Summary  

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: 

1. 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). 
2. 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.

Conclusion 

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.

Summary 

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.

Pharmaceuticals

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.  

Synthetic meat

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.

Conclusion

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.

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.

Looking ahead

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:

1. 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?
2. 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.

Looking Ahead

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.

Further Reading

Dec 5 Summary Workshop Report (2022) Bioeconomy Measurement and Language

Dec 7 Summary Workshop Report (2022) Bioeconomy Financial and Economic Tools

Summary

The U.S. bioeconomy commands millions of liters of bioproduction capacity, but only a tiny fraction of this capacity supports process optimization. Companies of all sizes face great pressures that limit their ability to commit resources to these important efforts. Consequently, the biomanufacturing industry is often forced to juggle sensitive, brittle production processes that don’t scale easily and are prone to disruption. As some recent failures of prominent companies demonstrate, this increases risk for the entire bioeconomy, and especially for the development of new companies and products.

To remedy this, the Department of Commerce should first allocate $80 million to seed a bioproduction R&D facility network that provides process optimization capability to the greater bioeconomy, followed by a $30 million process optimization challenge wherein participating facilities compete at workflow optimization, scaling, and transfer. Part one of the proposal requires rapid development, with the initial R&D facility network of four sites starting bioprocessing operations within 12 months of award. In addition to training workers for the greater bioeconomy, the facility network’s services would be available on a contract basis to any company at any stage of maturity. This work could include optimization for yield, scaling, process resilience, and/or technology transfer—all critical needs across the sector. After federal government startup funding, the network would transition toward financial independence, increasingly running on revenue from process optimization work, workforce training, and state/local support.

Part two of the plan lays out a biomanufacturing “Grand Challenge” in which participating network facilities compete to optimize a standardized biomanufacturing process. Prioritizing process resilience, security, and transferability in addition to yield, this effort would help set a new industry standard for what process optimization really means in addition to demonstrating what can be accomplished by the network facilities. With this demonstration of value, demand for facility services in other geographic locations would increase, spurring the growth of the facility network across the country.

By the end of the program, the U.S. biomanufacturing sector would see a number of benefits, including easier process innovation, a larger and better trained workforce, shortened product time to market, and reduced production risks.

Challenge & Opportunity

Biological products are, by definition, made by means of complex biological processes carried out by sensitive—some might even say fickle—microorganisms and cell lines. Determining the right steps and conditions to induce a microbe into producing a given product at a worthwhile yield is an arduous task. And once produced, the product needs to be extensively processed to make it pure, stable, and safe enough for shipping and use. Working out this entire production workflow takes a great deal of time, energy, and expertise, and the complexity of production workflows increases alongside the complexity of biological products. Many products fail at this point in development, keeping beneficial products out of the hands of end users and cutting off constructive contributions—revenue, jobs—to the larger bioeconomy. 

Once a bioproduction process is worked out at an R&D level, it must be scaled up to a much larger commercial level—another major point of failure for academic and commercial programs. Scaling up requires different equipment with its own controls and idiosyncrasies, each generating additional, sometimes unpredictable, complexities that must be corrected for or managed. The biomanufacturing industry has been asking for help with process scaling for years, and recent national initiatives, such as the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) and the BioIndustrial Manufacturing and Design Ecosystem (BioMADE), have sought to address this strategic need.

Each step on this road to the end market represents a chance for failure, and the risks are so high that the road is littered with failed companies that had a promising product that just couldn’t be made reliably or a brittle production process that blew up when performed at scale. The overarching competitive commercial environment doesn’t help, as new companies must rush from concept to production, often cutting corners along the way. Meanwhile, mature biomanufacturing companies often nurse small profit margins and must aggressively guard existing revenue streams, leaving little or no spare capacity to innovate and improve processes. All of these factors result in production workflows that are hastily constructed, poorly optimized, prone to scaling difficulties, and vulnerable to failure at multiple points. When—not if—process failures occur, the entire economy suffers, often in catastrophic ways. In the last several years alone, such failures have been witnessed at Emergent Biosciences, Dr Reddy’s, and Abbott, with any number of downstream effects. Society, too, misses out when more sustainable, environmentally friendly production methods are overlooked in favor of older, less efficient but more familiar ones. 

There is an urgent need for a national network of biomanufacturing facilities dedicated to process optimization and scaling—critical efforts that are too often overlooked or hastily glossed over, to the subsequent detriment of the entire bioeconomy. Available to any company at any stage of maturity, this facility network would operate on a contract basis to optimize biological production processes for stability, resilience, and technology transfer. The facilities would also assist with yield optimization, in addition to incorporating the specialized equipment designed to aid in scale-up risk analysis. Once established with government funding, the facility network would stand on its own, running on contract fees for process optimization and scale-up efforts. As demand for services grows, the facility network model could spread out geographically to support other markets.

This a highly opportune time for such a program. The COVID-19 pandemic has highlighted the essential importance of biomanufacturing capabilities—extending to the geopolitical level—as well as the fragility of many supply chains and processes. In response, the CHIPS and Science Act and Executive Order on Advancing Biotechnology and Biomanufacturing, among others, have provided directives to shore up U.S. biomanufacturing capacity and resilience. Project BOoST seeks to meet those directives all while building a workforce to support broader participation in a strong national bioeconomy.

Plan of Action

Project BOoST encompasses a $110 million ask spread out over four years and two overlapping phases: a first phase that quickly stands up a four-facility network to perform biomanufacturing process optimization, and a second phase that establishes a biomanufacturing “Grand Challenge” wherein facilities compete in the optimization of a standardized bioproduction process. 

Phase I: Establishing the facility network

The Department of Commerce should allocate $80 million over three years to establish the initial facility network at four sites in different regions of the country. The program would be structured as a competitive contract, with a preference for contract bidders who:

• Bring along industry and academic partners, as evidenced by MOUs or letters of support
• Have industry process optimization projects queued and ready to commence
• Integrate strong workforce development initiatives into their proposals
• Include an entrepreneurship support plan to help startups advance through manufacturing readiness levels 
• Leverage state and local matching funds and have a plan to grow state and local cost-share over time
• Prioritize process resilience (including supply chain) as much as yield optimization
• Prioritize data and process security, both in terms of intellectual property protection and cyber protection
• Propose robust means to facilitate process transfer, including developing data standards around process monitoring/measurement and the transfer process itself
• Have active means of promoting economic, environmental, social, and other forms of equity

Possible funding pathways include one of the bio-related Manufacturing Innovation Institutes (MIIs), such as NIIMBL, BioMADE, or BioFabUSA. At a minimum, partnerships would be established with these MIIs to disseminate helpful information gained from the facility network. The National Institute of Standards and Technology (NIST) could also be helpful in establishing data standards for technology transfer. The Bioeconomy Information Sharing and Analysis Center (BIO-ISAC) would be another important partner organization, helping to inform the facilities’ efforts to increase both cyber resilience of workflows and industry information sharing.

Funds would be earmarked for initial startup expenditures, including lease/purchase of appropriate buildings, equipment purchases, and initial salaries/benefits of operating personnel, trainers, and program support. Funding milestones would be configured to encourage rapid movement, including:

• 6-month milestone for start of workforce training programs
• 12-month milestone for start of bioprocess operations
• 12-month milestone for training program graduates obtaining industry jobs

Since no actual product made in these facilities would be directed toward regulated use (e.g., food, medical), there would likely be reduced need to build and operate the facilities at full Current Good Manufacturing Practice (CGMP) specification, allowing for significant time and cost savings. Of course, the ultimate intent is for optimized and scaled production processes to migrate back to regulated use where relevant, but process optimization need not be done in the same environment. Regardless, the facilities would be instrumented so as to facilitate bidirectional technology transfer. With detailed telemetry of processes and data traffic collected in a standardized manner from the network’s sites, organizations would have a much easier time bringing optimized, scaled processes from these facilities out to commercial production. This would result in faster parameter optimization, improved scale-up, increased workflow resilience, better product assurance, and streamlined tech transfer—all of which are major impediments and risks to growth of the U.S. bioeconomy.

Process optimization and scaling work would be accomplished on a contract basis with industry clients, with robust intellectual property protections in place to guard trade secrets. At the same time, anonymized information and techniques gathered from optimization and scaling efforts would be automatically shared with other sites in the network, enabling more globalized learning and more rapid method development. These lessons learned would also be organized and published to the relevant industry organizations, allowing these efforts to lift all ships across the bioeconomy. In this way, even a facility that failed to achieve sufficient economic self-sustainability would still make significant contributions to the industry knowledge base.

Focused on execution speed, each facility would be a public-private consortium, bringing together regional companies, universities, state and local governments, and others to create a locus of education, technology development, and job creation. In addition to hewing to provisions within the CHIPS and Science Act, this facility network would also match the “biomanufacturing infrastructure hubs” recommendation from the President’s Council of Advisors on Science and Technology.

Using the Regional Technology and Innovation Hubs model laid out in the CHIPS and Science Act, the facilities would be located near to, but not within, leading biotechnology centers, with an eye to benefiting small and rural communities where possible. All the aforementioned stakeholders would have a say in site location, with location criteria including: 

• Level of partnership with state and local governments
• Degree of involvement of local educational institutions
• Proximity to biomanufacturing industry
• Positive impact on economic/environmental/social equity of small and/or rural communities
• Availability of trainable workforce

Although some MIIs have innovation acceleration and/or improving production availability within their charters, to date no production capacity has been built specifically to address the critical issues of process optimization and scaling. Project BOoST would complement the ongoing work of the bio-focused MIIs. And since the aforementioned risks to the bioeconomy represent a strategic threat today, this execution plan is intentionally designed to move rapidly. Locating network facilities outside of costly metropolitan areas and not needing full cGMP certification means that an individual facility could be spun up in months as opposed to years and at much lower cost. These facilities would quickly be able to offer their benefits to industry, local economies, and workers looking to train into a growing job sector.

