 projects in the first year, with a total of $75 million over five years, in Grand Challenge1 funding for researchers or companies who can develop a scalable process for producing food-grade or pharmaceutical-grade amino acids or growth factors at a fraction of current costs (e.g., $100,000 per kg for growth factors, and $1.50 per kg for amino acids), with escalating prizes for greater cost reductions. Applicants can also demonstrate the development of scalably produced bioengineered growth factors that demonstrate increased efficacy and efficiency. Grand Challenges offer funding to incentivize productive competition among researchers to achieve specific goals; they may also offer prizes for achieving interim steps toward a larger goal.
ARPA-H and USDA are well-positioned to spur innovation in cost-effective precursor production. Decreasing the costs of producing amino acids and growth factors would enable the transformative development of biologics and animal-cell-based products like synthetic meat, which aligns well with ARPA-H’s goal of supporting the development of breakthrough medical and biological products and technologies. ARPA-H aims to use its $6.5 billion in funding from the FY22 federal budget to invest in three-to-five-year projects that will support breakthrough technologies that are not yet economically compelling or sufficiently feasible for companies to invest internally in their development. An example technology cited by the ARPA-H concept paper is “new manufacturing processes to create patient-specific T-cells to search and destroy malignant cells, decreasing costs from $100,000s to $1000s to make these therapies widely available.” Analogously, new manufacturing processes for animal cell culture inputs will make biosynthetic products more cost-effective and widely available, but the potential market is still speculative, making investment risky.
AgARDA was meant to complement AFRI, in its model for soliciting research proposals, and being able to jointly support projects like a Grand Challenge to scale up amino acids and growth factors provides reason to fund AgARDA at its authorized level. Because producing cell-based meat at cost parity to animal meat would be an agricultural achievement, lowering the cost of necessary inputs to cell-based meat production could fall under the scope of AgARDA.
Recommendation 2. Reward Grand Challenge winners who demonstrate scalability and provide BioPreferred program purchasing preference.
Researchers developing novel low-cost and high-efficiency production methodology for amino acids and growth factors will also need access to facilities and manufacturing test beds to ensure that their solutions can scale up to industrial levels of production. To support this, ARPA-H should make funding available to Grand Challenge winners to demonstrate scaling their solutions to hundreds of kilograms per year. This is aligned with the test-bed development mandated by the CHIPS and Science Act. This funding should include $15 million to establish five test-bed facilities (a similar facility at the University of Delaware was funded at $3 million) and an additional $3 million to provide vouchers of between $10,000 and $300,000 for use at test-bed facilities. (These amounts are similar to the vouchers provided by the California Department of Energy for its clean energy test-bed program.)
To support the establishment of a market for the novel production processes, USDA should add to its BioPreferred program a requirement that federal procurement give preference to winners of the Grand Challenge when purchasing amino acids or growth factors for the production of biologics and animal cell-derived products. The BioPreferred program requires that federal purchases favor bio-based products (e.g., biodegradable cutlery rather than plastic cutlery) where the bio-based product meets the requirements for the purchaser’s use of that product. This type of purchasing commitment would be especially valuable for Grand Challenge winners who identify novel production methods—such as molecular “farming” in plants or cell-free protein synthesis—whose startup costs make it difficult to bootstrap incremental growth in production. Requiring that federal purchasing give preference to Grand Challenge winners ensures a certain volume of demand for new suppliers to establish themselves without increasing costs for purchasers.
Stakeholder support for this Grand Challenge would include research universities; the alternative protein, peptide products, and synthetic protein industries; nonprofits supporting reduced peptide drug prices (such as the American Diabetes Association or the Boulder Peptide Foundation) and a reduction in animal agriculture (such as New Harvest or the Good Food Institute); and U.S. biomanufacturing supporters, including DoE and DoD. Companies and researchers working on novel methods for scalable amino acid and growth factor production will also support additional funding for technology-agnostic solutions (solutions that focus on characteristics of the end product rather than the method—such as precision fermentation, plant engineering, or cell-free synthesis—used to obtain the product).
