ADVANCED MANUFACTURING:

A Snapshot of Priority Technology Areas

Across the Federal Government

PRODUCT OF THE

Subcommittee for Advanced Manufacturing

OF THE NATIONAL SCIENCE AND TECHNOLOGY COUNCIL

April 2016
iii

EXECUTIVE OFFICE OF THE PRESIDENT

NATIONAL SCIENCE AND TECHNOLOGY COUNCIL

WASHINGTON, D.C. 20502

Dear Colleagues:

Manufacturing plays an outsized role in the U.S. economy: from the greatest economic multiplier 

of any other sector, to the creation of 4 additional jobs for every manufacturing job, it is clear 

that the manufacturing sector is a critical driver to our country’s prosperity and security. These

economic impacts grow as we add next-generation technologies: advanced manufacturing 

produces sophisticated and exclusive products that we can sell around the world, leading to 

greater economic prosperity and increasing the job multiplier to 16-to-1.

A vibrant manufacturing sector, especially one invigorated with the latest technologies, requires 

focused investments along the entire technology innovation pipeline. An innovation pipeline 

stocked with ideas, from the laboratory bench to the manufacturing shop floor, is required to “make 

it here” so that we can “sell it everywhere.” The advanced manufacturing processes and products 

we desire—the types that lead to greater economic prosperity—is the result of knowledge, 

accumulated through research and development, translated systematically into know-how.

A vibrant manufacturing sector also needs an equally vibrant workforce, educated in a multitude 

of fields from engineering to economics. These skilled craftsmen, technicians, designers, planners, 

researchers, engineers, and managers will be in high demand: over the next decade, we will need 

to fill nearly 3.5 million manufacturing jobs, although 2 million of these positions may remain 

unfilled due to a skills gap. In fact, at this moment, 80 percent of manufacturers currently report a 

moderate or serious shortage of qualified applicants for skilled and highly-skilled production 

positions.

Growing and sustaining the innovation ecosystem we envision for advanced manufacturing will 

require concerted efforts across government, industry, and academia. This document contributes 

to a shared vision of the most important technologies for U.S. competitiveness in manufacturing

by articulating a collection of advanced manufacturing technology areas and education and 

workforce development initiatives that are priorities for the Federal members of the Subcommittee 

for Advanced Manufacturing. This is a critical step towards identifying smart, strategic 

investments that build on our strengths—revving the engines of American ingenuity and honing

the skills of the world’s most productive workforce.

Sincerely,

Tom Kalil

Deputy Director for Technology and Innovation

Office of Science and Technology Policy
iv

The National Science and Technology Council 

The National Science and Technology Council (NSTC) is the principal means by which the Executive Branch 

coordinates science and technology policy across the Federal research and development enterprise. A 

primary objective of the NSTC is establishing clear national goals for Federal science and technology 

investments. The NSTC prepares research and development strategies that are coordinated across Federal

agencies to form investment packages aimed at accomplishing multiple national goals. The work of the 

NSTC is organized under committees that oversee subcommittees and working groups focused on 

different aspects of science and technology. More information is available at: 

www.whitehouse.gov/administration/eop/ostp/nstc.

The Subcommittee on Advanced Manufacturing

The NSTC Subcommittee on Advanced Manufacturing (SAM) serves as a forum for information-sharing, 

coordination, and consensus-building among participating agencies regarding Federal policy, programs, 

and budget guidance for advanced manufacturing. Originally chartered in 2012, the subcommittee seeks 

to identify: gaps in the Federal advanced manufacturing research and development portfolio and policies, 

programs and policies that support technology commercialization, methods of improving business 

climate, and opportunities for public-private collaboration. Regarding advanced manufacturing programs 

conducted by the Federal Government, the subcommittee engages in the identification and integration 

of multi-agency technical requirements, joint program planning and coordination, and development of 

joint strategies or multi-agency joint solicitations.

About this Document

This document was developed by the Subcommittee on Advanced Manufacturing (SAM). The document was 

published by the Office of Science and Technology Policy (OSTP).

Acknowledgements

Many individuals across the Federal Government contributed to this report and the work it describes. 

Particular recognition goes out to the lead authors and their key subject matter experts, who crafted the 

input and feedback of their interagency colleagues into this single document: Bill Goldner, Sonny 

Ramaswamy, and Valerie Reed (USDA); Jason Boehm, Dean DeLongchamp, and Heather Evans(DOC); Kristy 

Pottol, Adele Ratcliff, and Tracy Frost (DoD); Mark Johnson, Reuben Sarkar, and Andrew Steigerwald (DOE);

Jean Hu-Primmer and Sau L. Lee (HHS); Theresa Good and Bruce Kramer (NSF); Robbie Barbero, Megan 

Brewster, Austin Brown, Robert Strickling, and Lloyd Whitman (OSTP); and to Frank Pfefferkorn (AMNPO).

Copyright Information

This document is a work of the United States Government and is in the public domain (see 17 U.S.C. §105). 

Subject to the following stipulations, it may be distributed and copied with acknowledgement to OSTP. 

Copyrights to graphics included in this document are reserved by the original copyright holders or their 

assignees and are used here under the United States Government’s license and by permission. Requests 

to use any images must be made to the provider identified in the image credits or to OSTP if no provider 

is identified.

Printed in the United States of America, April 2016
v

Report prepared by

NATIONAL SCIENCE AND TECHNOLOGY COUNCIL

COMMITTEE ON TECHNOLOGY

SUBCOMMITTEE ON ADVANCED MANUFACTURING

National Science and Technology Council

Chair

John P. Holdren

Assistant to the President for Science 

and Technology and Director,

Office of Science and Technology Policy

Staff

Afua A. N. Bruce

Executive Director

Office of Science and Technology Policy

Committee on Technology

Chair

Thomas Kalil

Deputy Director, Technology and Innovation

Office of Science and Technology Policy

Staff

Terah Lyons

Executive Secretary

Office of Science and Technology Policy

Subcommittee on Advanced Manufacturing

Chairs

Thomas Kalil

Deputy Director, Technology and Innovation

Office of Science and Technology Policy

Jason Miller

Deputy Assistant to the President and Deputy 

Director

National Economic Council

Willie May

Under Secretary of Commerce for Standards and 

Technology, and Director,

National Institute of Standards and Technology

Staff

Megan Brewster

Fellow and Senior Policy Advisor for Advanced 

Manufacturing

Office of Science and Technology Policy

J.J. Raynor

Special Assistant to the President for Economic 

Policy

National Economic Council

Jason Boehm

Director, Program Coordination Office

National Institute of Standards and Technology

Rich Cavanagh

Director, Special Programs Office

National Institute of Standards and Technology
Advanced Manufacturing: A Snapshot of Priority Technology Areas Across the Federal Government

vi

Subcommittee Members

The following Federal departments and agencies are represented on the SAM:

Department of Agriculture

Department of Commerce

Department of Defense

Department of Education

Department of Energy

Department of Health and Human Services

Department of Homeland Security

Department of Labor

Department of Transportation

Environmental Protection Agency

National Aeronautics and Space Administration

National Science Foundation

Small Business Administration

The following offices of the Executive Office of the President are also represented on the SAM:

National Economic Council

Office of Management and Budget

Office of Science and Technology Policy
Advanced Manufacturing: A Snapshot of Priority Technology Areas Across the Federal Government

vii

Table of Contents

Introduction ..................................................................................................................................................2

Manufacturing Technology Areas of Emerging Priority................................................................................4

Advanced Materials Manufacturing .........................................................................................................4

Engineering Biology to Advance Biomanufacturing ...............................................................................11

Biomanufacturing for Regenerative Medicine........................................................................................17

Advanced Bioproducts Manufacturing ...................................................................................................23

Continuous Manufacturing of Pharmaceuticals.....................................................................................29

Manufacturing Technology Areas of Existing Priority.................................................................................35

Areas of Interest for Potential Future Investment .................................................................................35

Foci of the Manufacturing Innovation Institutes....................................................................................36

Additive Manufacturing ......................................................................................................................36

Advanced Composites.........................................................................................................................36

Digital Manufacturing and Design ......................................................................................................37

Flexible Hybrid Electronics..................................................................................................................37

Integrated Photonics...........................................................................................................................37

Lightweight Metals..............................................................................................................................38

Smart Manufacturing..........................................................................................................................38

Revolutionary Fibers and Textiles.......................................................................................................39

Wide Bandgap Electronics ..................................................................................................................39

Manufacturing Education and Workforce Training Priorities.....................................................................40

Conclusions.................................................................................................................................................44

Appendix A. Federal Participants in the NSTC SAM....................................................................................45

Appendix B: Technology Readiness Levels and Manufacturing Readiness Levels.....................................55

Abbreviations..............................................................................................................................................56
Advanced Manufacturing: A Snapshot of Priority Technology Areas Across the Federal Government

1

Executive Summary

Advanced manufacturing drives long-term economic prosperity and growth, and supports the missions of 

the Federal agencies participating in the NSTC Subcommittee for Advanced Manufacturing (SAM). A 

foundation of priority technology areas is needed to secure U.S. competitiveness in this sector, from which 

collaborations between government, industry, and academia may be built. This document captures 

technology areas in advanced manufacturing that are current priorities for the Federal Government, and 

are strong candidates for focused Federal investment and public-private collaboration. Emerging 

technology areas include advanced materials manufacturing, engineering biology to advance 

biomanufacturing, biomanufacturing for regenerative medicine, advanced bioproducts manufacturing, 

and continuous manufacturing of pharmaceuticals. In addition, the Federal Government has already 

announced a number of advanced manufacturing technology areas that are either the focus of substantial 

existing investments or that may be the subject of future programming. These existing technology areas 

similarly require support across the development pipeline to fully leverage current research and 

development investments and infrastructure. Finally, Federal education and workforce training programs

for manufacturing, which encourage strong industry involvement to ensure that today’s curricula meet 

tomorrow’s workforce needs, are highlighted.
2

Introduction

Advanced manufacturing1strengthens the U.S. economy and national security, produces high income 

jobs, and generates technological innovation—driving long-term economic prosperity and growth. 

Advanced manufacturing further supports the missions of many Federal agencies, from protecting 

national security and building U.S. competitiveness to strengthening the scientific and engineering 

enterprise and providing transformative science and technology solutions, and beyond.

Yet the importance of advanced manufacturing to winning the future was not always so clear. In fact, the 

U.S. manufacturing sector is still coming back from an era without this critical insight. U.S. manufacturers 

are currently reinvigorating plans for next-generation products that were shelved due to scarce capital,

retraining workers in the newest technologies required for competitiveness in a global marketplace, and 

rebuilding supply chains that were dismantled by years of offshoring. The transition to advanced 

manufacturing processes and products is actively underway across many industries, to the benefit of the 

entire nation.

Sustaining this progress and securing U.S. leadership in advanced manufacturing requires participation 

from government, industry, academia, and other key stakeholders. This broad ecosystem must align on 

the key technologies that underpin U.S. competitiveness in this sector to provide a foundation of priorities 

for public-private collaborations and a shared vision for how to advance them. Promising technologies are 

those that suffer from gaps in support for the pre-competitive research and development requisite to 

unleashing new industries. Collaborative efforts leverage common assets to the benefit of all 

stakeholders, overcoming the significant development cycle costs that are impractical for any single entity 

to bear alone. To this end, the Federal Government may serve as an unbiased entity to convene 

stakeholders, to address pre-competitive technologies. Indeed, these are key findings and 

recommendations from the President’s Council of Advisors on Science and Technology (PCAST) in its 2014 

Accelerating U.S. Advanced Manufacturing report.

2

This document captures technology areas in advanced manufacturing that are current priorities for the 

Federal Government and are strong candidates for focused Federal investment and public-private 

collaboration. Each technology area is defined, including its industry pull, cross-cutting impact, 

importance to national security and competitiveness, and utilization of current U.S. strengths and 

competencies. Major technical challenges and opportunities are outlined, and a sampling of current and 

planned Federal programs and initiatives is highlighted.

In addition to these emerging technology areas, the Federal Government has already announced a 

number of advanced manufacturing technology areas that are either the focus of substantial existing 

investments or that may be the subject of future programming. These existing priority areas similarly 

 

1

Advanced manufacturing Advanced manufacturing is a family of activities that (a) depend on the use and coordination of 

information, automation, computation, software, sensing, and networking, and/or (b) make use of cutting edge materials 

and emerging capabilities enabled by the physical and biological sciences, for example nanotechnology, chemistry, and 

biology. It involves both new ways to manufacture existing products, and the manufacture of new products emerging from 

new advanced technologies. President’s Council of Advisors on Science and Technology. Report to the President on Ensuring 

American Leadership in Advanced Manufacturing. June 2011. 

https://www.whitehouse.gov/sites/default/files/microsites/ostp/pcast-advanced-manufacturing-june2011.pdf

2

President’s Council of Advisors on Science and Technology. Report to the President: Accelerating U.S. Advanced 

Manufacturing. October 2014. 

https://www.whitehouse.gov/sites/default/files/microsites/ostp/PCAST/amp20_report_final.pdf
3

require support across the development pipeline to fully leverage current research and development

investments and infrastructure.

Scaling up advanced technologies from proofs-of-concept at the laboratory bench to world-class products 

on commercial shelves requires a steady stream of highly trained workers to bring the latest knowledge 

and skills into the workplace. A number of Federal programs captured in this document encourage strong 

industry involvement in manufacturing education and training, ensuring that today’s curricula meet 

tomorrow’s workforce needs.3

 

3

For more information, please see http://www.manufacturing.gov/ and the following reports by the President’s Council of 

Advisors on Science and Technology: Report to the President: Accelerating U.S. Advanced Manufacturing (October 2014) 

https://www.whitehouse.gov/sites/default/files/microsites/ostp/PCAST/amp20_report_final.pdf and Report to the President 

on Capturing Domestic Competitive Advantage in Advanced Manufacturing (July 2012) 

https://www.whitehouse.gov/sites/default/files/microsites/ostp/pcast_amp_steering_committee_report_final_july_17_201

2.pdf, and Report to the President on Ensuring American Leadership in Advanced Manufacturing (link above).
4

Manufacturing Technology Areas of Emerging Priority

Advanced manufacturing is enabled by a multitude of technologies. In this report, the Subcommittee on 

Advanced Manufacturing highlights five technology areas that are focuses of widespread interest and 

strong support among the Federal agencies involved in advanced manufacturing. These emerging 

technology areas are strong candidates for future investment and expanded collaboration between 

government, industry, and academia.

Advanced Materials Manufacturing

Description

Whether they be lightweight automotive components made from new alloys that are stronger than steel 

and only a fraction of the weight, or materials that have been engineered at the nanoscale to turn waste 

heat into electricity, advanced materials enable the production of new products with unprecedented 

functions. To fully capitalize on the emergence of new advanced materials, industry requires new tools 

and approaches to tailor their design and quickly produce them at scale. Advanced materials 

manufacturing cuts across a multitude of industries—such as automotive, aircraft, biomedical, and 

electronics—which are pillars of our national economy and also important to our national defense. This 

technology area leverages the historic leadership of U.S. industry in high-technology product 

manufacturing, as well as its significant intellectual leadership in materials simulation and 

nanofabrication.

Materials matter: the efficiencies of high-temperature turbine engines, biocompatibility of replacement 

joints and implants, operational life of advanced batteries, and sophisticated electronics that make our 

digital world possible are all determined by materials that have been invented and optimized for the 

application. These innovations shape today’s world and are essential for continued future innovation. Yet 

transitioning from an initial material discovery to commercial application typically takes decades. 

Recognizing the importance of advanced materials in supporting an innovation-driven U.S. manufacturing 

sector, the Administration introduced the Materials Genome Initiative4(MGI) in 2011 with the aim for the 

United States to discover, develop, manufacture, and deploy advanced materials twice as fast and at a 

fraction of the cost of current methods. This ambitious goal is within reach—some early successes5,6,7 have 

demonstrated that a systems-level approach to material design, optimization, and implementation can 

significantly reduce design time and cost while improving quality. The MGI is a holistic new approach to 

materials science that will greatly accelerate the pace of advanced materials manufacturing technology 

development because the properties of materials are almost always important to the manufacturing 

process or product.

The advanced properties of some materials are enabled by nanoscale features. The ability to scale the 

production of nanoscale materials, structures, devices, and systems in a reliable and cost-effective way is 

a key aspect of what is referred to as nanomanufacturing. The benefits of nanotechnology stem from the 

ability to tailor the key structures of materials at the nanoscale to enable new or improved properties; for 

 

4

https://www.mgi.gov/

5

Computational Thermodynamics: The Calphad Method, Cambridge University Press, Cambridge; B Kuehmann, B Tufts, P 

Trester, "Computational Design for Ultra High-Strength Alloy." Advanced Materials and Processes 2008, 37; New York, 2007; 

6

F Ronning, JL Sarrao, "Viewpoint: Materials Prediction Scores a Hit." Physics 2013, 109;

7 Horstemeyer, Integrated Computational Materials Engineering (ICME) for Metals: Using Multiscale Modeling to Invigorate 

Engineering Design with Science, Wiley-TMS, Hoboken, N.J, 2012.
5

example, to make materials stronger, lighter, more durable, more reactive, or better electrical conductors. 

Since 2001, the National Nanotechnology Initiative8(NNI) has served as the vehicle for coordinating 

nanotechnology research activities across the Federal Government. In recent years, a Nanomanufacturing 

Signature Initiative9 has brought together Federal agencies to address specific barriers to the scale-up of 

nanoscale materials systems, including those utilizing carbon nanomaterials in composites and 

nanocellulose.

Technical Challenges

The typical latency between the initial discovery of advanced materials and the ramp up from bench-scale 

production (grams) to full-scale, commercial manufacturing (kilograms, kilotons) is 10 to 20 years.10

Materials design and process development must be greatly accelerated to deliver timely solutions to 

important national needs, such as providing clean energy, enabling next-generation electronics, and 

strengthening our security and national defense. Although science and engineering have always provided 

models for developing new materials and processes, recent breakthroughs in materials modeling, theory, 

high-throughput computation, and data mining can now be exploited to significantly accelerate discovery 

and deployment of advanced materials while decreasing their cost.

Growth in materials characterization, modeling and simulation, and data analytics is underway; these new 

capabilities require continued support to realize the potential of advanced materials manufacturing. 

Lightweight structural composites, energy storage materials, and biomedical device materials are some 

of the materials that are often purposefully structured down to the nanometer scale. Better methods to 

understand their structure will enable us to determine the origins of improved performance when a new 

material is discovered, and to verify that the intended structure is obtained when new materials are 

designed. The high-quality data collected by these methods must be stored in repositories with broad and 

rapid access, which will fuel the development of data analytic approaches at massive scales, providing 

unprecedented opportunities to discover new materials and refine or improve existing ones. 