Phase II: Scale-up challenge

Approximately 30 months from program start, facilities that meet the aforementioned funding milestones and demonstrate continuous movement toward financial self-sustainability (as measured by a shift from federal to state, local, and industry support) would be eligible to participate in an additional $30 million, 18-month scale-up challenge, wherein they would receive a reference production workflow so they could compete at workflow optimization, scaling, and transfer.

In contrast to previous Grand Challenges, which typically have a unifying theme (e.g., cancer, clean energy) but relatively open goals and means, Project BOoST would be hyperfocused to ensure a high degree of applicability and benefit to the biomanufacturing industry. The starting reference production workflow would be provided at lab scale, with specifications of materials, processing steps, and instrument settings. From this starting point, participating facilities would be asked to characterize and optimize the starting workflow to produce maximal yield across a broad range of conditions; scale the workflow to a 1,000L batch level, again maximizing yield; and transfer the workflows at both scales to a competing facility both for verification purposes and for proof of transferability.

In addition, all competing workflows would be subject to red-teaming by an independent group of biomanufacturing and cybersecurity experts. This examination would serve as an important assessment of workflow resilience in the setting of equipment failure, supply chain issues, cyberattack, and other scenarios.

The winning facilities—represented by their workflows—would be determined by a combination of factors:

• Maximum yield
• Process transferability
• Resistance to external tampering
• Resilience in the setting of equipment/process/supply chain failure

The end result would be the practical demonstration and independent verification of the successful optimization, scale-up, and transfer of a production process—a major opportunity for learning and knowledge sharing across the entire industry.

Conclusion

Scientific innovation and advanced automation in biomanufacturing represent a potent double-edged sword. While they have allowed for incredible advances in biomanufacturing capability and capacity—to the benefit of all—they have also created complexities and dependencies that together constitute a strategic risk to the bioeconomy. This risk is a significant threat, with process failures already creating national headlines out of company collapses and congressional investigations. We propose to act now to create a biomanufacturing facility network dedicated to making production workflows more robust, resilient, and scalable, with a plan strongly biased toward rapid execution. Bringing together commercial entities, educational institutions, and multiple levels of government, Project BOoST will quickly create jobs, provide workforce development opportunities, and strengthen the bioeconomy as a whole.

Summary

The bioindustrial production of chemicals and other goods is a critical sector of the U.S. bioeconomy. However, the sector faces challenges such as drawn-out research and development timelines, low profit margins, the requirements to produce and sell product in vast quantities over long periods of time, and barriers to accessing scale-up capacity. Companies can find it challenging to rapidly exchange helpful knowledge, attract early-stage investors, access pilot-scale infrastructure to generate evidence that forecasts cost-effective production at scale, and obtain the financing to build or access domestic commercial-scale bioproduction, biomanufacturing, and downstream bioprocessing infrastructure and facilities.

The federal government has already recognized the need to take action to sustain and extend U.S. leadership in biotech and biomanufacturing. The recent Executive Order on advancing the U.S. bioeconomy and relevant provisions in the CHIPS and Science Law and the Inflation Reduction Law have put forward high aspirations, as well some funding, that could help stimulate the biotech and biomanufacturing ecosystem.

The U.S. government should create a Bio for America Program Office (BAPO) at the National Institute for Standards and Technology (NIST) to house a suite of initiatives that would lead to the creation of more well-paying U.S.-based biomanufacturing jobs, spur economic growth and development in areas of the country that haven’t historically benefited from biotech or biomanufacturing, and ensure more resilient U.S. supply chains, the more sustainable production of chemicals and other goods, and enhanced U.S. competitiveness.

Challenge and Opportunity

The bioeconomy—the part of the economy driven by the life sciences and biotech, and enabled by engineering, computing, and information science—has the potential to revolutionize human health, climate and energy, food security and sustainability, and supply chain stability, as well as support economic growth and well-paying jobs across the country. Indeed, the sector has already produced many breakthroughs, such as mRNA vaccines that help counter the devastating impacts of COVID-19 and genetically engineered microbes that provide nutrients to crops without the pollution associated with traditional fertilizers. Valued at over $950 billion, the U.S. bioeconomy accounts for more than five percent of the U.S. gross domestic product—more than the contribution from the construction industry and on par with the information sector.

However, without sufficient federal support and coordination, the U.S. risks ceding economic, national security, and societal benefits provided by a strong bioeconomy to competitors that are implementing cohesive strategies to advance their bioeconomies. For example, China aims to dominate the 21st-century bioeconomy and has prioritized the growth of its bioeconomy in its five-year plans. From 2016 to July 2021, the market value of publicly listed biopharmaceutical innovators from China increased approximately 127-fold across several major stock exchanges, to more than $380 billion, with biotechnology companies accounting for more than 47 percent of that valuation.

Bioindustrial manufacturing (nonpharmaceutical) is a critical segment of the bioeconomy but faces low profit margins combined with the need to produce and sell product in vast quantities over long timelines. It is challenging for companies to translate research and development into commercially viable efforts and attract investors to finance access to or construction of domestic bioproduction, biomanufacturing, and downstream bioprocessing infrastructure and facilities such as fermentation tanks and bioreactors. Furthermore, many biotech and synthetic biology companies face difficulty acquiring capital for scale-up, whether that requires building custom demonstration- or commercial-scale infrastructure, contracting with fee-for-service bioproduction organizations to outsource manufacturing in external facilities, or retooling existing equipment.

All this has the potential to lead to yet more instances of “designed in America, made elsewhere”: microbes that are engineered by U.S. companies to fabricate chemicals or other products could end up being used to produce at commercial scale abroad, which is not a recipe for economic growth and improving quality of life for residents of the U.S. Domestic manufacturers should be executing bioindustrial production so that more well-paying jobs are accessible in the U.S., with the added benefits of contributing to a more stable supply chain, which bolsters U.S. national and economic security.

The federal government has recognized the need for U.S. leadership in biotech and biomanufacturing: the recent Executive Order on advancing the U.S. bioeconomy and relevant provisions in the CHIPS and Science Law and the Inflation Reduction Act (IRA)  provide high-level aspirations and some actual dollars to bolster the biotech and biomanufacturing ecosystem. Indeed, some funds appropriated in the IRA could be used to meet biomanufacturing goals set in the CHIPS and Science Law and EO.

To reach its full potential, bioindustrial manufacturing requires additional support at various levels and may need as much as hundreds of billions of dollars in capital. There is an opportunity for the U.S. government to be intentional about accelerating the growth of the bioindustrial manufacturing sector, and reaping the economic, national security, and societal benefits that would come with it.

Public-private partnerships aimed at providing resources and capital for experimental development at early-stage companies, as well as bioindustrial production scale-up and commercialization projects that are techno-economically sound, would be a strong signal that the federal government is serious about leveraging bioindusty to meet human health, climate and energy, food security and sustainability, and supply chain stability needs, as well as support economic growth and well-paying jobs. Many of the investments by the U.S. taxpayers would be matched and multiplied by investments from nongovernment sources, amplifying the impact, and generating high return on investment for Americans in the form of well-paying jobs, breakthrough products, and more stable supply chains. Furthermore, the investment would show that the U.S. is committed to leveraging advanced manufacturing to raise quality of life for Americans and retain leadership in biotech and biomanufacturing.

Plan of Action

This plan focuses on four initiatives that address specific challenge points:

• A Bioindustrial Production Consortium (BPC), which would coordinate precompetitive efforts to address the measurements, tools, and standards needed for advancing both research and commercial products in the bioindustrial production space and would also collaborate with BioMADE, industry, government scientists, and other stakeholders.
• BAPO Ventures, which would coordinate both existing and new appropriations to seed a nonprofit partnership manager to launch a U.S. Bioindustrial Production Investment Portfolio that crowds-in additional capital from nonfederal government sources and makes calculated investments in early-stage, domestic bioindustrial production companies that demonstrate credible pathways to product commercialization.
• The Bioindustrial Production Scale-up Infrastructure Group (BPSIG), which would work with both the interagency and nonfederal government partners to conduct a comprehensive analysis of the U.S. bioindustrial production pilot- and intermediate-scale infrastructure landscape to develop a precision strategy for moving forward on domestic bioindustrial production scale-up capacity.
• A Bioindustrial Production Loan Program Office, which would rely on partners such as the U.S. Small Business Administration to provide debt financing for techno-economically sound, domestic demonstration- or commercial-scale bioindustrial production infrastructure projects

The proposed initiatives could all be housed in a new office at NIST called the Bio for America Program Office (BAPO), which would 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 would be an effective home for the BAPO given that 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 serves as a neutral convener for industry consortia, standards development organizations, federal labs, universities, public workshops, and interlaboratory comparability testing.

Bioindustrial Production Precompetitive Consortium

NIST should establish a Consortium, coordinated out of BAPO, to address the measurements, tools, and standards needed to advance both research and commercial bioindustrial products. The Consortium would convene industry, academia, and government to identify and address measurement, tool, and standards needs; enable members to work with NIST to develop those solutions and standards; leverage NIST expertise; and collaborate with related programs at other federal agencies. The Consortium could rapidly develop relationships with organizations such as the Bioindustrial Manufacturing and Design Ecosystem (BioMADE, a Manufacturing Innovation Institute that is part of the Manufacturing USA network), the Engineering Biology Research Consortium (EBRC), SynBioBeta, the Alternative Fuels & Chemicals Coalition (AFCC), the Synthetic Biology Coalition, the Joint BioEnergy Institute, and the Advanced Biofuels and Bioproducts Process Development Unit at Lawrence Berkeley National Laboratory, and the National Renewable Energy Laboratory’s pilot-scale Integrated Biorefinery Research Facility. It would also be useful to communicate with efforts in the biopharmaceutical space such as the Biomedical Advanced Research and Development Authority (BARDA) and the National Institute for Innovation in Manufacturing Biopharmaceuticals.