As another incentive, ARPA-H should solicit additional philanthropic and private funding for Grand Challenge winners, which could take the form of additional prize money or advance purchase commitment for a specified volume of amino acids or growth factors at a given threshold price, providing further incentive for bringing costs below the level specified by the Challenge.
Recommendation 3. To project future demand, DoD should commission an economic analysis of synthetic manufacturing pathway costs for common bioproducts, and include assessments of comparative costs in major international competitors (e.g., China, the European Union, the United Kingdom, Singapore, South Korea, Japan).
This analysis could be funded in part via BioMADE’s project calls for technology and innovation research. BioMADE received $87 million in DoD funding in 2020 for a seven-year period, plus an additional $450 million announced in 2023. Cost sharing for this project could come from the NSF Directorate for Technology, Innovation, and Partnerships or from the DoE’s Office of Science’s Biological and Environmental Research Program, which has supported techno-economic analyses of similar technologies, such as biofuels.
EO 14081 also includes DoD as a major contributor to building the bioeconomy. The DoD’s Tri-Service Biotechnology for a Resilient Supply Chain program will invest $270 million over five years to speed the application of research to product manufacturing. Decreasing the costs of amino acids and growth factors as inputs to manufacturing biologics could be part of this new program, depending on the forthcoming details of its implementation. Advancing cost-effective biomanufacturing will transform defense capabilities needed to maintain U.S. competitiveness, secure critical supply chains, and enhance resiliency of our troops and defense needs, including medicines, alternative foods, fuels, commodity and specialty chemicals, sensors, materials, and more. China recently declared a focus on synthetic animal protein production in its January 2022 Five Year Plan for Agriculture. Our trade relationship with China, which includes many agricultural products, may shift if China is able to successfully produce these products synthetically.
To support the development of an expansive and nimble biomanufacturing economy within the United States, federal agencies should ensure that the necessary inputs for creating biomanufactured products are as abundant and cost-effective as possible. Just as the cost to produce an almond is greatly dependent on the cost of water, the cost to manufacture a biological product in a cell-based manufacturing system depends on the cost of the inputs used to feed that system. Biomanufactured products that require amino acids and growth factors as inputs range from the medically necessary, like clotting factors and monoclonal antibodies, to the potentially monumental and industry-changing, like cell-based meat and dairy products. Federal actions to increase the feasibility and cost-effectiveness of manufacturing these products in the United States will beneficially affect the bioeconomy and biotechnology industry, the pharmaceutical and biomedical industries, and potentially the food and agriculture industries as well.
Similar grant funding through NINDS (CREATE Bio) and NIST (NIIMBL) for biomanufacturing initiatives devoted $10 million to $16 million in funding for 12-14 projects. The USDA recently awarded $10 million over five years to Tufts University to develop a National Institute for Cellular Agriculture, as part of a $146 million investment in 15 research projects announced in 2021 and distributed by the USDA-NIFA Agriculture and Food Research Initiative’s Sustainable Agricultural Systems (AFRI-SAS) program. AFRI-SAS supports workforce training and standardization of methods used in the production of cell-based meat, while Tufts’s broader research goals include evaluating the economics of production. Decreasing the cost of synthetic meat is key to developing a sustainable cellular agriculture program, and USDA could direct a portion of its AFRI-SAS funding to providing support for this initiative.
Yes. Current production methods for biological products, such as monoclonal antibody drugs, are sufficiently high that developing monoclonal antibodies for infectious diseases that primarily affect poor regions of the world is considered infeasible. Decreasing the costs of manufacturing these drugs through decreasing the costs of their inputs would make it economically possible to develop antibody drugs for diseases like malaria and zika, and biomedical innovation for other infectious diseases could follow. Similarly, decreasing the costs of amino acid and growth factor inputs would allow synthetic meat companies greater flexibility in the types of products and manufacturing processes they are able to use, increasing their ability to innovate.
