(NIST Special Publication 1097)
Acknowledgements

Thanks go to the many sponsors who contributed to this effort. 

Sponsor profiles are included in Appendix A. 

Energetics Incorporated AspenTech

Johns Hopkins University Waters Corporation

Bronze Sponsors

Human Genome Sciences IEEE USA

Silver Sponsors

American Autoimmune Related 

Diseases Association, Inc.

Montgomery County Department 

of Economic Development

Gold Sponsors

National Institute of Standards and Technology (NIST)

U.S. Pharmacopeia (USP)

Special thanks go to the many people who provided administrative, logistical, and other assistance to 

ensure the conference was a success. These include NIST staff Donna Kimball, Reenie Parris, 

Karen Startsman, Jeannie Kilpatrick, and Dianne Poster; and Energetics Incorporated,

who provided facilitators and prepared this conference report.

University of Maryland 

Biotechnology Institute 

(UMBI)
NIST Special Publication 1097 

[NIST Special Publication 903034]

Accelerating Innovation in 21st Century Biosciences: 

Identifying the Measurement, Standards, 

and Technological Challenges

Willie E. May

Michael D. Amos

Chemical Science and Technology Laboratory 

National Institute of Standards and Technology 

Gaithersburg, MD

Jennie Hunter-Cevera

University of Maryland Biotechnology Institute

Baltimore, MD

July 2009

U.S. Department of Commerce

Gary Locke, Secretary

National Institute of Standards and Technology

Patrick D. Gallagher, Deputy Director
Certain commercial entities, equipment, or materials may be identified in this document in order 

to describe an experimental procedure or concept adequately. Such identification is not intended 

to imply recommendation or endorsement by the National Institute of Standards and Technology, 

nor is it intended to imply that the entities, materials, or equipment are necessarily the best 

available for the purpose.

National Institute of Standards and Technology Special Publication 1097 [Special 

Publication 903034] Natl. Inst. Stand. Technol. Spec. Publ. 903034, 86 pages (July 2009)

CODEN: NSPUE2
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges i

Executive Summary ...................................................................................................iii

1.0 Introduction ........................................................................................................ 1

Importance of Measurement to the Biosciences ......................................................................... 1

Conference Overview ................................................................................................................ 1

Organization of the Report ......................................................................................................... 4

2.0 Agriculture .......................................................................................................... 5

Vision of the Future ................................................................................................................... 5

Broad Challenges ....................................................................................................................... 6

Role of Measurement ................................................................................................................. 8

Measurements and Standards Challenges ................................................................................. 10

Priority Measurement Topics ..................................................................................................... 12

3.0 Bioenergy ......................................................................................................... 17

Vision of the Future ................................................................................................................. 17

Broad Challenges ..................................................................................................................... 18

Role of Measurement ............................................................................................................... 21

Measurement and Standards Challenges .................................................................................. 22

Priority Measurement Topics ..................................................................................................... 23

4.0 Environment ..................................................................................................... 29

Vision of the Future ................................................................................................................. 29

Broad Challenges ..................................................................................................................... 30

Role of Measurement ............................................................................................................... 32

Measurements and Standards Challenges ................................................................................. 33

Priority Measurement Topics ..................................................................................................... 36

TABLE OF 

CONTENTS

TABLE OF 

CONTENTS
ii Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

TABLE OF 

CONTENTS

TABLE OF 

CONTENTS

5.0 Biopharmaceutical Manufacturing ..................................................................... 41

Vision of the Future ................................................................................................................. 41

Broad Challenges ..................................................................................................................... 43

Role of Measurement ............................................................................................................... 46

Measurement and Standards Challenges .................................................................................. 46

Priority Measurement Topics ..................................................................................................... 48

6.0 Medicine ........................................................................................................... 53

Vision of the Future ................................................................................................................. 53

Broad Challenges ..................................................................................................................... 55

Role of Measurement ............................................................................................................... 57

Measurement and Standards Challenges .................................................................................. 59

Priority Measurement Topics ..................................................................................................... 62

7.0 Hot Topics ......................................................................................................... 67

8.0 Universal Ideas and Observations ...................................................................... 71

Appendix A: Sponsor Profiles ................................................................................... 73

Appendix B: Technical Panel Participants ................................................................. 79

Appendix C: List Of Acronyms ................................................................................. 81
Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges iii

executive

summary

executive

summary

Overview

The science of understanding how biological systems 

operate and interact with one another (the biosciences) 

is increasingly important to global prosperity and 

quality of life. As the world’s population grows, so 

will the need for more efficient and sustainable ways 

to grow food, keep people healthy, produce energy, 

and manufacture biological drugs, therapeutics, and 

chemicals. These advances can only be realized by 

gaining a deeper understanding of how biological 

systems operate—an understanding that depends 

on advancing the state of the art in biosciences 

measurement.