The benefits to members would include access to a neutral forum for addressing precompetitive needs; participation in the development of experimental benchmarks, guidelines, and terminology; access to tools developed by the consortium ahead of public release; and institutional representation on the consortium steering committee. Members would contribute an annual fee of, for example, $20,000 or in-kind support of equivalent value, as well as sign a Cooperative Research and Development Agreement.

Congress should initially appropriate $20 million over five years to support the Consortium’s activities, and the Consortium could launch by putting forward a Notice of Consortium establishment and letter of interest form.

U.S. Bioindustrial Production Investment Portfolio

Early-stage companies are the engine for U.S. job creation, regional economic development, and technological innovation. A more consistent, yet scrupulous, source of funding for nascent companies in the bioindustrial production space would be catalytic. Using the BARDA Ventures-Global Health Investment Corporation (GHIC) Global Health Security Portfolio public-private partnership as a model, the U.S. government, coordinating both existing and new appropriations via BAPO Ventures, should seed a nonprofit partnership manager to launch a U.S. Bioindustrial Production Investment Portfolio. The portfolio would crowd-in additional capital and invest in early-stage, domestic bioindustrial production companies that share sound metrics and credible techno-economic analyses that they are on the path to product commercialization and profitability.

The portfolio’s nonprofit partnership manager should be empowered to crowd-in capital using return augmentation and risk mitigation incentives as they see fit. Measures that a venture fund could take to incentivize coinvestment could include but are not limited to:

• Taking a concessionary position in the waterfall (return calculation) to allow larger returns for coinvestors
• Capping their own returns to enable greater returns for coinvestors
• Implementing a convertible debt plan that would only reward a bioproduction company’s management team with equity after reaching key milestones
• Providing an opportunity for discounted buyout by other investors in future rounds
• In select cases, 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

Launching a U.S. Bioindustrial Production Investment Portfolio requires the following four steps.

1. Both existing and newly appropriated federal funds should be used to seed investments in the U.S. Bioindustrial Production Investment Portfolio.

Existing appropriations: Appropriations have already been made to some federal agencies through the IRA and other vehicles that could be used to seed the portfolio. BAPO Ventures should coordinate with the interagency, and agencies with available funds could contribute to directly seeding the portfolio. Some examples of existing funds to coordinate include:

• 2% of the $1 billion the Department of Defense (DoD) has allocated for investing in emerging biomanufacturing capabilities. As necessary, monies from these appropriations could be routed directly from DoD to a specific fund, or funds, within the portfolio that would only invest in qualified projects; any return expectations would need to be structured appropriately.
• 6% of the $5 billion the IRA recently appropriated to the Department of Energy (DOE) Loan Programs Office new Energy Infrastructure Reinvestment Financing Program. This appropriation is “to be leveraged for up to $250 billion in commitment authority for loan guarantees (including refinancing) of eligible projects,” and loans can be used to retool or repurpose energy infrastructure toward bioindustrial production or to use biotech to reduce pollution from operating energy infrastructure. Monies from this program could be loaned to a specific fund within the portfolio that only invests in qualified projects. The return expectations would need to be structured appropriately since there would be no return for many months and so no monies to make loan payments, and then ideally a big multiple of invested capital in the long term. The loan guarantees to the portfolio could be structured as debt with balloon payments, convertible debt, or participating preference, which essentially acts like debt but is structured as equity. The Small Business Administration Office of Investment and Innovation could be consulted to assist with this process.
• 8% of the $5.8 billion the IRA recently appropriated to the DOE Office of Clean Energy Demonstrations new Advanced Industrial Facilities Deployment Program. This appropriation provides financial assistance for incorporating advanced industrial technologies, such as biotech and bioindustrial production, to reduce emissions from making goods like steel, paper, concrete, and chemicals. Similar to the above, monies from this program could be routed to a specific fund within the portfolio that only invests in qualified projects.

New appropriations: Congress should appropriate $500 million in new funding for BAPO Ventures over five years to support BAPO Ventures personnel and operations and augment the portfolio. These funds would be critical since they could be applied for all-purpose venture capital investments in early-stage bioindustrial production companies. Congress should also grant BAPO Ventures, as well as other agencies or programs, any authority needed to transfer funds to the portfolio for these purposes.

2. Identify the nonprofit partnership manager.

BAPO Ventures should solicit proposals for an existing nonprofit partner to manage the U.S. Bioindustrial Production Investment Portfolio. Selection should be based on demonstrated track record of experience with and successful venture investments in bioindustrial manufacturing or a closely related space. Potential nonprofit partners include Breakthrough Energy Catalyst or America’s Frontier Fund. GHIC should also be consulted. 

3. Transfer funds from the appropriate U.S. government programs to funds within the portfolio and support the nonprofit partnership manager in crowding-in additional capital.

The nonprofit partnership manager will recruit capital from nonfederal government sources into the portfolio’s different funds with the aim of matching and/or exceeding the dedicated public funds to generate a multiplier effect and access even more capital. Capital from investors willing to take on risk equatable to venture capital would be the most viable targets.

4. The nonprofit partnership manager will use the portfolio’s funds to invest in U.S. early-stage bioindustrial production companies on the basis of sound techno-economic analyses and robust metrics.

The nonprofit partnership manager would invest in bioindustrial production companies that commit to hiring and manufacturing domestically and making products useful to Americans and the country, on the basis of robust techno-economic analyses of the companies’ commercial potential, and generate returns on investments. BAPO Ventures, as well as NIST writ large, would be accessible for technical assistance, if necessary. The nonprofit partnership manager would structure investments with co-funding from additional nonfederal government investors. As this public-private partnership generates investment returns, proceeds from the BAPO Ventures funding will be returned to the portfolio and its funds for reinvestment and sustainment of BAPO Ventures. If this evergreen fund begins to compete with, rather than incentivize, private market funding, or otherwise begins to be unproductive, the fund should be tapered off and/or sunset.

Bioindustrial Production Scale-up Infrastructure Group

It is critical for early-stage bioindustrial production companies to gather evidence that their production processes have the potential to be commercially viable at scale—or not. To learn this, companies need access to pilot- and intermediate-scale bioindustrial production infrastructure like fermenters and bioreactors, as well as modern downstream bioprocessing equipment. The BAPO should house a Bioindustrial Production Scale-up Infrastructure Group (BPSIG). which, as an initial step, would work with both the interagency and nonfederal government partners to conduct a comprehensive analysis of the U.S. bioindustrial production pilot- and intermediate-scale infrastructure landscape with the aim of informing a precision strategy for most effectively leveraging federal resources.

The BPSIG would aim to complete the landscape analysis in three months, seeking to understand deficiencies in capacities such as the different volumes of fermenters and bioreactors that are accessible (and the costs associated with their use) and modular downstream bioprocessing equipment accessibility. They should also identify existing facilities that have accessible capacity, such as corporations’ sites where capacity might be rented, toll facilities, or facilities that could be retooled or rehabilitated to provide the necessary pilot-scale capacity. BPSIG should engage with organizations such as Capacitor, the Bioprocess to Product Network, Royal DSM, DuPont, Cargill, BioMADE, Battelle, MITRE, and the Advanced Biofuels and Bioproducts Process Development Unit at Lawrence Berkeley National Laboratory when performing this evaluation.

If the assessment concludes that retooling existing sites or building new pilot- or intermediate-scale infrastructure is necessary, and that government support would be catalytic, some funds would already be available via existing appropriations, and new appropriations might also be necessary. Appropriations have already been made to some federal agencies through the IRA and other vehicles that could be coordinated by the BPSIG. BPSIG should coordinate with the interagency, and agencies with available funds could contribute directly to building the network. Existing funds to leverage include:

• The $1 billion the DoD has allocated for bioindustrial domestic manufacturing infrastructure. As appropriate, monies from this allocation could be routed directly from DoD to pilot-scale network projects that are within those monies’ purview.
• The $5 billion the IRA recently appropriated to the DOE Loan Programs Office new Energy Infrastructure Reinvestment Financing Program. This appropriation is “to be leveraged for up to $250 billion in commitment authority for loan guarantees (including refinancing) of eligible projects”; loans can be used to retool or repurpose energy infrastructure toward bioindustrial production or reduce pollution from operating energy infrastructure using biotech.

Additionally, Congress may need to make appropriations directly to BPSIG, which BPSIG could then allocate to other federal financing programs for retooling or building any additional pilot- or intermediate-scale bioindustrial production infrastructure projects outside the scope of existing pools of already-appropriated funds.

Bioindustrial Production Loan Program Office

To ensure techno-economically sound bioindustrial production companies can secure financing for demonstration- or commercial-scale infrastructure and equipment needs, Congress should enable an initiative within BAPO called the Bioindustrial Production Loan Programs Office (BPLPO) that replicates and improves the DOE LPO model. The BPLPO would be tailored to the bioindustrial production segment, without agencies’ science or technology mission area constraints (for instance, energy), offering flexible debt instruments and supporting large-scale projects. For example, assistance in the form of loan guarantees would help underwrite debt associated with launching bioproduction plants.

Coordination with DOE LPO, DOE Office of Clean Energy Demonstrations, the U.S. Small Business Association, the relevant U.S. Department of Agriculture loan programs, and other government agencies and offices would be key to avoid duplicating efforts and to incorporate lessons learned and best practices from existing efforts. Congress should appropriate an initial $5 billion for the BPLPO, authorizing the program for an initial 10 years.