In fact, a few non-U.S. companies are pursuing the production of synthetic growth factors as well as bioengineered platforms for lower-cost growth factor production. Israeli company BioBetter, Icelandic company ORF Genetics, UK-based CellRX, and Canadian company Future Fields are all working to decrease growth factor cost, while Japanese company Ajinomoto and Chinese companies such as Meihua Bio and Fosun Pharma are developing processes to decrease amino acid costs. Many of these companies receive subsidies or are funded by national venture funding dedicated to synthetic biology and the alternative protein sector. thus, U.S. federal funding of lower-cost amino acid and growth factor production would support the continued competitiveness of the national bioeconomy and demonstrate support for domestically manufactured bioengineered products.
Reducing the supply chain costs of manufacturing allows companies to increase manufacturing volumes, produce a wider range of products, and sell into more price-sensitive markets, all of which could result in job growth and the expansion of the biomanufacturing center. As an example of a product that has seen similar effects, solar panels and photovoltaic cells have seen substantial decreases in their costs of production, which have been coupled with job growth. Jobs in photovoltaics are seeing the largest increases among overall growth in renewable energy employment.
The techniques required to lower costs and scale production of amino acids and growth factors should translate to the production of other types of small molecules and proteins, and may even pave the way for more efficient and lower-cost production methods in chemical engineering, which shares some methods with bioengineering and biological manufacturing. For example, chemical engineering can involve the production of organic molecules and processing and filtration steps that are also used in the production of amino acids and growth factors.
Increased synthetic meat production will help address growing demands for meat and for protein-rich foods that the livestock industry currently struggles with in combination with other demands for land, water, agricultural products, and skilled labor. As an example, the recent U.S. egg shortage demonstrated that the livestock industry is susceptible to external production shocks caused by disease and unexpected environmental effects. Many large-scale meat companies, including giants like Cargill and Tyson Foods, see themselves as in the business of supplying protein, rather than the business of slaughtering animals, and have invested in plant-based-meat companies to broaden their portfolios. Expanding into synthetic meat is another way for animal agriculture to continue to serve meat to customers while incorporating new technological methods of production. If synthetic meat adoption expands rapidly enough to reduce the need for animal husbandry, farmers and ranchers will likely respond by shifting the types of products they produce, whether by growing more vegetables and plant crops or by raising animals for other industries.
The Advanced Bioeconomy Leadership Conference (ABLC), hosted by The Digest, convened leaders in and around the biofuels, biomaterial, and agriculture industries to discuss key issues that the “circular bioeconomy” currently faces. The circular bioeconomy refers to the concept that biotechnology, bioproduction, machine learning and artificial intelligence is used to create an economic system where waste products are repurposed to create high impact products.
After two and a half days of summits, mini-conferences and intense networking, here are our key insights gleaned from the conference.
Count All Carbon
Decarbonization and the goal of net zero emissions are undoubtedly crucial in the fight against the effects of climate change. These goals are also currently driving the biofuels, biomanufacturing, and agricultural sectors of industry. Production of sustainable aviation fuel (SAF), polymers using biowaste, and low-carbon feedstocks are some examples of how these industries are attempting to achieve decarbonization and net zero emissions.
“Count all the carbon” was the key phrase said throughout the entire conference. However, industry leaders acknowledged that it is easier said than done. There are currently many different ways to measure carbon intensities (CI), with the Argonne National Laboratory GREET model, which uses a life-cycle analysis approach, being the current favorite. However, all models – including GREET –, have nuances and differences resulting in different CI scores that vary based on methodology. This makes calculating CI scores confusing, which has huge ramifications for projects trying to determine eligibility for CI-score-based financial incentives. One possible solution for the U.S. government, possibly through NIST (in collaboration with the Department of Energy), would be to create guidelines around which model of calculation should be used, or to standardize one model across the board (taking internationally agreed-upon guidelines into account). Furthermore, the government can weigh in on the conversation of whether a price on carbon would be the better incentive tool to mitigate greenhouse gas emissions.