 

8

http://www.nano.gov/

9

http://www.nano.gov/NSINanomanufacturing

10 The National Academies of Science, Engineering, and Medicine. Integrated Computational Materials Engineering: A 

Transformational Discipline for Improved Competitiveness and National Security. The National Academies Press. 2008.
6

Figure 1. Lawrence Livermore National Laboratory researchers fabricated a graphene aerogel lattice by threedimensional (3D) printing into a predetermined architecture that improved its performance.

11

Research and development in support of a basis for pre-qualified material selection is only the beginning. 

The material must then be incorporated into products that can be efficiently manufactured at commercial 

scales. Current manufacturing process designs are typically not informed by a detailed understanding of 

the range of process conditions a material will experience; thus, the characterization and modeling of the 

manufacturing process itself emerges as a key challenge, and an essential element will be the availability 

of high-throughput, in-line metrology to collect data throughout the manufacturing processes. From this

data, models describing the process sequence will be developed, whether it be polymer extrusion, 

nanofabrication of electronics, nanocrystal solution growth, or the forming of sheet metal automotive 

parts. These models will provide design knowledge to accelerate the development of future processes 

and to reduce the margins needed for materials selection. To become valuable assets that enable closedloop process control and quality assurance, in-line measurement tools must be fast, economical, and 

sensitive to the nanoscale.

Finally, a manufactured product must be tested to ensure it meets performance targets and safety 

requirements. Improved characterization methods for materials and end-user performance will be 

required. Because new materials may have unforeseen hazards, it is critical to develop a system that 

ensures that potential environmental, health, and safety issues are addressed with a strategy that is 

grounded in the principles of risk assessment and of product life cycle analysis. 

 

11 Zhu, C., TY-J Han, EB Duoss, AM Golobic, JD Kuntz, CM Spadaccini, MA Worsley. "Highly compressible 3D periodic graphene 

aerogel microlattices." Nature Communications. 6 (2015): 6962.
7

Federal Investments

The current decade(s)-long delay between material discovery and deployment in commercial products, 

combined with industry’s increasingly shorter-term incentives to maintain cost parity, results in 

insufficient support for promising advanced materials manufacturing capabilities. The Federal 

Government must continue investments in basic research to drive innovation, while also turning the fruits 

of that investment into real advantages for industry, by mitigating the risk and delay inherent in 

transitioning to at-scale materials manufacturing through programs such as the NNI and MGI. Federal 

investments in advanced materials manufacturing cut across multiple agencies and impact every stage of 

the innovation lifecycle, from supporting cutting-edge research at U.S. universities and laboratories, to 

providing the infrastructure necessary to transition these advances from the laboratory to the 

marketplace. For example, Federal investments reported under the NNI12 provide support for 

nanotechnology research and development centers and networks, including the National Science 

Foundation’s (NSF’s) Center for High-rate Nanomanufacturing focused on high-rate, high-volume 

nanomanufacturing tools and process. Federal agencies participating in the MGI are engaging in a number 

of activities13 in support of MGI goals, including programs such as the Department of Defense’s (DoD’s) 

Automatic Flow for Materials Discovery, a U.S. Navy-funded multi-university research consortium home 

to a collaborative laboratory of scientists, technologists, and engineers sharing data and ideas to help 

equip the next generation materials workforce Other examples include the Department of Energy (DOE) 

Office of Energy Efficiency & Renewable Energy (EERE) Fuel Cell Technologies Office Database, which is 

supporting the integration of materials experimentation, computation, and theory by providing access to 

data that will accelerate the development of hydrogen storage materials; and the DOE Energy Materials 

Network for accelerated advanced materials development. Coordinated activities such as the 

Nanotechnology Signature Initiatives14 provide a framework for close and targeted program-level 

interagency collaboration in areas including nanomanufacturing, data infrastructure, and sensor 

development. It is imperative that Federal agencies coordinate in these areas and look for opportunities 

to partner with industry and academia. 

Federal agencies including DoD, National Institute of Standards and Technology (NIST), NSF, DOE, U.S. 

Department of Agriculture (USDA), National Aeronautics and Space Administration (NASA), and National 

Institutes of Health (NIH) intend to continue their support in fiscal year 2017 for advanced materials 

manufacturing across multiple fields. Two key goals include: (1) the development of data repositories and 

predictive software tools to facilitate the design of materials ranging from new structural metals to 

polymers that would enable directed self-assembly for new advanced electronic products; and (2) 

advanced sensor technology and nanofabrication tools to support the at-scale manufacture of material 

products including carbon-nanotube based composites, optical meta-materials, and biopharmaceuticals.

 

12 http://www.nano.gov/centers-networks

13 https://www.mgi.gov/activities

14 http://www.nano.gov/signatureinitiatives
8

Table 1. Selected examples of Federal investment in advanced materials manufacturing.

Lead(s) Title Scope

DoD DARPA Atoms to 

Product

This program of DoD’s Defense Advanced Research Projects Agency (DARPA) seeks to 

develop the technologies and processes required to assemble nanometer-scale 

components into systems, devices or materials that are at least millimeter-scale while 

maintaining “atomic-scale” behaviors and characteristics. (TRL 1/MRL 1) [A]

NSF Designing 

Materials to 

Revolutionize 

and Engineer 

our Future

This is the primary program by which NSF participates in the MGI for Global 

Competitiveness. This program supports activities that accelerate materials discovery 

and development by building the fundamental knowledge base needed to design and 

make materials with specific and desired functions or properties from first principles.

(TRL 1-2/MRL 1-2) [B]

NSF Materials 

Research 

Science and 

Engineering 

Centers

Materials Research Science and Engineering Centers provide sustained support of 

interdisciplinary materials research and education of the highest quality while addressing 

fundamental problems in science and engineering. These centers address research of a 

scope and complexity requiring the scale, synergy, and interdisciplinary interactions 

provided by a campus-based research center. They support materials research 

infrastructure in the United States, promote active collaboration between universities 

and other sectors, including industry and international institutions, and contribute to the 

development of a national network of university-based centers in materials research, 

education, and facilities. (TRL 1-2/MRL 1-2) [C]

NSF Directorate for 

Engineering: 

Advanced 

Manufacturing

The Directorate for Engineering supports fundamental research on manufacturing and 

building technologies across a wide range of materials and size scales, with emphases on 

efficiency, economy, and minimal environmental footprint. Research is supported to 

develop predictive and real-time models, novel experimental methods for manufacturing 

and assembly of macro, micro, and nanoscale devices and systems, and advanced sensing 

and control techniques for manufacturing processes. The Scalable Nanomanufacturing 

Program supports research on new manufacturing methods to overcome the scientific 

and engineering barriers that prevent the production of useful nanomaterials and 

nanostructures at an industrially relevant scale (TRL 1-3/MRL 1-3) [D]

NASA Physical Science 

Research 

Program

The Physical Science Research Program includes microgravity materials science research 

conducted on the International Space Station. NASA has recently initiated the 

MaterialsLab Program to execute research that will enhance our understanding of 

materials properties, enabling the development of higher-performing materials and 

processes for use both in space and on Earth. (TRL 1-3/MRL 1-3) [E]

DOC NIST NIST MGI In order to accelerate the discovery and development of new materials through 

utilization of the MGI paradigm, NIST is establishing the essential materials data and 

model exchange protocols and the means to ensure the quality of materials data and 

models, ultimately establishing new methods, metrologies, and capabilities necessary for 

accelerated materials development. Additionally, though its efforts to integrate these 

activities, NIST is working to test and disseminate its developed infrastructure and best 

practices to its stakeholders. (TRL 1-3/MRL 1-3) [F]

DOC NIST Center for 

Hierarchical 

Materials Design

The Center for Hierarchical Materials Design is a center of excellence for advanced 

materials research focusing on developing the next generation of computational tools, 

databases and experimental techniques to enable the accelerated design of novel 

materials and their integration to industry. (TRL 1-3/MRL 1-3) [G]

DOC NIST Material 

characterization 

for future 

computing 

systems

NIST is working to advance the measurements needed to support future electronics,

including pioneering research in molecular interfaces, condensed matter physics, and 

two-dimensional materials such as graphene. (TRL 1-4/MRL 1-3) [H]
9

Table 1. (Continued) Selected examples of Federal investment in advanced materials manufacturing.

Lead(s) Title Scope

DOE EERE Critical 

Materials 

Institute

This Energy Innovation Hub focuses on technologies that make better use of materials 

and eliminate the need for materials that are subject to supply disruptions. These critical 

materials (e.g., rare earth materials) are essential for U.S. competitiveness in clean 

energy. (TRL 1-7/MRL 1-7) [I]

DOC NIST NIST Center for 

Automotive 

Lightweighting

The objective of this center is to develop the measurement methodology, standards and 

analysis necessary for the U.S. auto industry and base metal suppliers to transition to 

advanced lightweight materials for auto body components without wasteful trial-anderror development cycles, and successfully transfer this technology to customers in 

industry. (TRL 1-4/MRL 1-4) [J]

DOE EERE National 

Laboratorybased 

Manufacturing 

Demonstration 

Facility

The Manufacturing Demonstration Facility (MDF) at Oak Ridge National Labs addresses

critical research, development and demonstration challenges in advanced manufacturing 

through peer reviewed, cost-matched technical projects. The MDF focuses on additive 

manufacturing and carbon fiber composites. (TRL 2-4/MRL 2-4) [K]

DoD DARPA STARnet The Semiconductor Technology Advanced Research Network (STARnet) program’s 

Function Accelerated nanoMaterial Engineering Center partners with leading U.S. 

microelectronics companies to explore and develop nonconventional nanomaterials, 

such as multiferroics, spintronics, and two-dimensional materials for advanced analog, 

memory, logic, and sensor applications. (TRL 3/MRL 3) [L]

DoD DARPA Tailorable 

Feedstock and 

Forming

This program seeks to develop a new composite material format (i.e., feedstock) and 

associated processing technologies (e.g., reconfigurable forming) to reduce 

manufacturing complexity and enable use of advanced materials for small parts weighing 

less than 20 pounds at costs competitive with aluminum. (TRL 3/MRL 3) [M]

NASA Game Changing 

Program

The Advanced Manufacturing Technologies project develops and matures innovative 

manufacturing processes and materials including: metallic joining, additive, composites, 

and digital manufacturing. The Nanotechnology Project is focused on the maturation, 

integration, and component level demonstration of high impact nanotechnologies for 

future use in NASA missions. (TRL 3-6/MRL 3-6) [N]

DoD DARPA Diverse 

Accessible 

Heterogeneous 

Integration

The goal of this program is to create a revolutionary capability in defense electronics to 

realize integrated circuits by combining chiplets of gallium nitride, indium phosphide, 

silicon, and other device materials and technologies at the chip scale, while making the 

capability broadly available to designers throughout the DoD. (TRL 4/MRL 4) [O]

[A] http://www.darpa.mil/program/atoms-to-product

[B] http://www.nsf.gov/funding/pgm_summ.jsp?pims_id=505073

[C] http://www.nsf.gov/funding/pgm_summ.jsp?pims_id=5295

[D] http://www.nsf.gov/funding/pgm_summ.jsp?pims_id=503287&org=CMMI&from=home

[E] http://www.nasa.gov/mission_pages/station/research/news/materialslab

[F] http://www.nist.gov/mgi/overview.cfm

[G] http://www.nist.gov/coe/advmat/index.cfm

[H] http://nist.gov/pml/div683/grp04/nedm.cfm, http://www.nist.gov/cnst/nne.cfm, and 

http://www.nist.gov/mml/msed/functional_polymer/DimMetNanofab.cfm

[I] http://cmi.ameslab.gov/

[J] http://www.nist.gov/lightweighting/

[K] http://web.ornl.gov/sci/manufacturing/mdf/

[L] http://www.darpa.mil/program/starnet

[M] http://www.darpa.mil/program/tailorable-feedstock-and-forming

[N] http://gcd.larc.nasa.gov/projects/advanced-manufacturing-technologies and 

http://gcd.larc.nasa.gov/projects/nanotechnology

[O] http://www.darpa.mil/program/diverse-accessible-heterogeneous-integration
10

The Energy Materials Network

In support of the MGI and advanced materials manufacturing, the Energy Materials Network (EMN) aims 

to accelerate the materials-to-market process by integrating materials development stages from 

discovery through functional design and qualification, while incorporating manufacturing processing,

scale-up considerations, and end-use performance. The EMN is composed of a broad set of national 

laboratory-led consortia for accelerated advanced materials research, development, and 

demonstration, where each consortium is focused on specific classes of materials and the most pressing 

challenges related to clean energy. These consortia will form the basis for a resource network of worldclass capabilities in materials design, synthesis, characterization, manufacturing, and digital data 

management and informatics. 

EMN Research Priorities Include:

(1) Integration of computational and experimental research: Increase access of computational 

resources to the experimental community, and vice versa, to accelerate both stages of 

research, development, and demonstration.

(2) Multi-scale computational tools: Enable the design of materials for specified lifetimes and 

reliabilities. Develop and experimentally validate tools that predict a material’s performance 

at service conditions.

(3) New methodologies and tools for modeling and validation of manufacturing processes: 

Develop a suite of validated predictive tools, sensors and diagnostics, and other 

methodologies to qualify the ability of manufacturing processes to reliably generate the 

requisite materials characteristics.

(4) Materials scale-up capabilities: Develop equipment and automation algorithms for the 

manufacture of novel materials, along with experimental and computational tools to predict 

material properties, at industry-ready scales.

(5) Digital data management and informatics: Develop digital data repositories of material 

properties that can be networked, are machine discoverable, and are accessible to data 

analytics algorithms that can rapidly identify unique trends or correlations. Harmonize digital 

data storage standards to be extensible, accessible, reliable, and interoperable. 

As part of this effort, DOE EERE will invest more than $40 million in fiscal year 2016 to establish the 

national laboratory-led consortia and fund competitive grant opportunities in the areas of lightweight 

materials, chemical reactions and catalysis, energy conversion materials, and coatings and packaging. In 

particular, these initial research efforts will focus on (1) low cost magnesium sheet alloys and processes 

compatible with automotive manufacturing; (2) next-generation catalysts for fuel cells that are free of 

the precious platinum group metals; (3) caloric materials that enable a paradigm shift in moving beyond 

today’s refrigerants for use in energy efficient, environmentally friendly heat pumping technologies; and 

(4) new coatings, thermally superior encapsulants, and glass alternatives that enable innovative, 

durable, and bankable photovoltaic module form factors.

In fiscal year 2017, more than $120 million in additional funding has been requested to continue efforts 

and expand scope of lightweight materials and chemical reactions and catalysis. These efforts will focus 

on (1) low cost precursors for carbon fiber, (2) more robust catalysts with increased conversion 

efficiencies for more cost competitive biofuels and bioproducts, (3) novel materials systems for 

production of cost-competitive renewable hydrogen through advanced water-splitting, and (4) 

advanced low pressure hydrogen storage technologies that exceed current energy densities.
11

Engineering Biology to Advance Biomanufacturing

Description

Engineering biology is the design and wholesale construction of new biological parts and systems, and the 

re-design of existing biological systems for tailored purposes. The field integrates engineering and 

computer-assisted design approaches with biological research, to harness the power of biological systems 

to manufacture products that are of benefit to mankind; for example, the antimalarial drug artemisinin 

and synthetic spider silk, which may be spun into materials stronger than Kevlar. Engineering biology 

leverages advances in synthetic biology, along with other novel technologies that enable the predictable 

design of biological systems. To date, engineering biology to advance biomanufacturing has mostly 

focused on large-scale processes (up to millions of gallons), where the engineered cells are used to 

produce a fuel, chemical, protein, or biomaterial. This is different than many biomedical applications of 

engineered cells in fields such as regenerative medicine (as described elsewhere in this document), where 

modest volumes of the cells themselves may be the product (for example, autologous stem cells for tissue 

engineering applications). It is becoming increasingly clear that advances in engineering biology (and 

synthetic biology) such as genome editing could be applied broadly for the manufacture of chemicals, 

materials, and cells. Engineering biology as a field evolved from the existing bioprocessing expertise within 

the United States (which enabled the production of enzymes and protein therapeutics), and incorporates 

new organism engineering technologies (including synthetic biology and rapid prototyping), 

standardization, and interoperability. This field is well positioned to accelerate the rate of introduction of 

new products manufactured using engineering biology to the market and grow the U.S. bioeconomy. 

The size of the U.S. bioeconomy is estimated at roughly $350 billion annually.15 Its growth is based in part 

upon rapid improvements in the design-build-test-learn cycle for creating new biological products, which 

include advances in genetic engineering, DNA sequencing, and high-throughput prototyping of biological 

systems, as well as the ability to quantitatively describe the behavior of biological systems. Discoveries 

such as clustered regularly-interspaced short palindromic repeats (CRISPR) have led to unprecedented 

precision in genome editing. Federal investment over the past decade has either directly or indirectly 

supported many of these advance through funding of centers, foundries, small businesses and individual 

researchers. The United States is currently a leader in engineering biology research and its supporting 

science and technology fields. However, further investment is needed to translate the development of 

these new tools into robust technologies that will support reproducible biomanufacturing, new chemicals 

that will replace petrochemical derived consumer products, and new materials that will support national 

security. Investment by the Federal Government in biomanufacturing associated with engineering biology 

has lagged behind other parts of the world, especially investments that deliberately leverage industry 

expertise and public-private partnerships, such as the European Commission’s “Framework Programmes.”

 

15 Industrialization of Biology: A Roadmap to Accelerate the Advanced Manufacturing of Chemicals (2015). Source: 

http://www.nap.edu/catalog/19001/industrialization-of-biology-a-roadmap-to-accelerate-the-advanced-manufacturing
12

Figure 2. (Left) Schematic of the core disciplines (white box), fundamental research (blue boxes), and applied 

research (tan boxes) underpinning advanced biomanufacturing. (Right). Synthetic biology can be used to engineer 

microbes to utilize new feedstocks, such as the sulfur shown in this artistic rendering. Federal investments in 

engineering biology have enabled such work. (Photo credit: Ginkgo Bioworks)

Technical Challenges

Biological systems are exquisitely complex, high-fidelity, self-replicating, adaptive, and responsive 

machines that utilize a wide range of starting materials and are refined by evolution. These features 

present intrinsic challenges and unique opportunities in engineering stable and robust biological systems 

for biomanufacturing purposes.

Evolution within the bioreactor is one of the inherent challenges to the design of reproducible, robust,

and stable biological processes for all of biomanufacturing. Whether at the genetic or epigenetic level, all 

biological systems are subject to evolutionary pressures. Multiple approaches to addressing the 

robustness and stability of biological processes used for manufacturing will be needed. These approaches 

include a clearer understanding of the biological mechanisms underlying DNA stability and repair, 

epigenetics, and evolution, as well as development of quantitative tools that enable the prediction of 

complex biological designs in a manufacturing environment. 