Conclusion

Launching a suite of public-private partnerships to advance domestic bioproduction would create more well-paying biomanufacturing jobs in the U.S., expand economic opportunity across the country by spreading the biotech and biomanufacturing footprint into nontraditional areas, produce more high-quality chemicals and goods in the U.S., and help meet national and economic security needs, such as strengthened supply chains and more sustainable production methods.

Summary

America’s bioeconomy is entering a once-in-a-generation moment. Research and development (R&D) breakthroughs have brought us to a scientific tipping point; at the same time, health and security threats are inspiring a new level of strategic coordination. Although we now have a strong base of fundamental science, we lack the equally powerful industrial foundation needed to put the “economy” in bioeconomy. Bioindustry, encompassing less flashy products (chemicals, plastics, fuels) and bio-enabling tools and capabilities, often fails to capture the attention and investment needed to connect research with use cases, commercialize, and scale. But without solutions and capabilities that span multiple applications and sectoral silos, our bioeconomy will stall at the lab door.

Rapid progress in strengthening American bioindustry is possible, but it demands a coordinated and concerted effort that taps the federal government’s unique combination of scale and highly effective lab-to-market incentive mechanisms. Streamlined funding of open and cross-disciplinary research, prize and challenge mechanisms, and market shaping through innovative procurement have all proven highly effective in the face of market failures and applied technology gaps like those seen in our bioindustry.

To refine, tailor, and manage its unique lab-to-market toolkit in this space, the federal government should establish a single coordinating entity to accelerate bioindustry in close partnership with stakeholder agencies. The Bioindustrial Research, Innovation, and Translation Engine (BRITE), housed within National Institute of Standards and Technology (NIST), would do this by:

• Coordinating and funding accessible, open topic research opportunities tackling the most pressing blockers of bioindustrial progress
• Designing and administering open innovation competitions and challenges that de-risk and accelerate use-inspired bioindustrial solutions
• Catalyzing bioindustrial markets through advance commitments and pooled procurement of innovative products and services
• Bringing strategic clarity and cohesion to federal investments in bioindustry, maximizing returns to all stakeholders

Challenge and Opportunity

After steadily gaining mindshare and momentum among policymakers, our bioeconomy has reached a once-in-a-generation moment. This has been amplified by the urgency of biothreats revealed during the COVID-19 pandemic, as well as the role that biotechnology and biopharmaceutical innovation played in the global response. While efforts to realize a comprehensive U.S. bioeconomy vision date back to 2012, the Biden Administration’s September 2022 Executive Order provides a clear and compelling new articulation of that vision and can serve as a platform for realizing it. Moreover, recent legislative actions, including the CHIPS and Science Law, Inflation Reduction Law, and various appropriations (see FAQ), have enabled a range of federal bioeconomy initiatives and investments.

The greatest barrier to meeting our bioeconomic moment is not one of fundamental science; it is the underdevelopment of America’s bioindustry. Bioindustry encompasses both the manufacturing of biochemicals, bioplastics, and biofuels as well as the tools, kits, and services that drive and enable the wider bioeconomy. There are very real technical, capability, and incentive barriers to bioindustrial progress, including:

• The unpredictability of performance, and associated trial-and-error requirements, when scaling bioprocesses beyond the lab
• Limited demonstration testbed and intermediate-scale facilities to enable scale-up experimentation and iteration
• A high degree of specialization in existing facilities, which limits accessibility to developers unless facilities can expand or retrofit
• Few existing data and task standards, reducing the interoperability of different tools and approaches
• Cost and inertia discouraging a more systematic transition to sustainable bioeconomy
• A culture that rewards discovery and publication over applied or translational research
• Traditional federal grant structures and criteria that reinforce said culture

Given these barriers, bioindustry is particularly susceptible to two “valleys of death”—one between a scientific breakthrough and a usable product and another between a market-ready product and deployment. In these valleys, typical innovation funders are disincentivized from high-risk / high-reward investment and struggle to achieve any sort of investment coherence or cohesion. A Congressional Research Service report notes that the very definition of bioeconomy varies widely across sectors and countries. Capital tends to isolate around one thematic area (e.g., climate, advanced materials, agriculture, health) rather than fueling systems-based, cross-cutting investments that grow the overall pie. This creates a high risk of duplicated effort and repetition of missteps. A Schmidt Futures task force report estimates that without a vibrant bioindustry, the U.S. risks losing out on at least $260 billion of annual economic opportunity that will otherwise go overseas. We will also face new economic and national security threats if we fail to establish resilient domestic bioeconomic supply chains and a robust competitive landscape.

The federal government stands alone in its ability to rapidly close the gaps that hold bioindustry back. Federal agencies are uniquely incentivized to bridge the valleys of death by tapping agencies’ unique portfolios of lab-to-market, demand-pull mechanisms. These include:

• Broad agency announcements (BAAs) for research. Federal Acquisition Regulations Part 6.102(d)(2) streamlines typical procurement competition requirements for research-oriented projects. This has been most successfully applied by the Biomedical Advanced Research and Development Authority’s (BARDA) Division of Research, Innovation, and Ventures (DRIVe) in the form of a BAA, calling for research projects related to biothreat mitigation. Under DRIVe’s EZ-BAA, projects that address broad and high-impact areas of interest (AOI) can receive up to $750,000 based on an abstract submission and negotiation with BARDA.¹ 
• Prize competitions and challenges. Increasingly an alternative to traditional grants, prizes expand flexibility, reduce reporting burden, and pay only for results based on performance against defined criteria. Prizes are particularly effective where a problem and need is clear, but the innovation pathway is uncertain—and may need to be redirected or accelerated based on serendipitous findings. Prizes are also a uniquely effective mechanism to bridge the gap between fundamental research and investment-ready solutions or businesses.
• Nontraditional acquisition. Beyond its role as an innovation catalyst, government can shape markets as a foundational customer, influencing other actors and nudging a sector toward self-sustenance. Procurement practices like Other Transaction Authorities (OTA) remove red tape in deploying nondilutive federal capital, which helps innovators reach scale and attract many times more private capital in a shorter time frame. In an OTA, a consortium of commercial and other providers can be established, satisfying competition requirements while enabling faster execution of transactions compared to traditional bid processes for each action. A MITRE analysis found the Department of Defense currently runs over 30 OTA consortia, and the Department of Homeland Security and National Geospatial-Intelligence Agency have also launched consortia. Beyond OTA, tools such as advance market commitments, strategic stockpile procurement, and federal financing (e.g., loan guarantee programs, development finance corporations) can provide innovators a critical first customer or early working capital.

The barriers to bioindustrial progress—complex technical gaps, incentive and market failures, and misalignment of innovation culture—are daunting. Encouragingly, they are just the sort of barriers that these federal lab-to-market and demand-pull mechanisms were designed to overcome.

What are the broader benefits of accelerating our bioindustry?

Building a more robust industrial foundation for our bioeconomy benefits the entire nation but has particular potential to close economic gaps in regions historically left behind. A range of different production infrastructure, from dormant plants to breweries, can be retrofit more efficiently, especially in places outside traditional biotechnology hubs. Broadening the range of bioindustrial tools and processes, and moving to scale manufacturing, will create new job opportunities beyond advanced researchers in labs. There are also many advantages to locating biomanufacturing infrastructure in proximity to rural areas rich in feedstocks. The intersection of place-based innovation and bioindustry has already been brought to life through efforts like the U.S. Department of Agriculture Bioproduct Pilot Program and will no doubt accelerate through the NSF Regional Innovation Engines opportunity, which will align use-inspired research, translation, and workforce development in new self-sustaining innovation hubs across the country.

Plan of Action

Business as usual will not realize the full potential of—or avoid the many pitfalls awaiting—our national bioeconomy strategy. The pace and scale of bioindustrial progress require us to tap into all of the capabilities and resources noted above. In general, we need more coordinated action across the public and private sectors, including streamlined R&D partnerships to close gaps in health vs. industrial applications; competitions and challenges that translate breakthroughs to real-world use; market-shaping activities to achieve scale; and strategic coordination of sustainable funding to maximize investment leverage.

A new, whole-of-government entity should be established to marshal federal tools, best practices, and investments toward shared priorities that are critical to American bioindustrial leadership. The Bioindustrial Research, Innovation, and Translation Engine (BRITE) will encompass open innovation programs, market-shaping activities, and stakeholder engagement. BRITE can be housed within a new NIST Bio for America Program Office and convene relevant program owners from core agencies with bioeconomy mandates: National Science Foundation (NSF), Department of Energy (DOE), Department of Defense (DOD), Department of Agriculture (USDA), and Department of Health and Human Services (HHS).

Streamlined R&D partnerships

BRITE can take advantage of the growing body of ideas and insights coming from academic and commercial communities through open and accessible calls for projects. This could be achieved through an EZ-BAA vehicle, modeled after BARDA DRIVe’s open call for projects that address a broad set of health security problems. The BRITE EZ-BAA would offer up to $500,000 for research and commercialization projects addressing a set of announced areas of interest (AOIs). Early engagement with BRITE through this program would improve the efficiency and win rate of technology development—and incentivize success-enabling design principles, such as designing for future biomanufacturing scale versus pure scientific outcomes. Initial AOIs could focus on scientific and technical rate limiters for growth in nonhealth bio, including development of novel high-performance biomaterials with features optimized for specific industrial use cases, or tailored to replace carbon-based inputs, as well as foundry-style projects that scale known, high-potential platforms—like spider silk protein or mycelium—with a wide array of potential use cases.