However, while the debate over how to count all the carbon persists, there appears to be broad consensus that to achieve net zero emissions, it will be important for technology to stay agnostic. Industry leaders agreed: it doesn’t matter what the technology is, as long as it helps to bring us toward decarbonization. They also suggested that if we were to focus on one technology, achieving decarbonization, and net zero emissions would likely become exponentially harder.
Scale-up & Feedstocks
Another prominent theme that persisted throughout the conference was the need for scale-up and the need for feedstocks. Currently, the Department of Energy (DOE) has issued a grand challenge to the biofuels industry in order to accelerate the domestic production of SAF in order to be able to provide 3 billion gallons per year by 2030 and 35 billion gallons per year by 2050. Major innovation and increased capacity is going to be needed in this sector in order to meet the goals of the U.S. government. However, the biofuels industry is not the only industry facing the issue of scale-up. Many biomanufacturing and fermentation companies agree that while upstream processing can be done easily, the challenge really arises with the downstream process when they try to scale. For both the biofuels and biomanufacturing industry, the creation of infrastructure is going to be vital in order for scale-up to be truly achieved within the U.S.
Furthermore, scale-up will also require the development of new and multi-use feedstocks. Increased production will necessitate more feedstocks – while some current feedstocks can be repurposed or reengineered for multi-use, brand new feedstocks will need to be developed as well in order to fulfill demand in the future. Innovation in this area will be key for the longevity of industries within the bioeconomy. Currently, the Bioenergy Technologies Office within the DOE is working on the fourth version of the Billion Ton report for 2023. The newest version of the report will discuss future feedstocks such as wood, waste, agricultural residue, and biomass crops such as algae. Furthermore they are also taking into consideration the use of wildfire waste and land resources in order to understand the full scope of the available feedstocks in the U.S.
De-risk Biofuels & Biomanufacturing
In order for innovation to occur within the bioeconomy, it was agreed that de-risking the biofuels and biomanufacturing industries would be needed in the sectors for long-term financial viability. Startup companies face the “Valley of Death”, or the point where startups transition from prototype to commercially available product. This transition period is impeded by different factors–scale-up being one such factor–but financing can also play a large role in this transition as well. Investors tend to be leery of startup companies due to the high risk involved traversing the valley. It was generally agreed that the U.S. government should provide guidance to the DOE (which finances a lot of startups) as to what loans they should underwrite in order to de-risk the industry and allow for novel innovations to flourish within the sector. Tax credits are another under-utilized tool–largely due to the complexity and lack of guidance behind them. Conference-goers agreed this is something the U.S. government should address and provide guidance on.
To further de-risk the industries, it was generally recommended that the supply chain sector and the infrastructure involved to support the U.S. supply chain needs to be evaluated, revamped, and increased. On March 22nd, 2023, the Office of Science and Technology Policy published the “Bold Goals for U.S. Biotechnology and Biomanufacturing”, in which, one of the goals for the Department of Commerce, was addressing the innovation needed to create a resilient supply chain.
It is unsurprising that the key themes found at the ABLC 2023 underscore the need for innovation, proper financing, infrastructure, and sustainability. These are the elements needed in order to drive the U.S. bioeconomy forward. While the U.S. bioeconomy faces many challenges ahead, industry, thought, academic, and other leaders are laser-focused on finding solutions.
The past year has been an exciting time for the bioeconomy as U.S. government agencies work to update their approaches and improve coordination to better support bio-based products and processes. Action within the government has been spurred by a September 2022 Executive Order on Advancing Biotechnology and Biomanufacturing Innovation and by the CHIPS and Science Act signed into law in August 2022. The Federation of American Scientists (FAS) received a grant to support policy development for the bioeconomy, and has worked to generate discussion and ideas that the government could pursue. In December, 2022, we conducted two multi-stakeholder, discussion-based bioeconomy policy workshops focused on Measurement and Language and on Financial and Economic Tools. We have also worked with outside experts to publish policy memos with specific ideas, including ways to improve coordination across the government and an approach for investing in biomanufacturing facilities.