One goal of synthetic biology is the development of fully interoperable biological parts and processes—

the realization of this goal, which could greatly benefit biomanufacturing, will require a deeper 

understanding of the complexity of biological systems, followed by an expansion of the current design 

space. For example, the predictable control of gene expression in eukaryotes is inherently more difficult 

than gene expression control in simpler organisms such as E. coli. Several factors contribute to challenges 

in expression control, such as the complexity of the organization of nucleic acids in chromatin and the 

highly interconnected and redundant biological circuitry (regulatory networks, metabolic networks, etc.). 

Also, the context of a genetic part (where the part is placed in the genome, with what spacers or 

insulators) dictates its performance. Further, current biomanufacturing relies largely on using existing 

gene-editing enzymes and chromosomal building blocks for the development of biologically derived 

products. There is an opportunity to expand the design space, not only in development of new enzymes 

that have novel reactive capacity or new proteins that have novel biomaterial properties, but also to use 

novel types of nucleic acids and different paradigms for codon usage. This may even open up the 

possibility of developing living, responsive materials. Interdisciplinary approaches that include biology, 

biomaterials, physics, chemistry, computer science, and engineering will be needed to address these 

challenges, both in the initial design and development of the new enzymes, proteins, or materials and in 

the translation of these processes to manufacturing.
13

Unlike traditional chemical manufacturing, where the environment of the chemical can be used as a 

reliable predictor of its probability of reaction, biological manufacturing systems (e.g., cells) are extremely 

sensitive and adaptable to even modest fluctuations in the environment (e.g., the reactor conditions).

This makes it difficult to predict the performance of an organism in a production-scale bioreactor 

(potentially thousands to millions of liters) based on the performance of that same organism in laboratoryscale test tubes and shake flasks (5 to 50 mL), especially given the likely heterogeneities in heat and mass 

transfer at the larger scale. The fact that reactor conditions—whether in a laboratory shake flask or a 

thousand liter bioreactor—further influence the performance of the biological system complicates the 

ability to predict performance. Current approaches to address these challenges have relied on the 

development of rapid prototyping technologies that enable high-throughput screening of designs; these 

approaches can be improved upon as the failure mechanisms of the designs are fully explored. Ultimately,

it may be feasible to program the organisms to function as living “chemostats” or “biostats,” which sense

and respond to the reactor’s changing environment to self-optimize the manufacturing process and yields.

In conclusion, both a better understanding of how environment impacts organism performance (or 

phenotype) and better design and engineering tools for scale-up are needed to address this challenge.

Federal Investments

Federal agencies including DoD (Air Force, Army, Navy, and DARPA), DOE, Federal Bureau of Investigation 

(FBI), HHS NIH, NASA, NIST, NSF, and USDA National Institute of Food and Agriculture (NIFA) have invested

in engineering biology for the past several years. There is significant breadth in the focus of these agencies’ 

activities—from those focused on understanding biological complexity and enabling the development of 

novel technologies; to developing computational and automation tools that will facilitate the design, 

construction, and testing of novel engineered organisms; to a focus on agency mission-specific 

applications. 

In addition to efforts to further the technology, NSF-funded researchers are also actively exploring how 

advances in engineering biology and synthetic biology will intersect with society, much in the same way 

as was done for the field of nanotechnology as it advanced in the early 21st century. Programs at NSF such 

as the Science, Technology and Society program, in collaboration with the basic science and engineering 

programs, currently support research in areas of public perception, risk, regulatory science, and other 

aspects of the technology that impact society. Other agencies have also been active in their support of 

research in ethical, legal, and social implications associated with engineering biology. Collaboration 

between agencies to date has focused on shared concerns such as public perception, environmental risk, 

and review of the regulatory processes associated with recent advances in the science. Workshops that 

focus on the environmental impact and public perception of risk associated with different technologies 

(including gene drives, genome editing, and possible environmental release of photosynthetic organisms) 

have been cosponsored and attended by representatives from many of the agencies that are investing in 

advances in the science.

A number of workshops convened by both NSF and NIST have been held to examine the need for 

standards and their community adoption. NIST has made significant progress in the industrial/commercial 

sector in community building around standards development and adoption. 

Potential interagency collaborations to realize the commercial potential of this field include joint 

solicitations in areas such as: nutritional security; design of more efficient and scalable approaches to 

promote the bioeconomy; design of novel, high-performance materials; and development of 

manufacturing capabilities. Interagency efforts may further seek to leverage past Federal investments in 

various centers and foundries, to enable broader access to these high throughput facilities to more rapidly 

advance progress in the field. 
14

Table 2. Selected examples of Federal investment in engineering biology

Lead(s) Title Scope

NIH Various 

programs

Production of novel technologies, therapeutics, and natural products, along with cell 

based therapies using engineering biology tools. NIH supports investigator-initiated 

projects in this area in many institutes including the National institute of General Medical 

Services, National Institute of Biomedical Imaging and Bioengineering, National Institute 

of Diabetes and Digestive and Kidney Diseases, and National Cancer Institute. (TRL 1-

3/MRL 1-3) [A]

NSF Core funding 

programs

Programs, including Small Business Innovation Research, in the Directorates for

Engineering; Biological Sciences; Mathematical and Physical Sciences; Social, Behavioral, 

and Economic Sciences; and Computer and Information Science and Engineering. These 

core funding programs focus on basic research in the science and engineering of 

biotechnology, synthetic biology, including educational programs and programs focused 

on societal impact and risk assessment. (TRL 1-4/MRL 1-4) [B]

DoD (DARPA, 

Air Force 

Research 

Laboratory 

and Office of 

Scientific 

Research, and 

Army 

Research 

Office)

Various 

programs

DARPA’s Living Foundries effort seeks to develop open-access, rapid design and 

prototyping foundries focused on engineering biology for the production of chemicals 

and materials precursors. The Air Force invests in the use of synthetic biology tools for 

the production of targeted metamaterials, allowing designers to create materials with 

defined compositions and morphology for antennas, sensors, and other applications. The 

Office of Naval Research seeks to biofabricate diverse products, such as inorganic 

materials, electronic materials, and fuels. Additional basic science efforts, notably those 

supported by the Army Research Office, will be useful for future manufacturing 

strategies. (TRL 1-3/MRL 1-3) [C]

NSF Various 

Centers 

These centers—including the Synthetic Biology Engineering Research Center (ERC), the 

Center for Biorenewable Chemicals, Science and Technology Centers, and Expeditions in 

Computing—focus on integrating basic research and development of complex systems as 

well as workforce development. Some center activities include industrial collaborations. 

The Synthetic Biology ERC specifically included a thrust in understanding the relationship 

between this new field with the public (e.g., public acceptance, legal and ethical 

frameworks, potential environmental impacts, regulatory burden, biosafety and 

biosecurity). New centers are being evaluated according to criteria including the 

recognition of ethical, legal, and social implications. (TRL 1-3/MRL 1-3) [D]

NIST Foundational 

Measurements 

and Standards 

for Engineering 

Biology

NIST is working to develop and establish the tools and methods necessary to assure 

reliability and confidence in biological measurements impacting everything from genomic 

analysis and disease diagnostics to the development of cell therapies and microbial 

engineering. (TRL 1-5/MRL 1-5) [E]

NASA Synthetic

biological 

membrane and 

BioNutrients

This program seeks the biomanufacture of a wide range of chemicals, food, and materials 

that would eliminate the need to carry payload into space. Specific examples include a 

biomimetic lipid membrane for wastewater processing (and the ability to biologically 

regenerate it in-situ) and biological generation in-situ of key nutritional supplements. 

(TRL 2-3/MRL 2-3) [F]

DOE 

Bioenergy 

Technologies 

Office

Conversion 

R&D Program

Multiple efforts at the National Labs, as well as competitively funded projects within 

academia and industry. The focus is on engineering biology for the production of fuels 

and chemicals from lignocellulosic biomass and various waste feedstocks. (TRL 2-5) [G]

FBI Foundry’s 

Biosafety and 

Biosecurity

Committee 

and Synthetic 

Yeast 2.0 

Project

FBI tracks advances in engineering biology for the potential for biosecurity and dual use 

concerns. In support of these programs, FBI will provide insights and awareness on 

security topics such as dual use (intentional misuse of legitimate research/technology), 

illicit economies, criminal enterprise, domestic/international terrorism, exploitation, or 

abuse. (TRL/MRL levels not applicable) [Weblinks not available for these efforts.]
15

[A] http://grants.nih.gov/grants/guide/pa-files/PAR-13-137.html, http://grants.nih.gov/grants/guide/pa-files/PA-16-040.html, 

and http://grants.nih.gov/grants/guide/pa-files/PAR-15-285.html

[B] http://www.nsf.gov/funding/pgm_summ.jsp?pims_id=504863, 

http://www.nsf.gov/funding/pgm_summ.jsp?pims_id=501024, 

http://www.nsf.gov/funding/pgm_summ.jsp?pims_id=6673, 

http://www.nsf.gov/funding/pgm_summ.jsp?pims_id=503417, 

http://www.nsf.gov/funding/pgm_summ.jsp?pims_id=5324, and http://www.nsf.gov/eng/iip/sbir/topics/BT.jsp

[C] http://www.darpa.mil/program/living-foundries, http://www.onr.navy.mil/en/Science-Technology/Departments/Code34/All-Programs/warfighter-protection-applications-342/Biomaterial-Bionanotechnology.aspx, and 

http://www.onr.navy.mil/en/Science-Technology/Departments/Code-34/All-Programs/warfighter-protection-applications342/Synthetic%20Biology.aspx. Additional basic science efforts of note include the Institute for Collaborative 

Biotechnologies http://www.arl.army.mil/www/default.cfm?page=510 and http://devarajgroup.ucsd.edu/research/

[D] http://www.nsf.gov/funding/pgm_summ.jsp?pims_id=5502, http://www.nsf.gov/eng/iip/iucrc/home.jsp, and 

http://www.nsf.gov/od/oia/programs/stc/index.jsp

[E] http://www.nist.gov/mml/bbd/index.cfm

[F] http://gcd.larc.nasa.gov/wp-content/uploads/2015/12/FS_SSB_151217.pdf

[G] http://www.energy.gov/eere/bioenergy/processing-and-conversion
16

 

16 The term “foundry” is used to emphasize that a standardized set of tools, parts, and chassis organisms (e.g., analogous to a 

set of production molds) can be combined with a set of interchangeable genomic parts to churn out, at very highthroughput, a large variety of different fuel and chemical products. Reusing the base set of chassis for each new product 

minimizes the amount of the process that needs to be designed from scratch. The term “foundry” as used here has a 

distinctly different meaning than a purpose-built facility such as a steel foundry.

DOE Synthetic Biology Foundry

The commercial development of a new biobased renewable chemical can currently cost hundreds of

millions of dollars and take more than a decade to develop. Engineering biology offers the potential to 

dramatically reduce the lead time and cost of bringing new renewable fuels and chemicals to market 

using industrially-relevant organisms, while improving the carbon conversion efficiency to desired 

products.

An open source Synthetic Biology Foundry16 dedicated to engineering biology could provide the 

foundation for 21st century biomanufacturing by making available: 

 Open strain-construction capability

 High throughput capability to test thousands of organism designs per year 

 Significantly improved design-build-test-lean cycle over state-of-the-art

 Capabilities to optimize molecule production from milligrams to hundreds of grams scale 

 Partnerships with many companies to identify and develop industrially-relevant host organisms

 Resources for smaller/start-up companies to speed commercialization of new molecules and organisms

Based on these needs, DOE EERE intends to establish a National Laboratory-led Synthetic Biology 

(SynBio) Foundry to leverage fundamental capabilities developed across multiple national laboratories 

to create a robust design-build-test-learn cycle and scale-up resource for rapidly, efficiently, and costeffectively producing fuels and chemicals at scale using synthetic biology techniques. The Foundry will 

function as a multi-lab effort leveraging both existing and newly acquired world-class resources within 

the national laboratories while working with external stakeholders through competitive grant awards, 

cooperative agreements, and work for others; enabling partners to leverage the effort’s synthetic 

biology tools and expertise, ultimately expediting industrial adoption of the technology.

The SynBio Foundry will establish a robust set of biomanufacturing principles, which would develop and 

use standardized DNA elements and commercially relevant and optimized host organisms going beyond 

current yeast and E. coli paradigms. From this foundation, the SynBio Foundry will seek to develop 

improved systems capability, processes for predictable scale-up, machine learning and mechanistic 

models, and standards and interoperability protocols. The SynBio Foundry will deliver a set of designbuild-test-learn cycle tools and an organism development package that will be easily transferred to the 

biotechnology industry, enabling the scale-up of multiple, high-impact chemicals in multiple industriallyrelevant host organisms. 

The development of a SynBio Foundry will build on $3 million in seed funding beginning in fiscal year 

2016 with an additional requested $35 million in fiscal year 2017. The requested funding will leverage 

recently developed synthetic biology resources to improve efficiencies in the conversion of biomass to 

fuels and related products. Funding may be further enhanced by other agencies that choose to fund 

activities within the SynBio Foundry.
17

Biomanufacturing for Regenerative Medicine

Description

Regenerative medicine, and the clinical use of stem cells, has the potential to repair or replace 

dysfunctional, degenerating, or absent cells, tissues, and organs. Such developments may one day restore 

the form, function, and appearance to our severely injured service members, dramatically reduce waitlists 

for organ transplants, increase the availability of essential cell-based therapies, and possibly reduce 

healthcare cost for treatments. Additionally, engineered cells can be used to redirect immune function 

and enable the emergence of “immuno-oncology.” Microphysiological systems (“organ-on-a-chip”), a 

small living and working model of a specific tissue or organ type, can greatly accelerate screening of drug 

candidates, probe disease mechanisms, and explore novel therapies. To realize the full potential of 

regenerative medicine, active cells, tissues, and organs (such as cardiovascular, renal, and neurologic) 

must be bioengineered and manufactured at scale.

Figure 3. Manufacturing of a bioengineered vascular conduit. (Left) A human acellular vessel. (Right) Phase 2 

manufacturing system for bioengineered, human acellular vessel. (Photo credit: Humacyte)

The Federal Government invested $2.89 billion between 2012-2014 in regenerative medicine, primarily 

for the development of therapeutic techniques and technologies.17 While there has been a steady increase 

in funding to demonstrate the possibility of regenerative biologic solutions to some vexing health 

concerns, there is a critical and growing need to focus on process engineering to achieve manufacturing 

reproducibility to increase the reach of the emerging therapeutics.

Technical Challenges

A significant challenge for development of regenerative medicine products and therapies is that the field 

is still transitioning from an academic enterprise to an industry-based, commercial enterprise. This 

transition requires a rigorous focus on starting materials, process, and final product characteristics to 

assure that products are safe, effective, and have a known potency and predictable shelf-life. The 

continued maturation of the regenerative medicine field is dependent on designing and developing robust 

production-scale manufacturing techniques, a refined set of measurements and standards that provide 

confidence in the product, evolutionary governance, harmonized regulations, workforce development, 

and supply chain diversification to support responsible and rapid development of regenerative medicine 

(cell, tissue, and organ bioengineering) technologies.

Important progress has been made in the basics of cell-based therapy and diagnostics, including: obtaining 

 

17 U.S. Government Accountability Office. Regenerative Medicine: Federal Investment, Information Sharing, and Challenges in 

an Evolving Field. July 23, 2015. http://gao.gov/products/GAO-15-553.
18

high-quality starting cells under current good manufacturing practices, improving the understanding and 

ability to control cellular and tissue phenotype (particularly for stem cells), developing bench-level 

systems for making therapies from cells and/or cells within an extracellular matrix, and producing large 

banks of pluripotent stem cells.

A fundamental challenge is the development of appropriate growth media for cells, in order to grow cells 

at the necessary scale for practical therapies and to assure consistency of product. Current systems are 

too inefficient for suspension-grown cells, largely non-existent for adherent cells, and patient-specific for 

engineered tissue. Research on efficient, safe production of cells and engineered tissues at commercial 

scale is required to ensure that these precision therapies will be economically and technically achievable.

The regenerative medicine therapeutics industry can learn from the traditional biopharmaceutical 

industry, in terms of how to control manufacturing products and processes. For example, regenerative 

medicine and pharmaceuticals share some conceptual challenges including bioreactor control, continuous 

manufacturing, scale-up of cell culture, distributed manufacturing of small personalized batch therapies, 

starting materials, and the use of disposables in manufacturing. Further, a goal of cell-based 

bioengineering is to strive towards the process control methods currently in development for

pharmaceutical continuous manufacturing (as described elsewhere in this document). Although each cell 

and tissue product is fundamentally unique, their bespoke manufacturing processes may follow a 

common process governance structure where manufacturing activity is quantified, standardized, and 

monitored.

Manufacturing cell and tissue products is significantly more challenging than manufacturing 

biopharmaceuticals. This is because manufacturing release criteria for bioengineered cells, tissue, and 

organs are largely undefined; the mechanisms by which these living products produce their effects are 

poorly understood; and they contain active cells which continue to grow and evolve. Additional challenges 

for manufacturing cell-based products stem from the complexity of the product and the bioreactor 

process. These challenges include appropriate design of bioreactors for adherent cells; characterization 

of the product with measurements that predict the clinical effectiveness of the product; determining 

tolerances of variation in cell types; how to store, ship, and deliver product with a very short (hours-long) 

shelf life; and how to assess the purity of the product in minutes or hours, instead of days. Development 

of methods to address the long-term storage of cells as manufacturing inventory is essential to increase

their flexibility, reliability, and cost-effectiveness.

As a result of the inherent complexity of these products, even with the application of advanced 

measurement science, effective manufacturing will continue to rely to some degree on the spirit of “the

process is the product.” This time-tested axiom of biologics18 manufacturing emphasizes the importance 

of managing the local environment at every step, as well as the unique challenges for each cell or tissue 

type, particularly when the therapeutic interest relies on active living cells over time. Current processes 

are poorly controlled, inefficient, and often inadequate for growing cells in suspension culture or on 

micro-carriers, while large-scale processes to grow cells within their extracellular matrix do not yet exist.