Innovation competitions and challenges

Engaging the broader scientific community through a research BAA will deliver novel and surprising ideas but will not itself advance actionable ideas to solve concrete problems. To complement a research BAA, BRITE can launch, cosponsor, or administer prize competitions and grand challenges. Open innovation programs accelerate solution development for even the most complex and stubborn bioindustrial development challenges. They are most successful when a clear ‘Goldilocks’ problem can be defined—narrow enough to be addressable by the market, but broad enough that solutions are not presupposed or prescribed. BRITE team members would work with sponsoring agencies to identify “prizeable” issues and optimize problem statements for the prize mechanism. Initial prizes or challenge series could address such diverse problems as:

• Electrobiological sensing to address environmental issues (air quality, water quality, etc.). The intersection of biology and electrical engineering is not always naturally incentivized, particularly outside health applications with high-dollar market potential. The use-inspired call to action of a prize would incentivize experts to cross disciplinary silos toward an underaddressed problem. 
• Novel technologies that expand testbed facility capabilities, such as multi-feedstock, multi-organism, multi-product platforms or easily implementable combination facility kits. Prizes would incentivize collaborative development and be able to provide nonmonetary support to deepen capabilities for a range of use cases.
• Workforce development and on-ramps to bioindustrial careers. The Department of Education (ED), Department of Labor (DOL), and other entities can use prizes to incentivize innovative tools and models for career preparation tailored to the coming needs in our bioindustrial workforce. Successful, analogous ED prizes have advanced project-based K-12 learning models, apprenticeship models for up- and reskilling, and innovative EdTech that helps learners develop in-demand competencies.

Once refined, problem statements can then be designed into single- or multistage competitions. Prize design parameters can be fine-tuned to the nature of the problem and the communities that have the potential to solve them. Using strategic design to balance the fidelity of solutions sought, scale and type of incentives on offer, and timeline for development or refinement maximizes the impact of prizes. One-off or series of single phase competitions can be used to quickly prime the pump and identify potential solutions and solvers. Multistage competitions that down-select to a high-potential cohort provide the added benefit of offering targeted technical assistance over and above prize funds. This form of support is often more valuable to solvers than money—and for bioindustrial challenges could include unique resources such as support for producing demonstration projects, access to third-party validation, and engagement with federal and external experts in science, standards, or regulations.

Market shaping

The quick and meaningful wins achieved through an EZ-BAA and open innovation programs need to be sustained by a robust bioindustrial marketplace. BRITE and partner agencies could draw upon nontraditional procurement mechanisms to amplify the ideas and products that emerge from research and innovation. Other Transaction Authorities could be developed to rapidly engage production capacity from a consortium of biomaterial demonstration and scale-up providers. Advance market commitments to fund procurement of biomaterials or production capacity can position agencies as tentpole customers for applied bioindustrial solutions. These could be executed through strategic national stockpiles, chemical reserves, or other critical product procurements.

Beyond procurement, BRITE can be a driving force across agencies to lower barriers to market entry development. Housed within NIST, BRITE would have a unique ability to directly translate research and innovation outcomes to inform new or revised biomanufacturing and bioindustrial standards. BRITE could also serve as a neutral party that supports alignment of incentives and development of interoperable platforms and standards, facilitating longer-term innovation while preserving private companies’ ability to succeed. Through relationships with various bioindustry regulators (Food and Drug Administration, Environmental Protection Agency, USDA), BRITE could facilitate clearer delineation and harmonization of regulatory responsibilities. This engagement could also better incorporate the current voice of science and technology in defining and refining bioindustry rules, experimental sandboxes, and optimization for different subsectors.

Finally, BRITE can shape the market from the grassroots, engaging a wider set of scientific and general communities in the growing bioindustry. As research and innovation activities ramp up, BRITE can convene prize winners to share insights and spur serendipitous collaborations. BRITE can also steer effective scientific communication on bioindustry, engage stakeholders more directly in the innovation process, and feed community insights back into future programs and priorities. BRITE can follow the example of accelerators like HHS’s LymeX, which actively engages clinical and scientific roundtables to inform prizes and strategy.

Case example: How BRITE activities coordinate for greater impact

The federal lab-to-market tools BRITE would foster are powerful in their own right. Applied in a coordinated fashion, they can rapidly bring transformative bioindustrial solutions to bear against intractable problems.

Consider how all facets of BRITE might contribute to a pressing, multifaceted problem like lead exposure:

• Through the EZ-BAA, BRITE calls for research projects that utilize cyanobacteria to remove elements and impurities in water while mitigating cytotoxic byproducts.
• In parallel, BRITE leads a prize competition for low-cost, bio-inspired tools for real-time lead monitoring and remediation, optimized for real-world use.
• Through a subsequent competition phase or new prize, BRITE runs an accelerator that advances user-centered development, optimizing for residents, school or facility administrators, and local leaders.
• BRITE coordinates an advance market commitment from EPA and the Department of Housing and Urban Development to fund procurement of novel remediation technology by local environmental agencies, housing associations, etc.

Sustainable funding

Based on analogous programs, including DOE American Made Challenges, an initial appropriation or discretionary allocation of $100–200 million is needed to catalyze BRITE’s standup and early wins. This could be assembled by pooling agency funds authorized for bioeconomy activities and/or unspent from recent appropriations (see Table A in FAQ). Private-sector partners or existing public-private partnerships (PPPs) could also support initial funding, though a new PPP likely could not be executed in the required timeframe. In the longer term, BRITE funding can be supported by one or more fit-to-purpose PPPs and should be enshrined in annual appropriations, following the example of KidneyX. Consistent funding is important to show commitment to bioindustrial innovation, enable more multiyear programs or recurring prize series, and provide resilience in the event of budget conflict. A minimum $15 million annual appropriation to sustain BRITE innovation activities could easily be input into one or a combination of bills (Agriculture, Commerce/Justice/State, and Energy and Water).

Conclusion

We are fortunate as a country to have a strong bench of talent working hard to push what is possible in our bioeconomy. They deserve tools and capabilities² that enable them to work smart, delivering a far greater return on the dollars we invest in our bio-driven future. It is not sustainable for the federal government to be the only customer driving bioindustrial progress. But as a catalytic force that bridges valleys of death and solves chicken-and-egg dilemmas, strategic government action to nurture bioindustry out of the lab and into markets will take us farther, faster. By fully utilizing the world-class mechanisms smart policymakers of the past have provided us, we can de-risk bioeconomic investments while yielding maximum benefit for our economy, security, and society.

For the United States, the economic, societal, and national security benefits of the life sciences are vast. The U.S. bioeconomy – the part of the economy driven by the life sciences and biotech, and enabled by engineering, computing, and information science – is valued at over $950 billion. Life sciences research leads to cleaner crops through pollution-free fertilizers, and access to life-saving vaccines, like those mRNA vaccines that helped counter the devastating impacts of COVID-19. And industries built on the life sciences create good-paying jobs across the country.

The 118th Congress can adopt policy to help drive U.S. biotech and biomanufacturing to grow regional prosperity, deliver on conservation goals, and improve U.S. competitiveness and resilience. Here are some ideas.

Advancing the U.S. Bioeconomy to Create Jobs and Bolster Competitiveness. Many provisions in the bipartisan CHIPS and Science Act are intended to enable the bioeconomy. Implementation should focus on three areas: cutting-edge R&D, fundamental and publicly available tools, and biomanufacturing. To further support fundamental research, Congress could direct the National Institutes of Health (NIH) to aim to maximize returns on its massive R&D budget by piloting novel funding mechanisms with evaluation through randomized control trials, funding more high-risk high-reward research, and dedicating more funding to early-career researchers. Congress could also establish a Plant Genome Research Institute (PGRI) that would drive plant genomics research and centralize federal government activities, helping to promote crop innovation and enable a diversified, localized, and resilient food system. And to ensure all Americans benefit fully, actions should be taken to address bias in medical technology at the development, testing and regulation, and market-deployment and evaluation phases.

To promote U.S. bioindustrial manufacturing scale-up and commercialization, Congress could authorize a Bio for America Program Office at the National Institute of Standards and Technology. With appropriations, the office would house a suite of initiatives:

• A Bioindustrial Production Consortium that coordinates precompetitive efforts helping to address the measurements, tools, and standards needed for advancing both research and commercial products in the bioindustrial production space, and that collaborates with BioMADE, industry, government scientists, and other stakeholders.
  
• BAPO Ventures, which would seed a nonprofit partnership manager to launch a U.S. Bioindustrial Production Investment Portfolio to crowd-in additional capital from non-federal government sources and makes calculated investments in early-stage, domestic bioindustrial production companies that demonstrate credible pathways to product commercialization.
  
• The Bioindustrial Production Scale-up Infrastructure Group, which as an initial step would work with both the interagency and non-federal government partners to conduct a comprehensive analysis of the U.S. bioindustrial production pilot- and intermediate-scale infrastructure landscape in order to develop a precision strategy for moving forward on domestic bioindustrial production scale-up capacity.
  
• A Bioindustrial Production Loan Program Office that relies on partners such as the U.S. Small Business Administration to help it provide debt financing for techno-economically sound, domestic demonstration- or commercial-scale bioindustrial production infrastructure projects.

Importantly, Congress can help prepare and invite more Americans into skilled jobs that support the bioeconomy, building a better future for Americans in all 50 states – including people of color, people with disabilities, and people from economically disadvantaged backgrounds – by funding modernized biology education, establishing world-class entrepreneurial hubs for biotechnology in non-traditional regions of the country, and supporting equitable access to industry-recognized certificates and work-based training.