As U.S. government agencies consider how to support the bioeconomy, it will be important to pay attention to industry perspectives on key hurdles, market failures, and ways the federal government could work to address those challenges. To better understand these perspectives, FAS conducted interviews with representatives from eight private sector companies that develop biotechnology capabilities and products. These companies pursue a wide range of different types of biomanufacturing, including: cell-free synthesis of biochemicals; fermentation for compounds that are high-value and low-volume; fermentation for compounds that are low-value and high-volume; and cellular and tissue culture. They also conduct business in a variety of bioeconomy sectors, including fuels, fragrances, specialty chemicals, pharmaceuticals, and biologics. Many are smaller, less established companies that are familiar with the challenges that the industry faces as opportunities and investment in the bioeconomy increase. Collectively, they represent a new generation of biotechnology companies that are expanding the possibilities for biotechnology products and biomanufacturing.
Key points and ideas from industry interviews
Building biomanufacturing physical infrastructure. Every interviewee believed that biomanufacturing infrastructure for scale-up and production was lacking in the U.S. Additional capacity is needed for many types of biomanufacturing; from fermentation to cell and tissue culture. Interviewees also said this applies at all stages of production, from pilot-scale to intermediate-scale to large-scale. One interviewee noted that the capacity crunch is particularly difficult for small companies, which sometimes will have to “beg” for fermentation time from larger companies who have better access to facilities.
Addressing pre-competitive challenges in the bioeconomy. Government funding of basic research is essential, but there is also a need for specific funding for biomanufacturing science. Multiple interviewees mentioned the Advanced Biofuels and Bioproducts Process Development Unit (ABPDU), the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL), and BioMADE as good investments for the federal government (though they also said that contracting and collaborating with these institutes can be difficult). Interviewees also believed that the federal government should work to develop standards for biomanufacturing processes and facilities, and that biodata infrastructure (e.g., Genbank) should be updated, modernized, and secured.
Ensuring the US government is a good financial partner. The federal government can sometimes provide good funding opportunities, but these opportunities are often inflexible and procedurally burdensome for applicants. Interviewees believed that government funding should be indirect, where possible, and that loans should include terms that allow long repayment timelines because many biomanufacturing investments take a long time to achieve sustainable revenues.
Developing a bioeconomy workforce. Multiple interviewees noted that it was difficult to find people with training in fermentation and other biomanufacturing processes, and that this type of training, including access to facilities, should be included in graduate school programs. Public-private partnerships that include academia and industry could facilitate these opportunities. Also, visa processes should be updated so that non-Americans with training in biomanufacturing or process engineering could be more easily hired.
Building incentives and removing barriers for bio-based products and processes. Interviewees came up with multiple ideas for how the US government could improve incentives and remove barriers for the bioeconomy, including: better identifying and prioritizing sustainable products and processes; updating the biotechnology regulatory system; updating the renewable fuel standards at EPA to accommodate new approaches; and improving incentives for bio-based government procurement (the Biopreferred Program is a good start, but needs to be revisited and expanded). Interviewees also believed that supply chain mapping of resources and products that support the bioeconomy would demonstrate vulnerabilities and increase incentives for investment in more secure, U.S.-based facilities.
Although the companies chosen for these interviews represent different business models, biotechnologies, and perspectives, common themes emerged regarding the challenges companies face and potential solutions to address them. In particular, every interviewee noted the need for biomanufacturing facilities at many scales and for many different types of applications. The industry representatives also had suggestions for how the U.S. government could help address pre-competitive issues in the bioeconomy (such as standards-setting and advancing biomanufacturing science) and ways that it could become a better financial partner for private companies. Other ideas included ways that federal agencies could support development of the bioeconomy workforce and could work to improve incentives for bio-based products and processes. As the bioeconomy advances, it will be important to ensure that industry voices continue to be included in policy development discussions.