 

18 Biologics can be composed of sugars, proteins, or nucleic acids or complex combinations of these substances, or may be 

living entities such as cells and tissues.
19

Federal Investments

The final commercial manufacturing process for any product is the purview and responsibility of the 

developer; however, Federal investments in development of generalizable approaches to common 

manufacturing design, development, scale-up, and scale-out challenges could serve to de-risk 

development of numerous products in the field. This may make the technology attractive enough for the 

pharmaceutical industry to adopt and use to develop a new class of therapeutics. One deliverable within 

five years could be a prototype for cell production on a larger scale: scaled-up, closed, and fully automated 

platforms with in-line environmental monitoring, continuous assays for cell phenotype/potency, 

cost/material efficiencies, and separations/purification systems for cells grown in suspension culture (e.g., 

red and white blood cells). Over ten years, adherent cells for organs (e.g., heart, liver, gut, lung) are 

desired, ideally within their appropriate matrices.

Ongoing programmatic funding continues from DoD, Food and Drug Administration (FDA), NIH, NIST, DOE 

National Nuclear Security Administration, NSF, and the Department of Veterans Affairs (VA) in developing 

the technologies that make up the regenerative medicine field.

Future support of regenerative medicine manufacturing technologies will continue to exhibit strong 

multidisciplinary and collaborative approaches. For example: 

 To manufacture specific tissues, a project team must have advanced engineering skills combined 

with a deep understanding of the physiology of those tissues and the organ systems in which 

those tissues function.

 Statistics and computational modeling will be critical for designing and testing the platforms 

that will shape the product development plan and the regulatory strategy.

 Controlling and characterizing the biologic activity through discovery, triggers, and terminations 

of the appropriate effector and control mechanisms at the individual cell and population levels 

will require the expertise of genomic scientists.

 A fundamental knowledge and understanding of developmental biology is required to deliver an 

adult phenotype and to regulate growth reproducibly over time.

 Efficiencies at each step are essential to keep costs and raw materials usage down, and to keep 

fragile products (i.e., cells, tissues) viable, while a constant focus on usability will ultimately help 

enable adoptability.

These technical challenges, among others, must be solved to advance this field into common medical use. 

Advancements in research and development (R&D) will be most efficiently translated to commercial 

products through close collaboration with the private sector.
20

Table 3. Selected examples of Federal investment in biomanufacturing for regenerative medicine.

Lead(s) Title Scope

NSF CBET Early Concept 

Grants for 

Exploratory 

Research

NSF’s Chemical, Bioengineering, Environmental and Transport Systems (CBET) division 

uses these exploratory research grants for Cellular Biomanufacturing to investigate key 

challenges in scale-up, such as efficiency of manufacture, reproducibility, and viability. 

(TRL 1-3/MRL 1-3) [A]

DOC NIST Advanced 

Manufacturing 

Technology

The Cell Manufacturing Consortium is currently funded to establish and strength 

industry-focused research consortia in order to identify future research directions and 

needs and create a roadmap for cell-based manufacturing which integrates research with 

the development of commercially viable manufacturing processes. (TRL 1-5/MRL 1-5) [B]

DOC NIST Measurements 

and Standards 

for Regenerative 

Medicine

NIST is developing fundamental measurement technologies (such as new image analysis 

technologies for cell characterization), collaborating with industry on immediate 

measurement needs (such as cell counting and viability), and developing international 

standards with industry and FDA that are necessary to enable the development of and 

the quality assurance of regenerative medicine products. (TRL 1-5/MRL 1-5) [C]

HHS FDA Mesenchymal 

Stem Cell 

Consortium

The Mesenchymal Stem Cell Consortium aims to develop strategies to facilitate the 

development and translation of stem cell-based regenerative medicine products. 

Because commonly used measures of cell identity and biological activity are often not 

well-correlated with and predictive of intended clinical outcomes, the consortium uses 

Mesenchymal Stem Cells as a prototype cell to identify more predictive measures to 

characterize cellular therapies. Such analytical techniques provide a potential approach 

to address variability issues presented by cell source and/or manufacturing conditions. 

(TRL 2-4/MRL 2-4) [D]

DoD (Armyled, Navy, 

Air Force), 

VA, NIH, and 

DHA

AFIRM The Armed Forces Institute of Regenerative Medicine (AFIRM) seeks to develop advanced 

restorative, diagnostic, and cell and tissue-based treatment options for our severely 

wounded service men and women. (TRL 2-7/MRL 1-6) [E]

DoD DARPA, 

HHS NIH, 

and FDA

Various 

Microphysiologi

cal Systems

programs

These programs are taking diverse approaches to develop microphysiological (“organ-ona-chip”) systems and determine the feasibility of an in vitro platform that uses human 

tissues to evaluate efficacy, safety, and toxicity of promising therapies. DARPA (TRL 

2/MRL 2), HHS NIH and FDA (TRL 4/MRL 3) [F]

HHS NIH 

NHLBI

Stem CellDerived Blood 

Products for 

Therapeutic Use 

Program

This program aims to address the scientific questions that remain despite considerable 

progress towards enabling and accelerating the use of stem cell-derived blood products 

as therapeutics. It also supports small business research to develop improved techniques 

and tools to enhance the production of clinically-relevant, functional stem cell-derived 

red blood cells or platelets in a more efficient and cost-effective manner. (TRL 4/MRL 3) 

[G]

HHS NIH 

NHLBI

Production 

Assistance for 

Cellular 

Therapies III

This is the continuation of a program to advance cellular therapy research in the areas of 

regeneration of damaged/diseased tissues, organs, biologic systems, and targeted 

treatments for serious diseases without effective therapies. This program provides 

qualified investigators with consulting, manufacturing, preclinical study, and regulatory 

expertise necessary for the development of novel cellular therapies in the area of heart, 

lung, and blood cellular therapy. (TRL 5/MRL 5) [H]
21

[A] http://nsf.gov/pubs/2015/nsf15065/nsf15065.jsp

[B] http://www.nist.gov/amo/amtech/index.cfm

[C] http://www.nist.gov/mml/bbd/cell-therapies.cfm

[D] http://www.fda.gov/BiologicsBloodVaccines/ScienceResearch/BiologicsResearchAreas/ucm127182.htm

[E] http://www.afirm.mil

[F] http://www.darpa.mil/program/microphysiological-systems and http://www.ncats.nih.gov/tissuechip

[G] http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-15-030.html

[H] http://www.fbo.gov/spg/HHS/NIH/NHLBI/NHLBI-ECB-HB-2016-09-JB/listing.html and 

http://www.fbo.gov/spg/HHS/NIH/NHLBI/NHLBI-ECB-HB-2016-08-JB/listing.html
22

 

19 http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-15-004.html

Bioreactors for Reparative Medicine Program

Bioreactor technology, which supports biologically-active environments, is an essential part of the 

research and development pathway. Recent trends have created a large potential market for 

breakthrough medical solutions led by tissue-engineered medical products. Yet, research successes for 

a variety of simple bioreactor systems have shown sustained, but limited, in vivo function. The NIH has 

an ongoing program to support multidisciplinary small business teams in the development of complex, 

three-dimensional engineering systems for growing heart, lung, or bone marrow tissue.19 Integrated 

devices will require a diverse array of scientific principles and technologies. Ultimately, bioreactor 

designs should provide the most physiologically relevant environment to promote correct threedimensional tissue growth and maintenance, which is also efficient, safe, and economical. Such devices 

should be made commercially available and be widely disseminated to researchers for application in 

translational science. These devices could support, for example, bioengineered trachea, vascular grafts, 

and other hollow-organ tissues that have made entry into clinical studies. Sophisticated and more 

standardized bioreactors will be critical for developing these and other complex, neo-organ 

technologies.

Bioreactor systems that deliver standardized, robust, and reliable lots of engineered tissue at scale for 

clinical and/or industrial use are not widely available. At a minimum, these platforms will need 

continuous monitoring (with high-content, functional assays) along the entire production line, 

automation to increase predictability and speed while minimizing possibilities for contamination, and 

supply chains for raw materials that are reliable and affordable. Additional needs and opportunities to 

grow and mature precursor cells at scale include devices for the growth of stem cells, which should 

integrate stem cell expansion with subsequent mechanical stimulation to enhance functional 

differentiation for use in complex tissues. Some tissues may require electrical pacing and conditioning 

as well. Another challenge for some cellular propagation is to establish stable protocols that do not 

require feeder layers and conditioned medium. At the organ level, tailored lung tissue bioreactor design 

plans are needed for gas and blood exchange interfaces, whereas design of cardiac tissue bioreactors 

might emphasize electrical and mechanical forces. Additionally, it may be possible to engineer threedimensional bone marrow organs that permit extensive blood stem cell self-renewal and hematopoiesis 

in vitro. Given the complexity of engineered constructs—often containing a combination of cells, 

scaffolds, and other factors—special challenges exist for tissue engineered product characterization, 

growth, and manufacturing protocol.
23

Advanced Bioproducts Manufacturing

Description 

The United States currently relies on the average use of more than 19 million barrels per day of petroleum 

for fuels and as a feedstock to make products ranging from chemicals to plastics to many everyday items. 

Bioproducts—high-value chemicals, bioreagents, materials, fuels, and other biobased intermediates 

derived from renewable biological resources such as agricultural and forest waste—hold strong promise 

to reduce this petroleum use and serve as the backbone of an emerging bioeconomy.

The United States currently uses about 400 million dry tons of biomass annually for fuels, heat, materials, 

and industrial enzymes with significant environmental and economic benefits.20 U.S. revenues from 

industrial biotechnology (fuels, enzymes, and materials) reached at least $125 billion in 2012 with 1.5 

million direct jobs across all sectors of the supply chain.

21 This economic impact has the potential to further 

grow the bioeconomy by an additional $100 billion by 2030, with the creation of an additional one million 

jobs, particularly in rural areas where feedstocks are grown.22 Bioproducts will reduce greenhouse gas

emissions and provide a stable domestic source for these products.

While the United States has made great strides in promoting the use of sustainably-produced feedstocks 

to fuel economic activity and growth, the bioeconomy is still in its early stages. Significant work remains 

to increase the use of bioproducts to replace a variety of petroleum-based fuels and products, make those 

bioproducts more cost-effective relative to petroleum-based products, and further improve the 

sustainability and environmental benefits of bioproducts.

 

20 https://www.whitehouse.gov/sites/default/files/microsites/ostp/national_bioeconomy_blueprint_april_2012.pdf

21 http://www.biopreferred.gov/BPResources/files/EconomicReport_6_12_2015.pdf

22 http://www.biomassboard.gov/pdfs/farb_2_18_16.pdf
24

Figure 4. A supply chain approach to advanced bioproducts manufacturing.

23 (Photo credit: DOE BETO)

Technical Challenges 

The U.S. Billion-Ton Update24 reports that the United States has the resources to produce significant 

volumes of bioproducts and biofuels, potentially replacing up to 30 percent of current petroleum use with 

renewable biomass in the next 15-20 years. Under those projections, the bioeconomy could provide 

feedstocks for the production of biofuels required by the Renewable Fuel Standard25 and beyond. For the 

United States to realize the full potential of a domestic bioeconomy, key barriers need to be addressed 

across the entire supply chain, including feedstocks, conversion, and integration.

26 Each of these areas 

face significant manufacturing challenges, as described here.

To provide a sustainable, reliable, and cost-effective supply of feedstocks appropriate for a variety of end 

uses, existing barriers such as cost, land use, and regional and source variations must be overcome. The 

inherently diverse nature of biomass feedstocks requires a fully-integrated logistics supply chain that 

includes harvesting practices, biomass preprocessing, transport, and storage systems tailored to the 

feedstock type. Today, the existing biofuels industry primarily employs conventional logistics systems 

developed for traditional agriculture and forestry systems. These are designed to move biomass short 

distances for limited-time storage (less than one year). Expanding usable feedstocks to include crop 

residues and purpose-grown energy crops can provide the raw materials for the manufacture of future 

bioproducts with superior environmental benefits. Conventional logistics systems are not well configured 

for a diverse, much larger set of feedstocks that are spread over larger areas. This currently creates unique 

transportation requirements, especially in areas with medium to low yields. Advanced logistics systems 

designed to deliver feedstocks with predictable physical and chemical characteristics, longer-term stability 

 

23 http://energy.gov/sites/prod/files/2015/04/f22/mypp_beto_march2015.pdf

24 http://energy.gov/eere/bioenergy/downloads/us-billion-ton-update-biomass-supply-bioenergy-and-bioproducts-industry

25 http://www.epa.gov/renewable-fuels-standards-program

26 http://energy.gov/qtr
25

during storage, and high-capacity bulk material handling characteristics can facilitate economically viable

transport over longer distances and ultimately lower the costs of delivery. Additionally, each conversion 

technology places specific demands on the feedstock quality and quantity that must be delivered to the 

biorefinery. 

The blending of feedstocks offers a possible solution to quality, cost, and regional diversity issues. 

Feedstock blending allows a biorefinery to collect less of any one feedstock, enabling biorefineries to pay 

a lower average price while reducing supply risk. An improved blend of feedstocks can meet refinery 

requirements such as lignin content while reducing the impact of potential supply disruptions, ultimately 

making more feedstock available from and across regions. Feedstock blending also hedges against

unintended supply disruptions to any one blend component. Preliminary results from two lignocellulosic 

biomass conversion facilities suggest that blending multiple preprocessed feedstocks enables the 

acquisition of higher biomass volumes and reduces feedstock variability to meet biorefinery in-feed 

specifications, while delivering feedstock to the biorefinery at $80/dry metric tonne.

27

Conversion is the overall process of converting delivered feedstocks into the variety of final fuels and 

products at the biorefinery; efficient, low-cost, reliable conversion technologies are a key requirement for 

scaling up advanced bioproduct manufacturing. Efficiently introducing feedstocks into a pressurized 

reactor at large scale is problematic due to feedstock inconsistencies, such as varying properties of 

moisture, ash, and contaminants. In addition to challenges of introducing dry feedstocks, new reactor 

processes and designs are needed for the feeding of wet feedstocks, such as waste cellulosic and wet algal 

biomass slurries into reactors. The preprocessing of these feedstocks to remove contaminants and ash 

must be tailored to the needs of the conversion catalysts and demonstrated at large enough scale to 

indicate commercial viability.

Conversion technologies range from low-temperature biological catalysis (including organisms) to hightemperature, high-pressure chemical catalysis. The development of a single conversion technology from 

TRL 5 to TRL 8 can take ten years in a supportive policy environment.28 To accelerate this timeline, 

dedicated investment in catalyst development is necessary. For example, a growing number of 

researchers are developing the tools and fundamental understanding required to engineer biological 

systems (as described elsewhere in this document). Continued expansion of the bioeconomy requires 

reduction in the time and cost associated with the design-build-test-learn cycle and ultimate scale-up of 

conversion technologies. 

Finally, feedstock and process variations can cause fouling, plugging, corrosion, or other disruptions in 

biorefinery operations. The lack of operational data on fully integrated systems over extended periods of

time presents large scale-up risks, thus representing a major barrier to a successful biomanufacturing 

industry. An improved understanding of process integration is essential for: (1) characterizing the complex 

interactions that exist between unit operations, (2) identifying impacts of inhibitors and fouling agents on 

catalytic and processing systems over commercial operation timeframes, and (3) enabling the generation 

of predictive engineering models that can guide process optimization or scale-up efforts and enable 

process control. 

Federal Investments 

A robust and stable supply chain connecting diverse feedstocks to production facilities and markets is 

 

27 From the Sugar Platform to Biofuels and Biochemicals, Final Report for the European Commission Directorate, General 

Energy, April 2015

28 From the Sugar Platform to Biofuels and Biochemicals, Final Report for the European Commission Directorate, General 

Energy, April 2015
26

essential to the success of advanced bioproduct manufacturing at scale. Supported by public-private 

collaborations, the Federal Government is continuing its systematic effort to expand the sustainable 

production and use of biomass by supporting research and development activities across the entire supply 

chain. The broad array of Federal activities is coordinated through the Biomass Research and 

Development Board co-chaired by the DOE and USDA.

29

Initial Federal investments have helped establish some of the requisite processes and platforms needed 

to generate high-value intermediate and end-use products, supporting the growth of bioproduct 

manufacturing in the United States. Examples include genomic research on bioenergy feedstock crops and 

unique processes and microbes to convert feedstocks into bioproducts, exploration of sustainable 

management practices, development of biomass conversion processes and expansion of bioenergy 

infrastructure, and cost/benefit estimates of renewable energy and byproducts production. These 

investments leverage corporate research and private investment, leading to more applications, lower 

costs, and superior sustainability of future renewable fuels and chemicals.

Additional public-private investment focused on cross-cutting bioproducts manufacturing capabilities is 

needed, for example to:

 demonstrate commercial-scale biomass feedstock delivery systems taking advantage of the 

regional feedstock supplies of wastes, residues and energy crops;

 establish common processes and chemical platforms leading to the efficient yield of high-value 

intermediates that can be used in the production of a diverse array of end-use bio-products (for 

example, hydrolysis of mixed biomass streams to sugar intermediates for further downstream 

processing to fuels and chemicals); and 

 support commercialization through risk reduction and scale up of common process steps (such as 

feedstock pre-processing and handling) that will benefit a wide array of processing configurations 

to meet the needs of the diverse feedstocks and end products. 

Such multi-stakeholder investment will serve to increase U.S. leadership in the innovation of agricultural 

bioproducts manufacturing for industrial adaptation and commercial applications and grow new 

agroindustry.

 

29 http://www.biomassboard.gov/
27

Table 4. Selected examples of Federal investment in advanced bioproducts manufacturing.

Lead(s) Title Scope

NSF Chemical, 

Bioengineerin

g, 

Environmental 

and Transport 

Systems

Energy for 

Sustainability 

Program

Fundamental research on innovative approaches that lead to the intensification of 

biofuel and bioenergy processes is an emphasis area of this program. Includes 

biological, thermochemical, or thermocatalytic routes for the conversion of 

lignocellulosic biomass to advanced biofuels beyond cellulosic ethanol, microbial fuel 

cells and production of hydrogen, hydrocarbons and lipids from autotropic, 

phototrophic or heterotrophic microorganisms. (TRL 1-3/MRL 1-3) [A]

DOE 

Bioenergy 

Technologies 

Office

Feedstock 

Logistics and 

Advanced Algal 

System Program

This program supports intramural and extramural applied R&D to develop new 

feedstock logistics technologies and landscape design systems that reduce costs 

along each step of the bioenergy supply chain including algal production systems. 