Biotech can also be leveraged to fast-track our nation’s capability to deliver on conservation goals, remediate contaminated habitats, and detect dangerous environmental toxins and pathogens. To that end, Congress could establish a national center to achieve several important goals:

• Provide competitive grant funding across three key tracks – carbon capture, bioremediation, biomonitoring – to catalyze comprehensive environmental biotechnology research
• House a bioethics council to develop and update guidelines for safe, equitable environmental biotechnology use
• Manage testbeds to efficiently prototype environmental biotechnology solutions; and
• Facilitate public-private partnerships to help transition solutions from prototype to commercial scale.

Safeguarding Americans Against Biological Threats. The human and economic toll of COVID-19 has shown the need to be better prepared for future pandemics and epidemics. And yet, there is currently little to no economic incentive for pharmaceutical companies to engage in vaccine research for infectious diseases that have not, and yet could, cause a pandemic. To address this market failure, the U.S. should incentivize vaccine development for priority emerging infectious diseases through federal financing. Specifically, Congress should authorize and appropriate $10 billion to the Biomedical Advanced Research and Development Authority (BARDA) over 10 years to create an investment fund that would:

• Leverage demand-pull mechanisms to purchase vaccines in bulk during future outbreaks and promote innovation in vaccine R&D
• Support manufacturing and distribution facilities
• Provide limited government guarantees, equities, and securities to investors in vaccine development.

Masks, especially high quality respirators, are disease-agnostic tools that can help reduce infections from respiratory diseases like the flu virus and RSV. In turn, this can reduce the burden on doctors and hospitals, and avoid additional healthcare. To that end, the mail delivery system used to distribute COVID-19 diagnostic tests should be augmented by the addition of a masks via mail program. The COVID-19 test mailing program should be restarted and expanded to include an option for ordering one box of 10 free N95 masks every quarter, for those Americans who wish to participate. Additionally, rotating face-mask inventory from the Strategic National Stockpile in a “first in, first out” method will prevent masks from being stored past their recommended shelf life, and promote continual replenishment of the U.S.’s stockpile. The recent National Strategy for a Resilient Public Health Supply Chain, as well as the bipartisan PPE in America Act (H.R.1436) and the bipartisan PREVENT Pandemics Act (S.3799), all advocate for a rotating stock system; however, steps must be taken to better operationalize its implementation and instate a timeline. Congress should authorize the Administration for Strategic Preparedness and Response to grant the HHS Coordination Operations and Response Element key management and distribution responsibilities for critical diagnostic and preventative measures like tests and masks.

The impact of the COVID-19 pandemic was significantly worsened by the presence of diseases that persist at relatively stable case numbers within a particular region. Additional infections paired with COVID-19 infections can lead to lower survival rates and longer hospital stays, creating a drain on resources as well as higher morbidity and mortality effects. Congress should thus authorize an initiative within the Centers for Disease Control and Prevention that enhances the reporting and tracking of regional diseases and helps reduce the data gap that prevents actions and responses to countering circulating diseases. The initiative could be incorporated into S. 3814, the bipartisan Modernizing Biosurveillance Capabilities and Epidemic Forecasting Act.

Finally, the bipartisan Pandemic and All-Hazards Preparedness and Advancing Innovation Act of 2019 (PAHPAIA) will expire in 2023. This law contains several integral provisions for national health security, public health preparedness, biosurveillance, and emergency medical countermeasures, as well as authorizations for BARDA and the Assistant Secretary for Preparedness and Response (ASPR). Congress should re-authorize PAHPAIA, as it forms the bedrock of America’s pandemic preparedness architecture, and consider expanding its purview to address aspects of other U.S. challenges such as wildfires and antimicrobial resistance.

Appropriations Recommendations

Bioeconomy in CHIPS and Science. There are many provisions critical to the U.S. bioeconomy in the CHIPS and Science Law, which Congress should ensure receive robust appropriations. These include:

• Coordinating and strategy activities in Title IV, focused on Bioeconomy Research and Development;
• Title III, Subtitle G, National Science Foundation Directorate for Technology, Innovation, and Partnerships. The directorate is authorized at $3.4 billion overall in FY 2024. The list of critical technologies the new directorate is intended to advance (Section 10387) includes biotechnology, medical technology, genomics, and synthetic biology, all relevant to the bioeconomy. The directorate also funds the Regional Innovation Engines program promoting biotech partnerships and commercialization efforts across the U.S. in biotech.
• Title II, Section 10221, which directs the National Institute of Standards and Technology to conduct an array of activities in engineering biology and biometrology.
• Title I, Section 10103, Department of Energy (DOE) Biological and Environmental Research (authorized at $947 million in FY 2024), which funds an array of fundamental research in the biosciences.
• Title I, Section 10112, Office of Science Emerging Biological Threat Preparedness Research Initiative (authorized at $50 million in FY 2024), which establishes a cross-cutting program to leverage DOE analytical resources and tools, user facilities, and advanced computational and networking capabilities to support efforts that prevent, prepare for, predict, and respond to biological threats to national security, including infectious diseases.

Congress should provide robust appropriations to all activities, as close to the CHIPS authorizations as possible, to ensure a dynamic and innovative bioeconomy sector.

Bioproduct Pilot Program. The National Institute of Food and Agriculture’s (NIFA) Bioproduct Pilot Program (created in the Infrastructure Investment and Jobs Act, Sec. 70501) is intended to increase economic activity in rural areas of the U.S. while also lowering commercialization risks associated with bringing biobased products to market. The program aims to study the benefits of using materials derived from covered agricultural commodities for manufacture of construction and consumer products. The program’s work also enables the development of a more circular economy, where finite resources are not just extracted and consumed but also regenerated in a sustainable manner. Adopting a more circular economy ensures that wealth and other economic benefits in the form of jobs and other opportunities are created, and stay in, rural communities, while learnings can be shared throughout the U.S. innovation ecosystem.

A total of up to $5 million is available for the program for each of FY 2022 and FY 2023. The availability of funds for the program should be extended through FY 2028, with yearly increases to a level above $5 million per year according to the requests of NIFA/the program team.

Scaling and Regionalizing Networked Bioindustrial Manufacturing. The 2023 NDAA (Division A, Section 215) directs the Secretary of Defense to establish and expand a network of manufacturing innovation institutes and intermediate scale facilities for R&D, piloting, and scaling of innovative bioindustrial manufacturing processes and products. Support for these activities is critical to ensure the industrial base can leverage bioindustrial manufacturing processes for the production of chemicals, materials, and other products necessary to support national security and secure fragile supply chains. Congress should provide $500 million in appropriations across national security bioeconomy activities including $300 million for biomanufacturing innovation institutes, in accord with the NDAA.

Countering Global Malnutrition to Enhance U.S. Security. Due to the COVID-19 pandemic, environmental impacts, and conflicts like the war in Ukraine, global rates of malnutrition are at eight percent and are forecast to become even worse. Providing life-saving treatment around the world serves a core American value of humanitarianism, and a priority for U.S. national security – the newly released National Security Strategy dedicates an entire section to food insecurity.

In 2021 legislation, Congress directed USAID to advance programs to prevent and treat malnutrition around the world and develop a Global Nutrition Coordination Plan. That legislation also directed USAID to create the Nutrition Leadership Council, which can help elevate nutrition programs across U.S. global health interventions and foster collaboration with other sectors, development agencies, partner governments, and local actors. These are important steps to create a centralized food security program with harmonized funding – a system to deploy a more effective response to end global malnutrition and improve U.S. national security.

Congress should work with the Administration to begin scaling up global malnutrition assistance in FY 2024, in accord with the 2021 legislation.

Supporting the U.S. Emergency Response Workforce. The National Disaster Medical System (NDMS) is an integral part of the United States’ pandemic and hazards preparedness and response infrastructure. NDMS has a unique ability to coordinate and deliver emergency medical services to both federal and state, local, tribal, or territorial (SLTT) agencies. During the COVID-19 pandemic, NDMS deployed all across the country to provide training, medical care, coordinate medical supply delivery, and ensure effective communication. Additional appropriations would go toward hiring more personnel and bolstering in-person activities in the wake of COVID-19. Congress should ensure NDMS is funded up to FY 2024 request levels.

Summary

Plants are an important yet often overlooked national asset. We propose creating a Plant Genome Project (PGP), a robust Human Genome Project-style initiative to build a comprehensive dataset of genetic information on all plant species, starting with the 7,000 plant species that have historically been cultivated for food and prioritizing plants that are endangered by climate change and habitat loss. In parallel, we recommend expanding the National Plant Germplasm System (NPGS) to include genomic-standard repositories that connect plant genetic information to physical seed/plant material. The PGP will mobilize a whole-of-government approach to advance genomic science, lower costs, and increase access to plant genomic information. By creating a fully sequenced national germplasm repository and leveraging modern software and data science tools, we will unlock the U.S. bioeconomy, promote crop innovation, and help enable a diversified, localized, and climate-resilient food system.

Challenge and Opportunity

Plants provide our food, animal feed, medicinal compounds, and the fiber and fuel required for economic development. Plants contribute to biodiversity and are critical for the existence of all other living creatures. Plants also sequester atmospheric carbon, thereby combating climate change and sustaining the health of our planet. 

However, as a result of climate change and human practices, we have been losing plants at an alarming rate. Nearly 40% of the world’s 435,000 unique land plant species are extremely rare and at risk of extinction due to climate change. More than 90% of crop varieties have disappeared from fields worldwide as farmers have abandoned diverse local crop varieties in favor of genetically uniform, commercial varieties. 

We currently depend on just 15 plants to provide almost all of the world’s food, making our global food supply extremely vulnerable to climate change, new diseases, and geopolitical upheaval—problems that will be exacerbated as the world’s population rises to 10 billion by 2050. 