Despite major breakthroughs and discoveries in recent 

years, our understanding of biological systems still 

faces many challenges. Biology is an informational 

science that depends on accurate measurements 

and standards. Whether quantifying the amount 

of protein in a cancer cell or the rate at which an 

organism converts sugar to alcohol, measurements are 

the foundation for improving our understanding of 

biological systems. 

To identify measurement challenges in the biosciences, 

the National Institute of Standards and Technology (NIST) and the University of Maryland Biotechnology 

Institute (UMBI) co-hosted an international conference, Accelerating Innovation in 21st Century Biosciences: 

Identifying the Measurement, Standards, and Technological Challenges, on October 19-22, 2008, in 

Gaithersburg, Maryland. 

Attended by leading bioscience professionals from all over the world, this landmark event was a first-time 

opportunity to discuss the global measurement and standards challenges to innovation in key bioscience 

areas (Exhibit E.1). Bioscience practitioners with diverse backgrounds met to share the views of international 

policymakers, create opportunities for networking and collaboration, and discuss opportunities and 

challenges. This report provides an overview of the conference and the important ideas generated by experts 

in the field.

Priority Measurement and Standards Challenges

An important outcome of the conference is a prioritized list of challenges that can be used to guide future 

research at NIST and the measurement and standards community worldwide. These priorities are summarized 

in Exhibit E.2.

Exhibit E.1 Conference Focus Areas

Agriculture - increasing yield, quality, and safety in 

the world’s food supply

Bioenergy - obtaining sustainable energy from 

biological sources

Environment - understanding our planet through 

linking molecules to ecosystems

Biopharmaceutical Manufacturing - obtaining 

higher quality products through better bioprocess 

measurements

Medicine - improving health through measurement of 

complex biological signatures

Hot Topics - unrecognized, overlooked, 

underestimated, and often ignored measurement 

needs in the biosciences, including

•	 Agriculture viability

•	 Antibiotic and antiviral drug resistance

•	 Environmental bioremediation

•	 Environmental bioterrorism monitoring

•	 Marine versus terrestrial sources of bioenergy

•	 Personalized medicine

•	 Stem cell therapy

•	 Synthetic biology
iv Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

Agriculture - Standards and 

standardized methods are a 

priority, as they assure confidence 

and consistency in biological 

measurements of plant/animal 

systems and their ecological 

and environmental interactions. 

As markets continue to expand 

globally, international standards 

will be important to assure 

worldwide product acceptance. 

Improved measurement 

methods are also needed to 

achieve greater accuracy, speed 

of measurements and analysis, 

and real-time, remote capability. 

Innovative technologies are 

needed to measure complex 

biological system parameters, 

such as water in plants, structures 

of microbiota, and reversible 

interactions in living systems. 

Assimilation and dissemination 

of data and accessible 

bioinformatics systems are 

critical and remain a significant 

challenge. Sustainable 

agriculture will require 

consensus on how to measure 

sustainability and life-cycle 

impacts. Ensuring that sustainable 

practices are attractive to farmers 

and livestock operators, and 

communicating the true cost 

of sustainability, are both key 

challenges.

Bioenergy - Improved characterization methods for various forms of biomass in terms of composition, 

reliability, quality, and enzyme activity, are needed, particularly for next-generation biofuels. Methods are also 

needed to monitor the characteristics of biomass in production and harvesting; during conversion processes; 

and in storage, transport, and delivery. The standardization and sustainability of biofuels is a global 

challenge that requires nations to work together. Standards are needed to establish the performance and 

sustainability of biofuels regardless of feedstock. Ensuring consistent measurements and standards across 

the biofuels supply chain requires an extensive network of measurement methods. While some exist, many 

others need to be developed, particularly for biomass production. On the production side, characterizing 

the breakdown mechanisms of and measuring the parameters relevant to the recalcitrance of cellulosic 

biomass are key challenges to unlocking the energy potential of non-food biomass resources such as 

perennial grasses, wood energy crops, and agricultural residues.