(TRL 2-5/MRL 2-5) [B]

DOE 

Bioenergy 

Technologies 

Office

Conversion R&D 

Program

This program supports intramural and extramural R&D on conversion pathways using 

varied feedstocks and technologies for the production of higher value bioproducts, in 

support of increased production of biofuels in a biorefinery. Work includes both 

cellulosic and algal-derived bioproducts, to improve the overall economics of fuels, 

and development of downstream processing, to upgrade biomass derived 

intermediates into fuels and bioproducts. (TRL 2-5/MRL 2-5) [C]

USDA NIFA Agriculture and 

Food Research 

Initiative

Programs

NIFA supports extramural research, development, and demonstration of the whole 

supply chain for the sustainable production of bioenergy and bioproducts, including 

feedstock production and conversion processes and nanocellulosic materials and 

products. Efforts also include technical, economic and life-cycle analysis, and 

education and workforce development to support the growing bioeconomy. (TRL 2-

7/MRL 2-7) [D]

USDA NIFA, 

Agriculture 

Research 

Service, and 

Forest Service

Various programs Intramural and extramural basic and applied research in conversion (fuels, chemicals, 

products). (TRL 2-6/MRL 2-6) [E]

DOE 

Bioenergy 

Technologies 

Office

Demonstration 

and Market 

Transformation

These extramural pilot- and demonstration-scale integrated biorefinery projects are

cost-shared with industry to de-risk first-of-a-kind technologies and prove out 

integrated processes at scale. Acceptable biorefinery demonstrations include 

production of bioproducts in support of the overall economics of the biorefinery.

(TRL 6-8/MRL 6-8) [F]

USDA Rural 

Development

Biorefinery 

Commercialization 

Assistance 

Program

This program provides commercialization assistance (loan guarantee) to first-of-akind biorefineries. (TRL 8-9/MRL 8-9) [G]

DoD Navy/ 

Defense 

Production 

Act

Advanced Drop-in 

Biofuel Production 

Project

Commercial Scale alternative fuel production in integrated biorefineries, cost shared 

with DOE and USDA. (TRL 8-9/MRL 8-9) [Weblinks not available for these efforts.]

[A] http://www.nsf.gov/funding/pgm_summ.jsp?pims_id=501026&org=CBET&from=home

[B] http://www.energy.gov/eere/bioenergy/biomass-feedstocks and http://energy.gov/eere/bioenergy/algal-biofuels

[C] http://www.energy.gov/eere/bioenergy/processing-and-conversion

[D] http://nifa.usda.gov/program/agriculture-and-food-research-initiative-afri

[E] http://nifa.usda.gov/funding-opportunity/biomass-research-and-development-initiative-brdi, 

http://www.ars.usda.gov/main/main.htm, and http://www.fs.fed.us

[F] http://www.energy.gov/eere/bioenergy/integrated-biorefineries

[G] www.rd.usda.gov
28

 

30 http://www.reeis.usda.gov/web/crisprojectpages/0225162-integrated-biorefinery-at-the-domtar-plymouth-north-carolinapulp-mill.html

Integrated Biorefinery Demonstration at Semi-Works Scale

The pulp and paper industry is the largest producer and user of biomass energy in the United States, 

representing the ideal platform to launch the emerging integrated biofuel and bioproduct industries. In 

2012, the Joint USDA-DOE Biomass Research and Development Initiative awarded $7 million, costshared with industry, to enable a demonstration of an integrated biorefinery at the semi-works scale, 

while allowing the participating company to increase its revenue streams and preserve 121 jobs.

Domtar, a Fortune 500 company, is the largest manufacturer of uncoated freesheet paper in North 

America, processing well over 20 million green tons of biomass per year. Building on work initiated by 

Domtar in 2010, the initiative funded a three-year project to construct a semi-works demonstration 

plant. This involved the demonstration at-scale of two main technologies, acid hydrolysis of biomass 

and lignin removal technology, to convert low-value mill side streams and waste streams into highervalue sugar, tall oil, and lignin intermediates for drop-in markets. (The logistics for feedstock for woodbased biorefineries are already commercially available through an established supply chain and is nearly 

all derived from sustainably-grown trees.) Ultimately, Domtar successfully installed a commercial-scale 

lignin separation plant in Plymouth, North Carolina.

30
29

Continuous Manufacturing of Pharmaceuticals

Description

Continuous manufacturing is the integration of multiple manufacturing process systems into a single 

system, based on model controls, to enable continuous product flow and recovery as input raw materials 

are added to the manufacturing process. Pilot studies in the pharmaceutical and biotechnology industries

suggest that continuous manufacturing may have a multitude of benefits in these industries, such as: 

reducing the manufacturing facility footprint by 10 to 100 times; eliminating intermediate product 

batches and their associated storage and testing; reducing the amount of incoming raw materials and final 

product waste; streamlining manufacturing processes and shortening manufacturing cycle times; 

increasing production yields and overall product manufacturing efficiency; improving product quality with 

advanced control systems; and enabling real-time release testing. Continuous manufacturing may reduce

manufacturing costs, which currently consume as much as 27 percent of the revenue for many 

pharmaceutical companies, by up to 40 to 50 percent. 

Continuous manufacturing strategies are widely used in many private sectors including food, chemical, 

and petroleum industries. However, the broad adoption of such strategies has lagged behind in the 

pharmaceutical and biotechnology industry because of the product development paradigm. This 

paradigm does not emphasize process optimization due to the uncertainty concerning the clinical 

outcome and the historical regulatory environment that drove production towards fixed “lock-in” 

processes for the entirety of the product lifecycle. The broad industry interest in continuous 

manufacturing includes small-molecule and biologic manufacturers; contract manufacturing 

organizations; and equipment, instrument, control, and excipient supply companies. The implementation 

of end-to-end continuous manufacturing (i.e., the integration of drug substance and drug product 

manufacturing into a single continuous process) requires leveraging U.S. capabilities in pharmaceutical 

sciences, systems engineering, and real–time sensing.

Continuous manufacturing promises to improve the agility, flexibility, and robustness in the manufacture 

of pharmaceuticals, helping to mitigate the public health threat arising from drug shortages. The advent 

of personalized medicine, as well as drugs seeking orphan drug designation, necessitates the production 

of smaller batches of drugs due to the smaller target-patient populations. A similar concept applies to 

medical countermeasures development for low probability-high consequence events—such as those 

caused by chemical, biological, radiological/nuclear, and emerging infectious disease threats—as these 

medical countermeasures likely do not have high commercial promise except to the Federal Government

for national preparedness purposes. The many benefits of continuous manufacturing (e.g., through 

flexible platform technologies that utilize modular or plug-and-play equipment) may enable the rapid, 

domestic production of medical countermeasures, enhancing U.S. preparedness and response. 
30

Figure 5. Schematic diagram of continuous manufacturing, including a photograph of a first-of-its-kind continuous 

finished dosage form process for a recently approved cystic fibrosis drug.31 The footprint of this tableting facility is 

approximately 4 percent of that of the footprint of a traditional facility needed to do the same process. (Photo 

credit: Vertex)

Technical Challenges

Challenges to continuous manufacturing adoption include both process development technical hurdles 

and scientific and regulatory challenges involved with navigating away from a “batch-centric” regulatory 

paradigm.

The development of a continuous manufacturing design requires a systems-based approach and the 

integration of multiple existing technologies. Advances in process modeling and simulation may facilitate 

the optimization of equipment configurations, manufacturing routes, and advanced control systems; as 

well as connecting the impact of material properties with model parameters to generate models that are 

transferrable from one formulation to the next. Modular or plug-and-play type equipment with re-usable,

flexible, or interchangeable parts that can be connected in a different order are needed to enable flexible 

manufacturing and platform technologies for continuous manufacturing. This is especially important for 

certain specialty (orphan or breakthrough) drugs in the pharmaceutical industry, which may be 

manufactured using equipment that can be configured to produce small quantities of a diverse portfolio 

of products. 

The manufacture of a traditional small molecule drug substance usually requires many novel chemical 

synthesis steps, necessitating multiple rounds of isolation and purification, adding complexity to the 

design of a flexible integrated continuous process. The switch to continuous processing may necessitate 

new process technologies and synthetic routes to streamline the system. To accomplish this, individual 

 

31 http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm453565.htm and 

http://connect.dcat.org/blogs/patricia-van-arnum/2015/09/18/manufacturing-trends-in-continuous-mode
31

drug manufacturers currently require expensive, highly specialized equipment that may not be 

commercially available; these bespoke and typically proprietary investments generate information 

asymmetries in the field, hindering the development of platform technologies. Development of flow 

chemistry toolboxes, including highly selective chemistries that allow the use of simple and effective 

continuous purification technologies, is needed. 

The manufacture of larger molecule biotechnology products utilizes biological substrates to produce the 

final product (e.g., perfusion and fermentation systems). The established configuration of perfusion 

bioreactor-cell retention devices will likely remain conceptually similar in the future, but improvements 

are necessary to realize a truly continuous platform. These include the development of robust and stable 

cell lines that maintain high productivity over prolonged time periods (e.g., 2-3 months), design of media 

formulations to support high cell density, and optimization of bioreactor conditions to provide the high 

cell density at high viability and positive growth rates. Various enabling technologies, such as automatic

cell density control, efficient oxygenation and ventilation, and foam control, must be developed and 

optimized. Significant development is still needed for continuous downstream purification and drug 

product formulation technologies. For example, although laboratory- and pilot-scale continuous 

chromatography systems exist, scale-up remains a challenge. Novel downstream unit operations are also 

needed, such as continuous viral inactivation and removal. An important design requirement for all 

continuous downstream unit operations is that they must operate over prolonged periods under stringent 

sterility control conditions, which will require novel and unconventional solutions.

The seamless integration of real-time analytics throughout the synthesis and downstream processes is 

needed for reliable, long-term continuous operation adhering to tight quality specifications. 

Physicochemical parameters such as UV absorbance, pH, conductivity, flow rate, pressure, and 

temperature are reliably monitored in continuous systems using technologies that are well established in 

batch processing. On the other hand, biotechnology processes require additional process analytical 

technologies to provide real-time product quality attributes (e.g., activity, aggregation, glycosylation, 

impurity level). In fact, bioprocessing equipment, instrumentation, and sensors for monitoring, 

controlling, and sampling are often customized to meet product-specific needs, restricting their 

widespread adoption in other continuously manufactured product lines. 

Whereas localized autonomous systems are sufficient for individual unit operations in batch processing, 

continuous manufacturing integrates unit operations over the entire process chain, requiring global

coordination by a supervisory control system. Such a system must be able to perform oversight functions 

such as process monitoring, process optimization, and exception handling. The software and hardware 

systems should provide a high degree of automation and require minimal operator involvement. 

Standards for aligning local and global control with an improved user interface and the capability for 

integration with new unit operations will also facilitate continuous manufacturing.

Although the continuous input of an active pharmaceutical ingredient in the manufacturing of a drug

product formulation has seen some success (as has the production of biotechnology products by means 

of continuous perfusion bioreactors), true end-to-end continuous manufacturing from reagents to drug 

product at a commercial scale has yet to be realized. Economic drivers also need to be considered, as the 

current inventory of available batch manufacturing facilities may discourage investment in continuous 

manufacturing. 
32

Federal Investments

While promising at the laboratory scale, the technologies and equipment enabling continuous 

manufacturing at the commercial scale are not widely available or accessible. Consequently, continuous 

manufacturing technology is currently in need of further interest and resources from industry, 

government, and regulatory authorities to translate proofs-of-concept to widespread commercial 

adoption. Future Federal investments may focus on broadly applicable and enabling technologies, 

demonstrating their return-on-investment required for mainstream adoption. Process equipment and 

instrumentation necessary for the continuous manufacturing of large molecules will likely come from 

smaller, non-traditional biotechnology suppliers seeking to expand their market share, and therefore 

could be incentivized by government support.
33

Table 5. Selected examples of Federal investment in continuous manufacturing of pharmaceuticals.

Lead(s) Title Scope

NSF Engineering 

Research Center

for Structure 

Organic 

Particulate 

Systems

This effort aims to build the fundamental science base for the rational design, 

development and manufacturing of structured organic composite particulate products 

for the pharmaceutical, food, and agrochemical industries. (TRL 1-4/MRL 1-4) [A]

DOC NIST Biomanufacturing 

Program

The NIST Biomanufacturing Program supports the U.S. biopharmaceutical industry 

through the delivery of standards, measurement science, and tools to enable the more 

efficient characterization and manufacture of protein-based drugs. (TRL 2-5/MRL 2-5) 

[B]

DoD DARPA Pharmacy On 

Demand and 

Biologicallyderived Medicines 

On Demand

These efforts aim to enable timely response to patient needs and emergent threats by 

developing miniaturized and distributed manufacturing platforms to produce multiple 

small-molecule active pharmaceutical ingredients and protein therapeutics on demand. 

(TRL 3/MRL 3). [C]

BARDA Development 

Through Phase 3: 

Novel antiviral for 

the Treatment of 

Influenza

Exploratory studies to incorporate continuous manufacturing technology into Janssen 

products under contract to Biomedical Advanced Research and Development Authority 

(BARDA). (TRL 7/ MRL 8) [D]*

BARDA Advanced 

Development of 

Rempex 

Carbavance

Exploratory studies to incorporate continuous manufacturing technology into 

Carbavance manufacturing process under contract to BARDA. (TRL 7/ MRL 8) [E]*

FDA CDER Advanced 

Research and 

Development of 

Regulatory 

Science

The Center for Drug Evaluation and Research (CDER) approved the first 

pharmaceuticals produced by continuous manufacturing and by additive 

manufacturing, and recently issued a broad-area announcement with BARDA to 

support emerging and enabling technologies for continuous manufacturing. (TRL 

5/MRL 6 for emerging technologies, TRL 7/MRL 8 for enabling technologies) [F]

FDA CDER Development of 

Modeling Tools 

for Quality Risk 

Management

This effort aims to develop process simulation and modeling platforms for integrated 

pharmaceutical manufacturing processes. Specifically, the project will focus on 

manufacturing processes for solid based drug products, which comprise the majority of 

pharmaceutical products. The tools developed during this project will be used to 

facilitate the risk assessment of manufacturing processes and control strategies. 

(TRL 6/MRL 7) [G]

[A] http://www.nsf.gov/awardsearch/showAward?AWD_ID=0540855, http://erc-assoc.org/content/erc-structured-organicparticulate-systems , and http://ercforsops.org/

[B] http://www.nist.gov/mml/bmd/biomanufacturing.cfm

[C] http://www.darpa.mil/program/battlefield-medicine

[D] http://www.hhs.gov/about/news/2015/09/28/hhs-sponsors-development-of-drug-for-hospitalized-influenzapatients.html#

[E] http://www.hhs.gov/about/news/2014/02/05/hhs-funds-drug-for-bioterrorism-antimicrobial-resistant-infections.html

[F] http://www.fbo.gov/spg/HHS/FDA/DCASC/FDABAA-15-00121/listing.html

[G] https://grants.nih.gov/grants/guide/rfa-files/RFA-FD-14-083.html

* The candidate products are at an HHS technology readiness level of 6/7 according to the following website 

(https://www.medicalcountermeasures.gov/federal-initiatives/guidance/integrated-trls.aspx) and estimated to correspond to 

7/8 according to the TRL/MRL table found in Appendix B. 
34

A Whole-of-Government Approach to Continuous Manufacturing of Pharmaceuticals

The Federal Government coordinates and fosters a logical progression of technology maturity towards 

commercial adoption in the field of continuous manufacturing of pharmaceuticals. Federal investments 

in the basic and emerging science and technology for continuous manufacturing are provided by the 

National Science Foundation, National Institutes of Health, National Institute of Standards and 

Technology, and Department of Defense. These investments are well positioned for continued evolution 

from proof-of-concept to TRL 6 or higher, which can then be transitioned within the private sector in 

collaboration with the Biomedical Advanced Research and Development Authority (BARDA) for the 

continued advanced development of BARDA priority medical countermeasures towards regulatory 

approval. Additionally, these Federal investments serve as workforce development opportunities for 

scientists and engineers who shepherd technologies through the transition into commercial continuous 

manufacturing. The Food and Drug Administration (FDA) plays an integral regulatory role from early 

product development through drug approval. In this role, the FDA provides not only the regulatory 

guidance and oversight, but also collaborates with drug developers to evolve the regulatory paradigm 

from batch-centric to continuous manufacturing-centric using scientific and data-driven methodologies 

to facilitate future approvals, thereby encouraging commercial adoption of continuous manufacturing.
35

Manufacturing Technology Areas of Existing Priority

In addition to the priority emerging technology areas highlighted elsewhere in this document, there are a 

number of topics which are the subject of Federal agency interest that have been announced publicly, 

either for potential future investment or as the focus of an existing Manufacturing Innovation Institute.

Areas of Interest for Potential Future Investment

The following announcements have been made by agencies as areas of interest for potential future 

Federal support. Please see the weblinks for additional information about these technology areas and 

their current status.

 NIST released a Federal Funding Opportunity notice to establish and operate one or more National 

Network for Manufacturing Innovation (NNMI) Institutes.32 As an open-topic competition, NIST 

will accept applications for a proposed Institute in any area of advanced manufacturing, so long 

as it does not duplicate the technical scope and programs of current Institutes within the NNMI 

or technical focus area(s) of on-going Institute funding opportunities. Like the other institutesthat 

are part of the NNMI, the NIST institutes will be private-public partnerships that foster 

collaboration among industry, academia, nonprofits and government agencies. Through the 

institutes, these stakeholders will work to accelerate U.S. innovation and increase 

competitiveness by investing in industrially relevant, cross-cutting advanced manufacturing 

technologies and processes.

 DoD issued a Request for Information33 to consider input from industry, academia, prospective 

non-profit organizations, and other stakeholders as part of an effort to select and scope the 

technology focus areas for as many as two more Manufacturing Innovation Institutes. Each 

institute is launched with Federal funding typically in the range of $70 million to $120 million, 

leveraging a minimum of 1:1 non-Federal co-investment, over a five to seven years. Technical 

areas of interest include:

o Advanced Machine Tools and Control Systems

o Assistive and Soft Robotics

o Bioengineering for Regenerative Medicine

o Bioprinting across Technology Sectors

o Certification, Assessment and Qualification

o Open topic (Request for Information responders may suggest)

o Securing the Manufacturing Digital Thread – Cybersecurity for Manufacturing

 The DOE Advanced Manufacturing Office has recently completed a series of workshops to identify 

potential topics for future investments, including up to 2 new Manufacturing Innovation Institutes 

(with anticipated solicitation release in early 2016). The technical areas covered in the workshops 

are:

 

32 http://www.nist.gov/amo/nnmi/2016competition.cfm

33 The solicitation number is RFI-AFRL-RQKM-2016-0009 and can be viewed on the FedBizOps website:

http://www.fbo.gov/spg/USAF/AFMC/AFRLWRS/RFI-AFRL-RQKM-2016-0009/listing.html
36

o Chemical and Thermal Process Intensification34

o Sustainability in Manufacturing35

o High Value Roll-to-Roll Manufacturing36

o Materials for Harsh Service Conditions37

Foci of the Manufacturing Innovation Institutes

The following technology areas have already been the subject of significant Administration effort, such as

through the existing Manufacturing Innovation Institutes that make up the NNMI (as of February 2016). 