We are in a race against time to stop the loss of plant biodiversity—and at the same time, we desperately need to increase the diversity in our cultivated crops. To do this, we must catalog, decode, and preserve valuable data on all existing plants. Yet more than two decades since we sequenced the first plant genome, genome sequence information exists for only 798 plant species—a small fraction of all plant diversity.

Although large agriculture companies have made substantial investments in plant genome sequencing, this genetic information is focused on a small number of crops and is not publicly available. What little information we have is siloed, known only to large corporations and not openly available to researchers, farmers, or policymakers. This is especially true for nations in the Global South, who are not usually included in most genome sequencing projects. Furthermore, current data in existing germplasm repositories, State Agricultural Experiment Stations, and land-grant universities is not easily accessible online, making it nearly impossible for researchers in both public and private settings to explore. These U.S. government collections and resources of germplasm and herbaria, documented by the Interagency Working Group on Scientific Collections, have untapped potential to catalyze the bioeconomy and mobilize investment in the next generation of plant genetic advancements and, as a result, food security and new economic opportunities.

Twenty years ago, the United States launched the Human Genome Project (HGP), a shared knowledge-mapping initiative funded by the federal government. We continue to benefit from this initiative, which has identified the cause of many human diseases and enabled the development of new medicines and diagnostics. The HGP had a $5.4 billion price tag ($2.7 billion from U.S. contributions) but resulted in more than $14.5 billion in follow-on genomics investments that enabled the field to rapidly develop and deploy cutting-edge sequencing and other technologies, leading to a drop in genomic sequencing cost from $300 million per genome to less than $1,000.

Today, we need a Human Genome Project for plants—a unified Plant Genome Project that will create a global database of genetic information on all plants to increase food security and unlock plant innovation for generations to come. Collecting, sequencing, decoding, and cataloging the nation’s plant species will fill a key gap in our national natural capital accounting strategy. The PGP will complement existing conservation initiatives led by the Office of Science and Technology Policy (OSTP) and other agencies, by deepening our understanding of America’s unique biodiversity and its potential benefits to society. Such research and innovation investment would also benefit government initiatives like USAID’s Feed the Future (FTF) Initiative, particularly the Global Food Security Research Strategy, around climate-smart agriculture and genetic diversity of crops. 

PGP-driven advancements in genomic technology and information about U.S. plant genetic diversity will create opportunities to grow the U.S. bioeconomy, create new jobs, and incentivize industry investment. The PGP will also create opportunities to make our food system more climate-resilient and improve national health and well-being. By extending this effort internationally, and ensuring that the Global South is empowered to contribute to and take advantage of these genetic advancements, we can help mitigate climate change, enhance global food security, and promote equitable plant science innovation.

Plan of Action

The Biden Administration should launch a Plant Genome Project to support and enable a whole-of-government approach to advancing plant genomics and the bioeconomy. The PGP will build a comprehensive, open-access dataset of genetic and biological information on all plant species, starting with the 7,000 plant species that have historically been cultivated for food and prioritizing plants that are endangered by climate change and habitat loss. The PGP will convene key stakeholders and technical talent in a novel coalition of partnerships across public and private sectors. We anticipate that the PGP, like the Human Genome Project, will jump-start new technologies that will further drive down the cost of sequencing and advance a new era for plant science innovation and the U.S. bioeconomy. Our plan envisions two Phases and seven Key Actions. 

Phase 1: PGP Planning and Formation

Action 1: Create the Plant Genomics and U.S. Bioeconomy Interagency Working Group

The White House OSTP should convene a Plant Genomics and U.S. Bioeconomy Interagency Working Group to coordinate the creation of a Plant Genome Project and initiate efforts to consult with industry, academic, philanthropy, and social sector partners. The Working Group should include representatives from OSTP, U.S. Department of Agriculture (USDA) and its Agricultural Research Service (ARS), National Plant Germplasm System, Department of Commerce, Department of Interior, National Science Foundation (NSF), National Institutes of Health (NIH), Smithsonian Institution, Environmental Protection Agency, State Department’s Office of Science and Technology Adviser, and USAID’s Feed the Future Initiative. The Working Group should:

• Identify experts and resources to enable the PGP and work with multi-sector entities, including within USDA, to identify sources of seeds/plants in the United States.
• Conduct a kickoff meeting with OSTP and identify a team that includes NPGS representatives to inventory existing resources, coordinate seed collection efforts, and create connectivity with the PGP.
• Provide recommendations on working with international institutes in the Global North (e.g., Global Biodiversity Information Facility and Earth BioGenome Project) and the Global South (e.g., The African BioGenome Project, the International Potato Center and others). The Earth BioGenome Project’s work on green plants and initial genomic quality standards offers potential starting points for collaboration.
• Create recommendations for the nation’s first Plant Genome Research Institute to drive initial and future efforts in obtaining plant genome information and accelerating innovative research in plant genomics.

Action 2: Launch a White House Summit on Plant Genomics Innovation and Food Security

The Biden Administration should bring together multi-sector (agriculture industry, farmers, academics, and philanthropy) and agency partners with the expertise, resource access, and interest in increasing domestic food security and climate resilience. The Summit will secure commitments for the PGP’s initial activities and identify ways to harmonize existing data and advances in plant genomics. The Summit and follow-up activities should outline the steps that the Working Group will take to identify, combine, and encourage the distribution and access of existing plant genome data. Since public-private partnerships play a core enabling role in the strategy, the Summit should also determine opportunities for potential partners, novel financing through philanthropy, and international cooperation. 

Action 3: Convene Potential International Collaborators and Partners

International cooperation should be explored from the start (beginning with the Working Group and the White House Summit) to ensure that sequencing is conducted not just at a handful of institutions in the Global North but that countries in the Global South are included and all information is made publicly available. 

• During the annual UN General Assembly Summit, OSTP should convene a forum of key leaders across multiple countries, international NGOs, Fortune 1000 companies, and academia. 
• This forum will drive international public-private commitments to action that support the launch of the PGP. 
• This forum should produce a yearly report–the first of its kind, on progress at the intersection of technological and data-driven advances in plant and crop innovation, preserving plant biodiversity, ending hunger, achieving food security, and improving nutrition. 
• This work could culminate in a flagship announcement of new commitments tied to the UN’s 2030 Agenda for Sustainable Development. Various champions and experts on The Nagoya Protocol, Convention on Biological Diversity (CBD), and others working with The Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) should be included.

We envision at least one comprehensive germplasm seed bank in each country or geographical region similar to the Svalbard seed vault or The Royal Botanic Garden at Kew and sequencing contributions from multiple international organizations such as Beijing Genomics Institute and the Sanger Institute. 

Phase 2: PGP Formalization and Launch

Action 4: Launch the Plant Genome Research Institute to centralize and coordinate plant genome sequencing

Congress should create a Plant Genome Research Institute (PGRI) that will drive plant genomics research and be the central owner of U.S. government activities. The PGRI would centralize funding and U.S. government ownership over the PGP. We anticipate the PGP would require $2.5 billion over 10 years, with investment frontloaded and funding raised through matched commitments from philanthropy, public, and private sources. The PGRI could be a virtual institute structured as a distributed collaboration between multiple universities and research centers with centralized project management. PGRI funding could also incorporate novel funding mechanisms akin to the BRAIN Initiative through U.S. philanthropy and private sector collaboration (e.g., Science Philanthropy Alliance). The PGRI would:

• Identify key strategic public and private partners to join the coalition that prioritizes and undertakes the sequencing projects. 
• Coordinate sequencing that will be conducted at sequencing centers funded by the PGRI while ensuring that all current consortia and initiatives for plant genome sequencing are included and connected.
• Define metrics for gene sequencing (e.g., accuracy, capacity, and cost of finished sequence), genome assembly, and genetic/physical map creation. 
• Engage with industry providers of novel sequencing technology to bring down costs. 
• Develop the final operational plan with timelines and funders outside the U.S. government in philanthropy and the private sector.
• Promote the development of novel bioinformatic and computational tools to facilitate gene assembly in polyploid plant genomes and view reference genomes of various plant species and varieties.
• Based on recommendations from the Working Group, select the agency or offices best positioned to house and maintain the data. 
• Implement FAIR standards for data storage and dissemination and ensure an open-access, user-friendly interface for the final software platform. This could be achieved through a current database such as GenBank.
• Run an open challenge to share existing genome sequence data that is currently not publicly available and ensure that receiving centers undertake appropriate validation and quality control of all imported data. 

Action 5: Expand and Strengthen NPGS-Managed Seed Repositories

We recommend strengthening the distributed seed repository managed by the U.S. National Plant Germplasm System and building a comprehensive and open-source catalog of plant genetic information tied to physical samples. The NPGS already stores seed collections at state land-grant universities in a collaborative effort to safeguard the genetic diversity of agriculturally important plants and may need additional funding to expand its work and increase visibility and access. 

• Bring in new partnerships, funding, and technical expertise from the private sector, a major user of the NPGS collections and the primary means by which new and improved plants are commercialized. 

• Provide funding to create structured and highly annotated datasets of seed profiles with taxonomic data and other criteria such as phenotypic/physical attributes, local usage, commercial characteristics, and rarity. 
• Automatically feed data from all new and existing germplasm repositories into the PGP, linking existing physical germplasm data to novel genetic data and connecting genomic and genetic data with taxonomic information.
• Invite computer scientists to develop novel data-driven algorithms and machine-learning models incorporating newly collected genomic data to identify plant varieties that might be especially climate resilient. (This potential innovation has been demonstrated in machine-vision research involving digitized herbarium specimens).