To strengthen the U.S. lead in the bioeconomy, Congress recently passed the CHIPS & Science Act of 2022. While the main body of this bill is related to semiconductors, this bill also lays out a solid base for the bioeconomy. Shortly after the passing of the CHIPS & Science Act, the White House also published an Executive Order that detailed key actions the government needed to take to secure the U.S. bioeconomy, touching on production capacity, market opportunities, workforce, and more.
While both the congressional bill and the Executive Order outline a wide path forward for the U.S. bioeconomy, key parts of the equation still need to be defined:
- What areas of industry make up the bioeconomy?
- What factors should or should not be considered when measuring the bioeconomy?
- Which federal agencies should coordinate the bioeconomy?
- What are the current barriers that the bioeconomy faces to grow?
This provides a unique opportunity for experts to contribute to current and future legislation and action in their own field.
To drive innovative ideas, the Federation of American Scientists and the Day One Project hosted a Bioeconomy Policy Development Sprint, where experts in the field submitted ideas about how to better shape the U.S. bioeconomy, answering the above questions and more. From these ideas, we published three bold memos:
- Jon Roberts on “Accelerating the Bioindustry Through Research, Innovation, and Translation.”
- Mike Fisher on “Advancing the U.S. Bioindustrial Production Sector.”
- Ed Chung & Charles Fracchia on “Project BOoST: A Biomanufacturing Test Facility Network for Bioprocess Optimization, Scaling, and Training.”
These memos inject the conversation with creative and bold solutions to shape the U.S. bioeconomy into a powerhouse, and guarantee future American success and leadership.
Some of these solutions propose the creation of a single coordinating entity to accelerate the bioindustry, such as The Bioindustrial Research, Innovation, and Translation Engine (BRITE), housed within National Institute of Standards and Technology (NIST) or the Bio for America Program Office (BAPO) at the National Institute for Standards and Technology (NIST) within the Department of Commerce. Other proposed solutions call for the Department of Commerce to create a network of Research & Development facilities and to create Grand Challenges to foster innovation.
Both the White House Executive Order and the CHIPS & Science Act tap different agencies to work toward understanding their parts of the bioeconomy, such as the Department of Commerce, Department of Defense, National Institute of Health, and National Science Foundation. To coordinate these efforts, an interagency committee housed in the Office of Science and Technology Policy (OSTP) with a co-chair from one of these agencies will be vital for the U.S. bioeconomy to be prosperous long term.
As for who the co-chair of this interagency committee will be, the published memos make it clear that the Department of Commerce should play a role in coordinating the bioeconomy. Which, ultimately, makes sense. The Department of Commerce’s mission is to create conditions of economic growth, and this should include creating conditions for bioeconomic growth.
There is no doubt that a strong bioeconomy is key to maintain U.S. competitiveness and manufacturing. McKinsey Insights suggests nearly 60% of the physical inputs to the global economy could, in principle, be produced biologically. As of 2016, the U.S. bioeconomy made up nearly 5.1 % of the U.S. gross domestic product and was worth over $400 billion. Its share of the total U.S. economy has only grown since then and is valued to increase by $30 trillion over the next two decades. But to realize that $30 trillion, the U.S. needs legislative and executive support to grow and innovate our bioindustrial and biotechnological sector, which ultimately needs to be coordinated through both OSTP and the Department of Commerce input from experts is required to inject the conversation with creative and bold solutions to shape the U.S. bioeconomy into a powerhouse, and guarantee future American success and leadership.
For more information about how you can contribute to the growing bioeconomy, visit our Bioeconomy Policy Development Sprint page.
Over the past year, there have been significant policy advances related to the US bioeconomy—the part of the economy driven by the life sciences and biotech, and enabled by engineering, computing, and information science.1 The bioeconomy includes a wide range of products and processes, from mRNA vaccines and drought-resistant crops to microbial fertilizers and bioindustrial fermentation. Rapid advances in biotechnology tools and capabilities have expanded the possibilities for bio-based products, and the U.S. government is looking for ways that it can best support this burgeoning sector of the economy. In addition to several reports and recommendations from outside experts and committees,23 action within federal government agencies has been spurred by the September 2022 Executive Order on Advancing Biotechnology and Biomanufacturing Innovation for a Sustainable, Safe, and Secure American Bioeconomy (EO 14081) and by the CHIPS and Science Act signed into law in August 2022.