The Federal Government intends to continue supporting these areas along the technology development 

pipeline, in order to leverage the distinctive innovation capabilities to-date for the advancement of 

agencies’ missions and overall U.S. industry competitiveness.

Additive Manufacturing

Additive Manufacturing is defined as a process of joining materials to make objects from threedimensional model data, usually layer upon layer, as opposed to subtractive manufacturing 

methodologies. Additive manufacturing can encompass metals, polymers, and electronics. Additive 

manufacturing can apply to a range of structural and functional materials and to a range of components 

for defense and energy applications. An advantage of additive manufacturing is that parts can be 

fabricated as soon as the three-dimensional digital description of the part is created, thus establishing a 

new market for on-demand, mass customization manufacturing. Most importantly, these processes 

minimize material waste and tooling requirements, as well as drastically compress the supply chain. In 

addition, novel components and structures can be produced from additive manufacturing processes that 

cannot be cost effectively produced from conventional manufacturing processes such as casting, molding, 

and forging.

Established in partnership with DoD and headquartered in Youngstown, OH, America Makes is the 

National Additive Manufacturing Innovation Institute serving as the national accelerator for additive 

manufacturing and 3D printing. This Institute is developing the standards, tools, education, and research 

required to accelerate the U.S. manufacturing sector into a dominant, global economic force. Specifically, 

five technical areas are addressed in the America Makes Additive Manufacturing Technology Roadmap: 

design, material, process, value chain, and additive manufacturing genome. 

Additional information can be found at: https://americamakes.us/about/overview

Advanced Composites

Lightweight, high-strength, and high-stiffness composite materials have been identified as a key 

crosscutting technology in U.S. clean energy manufacturing, with the potential to reinvent an energy 

efficient transportation sector, enable efficient power generation, and increase renewable power 

production. Priority challenges include: high costs; low production speeds (long cycle times); high 

manufacturing energy intensity of composite materials; recyclability; and a need to improve design, 

 

34 http://energy.gov/eere/amo/downloads/process-intensification-workshop-september-29-30-2015

35 http://energy.gov/eere/downloads/workshop-sustainability-manufacturing-january-6-7

36 http://energy.gov/eere/amo/downloads/workshop-high-value-roll-roll-hv-r2r-manufacturing-innovation-december-2-3-2015

37 http://energy.gov/eere/amo/downloads/workshop-materials-harsh-service-conditions-november-19-20-2015
37

modeling, and inspection tools for composites to meet commercial and regulatory demands.

To accelerate the technological advances and research in manufacturing needed to reach cost and 

performance targets—from constituent materials production to final composite structure fabrication—

the President announced the Institute for Advanced Composite Materials Innovation (IACMI). Supported 

by DOE’s Advanced Manufacturing Office and focused on research, development, and demonstration 

programs, IACMI brings together industry, research institutions, and state partners committed to 

accelerating development and adoption of manufacturing technologies for low-cost, energy-efficient 

manufacturing of advanced polymer composites. 

Additional information can be found at: http://iacmi.org/about-us/

Digital Manufacturing and Design

Digital manufacturing is the use of an integrated, computer-based system comprised of simulation, threedimensional visualization, analytics and various collaboration tools to create product and manufacturing 

process definitions simultaneously. Design innovation is the ability to apply these technologies, tools, and 

products to re-imagine the entire manufacturing process from end to end.

The Digital Manufacturing and Design Innovation Institute (DMDII), headquartered on Chicago’s Goose 

Island, is in a public-private partnership with the DoD, acting as a first-of-its-kind manufacturing applied 

research and development lab.

DMDII focuses on enterprise-wide utilization of the digital thread, enabling highly integrated design and 

manufacturing of complex products in order to reduce time and cost, as well as accelerate the pace of 

new products coming to market. Processes developed within DMDII that create an open and collaborative 

environment will help retain supply chain knowledge and improve capabilities to produce low volume, 

complex systems. 

Additional information can be found at: http://dmdii.uilabs.org/the-institute/vision

Flexible Hybrid Electronics

Flexible hybrid electronics preserve the full operation of traditional electronic circuits, but in novel flexible 

architectures and form factors that are conformal, allowing for bending, stretching, or folding. These 

highly functional devices can be attached to curved, irregular, and often stretched objects, and have the 

potential to expand traditional electronic packaging to new form factors, enabling new classes of 

commercial and DoD technologies. Examples include medical devices and sensors, sensors to monitor 

structural or vehicle performance, sensors interoperating through the Internet or as sensor clusters to 

monitor physical positions, wearable performance or information devices, robotics, human-robotic 

interface devices, and lightweight human-portable electronic systems. 

In support of this technology area, the DoD established NextFlex, an end-to-end, sustainable 

Manufacturing Innovation Institute focused on flexible hybrid electronics manufacturing technology, 

headquartered in San Jose, CA. The Institute’s core focus is on manufacturing assembly and integration, 

system integration demonstrations, innovative printing processes, thin device processes, materials 

manufacturability and scale-up, modeling and design tools, and education and training. 

Additional information can be found at: http://www.nextflex.us/nnmi/

Integrated Photonics

Integrated photonics encompass the integration of multiple lithographically-defined photonic and 

electronic components and devices (for example, lasers, detectors, waveguides and passive structures, 
38

modulators, electronic controls, and optical interconnects) on a single substrate with nanoscale features.

The key benefits of integrating these components include simplified system design, enhanced systems 

performance, reduced component space and power consumption requirements, and improved 

component performance and reliability while enabling new capabilities and functionality with lower costs. 

Today’s integrated photonics manufacturing community is made up of a collection of interrelated, largely 

independent businesses, organizations, and activities that together form an ecosystem, but one that 

currently lacks the organization and aggregated market strength needed to efficiently innovate 

manufacturing technologies for cost-effective design, fabrication, testing, assembly, and packaging of 

integrated photonic devices. 

To address this, the DoD established the American Institute for Manufacturing Integrated Photonics, 

headquartered in Rochester, NY. Reflecting industry priorities, the Integrated Photonics Manufacturing 

Innovation Institute’s principal concerns will be initially five critical topics: computer-aided design tool 

development; chip fabrication process design kit development; automated testing, assembly, and 

packaging; prototype demonstrations; and workforce development through focused education and 

training. 

Additional information can be found at: http://www.aimphotonics.com/overview/

Lightweight Metals

Lightweight and modern metals offer significant system performance enhancements and greater energy 

efficiency. The availability of advanced lightweight metals is a pervasive factor in improving the 

performance of many systems in defense, energy, transportation and general engineered products, each 

representing large sectors of the U.S. economy. Moreover, lightweight metals have additional applications 

in areas such as wind turbines, medical technology, pressure vessels, and alternative energy sources.

The Lightweight Innovations for Tomorrow (LIFT) Institute, headquarter in Detroit, MI, was established 

through a public-private partnership with the DoD to advance our national fabricated metal product and 

transportation equipment subsectors. The Institute brings together the Federal and State Governments, 

leading manufacturers, professional societies and organizations, universities, and other research partners. 

The institute’s mission is to serve U.S. manufacturing by acting as the bridge between basic research and 

final product commercialization of new, advanced lightweight materials and innovative manufacturing 

technologies and practices. 

Additional information can be found at: http://lift.technology/

Smart Manufacturing

Smart manufacturing—the convergence of information and communications technologies with 

manufacturing processes to drive unprecedented real-time control of energy, productivity, and costs 

across factories and companies—was identified by the President’s Council of Advisors on Science and 

Technology38 as one of the highest-priority manufacturing technology areas in need of Federal

investment. Harnessing advanced sensors, controls, information technology processes and platforms, and 

advanced energy management systems, smart manufacturing has the potential to drive energy efficiency 

and U.S. manufacturing competitiveness in a range of sectors. 

The Advanced Manufacturing Office at DOE released a Request for Information in October 2015 to stand 

 

38 President’s Council of Advisors on Science and Technology. Report to the President: Accelerating U.S. Advanced 

Manufacturing. October 2014. 

https://www.whitehouse.gov/sites/default/files/microsites/ostp/PCAST/amp20_report_final.pdf
39

up a Clean Energy Manufacturing Innovation Institute around the topic of Smart Manufacturing—the 9th 

Institute in the National Network for Manufacturing Innovation. Representing roughly $70 million in 

Federal investment, this public-private partnership will address mid-TRL R&D needs for the software and 

physical hardware necessary to support Smart Manufacturing, as well as soft barriers like education, 

supply chain dissemination, integration with existing infrastructure, and workforce. 

Additional information can be found at: http://www.energy.gov/articles/energy-department-announces70-million-innovation-institute-smart-manufacturing

Revolutionary Fibers and Textiles

Scientific advances have enabled fibers and textiles with extraordinary properties including strength, 

flame resistance, and electrical conductivity. These types of fibers and textiles are composed of specialty 

fabrics, industrial fabrics, electronic textiles, and advanced textiles. These technical textiles are built upon 

a foundation of synthetic, natural fiber blends and/or multi-material fibers that have a wide range of 

applications, in both the defense and commercial sectors, which go beyond traditional wearable fabrics. 

The DoD announced the competition for a Revolutionary Fibers and Textiles Manufacturing Innovation 

Institute on March 18, 2015. The Federal Government expects the Revolutionary Fibers and Textiles 

Manufacturing Innovation Institute to support an end-to-end ecosystem in the United States for 

revolutionary fibers and textiles manufacturing and include domestic manufacturing development 

facilities to scale up manufacturing processes. The Revolutionary Fibers and Textiles Manufacturing 

Innovation Institute positions the domestic industrial base to recapture and secure U.S. leadership in the 

technical and smart-textile marketplace. 

Additional information can be found at: http://www.manufacturing.gov/rft-mii.html

Wide Bandgap Electronics

Wide bandgap semiconductor materials allow power electronic components to be smaller, faster, more 

reliable, and more efficient than their silicon-based counterparts. These capabilities make it possible to 

reduce weight, volume, and life-cycle costs in a wide range of power applications. If widespread adoption 

of these technologies is realized in even a limited set of applications, then 40,100 GWh (137 TBtu) of 

electrical power savings in the United States could be achieved annually. With higher volume production, 

the high cost of wide bandgap substrate and epitaxial deposition, which is currently tied to small 

production volumes and high manufacturing costs, is expected to decrease.

As part of the NNMI, the DOE Advanced Manufacturing Office is currently supporting PowerAmerica. Led 

by North Carolina State University, PowerAmerica focuses on making wide bandgap semiconductor 

technologies cost-competitive with the silicon-based power electronics that are currently used. The 

Institute is establishing a collaborative community that will create, showcase, and deploy new power 

electronic capabilities, products, and processes that can impact commercial production, build workforce 

skills, enhance manufacturing capabilities, and foster long-term economic growth in the region and across 

the nation. Additional information can be found at: http://www.poweramericainstitute.com/
40

Manufacturing Education and Workforce Training Priorities

Description

U.S. manufacturing industries employ over 12 million people39 and have diverse workforce needs, drawing 

skillsets from engineering, computer science, biology, mathematics, economics, and psychology, among 

other disciplines. Manufacturing requires highly-skilled craftsmen, technicians, designers, planners, 

researchers, engineers, and managers, whose specialized educations span the spectrum from theory to 

practice. 

Manufacturing is typically carried out on expensive, specialized equipment that is often impractical to 

accurately duplicate or simulate in an educational setting. Therefore, it is important for manufacturing 

industries to play an active role in the educational process to ensure proper training for the next 

generation of their workforce. Research collaborations connecting engineers from industry with university 

students, involvement of companies in equipping laboratories and designing curricula for community 

college programs, and hosting “how it’s made” field trips to factoriesfor elementary and secondary school 

students all help to bridge from theory to practice and orient students towards the actual needs of the 

companies for which they will be working.

While manufacturing jobs are high-paying, high-technology jobs, individual career choices are often based 

on an obsolete view of manufacturing. This dynamic puts a premium on providing educational experiences 

at every level of education, from primary school to postgraduate, that accurately reflect the challenges 

and opportunities of advanced manufacturing. 

Federal Investments

Federal agencies have innovated education and workforce training programs to address these key 

challenges, and resulting investments range from specialized technician training at community colleges to 

student education in graduate research programs at world-leading research universities.

The NSF’s Advanced Technological Education program supports collaborations between academic 

institutions and industry to improve the education of technicians for high-technology fields at two-year 

community and technical colleges, with components that reach down to the secondary school and up to 

the undergraduate university levels. The program, launched in 1993 in response to the Scientific and 

Advanced Technology Act of 1992, currently supports seven advanced manufacturing Advanced 

Technology Education Centers.40 Advanced Technology Education Centers have developed curricular 

materials and skills standards in collaboration with industry, provided professional development for 

secondary school teachers and both 2-year and 4-year faculty, and developed clearly articulated career

pathways into the supported industries. For example, The Florida Advanced Technological Education 

Center links employers with a network of ten community and state colleges across Florida. The Center’s 

state-wide Engineering Technology Associate Degree Program focuses on a set of core courses covering 

introductory computer-aided drafting, electronics, instrumentation and testing, processes and materials, 

quality, and safety, and integratesindustry validated stackable credentialsinto a 2-year technician training 

curriculum. Over 140 companies have participated in these education and outreach activities since the 

founding of the center in 2004.

The Manufacturing Innovation Institutes of the NNMI connect talented and experienced manufacturing 

professionals with upcoming generations of students to provide real-world training for their future 

 

39 www.bls.gov/iag/tgs/iag31-33.htm#workforce

40 http://www.nsf.gov/funding/pgm_summ.jsp?pims_id=5464 and www.atecenters.org/advanced-manufacturing-technologies
41

manufacturing workforce. For example, the Lightweight Innovations for Tomorrow Manufacturing 

Innovation Institute has launched an advanced manufacturing apprenticeship learning pathways model 

with Jefferson Community and Technical College in Louisville, Kentucky. This new initiative will both 

develop a pipeline of trained entry-level workers and implement an accelerated, modularized and skillsbased program for those in the current workforce who are in need of continuing education and training.

Many local companies, from Fortune 100 companies to small and medium-sized manufacturers, have 

expressed interest in training and hiring apprentices through the program. The Institute has also 

established the Right Skills NOW program for computer numerical control machinist training with 

Vincennes University. This accelerated program of study transitions veterans to jobs as skilled computer 

numerical control machinists and incorporates national credentials from the National Institute for 

Metalworking Skills. Veterans participating in the Right Skills NOW program will train at the newly built 

Gene Haas Training Center, a state-of-the-art, 23,000 square foot facility. Partner companies mentor 

trainees during training and graduates are immediately placed in positions in industry after program 

completion.

The Departments of Labor and Education have deployed nearly $1 billion through the Trade Adjustment 

Assistance Community College and Career Training (TAACCCT) grant program41 to strengthen 

manufacturing curricula at community colleges across the country and train America’s workforce. Funded 

programs range from short-term certificate programs to associates degrees and many of the TAACCCT 

programs offer stackable credentials that provide skills for rapid entry in to the workforce and upgrading 

skills on the job. Manufacturing subsectors addressed include medical devices, additive manufacturing 

and3D printing, advanced manufacturing, advanced materials, robotics and mechatronics, and more 

traditional occupational areas, such as computer numerical control machining and welding. Henry Ford 

Community College, in Dearborn, Michigan, is the lead of the Multi-State Advanced Manufacturing 

Consortium project and provides an example of the numerous TAACCCT manufacturing collaborations 

currently under way. This project will establish a model that is applicable to many industries. The strategy 

incorporates a competency-based, industry-driven, credentialed manufacturing curriculum; new 

instructional design and delivery systems to accelerate and contextualize learning; improved student 

support, success, and placement strategies; and administrative structures to support instructional 

redesign. Five of the top seven global automobile manufacturers and other major manufacturers are 

collaborating in the program.

The Jobs and Innovation Accelerator Challenge in Advanced Manufacturing—a joint program of the 

Departments of Labor, Commerce, and Energy and the Small Business Administration—supports local 

efforts to spur job creation by connecting innovative small suppliers with large companies, linking 

research with start-ups that can commercialize new ideas, and providing trained workers with the skills 

they need to help their companies capitalize on business opportunities. Similarly, the Departments of 

Commerce and Labor and the Delta Regional Authority support the Make It In America grant program.

Make It In America grants encourage businesses to build and/or expand their operations in the United 

States through multiple mechanisms, including targeted training and employment activities that support 

the skill-building and career advancement needs of U.S. workers, thereby strengthening America’s highlyskilled and diverse workforce. For example, Make It In America grantee South Carolina Appalachian 

Council of Governments supports workforce development, economic development, and job creation 

through electronic access to industry-recognized, high-technology educational programs using a variety 

of electronic tools, increasing efficiency in industry supply chain management and Innovation Engineering 

and increasing human capital capacity through training activities with embedded industry credentials.

 

41 https://www.doleta.gov/taaccct/
42

South Carolina Appalachian Council of Governments is connecting current and former students with 

interested employers through networks formed by instructors, corporate representatives, and other 

community contacts.

More recently, the Department of Labor invested $175 million through the American Apprenticeship 

Initiative grant competition to train and hire more than 34,000 new apprentices in high-growth and hightechnology industries in the next five years. 27 of the 46 American Apprenticeship Initiative grants include 

advanced manufacturing as a targeted sector.

The NSF’s Industry/University Cooperative Research Centers (I/UCRC) Program42 and the Engineering 

Research Center (ERC) Program43 bring an industry-focused orientation to academic research that enables 

students to be productive employees from their first day on the job. I/UCRC Program graduate and 

undergraduate students perform precompetitive research on industry-validated projects in multimember, sustained collaborations between industry, academia, and government. NSF provides a financial 

and procedural framework for membership and operations, in addition to best practices learned over 

decades of fostering public-private partnerships. As an example, one of the ten advanced manufacturing 

Centers currently supported is the I/UCRC Program on Intelligent Maintenance Systems, a partnership 

with over 40 current member companies and the Universities of Cincinnati, Michigan and Texas and the 

Missouri University of Science and Technology. This partnership utilizes advanced sensing, the Internetof-Things, and data analytics to enable products and systems to achieve near-zero breakdown 

performance. Funding is largely provided by industry and the project agenda is jointly determined by 

Center leadership and industry members, with over 100 projects conducted over the life of the Center.

According to the 2012 Measuring the Economic Impacts of the NSF Industry/University Cooperative 

Research Centers Program: A Feasibility Study,

44 the Center delivered its members over $800 million in

combined benefits over its first ten years.