Action 6: Create a Plant Innovation Fund within AgARDA

The Agriculture Advanced Research and Development Authority (AgARDA) is a USDA-based advanced research projects agency like DARPA but for agriculture research. The 2018 Farm Bill authorized AgARDA’s creation to tackle highly ambitious projects that are likely to have an outsize impact on agricultural and environmental challenges—such as the PGP. The existing AgARDA Roadmap could guide program setup. 

• The Administration should launch BioDRIVe, a $100 million public natural assets fund targeted at plant innovation and biodiversity gains inspired by the DRIVe program focused on preventing future pandemics. If traditional federal funding mechanisms are inadequate, such data-driven investment vehicles/flexible funding tools could also include philanthropic funding mechanisms and be integrated within the PGRI. This would promote public-private partnerships and de-risk promising technologies that drive innovation for food security and biodiversity conservation.
• Through its RFP process, AgARDA could help drive key agricultural innovation that arises from the PGP, such as creating stronger, more climate-resilient, disease-resistant, or nutritionally superior plants and identifying plants that can break down pollutants or produce novel enzymes and products. AgARDA is ready to go as soon as it receives funding through the annual Congressional funding process.  

Phase 3: Long-Term, Tandem Bioeconomy Investments

Action 7: Bioeconomy Workforce Development and Plant Science Education

Invest in plant science and technical workforce development to build a sustainable foundation for global plant innovation and enable long-term growth in the U.S. bioeconomy. 

• Use the PGRI as a platform for a renewed focus on training world-class botanists, plant breeders, horticulturists, and agronomists. A networked effort to train the next generation of plant scientists, similar to the 100Kin10 initiative that successfully trained 100,000 new STEM teachers in 10 years, could be very useful. Funding could be targeted to scholarships in these areas at universities, community colleges, and scientific associations such as the American Society of Agronomy. We also recommend increasing emphasis on plant science in K-12 education. 
• Build stronger ties between the plant science industry and the engineering workforce to support the growing data and technology needs for plant science research. This could include bringing in science and engineering fellows from existing fellowship programs to help build new software and data science tools for plant science.
• Launch a fellowship program in partnership with NSF, USDA, and scientific associations such as the American Association for the Advancement of Science or the American Society of Plant Biologists for talented plant biologists, agricultural researchers, and data and software engineers to serve a yearlong “tour of duty” in public service, where they would work internationally to collect, maintain, and expand the plant genome database. Existing and new repositories could benefit from this talent pool, and these cohorts of fellows would disseminate knowledge of the database throughout their careers, helping to achieve adoption at scale.

Conclusion

We are in a race against time to identify, decode, catalog, preserve, and cultivate the critical biodiversity of the world’s plant species before they are lost forever. By creating the world’s first comprehensive, open-access catalog of plant genetic information tied to physical samples, the Plant Genome Project will unlock plant innovation for food security, help preserve plant biodiversity in a changing climate, and advance the bioeconomy. The PGP’s whole-of-government approach will accelerate a global effort to secure our food systems and the health of the planet while catalyzing a new era of plant science, agricultural innovation and co-operation.

Congress had a lot more on its agenda than semiconductors when compiling the CHIPS and Science Act of 2022. The bill–law as of yesterday–puts forward an expansive framework to advance U.S. innovation broadly, including in areas that feed into a critical sector: the bioeconomy. 

The U.S. bioeconomy–the part of the economy driven by the life sciences and biotech, and enabled by engineering, computing, and information science–has already produced many breakthroughs, such as mRNA vaccines that help counter the devastating impacts of COVID-19, or genetically engineered microbes that provide nutrients to crops without the pollution associated with traditional fertilizers. Valued at over $950 billion, the U.S. bioeconomy accounts for more than five percent of the U.S. gross domestic product–more than the contribution from the construction industry, and on par with the contribution of the information sector.

However, without sufficient support from and coordination of federal resources, the U.S. bioeconomy risks ceding ground to competitors that are implementing cohesive strategies to advance their bioeconomies. For example, China aims to dominate the 21st century bioeconomy and has prioritized growth of its bioeconomy in its five-year plans. From 2016 to July 2021, the market value of publicly listed biopharmaceutical innovators from China increased approximately 127-fold across several major stock exchanges, to more than $380 billion, with biotechnology companies accounting for more than 47 percent of that valuation.

To improve the likelihood that the U.S. advances its leadership of the bioeconomy and continues to reap the bulk of the bioeconomy’s economic, national security, and societal benefits, key provisions in the new law are intended to ensure a strong U.S. bio-workforce and the execution of leading-edge bioinnovation in America.

Select highlights 

There’s quite a list of provisions in the CHIPS and Science Act relevant to promoting the U.S. bioeconomy. Some of the substantial ones that jumped off the page are presented below.

Opportunities to take action to shape the new bioeconomy policy landscape

Now that the CHIPS and Science Act is law, how might the community with a stake in the bioeconomy continue to work to shape the policy landscape?

For one, while the new law mandates actions to support the bioeconomy, the appropriation of funding to support the agencies in fiscal year 2023 has stalled so far. Congress should finish the job and provide funding, and further advocacy before Congress to press for the appropriations process to be completed may be warranted.

Furthermore, the interagency committee that will coordinate much of this work will be composed of many federal agencies, and it will be important for all the right voices to be at the table. That should include agency personnel who work to support fundamental research, experimental development, commercialization, and equity, ethical, legal, environmental, safety, security, and social issues. In addition, the director of the White House Office of Science and Technology Policy (OSTP) will select a co-chairperson from among the members of the interagency committee. This all presents an opportunity for the community to connect with OSTP to encourage the right agencies to serve on the committee, and to serve as co-chair.

An office established by the President will serve as the point of contact on federal activities related to the bioeconomy for government organizations, academia, industry, professional societies, State governments, interested citizen groups, and others to exchange technical and programmatic information. Once up and running, this office will be the place to go to discuss R&D, commercialization, social issues, and more. Notably, while this office will, in part, support the interagency committee and oversee the coordination of much of this work, the CHIPS and Science Act does not specify where the office should be housed within the federal government, providing another opportunity for the community to engage with policymakers to press for the most effective positioning of the office.

There will also be opportunities to engage with the National Academies, which were charged, under National Science Foundation contract, to “conduct a review, and make recommendations with respect to, the ethical, legal, environmental, safety, security, and other appropriate societal issues related to” R&D in areas that undergird the bioeconomy. This might involve making comments during study committee meetings’ open sessions, submitting written comments in response to requests, or communicating with the members who are selected to make up the committee. The National Academies report is due to Congress within two years, and is also likely to be influential with officials in the executive branch.

A call to action–we want to hear from you!

Provisions relevant to the bioeconomy are written throughout the CHIPS and Science Act. If you are interested in what else is included, you can review some summary materials or read pages 625-650 of the bill itself (Title IV–Bioeconomy Research and Development), and do some keyword searching on terms like “biomanufacturing,” “genomics,” “biological,” “microbial,” and so on to find other related provisions. And if you’d like, let us know what stands out to you, or how you might take action to impact the new policy landscape, by submitting your thoughts via this form. We would be happy to connect with you if there are opportunities to develop your ideas and engage with policymakers.

Now is a moment of significant opportunity to engage with federal officials implementing the new federal bioeconomy strategy, and we should seize it.

Opportunities to take action to shape the new bioeconomy policy landscape

Now that the CHIPS and Science Act is law, how might the community with a stake in the bioeconomy continue to work to shape the policy landscape?

For one, while the new law mandates actions to support the bioeconomy, the appropriation of funding to support the agencies in fiscal year 2023 has stalled so far. Congress should finish the job and provide funding, and further advocacy before Congress to press for the appropriations process to be completed may be warranted.

Furthermore, the interagency committee that will coordinate much of this work will be composed of many federal agencies, and it will be important for all the right voices to be at the table. That should include agency personnel who work to support fundamental research, experimental development, commercialization, and equity, ethical, legal, environmental, safety, security, and social issues. In addition, the director of the White House Office of Science and Technology Policy (OSTP) will select a co-chairperson from among the members of the interagency committee. This all presents an opportunity for the community to connect with OSTP to encourage the right agencies to serve on the committee, and to serve as co-chair.

An office established by the President will serve as the point of contact on federal activities related to the bioeconomy for government organizations, academia, industry, professional societies, State governments, interested citizen groups, and others to exchange technical and programmatic information. Once up and running, this office will be the place to go to discuss R&D, commercialization, social issues, and more. Notably, while this office will, in part, support the interagency committee and oversee the coordination of much of this work, the CHIPS and Science Act does not specify where the office should be housed within the federal government, providing another opportunity for the community to engage with policymakers to press for the most effective positioning of the office.

There will also be opportunities to engage with the National Academies, which were charged, under National Science Foundation contract, to “conduct a review, and make recommendations with respect to, the ethical, legal, environmental, safety, security, and other appropriate societal issues related to” R&D in areas that undergird the bioeconomy. This might involve making comments during study committee meetings’ open sessions, submitting written comments in response to requests, or communicating with the members who are selected to make up the committee. The National Academies report is due to Congress within two years, and is also likely to be influential with officials in the executive branch.

A call to action–we want to hear from you!

Provisions relevant to the bioeconomy are written throughout the CHIPS and Science Act. If you are interested in what else is included, you can review some summary materials or read pages 625-650 of the bill itself (Title IV–Bioeconomy Research and Development), and do some keyword searching on terms like “biomanufacturing,” “genomics,” “biological,” “microbial,” and so on to find other related provisions. And if you’d like, let us know what stands out to you, or how you might take action to impact the new policy landscape, by submitting your thoughts via this form. We would be happy to connect with you if there are opportunities to develop your ideas and engage with policymakers.

Now is a moment of significant opportunity to engage with federal officials implementing the new federal bioeconomy strategy, and we should seize it.