Two key areas of discussion for federal government policy on the bioeconomy are:
- Measurement and Language: How should the U.S. government quantify, measure, and track the size and shape of the bioeconomy? What “counts” as part of the bioeconomy?
- Financial and Economic Tools: How can government funding be most effective at seeding long-term growth in the bioeconomy? What criteria should be used to prioritize?
To generate ideas and support discussion related to bioeconomy policy, FAS hosted two half-day, multi-stakeholder, discussion-based workshops on December 5 and December 7, 2022, focused on these topics. Each workshop included representatives and experts from academia, industry, non-governmental organizations, and the U.S. government.
Key Insights and Ideas about Measurement and Language
Discussion at the December 5, 2022 workshop focused on measurement and language for the bioeconomy. Panels and break-out sessions raised several key themes as well as specific ideas that the U.S. government should pursue. Key themes included:
- Simple economic metrics (e.g. those captured by NAICS or NAPCS) by themselves may not be adequate to capture the value of the bioeconomy. We should develop metrics that better capture meaningful endpoints such as sustainability, equity, or security.
- Success of US government actions on the bioeconomy will be measured by how well they establish the U.S. as a leader in this sector, not only by economic indicators, but also by the extent to which non-U.S. companies and governments adopt U.S. metrics, terminology, investment approaches, standards, and practices.
Specific recommendations for the U.S. government included:
- Update NAICS and NAPCS in a way that is analogous to the way other types of technologies with cross-sectoral economic contributions are tracked, such as semiconductors and communications technologies.
- Develop a shared resource (e.g. a website or “dashboard”) that provides up to date economic data on the bioeconomy as well as any other metrics that are developed.
- Improve incentives for the bioeconomy by pursuing government subsidies; using federal procurement to support bio-based products and processes; and streamlining and harmonizing processes throughout the bioeconomy policy landscape (including risk assessment and regulation).
- Secure supply chains for the bioeconomy by improving incentives to keep companies in the U.S. and by working to define the critical bioeconomy infrastructure (i.e. key components, products, and capabilities) and develop plans for strategic reserves.
Key Insights and Ideas about Financial and Economic Tools
The December 7, 2022 workshop focused on government-based financial and economic tools and how they can best support the bioeconomy. Speakers provided context by describing the ways that the U.S. government is already planning to support regional biomanufacturing infrastructure through the National Science Foundation’s Regional Innovation Engine program and through the Department of Commerce’s Build Back Better Regional Challenge. Workshop participants also generated a range of specific ideas, including investment in networks of biomanufacturing infrastructure, direct government investment (e.g. tax incentives, subsidies, procurement, and improved grant opportunities) as well as development of resources and education to support small companies. Diverse workforce development was also identified as a critical factor, with an emphasis on programs and partnerships for technical programs and community colleges rather than Ph.D.-level education. The discussions revealed two overarching themes:
- There is a need for investments in a wide diversity of scale-up facilities and infrastructure for bio-based products.
- Investments will need to be sustained over time. Because biomanufacturing is rapidly advancing, ongoing funding will be needed to ensure that the facilities that are built and workforce development programs that are established now will be able to change and adapt in the future.
As the U.S. government ramps up its activities in the bioeconomy, it will be important to keep the conversation going. Executive Order 14081 outlined specific actions related to the bioeconomy that federal agencies are working to complete; in many cases, these will require public input. The Office of Science and Technology Policy has already released two public Requests for Information, one to ask for feedback on the structure and activities of an overarching National Biomanufacturing and Biotechnology Initiative and the other focusing on challenges to the U.S. biotechnology regulatory system. Though the date to submit comments on these two requests is already past, there will be other opportunities to provide input to the federal government in the coming months. FAS will continue to track these developments, convene experts and stakeholders to support policy decision making, and contribute to the discussion.