Whether in or out of school, significant learning takes place in informal settings where access to learning 

tools and mentors accelerates independent study. Recognition of the importance of bringing this modality 

to manufacturing is growing, including White House Maker Faires

45 that highlighted the importance of the 

maker movement and demonstrated today’s do-it-yourself as tomorrow’s “Made in America.” In recent 

years, the affordability and capabilities of desktop manufacturing equipment and the availability of 

makerspaces have all increased, making it easier for people to design and fabricate products and bring 

them to market. Individuals are self-identifying as makers and, in doing so, are forming communities of 

interest that facilitate the sharing of technical information and launching of crowdfunding campaigns to 

scale production of their products and become entrepreneurs. Investments in research to develop the 

next generation of low-cost tools and technologies for design and fabrication will be required to continue 

to advance the variety of things that individuals can create and produce in the United States. Finding 

innovative approaches to help makersscale more easily from small batch manufacturing to larger volumes 

will be critical to the growth and sustainability of these business in the United States.

 

42 http://www.nsf.gov/eng/iip/iucrc/program.jsp

43 http://www.nsf.gov/funding/pgm_summ.jsp?pims_id=5502

44 https://www.ncsu.edu/iucrc/PDFs/IUCRC_EconImpactFeasibilityReport_Final.pdf

45 www.whitehouse.gov/nation-of-makers
43

 

46 http://nsf.gov/pubs/2015/nsf15061/nsf15061.jsp

47 https://www.whitehouse.gov/blog/2015/12/10/makers-military

Among such efforts, NSF’s Cybermanufacturing research and educational awards46 are helping to define 

the requirements for an application-based manufacturing infrastructure that can be accessed by makers

through the web. University classrooms and laboratories provide a nearly ideal environment for 

researching, developing and exercising such innovations. In addition, DARPA's Manufacturing 

Experimentation and Outreach Two program enhances defense readiness by developing and 

demonstrating new manufacturing training, tools and materials for those who will be called on to use, 

maintain, and adapt high-technology systems in low-technology environments. DARPA envisions that 

project-based curricula employing this program’s design and prototyping tools will teach a deeper 

understanding of high-technology systems and better enable future competence in the maintenance and 

adaptation of such systems through the manufacture of as-designed components or the design and 

manufacture of new components. Through this program, for example, DARPA and the U.S. Navy installed 

a pilot fabrication laboratory, or Fab Lab, at the Mid-Atlantic Regional Maintenance Center in Norfolk, 

Virginia, working with the Fab Foundation.47 These programs are examples of how Federal agencies are 

leveraging existing assets and resources and investing in the development of new tools and technologies 

to democratize design, prototyping, and manufacturing skills and capabilities for individuals throughout 

the United States.
44

Conclusions

U.S. advanced manufacturing supports long-term economic prosperity, security, and growth, as well as 

the missions of the Federal agencies of the Subcommittee for Advanced Manufacturing. To unleash the 

advanced manufacturing industries of the future, and ensure U.S leadership in these industries, concerted 

efforts of government, industry, and academia must focus on the key technologies that underpin U.S. 

competitiveness. In particular, collaborative pre-competitive research and development should leverage

common assets to the benefit of all stakeholders, overcoming the significant development cycle costs that 

are impractical for any single entity to bear alone.

This report provides a collection of emerging technology areas in advanced manufacturing that are 

priorities for Federal members of the Subcommittee for Advanced Manufacturing and that are strong 

candidates for focused Federal investment and public-private collaboration. These areas include:

 Advanced materials manufacturing

 Engineering biology to advance biomanufacturing

 Biomanufacturing for regenerative medicine

 Advanced bioproducts manufacturing

 Continuous manufacturing of pharmaceuticals

This report further captures a number of existing technology areas, which are already the topics of

substantial existing investments (such as the Manufacturing Innovation Institutes) or that may be the 

subject of future programming. 

In recognition of the critical role of education and workforce training in building and sustaining 

Tomorrow’s advanced manufacturing industries, an array of Federal programs that encourage strong 

industry involvement are described.
45

Appendix A. Federal Participants in the NSTC SAM

The National Economic Council 

The National Economic Council was established in 1993 to advise the President on U.S. and global 

economic policy. The National Economic Council has four principal functions: to coordinate policy-making 

for domestic and international economic issues, to coordinate economic policy advice for the President, 

to ensure that policy decisions and programs are consistent with the President's economic goals, and to 

monitor implementation of the President's economic policy agenda. More information is available at

https://www.whitehouse.gov/administration/eop/nec. 

Office of Management and Budget

More information is available at https://www.whitehouse.gov/omb/.

The Office of Science and Technology Policy 

The Office of Science and Technology Policy (OSTP) was established by the National Science and 

Technology Policy, Organization, and Priorities Act of 1976. OSTP’s responsibilities include advising the 

President in policy formulation and budget development on questions in which science and technology 

are important elements; articulating the President’s science and technology policy and programs; and 

fostering strong collaborations among Federal, state, and local governments, and the scientific 

communities in industry and academia. The Director of OSTP also serves as Assistant to the President for 

Science and Technology and manages the National Science and Technology Council (NSTC). More 

information is available at https://www.ostp.gov.

Department of Agriculture

Worldwide, the bioenergy and bioproducts industries are emerging as new and rapidly growing sectors; 

given the high productivity of the U.S. agricultural sector, biobased product manufacturing is a significant 

opportunity for the United States to support growth of a bioeconomy. Expansion of the bioeconomy has 

the potential to sustainably harvest and utilize one billion tons of new biomass in the United States 

without affecting existing farm and forestry product markets, growing the current market five-fold over 

the next fifteen years and adding $500 billion to the annual bioeconomy.

The agricultural sector is essential for ensuring sustainable, reliable, and accessible production of 

bioenergy and biobased products that: (1) replace the use of petroleum and other strategic materials that 

would otherwise need to be imported; (2) create higher-value revenue streams for producers in rural and 

agricultural communities; (3) improve the nutrition and well-being of animals and humans; and (4) provide 

ecosystem services such as ensuring clean air and water, biodiversity, and nutrient cycling to the 

environment and society. 

The U.S. Department of Agriculture recognizes the role that manufacturing plays in maximizing the 

benefits of a sustainable, rural economy. Areas of interest include biomanufacturing and bioproducts 

development to: (1) establish processes and chemical platforms leading to high-value intermediate and 

end-use products, (2) support commercialization of products developed from basic and applied research, 

(3) build domestic capability for ongoing biomanufacturing and bioproducts development, and 4) educate 

and train needed workforce. The growth of the bioeconomy also depends upon understanding and 

addressing the entire supply chain of the bioeconomy, rural America’s role in the bioeconomy, and the 

role of research and development.
46

In addition, nanocellulose materials have enormous promise to bring about fundamental changes in and 

significant benefit from our Nation’s use of renewable resources. These cellulose nanomaterials when 

derived from trees: (1) are renewable and sustainable; (2) are produced in trees via photosynthesis from 

solar energy, atmospheric carbon dioxide, and water; (3) store carbon; and (4) depending upon how long 

cellulose-based products remain in service, are carbon negative or carbon neutral. Cellulosic nanocrystals, 

for example, are predicted to have strength properties comparable to Kevlar, have piezoelectric 

properties comparable to quartz, and can be manipulated to produce photonic structures. Current global 

research directions in cellulose nanomaterials indicate that this material could be used for a variety of 

new and improved product applications, including lighter and stronger paper and paperboard products, 

lighter and stronger building materials, wood products with improved durability, barrier coatings, body 

armor, automobile and airplane composite panels, electronics, biomedical applications, and replacement 

of petrochemicals in plastics and composites.

Department of Commerce

Innovation results from initial advances that lead to additional technology and process improvements, 

with resulting benefits accruing to industry, the economy, and society as a whole. Innovation in advanced 

manufacturing begins with the generation of new ideas that are refined and matured through applied 

research, development, and invention. Manufacturers then scale those ideas for mass production in order 

to generate process improvements and make new products. The experience and knowledge gained 

through manufacturing then leads to new ideas that start the cycle again. The Department of Commerce 

(DOC) has central responsibility for supporting and expanding each part of this cycle and has the 

relationships with businesses necessary to identify the workforce skills needed to support new and 

growing industries.

The Department increases regional and national capacity for innovative manufacturing through 

partnerships with state and local governments, academic institutions, and the private sector. Through the 

Department’s convening power, regional economic development programs, and statistical and economic 

analysis, it empowers industry-driven solutions to the shortage of high demand skills. Finally, the 

Department supports research and development leading to transformative changes in technology and 

promotes intellectual property policy that supports and protects innovation. By supporting public-private 

partnerships, such as the National Network for Manufacturing Innovation (NNMI), the Department helps 

to accelerate technology development and commercialization, and strengthen the Nation’s position in the 

global competition for new products, new markets, and new jobs. 

National Institute of Standards and Technology 

The National Institute of Standards and Technology (NIST) mission is: To promote U.S. innovation and industrial 

competitiveness by advancing measurement science, standards, and technology in ways that enhance economic 

security and improve our quality of life. For more than 110 years, NIST has maintained the national standards 

of measurement, a role that the U.S. Constitution assigns to the Federal Government to ensure fairness in the 

marketplace. Today, the NIST Laboratories address increasingly complex measurement challenges, ranging from 

the very small (nanoscale devices) to the very large (vehicles and buildings), and from the physical (renewable 

energy sources) to the virtual (cybersecurity and cloud computing). As new technologies develop and evolve, 

NIST’s measurement research and services remain central to innovation, productivity, trade, and public safety. 

NIST promotes the use of measurements based on the international system of units (SI). The measurement 

science research at NIST is useful to all science and engineering disciplines, including a robust research portfolio 

targeting the specific technical challenges associated with advanced manufacturing. In addition, the NIST 

Manufacturing Extension Partnership (MEP) is a critical resource to engage small- and medium-sized

manufacturers to develop new products, expand into global markets, and adopt new technologies, such as those 
47

in development in the NNMI Manufacturing Innovation Institutes. More information is available at

http://nist.gov/.

The Advanced Manufacturing National Program Office

Hosted at NIST, the Advanced Manufacturing National Program Office (AMNPO) is an interagency team with 

participation from Federal agencies involved in advanced manufacturing. Principal participant agencies 

currently include the Departments of Commerce, Defense, Education, and Energy, the National Aeronautics and 

Space Administration, and the National Science Foundation. Established in 2012, the Advanced Manufacturing 

National Program Office reports to the Executive Office of the President and operates under the NSTC on crossagency initiatives. The office reports to the Secretary of Commerce in its role as the “the National Office of the 

Network for Manufacturing Innovation Program,” also referred to as the “National Program Office,” as 

described by the Revitalize American Manufacturing and Innovation Act of 2014.48 More information is available 

at http://www.manufacturing.gov.

Department of Defense

The Department of Defense (DoD) requires a mechanism for shaping and developing the domestic design 

and manufacturing industrial base in support of national security needs. There is a need to advance the 

maturity of manufacturing processes in order to bridge the gap from research and development to fullscale production and aid in the economical and timely acquisition of weapon systems and components. 

New emerging technologies hold strategic promise for the DoD, but their fragmented and frail ecosystems 

are at risk of collapse due to infrastructure and workforce complexities. An ecosystem established for DoD 

requirements only is insufficient to establish a robust and sustainable ecosystem, therefore advanced 

manufacturing ecosystems must be built on common commercial and defense manufacturing and design 

challenges for shared risks and shared benefits. 

The DoD Manufacturing Innovation Institutes, a key investment strategy for DoD, are designed to 

overcome many of these challenges by advancing manufacturing innovation for specific, focused 

technology area manufacturing ecosystems. As of March 2016, there are five DoD Institutes in operation 

for additive manufacturing, digital manufacturing, lightweight metals, integrated photonics, and flexible 

hybrid electronics. A sixth for revolutionary fibers and textiles is scheduled for award early this year and 

two additional Manufacturing Innovation Institutes are planned over the next two years.

Department of Education

The Department of Education supports education at all levels with across-the-board relevance to the 

knowledge and skill needs of the economy. Particular programs and initiatives focus on science, 

technology, engineering, and mathematics fields, which are especially important in building the 

technically skilled workforce needed by the manufacturing sector. Most significantly, the Department 

administers funds that support career and technical education programs in local education agencies and 

community colleges across the nation. Further, the Department conducts leadership and technical 

assistance activities to promote quality career and technical education programs that are well articulated 

between secondary and postsecondary levels, and lead to successful careers. A particular focus for 

leadership and assistance programs is on advanced manufacturing, and the Department is supporting 

Federal efforts to revive this sector through its support for the technical skills agenda.

 

48 Consolidated and Further Continuing Appropriations Act, 2015, Title VII — Revitalize American Manufacturing and Innovation 

Act of 2014, codified at 15 U.S.C. § 278s.
48

The Department has been active in helping develop NNMI from its formation, and collaborates with other 

Federal agencies, in particular those that focus on the knowledge and skill needs of the economy and 

efforts related to student success. 

Department of Energy

The DOE mission is to ensure America’s security and prosperity by addressing its energy, environmental 

and nuclear challenges through transformative science and technology solutions. This includes catalyzing 

the timely, material, and efficient transformation of the nation’s energy system and securing U.S. 

leadership in clean energy technologies, as well as maintaining a vibrant U.S. effort in science and 

engineering as a cornerstone of our economic prosperity. To accomplish these goals, the DOE has 

established the Clean Energy Manufacturing Initiative as a cross-cutting initiative within the Department 

to strengthen U.S. clean energy manufacturing competitiveness and to increase U.S. manufacturing 

competitiveness across the board by boosting energy productivity and leveraging low-cost domestic 

energy resources and feedstocks. Clean energy manufacturing involves the minimization of the energy 

and environmental impacts of the production, use, and disposal of manufactured goods, which range from 

fundamental commodities such as metals and chemicals to sophisticated final-use products such as 

automobiles and wind turbine blades. The manufacturing sector, a subset of the industrial sector, 

consumes 25 exajoules (24 quads) of primary energy annually in the United States—about 79% of total 

industrial energy use. The DOE partners with private and public stakeholders to support the research, 

development, and deployment of innovative technologies that can improve U.S. competitiveness, save 

energy, and ensure global leadership in advanced manufacturing and clean energy technologies.

The DOE uses Manufacturing Innovation Institutes, which are executed through the Advanced 

Manufacturing Office, to develop energy efficiency and renewable energy technologies to support the 

Clean Energy Manufacturing Initiative. To date, the DOE has awarded two Manufacturing Innovation 

Institutes. The first, PowerAmerica, is focused on wide bandgap semiconductor technologies for next 

generation power electronics. The second, the Institute for Advanced Composites Manufacturing 

Innovation, is focused on composite technologies for vehicles, wind turbine blades, and compressed gas 

storage tanks. A third Institute, Smart Manufacturing: Advanced Sensors, Controls, Platforms and 

Modelling for Manufacturing, has been issued as an open competitive solicitation at the time of this 

report.

The DOE led Institute topics have been identified through extensive public engagement and are aligned 

with the DOE and EERE mission in clean energy science and technology.49 Specific topical areas are further 

informed by the DOE Quadrennial Technology Review, particularly the clean energy opportunities for 

advanced manufacturing.50

Department of Health and Human Services

Biomedical Advanced Research and Development Authority

The Biomedical Advanced Research and Development Authority (BARDA), within the Office of the Assistant 

Secretary for Preparedness and Response in the U.S. Department of Health and Human Services, was 

established through the enactment of the 2006 Pandemic and All-Hazards Preparedness Act (PAHPA) and 

reaffirmed by the 2013 Pandemic and All-Hazards Preparedness Reauthorization Act (PAHPRA), to provide 

an integrated, systematic approach to the development and purchase of the necessary vaccines, drugs, 

 

49 http://energy.gov/eere/downloads/eere-strategic-plan

50 http://energy.gov/downloads/chapter-6-innovating-clean-energy-technologies-advanced-manufacturing
49

therapies, and diagnostic tools for public health medical emergencies.

BARDA'S overarching vision is of a Nation with the capability to respond quickly and effectively to 

deliberate, natural, and emerging threats so as to minimize their impact and recover promptly. A critical 

enabling factor for the realization of this vision is the existence of a robust domestic pharmaceutical and 

biotechnology sector that actively collaborates with the Federal Government to address unmet medical 

countermeasure and public health requirements.

BARDA's mission is to develop and procure needed medical countermeasures—including vaccines, 

therapeutics, diagnostics, and non-pharmaceutical countermeasures—against a broad array of public 

health threats, whether natural or intentional in origin. BARDA was created to address gaps in the Federal 

Government medical countermeasure development and procurement process and to bridge the "valley of 

death" that separates candidates identified in early research from potential FDA licensure/approval by 

providing funding, technical support and services necessary to advance candidate products through the 

developmental pipeline. 

Food and Drug Administration

The U.S. Food and Drug Administration (FDA) is an agency within the Department of Health and Human 

Services. FDA is responsible for promoting and protecting the public health by assuring the safety and 

efficacy of human and veterinary drugs, vaccines, blood, and other biological products, medical devices and 

radiation-emitting products. Issues in pharmaceutical manufacturing have the potential to significantly 

impact patient care, in that failures in quality may result in product recalls and harm to patients.

Additionally, failures in product or facility quality are a major factor leading to disruptions in supply of 

medicines. Modernizing manufacturing technology may lead to a more robust manufacturing process and 

greater assurance that the drug products manufactured in any given period of time will provide the 

expected clinical performance.

The FDA laid out a 21st Century vision to modernize the regulation. To support this vision and mission, the 

FDA conducts research to support the development of scientific standards and policies in the composition, 

quality, safety, and effectiveness of human drug products to meet public health needs; identifies, evaluates, 

and develops relevant technologies to assess the safety and efficacy of human drug products; conducts 

research studies to address unresolved regulatory science questions and to prepare for issues related 

emerging technologies; and collaborates with academia, industry, and other government agencies to 

stimulate development of novel manufacturing and characterization technologies.

To complement its research program, the FDA has created an Emerging Technology Team to serve as the 

primary point of contact for companies that are interested in implementing emerging manufacturing 

technology in the manufacture of their drug products. The Emerging Technology Team will answer 

sponsor/applicant questions about the information FDA expects to see in their submission; identify and 

help facilitate regulatory review of a new manufacturing technology in accordance with existing legal and 

regulatory standards, guidance, and agency policy related to quality assessment; serve as the lead or colead on the quality assessment team and make the final quality recommendation regarding the potential 

approval of submissions in the program; and identify and capture resolution to policy issues that may inform 

FDA approaches and recommendations regarding future submissions that involve the same technology. 

More information is available in the draft guidance: 

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM4788

21.pdf

National Institutes of Health

NIH’s mission is to seek fundamental knowledge about the nature and behavior of living systems and the

application of that knowledge to enhance health, lengthen life, and reduce illness and disability. The goals 

of the agency are to foster fundamental creative discoveries, innovative research strategies, and their 

applications as a basis for ultimately protecting and improving health; to develop, maintain, and renew 

scientific human and physical resources that will ensure the Nation's capability to prevent disease; to 
50

expand the knowledge base in medical and associated sciences in order to enhance the Nation's economic 

well-being and ensure a continued high return on the public investment in research; and to exemplify and 

promote the highest level of scientific integrity, public accountability, and social responsibility in the 

conduct of science.

In realizing these goals, the NIH provides leadership and direction to programs designed to improve the 

health of the Nation by conducting and supporting research in harnessing new technologies to improve 

health. Rapid expansion of technological capabilities has opened new horizons for biomedical research. 

Innovative research methods stimulated by technological and engineering advances are facilitating the 

development of new strategies to diagnose, prevent, and treat a host of diseases. Technology also facilitates 

the integration of previously disparate fields, such as biology and electronics, enabling NIH to cultivate new 

lines of medical research and practice.

Department of Homeland Security

The Department of Homeland Security (DHS) seeks to achieve a safe, secure, and resilient homeland. 

Given the current and projected threat environments, technology and research and development (R&D)

are the bridge to the future of homeland security. The most effective and efficient changes will come with 

the smart application of science and technical expertise to develop force-multiplying solutions. These 

technology-based solutions will provide homeland security operators and first responders the upper hand 

in their respective operational spaces. They will also enable the Homeland Security Enterprise to expand 

capabilities and security coverage. DHS leverages the Integrated Product Team processthat aligns mission 

areas and incorporates a Science and Technology Directorate-led technology assessment for all major 

acquisitions. Integrated Product Teams are tasked to identify DHS capability gaps and coordinate R&D to 

close those gaps across departmental mission areas. Additionally, the Science and Technology 

Directorate’s Targeted Innovative Technology Acceleration Network and Responder Technology Alliance 

programs, in collaboration with the Homeland Security Industrial Base, strive to smartly manufacture and 

deliver technology solutions for the Homeland Security Enterprise and first responder community. 

Each of the five Science and Technology Directorate’s Homeland Security Advanced Research Projects

Agency divisions and the three First Responders Group divisions, as well as the Apex programs and 

Technology Engines, have developed Capability Roadmaps aligned to the needs of their operational end 

users. These high-level roadmaps formalize a vision, identify strategic drivers, and list R&D objectives for 

the next five years. The roadmaps are constantly evolving documents, serving three primary 

organizational functions: (1) to build consensus among a diverse set of end users with similar operational 

requirements; (2) to develop a framework that directly links a strategy to tactics; and (3) to provide a 

framework to coordinate planning, research, development, and acquisition activities across the various 

groups involved.

Department of Labor

The Department of Labor’s mission is to foster, promote, and develop the welfare of the wage earners, 

job seekers, and retirees of the United States; improve working conditions; advance opportunities for 

profitable employment; and assure work-related benefits and rights. The rapidly changing manufacturing 

workplace has led to the growing demand for workers and concerted efforts to support the sector through 

national, state, and local economic and workforce development activity. In alignment with its mission, the 

Department of Labor administers several grant programs that seek to increase the number of skilled 

workers in the high-demand manufacturing field. These include the Trade Adjustment Assistance 

Community College and Career Training Grant Program, Jobs Accelerator Innovation Challenge, Make It 

In America Grant Program, and American Apprenticeship Grant Program. The Department is also 

supporting in a White House-led initiative, Investing in Manufacturing Communities Partnership, that aims 
51

to spur communities to develop integrated, long-term economic development strategies that sharpen 

their competitive edge in attracting global manufacturers and their supply chains to our local 

communities—increasing investment and creating jobs. 

Department of Transportation

Advances in automotive electronics have enabled many capabilities that have seen more electronics 

packed into vehicles than ever before. Capabilities like GPS, Wi-Fi, Bluetooth, radar, eye detection systems 

and infotainment, and more recently, connected vehicles, improve safety and efficiency on the roads and 

enhance the overall driving experience. The manufacturing of these critical components and ensuring the 

integrity of the devices as they are made is becoming increasingly important and has come to the attention 

of the suppliers, as well as their customers and the Department of Transportation.

The stringent requirements of the automotive regulatory environment necessitate strong engineering and 

validation capability, along with state-of-the-art manufacturing. The current state of manufacturing of 

automotive electronics does not support component integrity protection. In addition, with much of the 

production currently done off-shore, ensuring the stringent manufacturing process is proving to be a 

challenge. The Department of Transportation is exploring a collaborative effort involving automotive 

electronic component manufacturers to identify ways to better ensure the integrity of the manufacturing 

process.

Environmental Protection Agency

Under the authorities of the Pollution Prevention Act of 1990, the Environmental Protection Agency (EPA) 

promotes source reduction to eliminate or reduce pollution at its source. One section in the Pollution 

Prevention Act of 1990 asks EPA to establish a grant program for states in order to support programs that: 

(1) make specific technical assistance available to businesses seeking information about source reduction 

opportunities, including funding for experts to provide onsite technical advice to businesses seeking 

assistance and to assist in the development of source reduction plans; (2) target assistance to businesses 

for whom lack of information is an impediment to source reduction; (3) provide training in source 

reduction techniques. Such training may be provided through local engineering schools or any other 

appropriate means. EPA’s Pollution Prevention grant program reduces millions of pounds of pollution, a 

million metric tons of carbon dioxide equivalents and nearly a billion gallons of water use every year. 

Under the Pollution Prevention Program, EPA also supports U.S. manufacturers seeking to improve their 

economic performance and competitiveness through improved environmental performance. The 

Presidential Green Chemistry Challenge Awards promote the environmental and economic benefits of 

developing and using novel green chemistry. These prestigious annual awards recognize chemical 

technologies that incorporate the principles of green chemistry into chemical design, manufacture, and 

use. EPA’s Office of Chemical Safety and Pollution Prevention sponsors the Presidential Green Chemistry 

Challenge Awards, in partnership with the American Chemical Society Green Chemistry Institute and other 

members of the chemical community including industry, trade associations, academic institutions, and 

other government agencies. Through 2015, the 104 winning technologies have made billions of pounds 

of progress, including: 826 million pounds of hazardous chemicals and solvents eliminated each year—

enough to fill almost 3,800 railroad tank cars or a train nearly 47 miles long; 21 billion gallons of water 

saved each year—the amount used by 820,000 people annually; 7.8 billion pounds of carbon dioxide 

equivalents released to air eliminated each year—equal to taking 810,000 automobiles off the road.

EPA also develops standards, criteria documents, and ecolabeling programs for products as part of its 

mission to protect human health and the environment. Examples of EPA ecolabeling programs include 

ENERGY STARTM, WaterSense®, and Safer Choice. They are noteworthy examples of Federal leadership in 
52

advancing energy efficiency, water efficiency, and green chemistry, respectively, and reflect EPA's 

commitment to objective, fact-based decision-making, grounded in scientific reasoning and principles, 

and using the best available data. The Economy, Energy and Environment Program is a Federal technical 

assistance framework helping communities, manufacturers, and manufacturing supply chains adapt and 

thrive in today's green economy. EPA and five other Federal agencies have pooled their resources to 

support small and medium-sized manufacturers with customized assessments. The Economy, Energy and 

Environment Program is helping communities across the country reduce pollution and energy use while 

increasing profits and creating new job opportunities.

National Aeronautics and Space Administration

The National Aeronautics and Space Administration (NASA) depends on manufacturing innovation to 

enhance its technical and scientific capabilities in aeronautics and space exploration. NASA will support 

the NNMI Program through funded research and development to help stimulate its mission-related 

capacity for innovation and economic growth within the government, at universities, and at industrial 

companies. 

NASA’s Space Technology Mission Directorate serves as the agency’s principal organization supporting the 

NNMI Program. The Space Technology Mission Directorate rapidly develops, demonstrates, and infuses 

revolutionary, high-payoff technologies through transparent, collaborative partnerships, expanding the 

boundaries of the aerospace enterprise. By investing in bold, broadly applicable, disruptive technology 

that industry cannot tackle today, the Space Technology Mission Directorate seeks to mature the 

technology required for NASA’s future missions in science and exploration while proving the capabilities 

and lowering the cost for other government agencies and commercial space activities. These collective 

efforts give NASA the ability to do first-of-a-kind missions and longer-term advancements in research and 

technology—those beyond what industry will take on and those focused on national advancement in 

aeronautics and space that also align with NASA’s role in the NNMI Program.

NASA will leverage the NNMI Program to support advanced manufacturing technology research and 

development as a critical means of addressing improved affordability, enhanced performance, and 

improved safety and reliability for NASA’s aerospace research and development efforts. NASA 

investments span low, medium, and high TRLs through multiple NASA programs including Small Business 

Innovation Research Program, Small Business Technology Transfer, Space Technology Research Grants, 

Game Changing Development, Technology Demonstration Missions, and other grant opportunities. 

Advanced manufacturing research and development at NASA is focused in several areas: cutting-edge 

materials, additive manufacturing (3D printing), polymer matrix composites, metals processing/joining, 

robotics, computational physics-based modeling, non-destructive evaluation, and other highly specialized 

areas. This research and development is conducted through a combination of in-house activities at NASA 

centers, competitively funded research with universities and industry, and collaborations with other 

agencies, universities, and industry. The rapid infusion of advanced manufacturing technologies into 

mission applications is a major emphasis of NASA's technology investment plan.

NASA is expanding its efforts to engage industry and academia on advanced manufacturing topics central 

to the nation’s space mission through its National Center of Advanced Manufacturing, with a particular 

focus to develop “technology testbeds” within its research facilities and manufacturing technologies that 

reduce the weight of materials during space flight.

NASA has participated in the NNMI since its inception and is committed to partnering with other 

participating agencies to identify key technical challenges in advanced manufacturing research and 
53

development, focus resources to address these challenges, and accelerate the development of advanced 

manufacturing breakthroughs and their translation into commercial products.

National Science Foundation

The National Science Foundation (NSF) supports fundamental advanced manufacturing research, 

education, and workforce training in its Directorates for Engineering, Computer and Information Science 

and Engineering, Mathematical and Physical Sciences, and Education and Human Resources. It also 

promotes advanced manufacturing innovation through a variety of translational research programs, 

including the Small Business Innovation Research, Small Business Technology Transfer, and Grant 

Opportunities for Academic Liaison with Industry Programs, and by partnering with industry, states, and 

other agencies. In fiscal year 2015, the NSF and NIST jointly established and funded MForesight: Alliance 

for Manufacturing Foresight, a think-and-do tank that harnesses the expertise of the broad U.S.-based 

manufacturing community to forecast future advanced manufacturing technologies.

The NSF advanced manufacturing investment is primarily through its Cyber-enabled Materials, 

Manufacturing, and Smart Systems priority area. These programs support fundamental research leading 

to transformative advances in manufacturing that address size scales from nanometers to kilometers, 

including process modeling, advanced sensing and control techniques, smart manufacturing using 

sustainable materials, chemical and biological reactor design and control, and manufacturing processes 

and enabling technology to support a broad range of industries, with emphases on efficiency, economy, 

and minimal environmental impact. Advanced manufacturing is also supported through the Engineering 

Research Centers, Industry/University Cooperative Research Centers, and Advanced Technology 

Education programs. With an emphasis on two-year colleges, the Advanced Technology Education

program focuses on the education of technicians for the high-technology fields that drive our nation's 

economy.

All NSF programs welcome the submission of proposals to collaborate with Manufacturing Innovation 

Institutes in cutting-edge research and educational projects. Projects that are currently funded by NSF are 

also encouraged to request funding supplements to perform collaborate research and/or educational 

projects with Institutes. It is expected that the incorporation of the resources, expertise, and experience 

of Institute members will increase the competitiveness of such proposals in merit review.

Small Business Administration

The U.S. Small Business Administration (SBA) was created in 1953 as an independent agency of the Federal 

Government to aid, counsel, assist, and protect the interests of small business concerns, to preserve free 

competitive enterprise, and to maintain and strengthen the overall economy of our nation. The SBA 

recognizes that small business is critical to our economic recovery and strength, to building America's 

future, and to helping the United States compete in today's global marketplace. Although SBA has grown 

and evolved since its establishment, the bottom-line mission remains the same. The SBA helps Americans 

start, build, and grow businesses. Through an extensive network of field offices and partnerships with 

public and private organizations, SBA delivers its services to people throughout the United States, Puerto 

Rico, the U.S. Virgin Islands and Guam.

SBA’s Office of Investment and Innovation’s mission is to stimulate the economy by providing small 

businesses and entrepreneurs access to capital investment via our Small Business Investment Company

(SBIC). The SBIC program is a growth capital program with over $25 billion of assets under management 

spread across 303 private-public partnerships comprised of private equity, venture capital, and structured 

lending funds, making it one of the largest fund of funds focused on capitalizing American small 
54

businesses.

As of today, roughly 25% of SBIC dollars are invested in manufacturing. In addition, SBA is uniquely suited 

to play a key part in encouraging the growth of advanced manufacturing in the United States because it 

plays a central role in realizing the benefits of technological innovation and in the overall growth and 

health of the U.S. economy. To support this effort, the SBA is proposing the Scale-Up Manufacturing 

Investment Companies (SUMIC) program to support innovative manufacturing technologies scaling up 

their first commercial production facilities in the United States. The loan guaranty program would support 

private funds, operating similarly to the SBIC debt guaranty program, except with a much larger fund and 

project size necessary to support the needs of manufacturing scale-up efforts. 

Investment in small innovative manufacturers will promote the development of cutting edge 

manufacturing technologies by smoothing the pathway from prototype to production for new processes, 

tools, and methodologies. By leveraging industry and non-federal co-investment in innovation 

opportunities that will lead to improved manufacturing capabilities, SUMIC will help to bridge the gap 

between fundamental technical discoveries in the United States and products manufactured here.

Furthermore, U.S. manufacturers individually are challenged to fund these technology development 

functions, and small- and medium-size manufacturers struggle with investing in prototyping and scale up 

of new technologies and potential products. This initiative would help provide the critical mass and 

knowledge base necessary to address these challenges. Partnerships that bring diverse organizations 

together to accelerate innovation for advanced manufacturing create a stronger innovation system and 

link those innovations more directly to domestic production capabilities. This proposal builds on the 

success of models deployed in other countries.
55

Appendix B: 

Technology Readiness Levels and Manufacturing Readiness Levels

Technology readiness levels (TRLs) and Manufacturing readiness levels (MRLs) are used by the 

Department of Defense, other Federal agencies, and industry to assess the maturity of new 

technologies.51

TRL 1: Basic principles observed and 

reported

MRL 1: Basic manufacturing 

implications identified

TRL 2: Technology concept or 

application formulated

MRL 2: Manufacturing concepts 

Identified

TRL 3: Experimental and analytical 

critical function and 

characteristic proof of concept

MRL 3: Manufacturing proof of concept 

developed

TRL 4: Component or breadboard 

validation in a laboratory 

environment

MRL 4: Capability to produce the 

technology in a laboratory 

environment

TRL 5: Component or breadboard 

validation in a relevant 

environment

MRL 5: Capability to produce prototype 

components in a production 

relevant environment

TRL 6: System or subsystem model or 

prototype demonstrated in a 

relevant environment

MRL 6: Capability to produce a 

prototype system or subsystem 

in a production relevant 

environment

TRL 7: System prototype 

demonstration in an operational 

environment

MRL 7: Capability to produce systems, 

subsystems, or components in a 

production representative 

environment

TRL 8: Actual system completed and 

qualified through test and 

demonstration

MRL 8: Pilot line capability 

demonstrated; ready to begin 

low rate initial production

TRL 9: Actual system proven through 

successful mission operations

MRL 9: Low rate production 

demonstrated; capability in 

place to begin full rate 

production

MRL 10: Full rate production

demonstrated and lean 

production practices in place

 

51 Manufacturing Readiness Level (MRL) Deskbook: Version 2.4. Prepared by the OSD Manufacturing Technology Program in 

collaboration with The Joint Service/Industry MRL Working Group. DoD (U.S. Department of Defense). 2015. Washington, 

DC: U.S. Government Printing Office.
56

Abbreviations

AMNPO Advanced Manufacturing National Program Office

ARPA-E Advanced Research Projects Agency-Energy

BARDA Biomedical Advanced Research and Development Authority

CBET Chemical, Bioengineering, Environmental and Transport Systems

CDER Center for Drug Evaluation and Research

CRISPR Clustered Regularly-interspaced Short Palindromic Repeats

DARPA Defense Advanced Research Projects Agency

DMDII Digital Manufacturing and Design Innovation Institute

DMREF Designing Materials to Revolutionize and Engineer our Future 

DOC Department of Commerce

DoD Department of Defense

DOE BETO Department of Energy Bioenergy Technologies Office

DOE Department of Energy

DOT Department of Transportation

EAGER Early-concept Grants for Exploratory Research

EERE Energy Efficiency and Renewable Energy

EMN Energy Materials Network 

EPA Environmental Protection Agency

ERC Engineering Research Centers

FBI Federal Bureau of Investigation

FDA Food and Drug Administration

HHS Health and Human Services

HPC High Performance Computing

IACMI Institute for Advanced Composites Manufacturing Innovation

I/UCRC Industry/University Cooperative Research Centers

LIFT Lightweight Innovations for Tomorrow

MDF Manufacturing Demonstration Facility

MEP Manufacturing Extension Partnership

MGI Materials Genome Initiative

MRL Manufacturing Readiness Level

NASA National Aeronautics and Space Administration

NCAL NIST Center for Automotive Lightweighting
57

NCATS National Center for Advancing Translational Sciences

NCI National Cancer Institute

NHLBI National Heart, Lung and Blood Institute

NIBIB National Institute of Biomedical Imaging and Bioengineering

NIDDK National Institute of Diabetes and Digestive and Kidney Diseases

NIFA National Institute of Food and Agriculture

NIGMS National Institute of General Medical Sciences

NIH National Institutes of Health

NIST National Institute of Standards and Technology

NNI National Nanotechnology Initiative

NNMI National Network for Manufacturing Innovation

NNSA National Nuclear Security Administration

NSF National Science Foundation

NSTC National Science and Technology Council

OSTP Office of Science and Technology Policy

PACT Production Assistance for Cellular Therapies

PCAST President’s Council of Advisors on Science and Technology

R&D Research and Development

SAM Subcommittee on Advanced Manufacturing

SBA Small Business Administration

SI International System of Units

STARnet Semiconductor Technology Advanced Research Network

STEM Science, Technology, Engineering, and Mathematics

TAACCCT Trade Adjustment Assistance Community College and Career Training

TRL Technology Readiness Level

USDA U.S. Department of Agriculture

VA Department of Veterans Affairs