EXECUTIVE

SUMMARY

EXECUTIVE

SUMMARY

Agriculture

Bioenergy

Environment

Biopharmaceutical

Manufacturing

Medicine

Analytical tools and

technologies for

composition of

agricultural systems

Bioinformatics

for agriculture

Real-time remote

and non-invasive

measurements for

agriculture

Standard reference

data and reference

materials for bioenergy

technologies

Consensus metrics

for greenhouse

gases, land use,

and sustainability

International

compatibility of

biofuels

Fuel compliance

inspection tools for

retail biofuel products

Breakdown

mechanisms of

cellulosic materials

Biomarkers and

indicators for

assessing the health

of ecosystems

Definition of

system properties

from molecular

properties

Reliable integration

of complex

environmental data

for decision making

Next-generation

manufacturing tools

In-process and endproduct measurements

Standard

reference data for

biotechnologies

Optimized sampling

approaches for

biological

manufacturing

processes

Phenotype

standardization,

outcomes, and

disease definitions

and activity

Understanding

clinical and

biological

phenotypes for

therapeutics

Reference materials

and standardization

across platforms

Consensus approaches

and markers for sample

integrity

Better methodologies and practices for sample handling

More robust protein measurements

High-throughput multiplexed measurements

Improved tools and standards for bioinformatics

Improved tools and standards to ensure confidence in data

and enable comparability across platforms

ο

ο

ο

ο

ο

Universal Measurements and Standards Needs

Exhibit E.2 Priority Measurement and Standards Challenges for Biosciences
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges v

Environment - Priority challenges for obtaining system properties involve defining the critical attributes 

of ecosystems, determining the measures of system health, and identifying the indicators that provide early 

warning of changes in ecosystem health that are important to sustaining human well-being. Standardized, 

validated methods for the development and use of biomarkers are currently lacking and are critical to 

effective early warning systems. Issues such as natural variability, specificity of biomarkers, and variability 

across environmental conditions impede standardization and need to be addressed. The major challenge to 

incorporating broad perspective variables (e.g., resource and land use, air and water transport, climate 

change) will depend on the effective integration of diverse data at different scales, from the molecular to 

systems level. Effective early warning systems will require an array of measurement technologies ranging from 

DNA probes to satellites, geographic information systems (GIS), and others. A greater understanding of the 

links between external drivers and stressors affecting ecosystem health, environmental exposures, 

and system-level responses is needed as a foundation for an environmental early warning system. This 

knowledge is impeded by the growing magnitude and diversity of toxins, chemicals, hazardous compounds, 

pathogens, diseases, and other stressors released into water, air, land, and living systems. New measurements 

and standards, including sampling methods, are required for toxins, microbial contaminants, pathogens, and 

many other threats to a healthy environment. 

Biopharmaceutical Manufacturing - Controlling and monitoring biological manufacturing 

processes that work with living cells is difficult due to a high degree of uncertainty, both in processing and 

obtaining desired product attributes. The ability to make measurements in complex matrices in a process 

environment and obtain samples online and in-process remains a significant challenge. Without 

understanding the mechanisms behind product variability, obtaining the desired attributes becomes an 

iterative process. Finding simpler ways to mimic complex systems (e.g., immune system assay), more accurate 

bioassays, and measuring in vivo changes could improve pathways to reliable product attributes. Tools 

for measuring system parameters such as structural properties, aggregation, oxidation, and others, 

will ultimately pave the way for predictive biotechnology and product development. The high cost of 

measurement remains a significant impediment in today’s biomanufacturing environment. 

Medicine - Developing sampling standards and protocols for the proper processing, handling, and 

treatment of cells, tissues, and other biological samples is a high priority. Without standard methods, the 

result is questionable sample integrity, poor reproducibility of results, and difficulty in performing credible 

analysis. Definitions and standards for phenotype data are also critical; these are needed to help identify, 

characterize, and predict disease pathways, activity, and disease and treatment outcomes. Standardization 

of data and assays across biological platforms is a priority, but is hindered by the diversity of platforms 

and a lack of interoperability and comparability among platforms. There is a need for clear definition of 

reference points, and improved traceability of measurements to reference points. Information exchange

and ensuring consistency of information continues to be a major challenge. 

Universal Ideas and Observations 

The universal, crosscutting needs identified across all biosciences are:

• Better methodologies and practices for sample handling

• More robust protein measurements

• High-throughput multiplexed measurements

• Improved tools and standards for bioinformatics

• Improved tools and standards to ensure confidence in data and enable comparability across platforms

EXECUTIVE 

SUMMARY

EXECUTIVE 

SUMMARY
vi Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

Observations that emerged from the conference include the following:

• Improvements in the biosciences are key to global economic security and quality of life in the future

• A much deeper understanding of complex biological systems is needed

• Highly sophisticated measurements are needed in order to study the relevant changes that occur in

complex biomolecular networks

• Major measurement challenges exist that are stifling innovation in the biosciences

• Current technology is inadequate due to a very limited measurement infrastructure that allows scientists to

have confidence in only a very small percentage of the biomeasurements being conducted

• New multiplex, multiparametric measurement technologies must be invented and developed

• These new measurement systems will rely heavily on the accuracy and comparability of the data obtained

from current technologies as a basis upon which to build the new systems

• Standardization of current measurement technologies will be needed to enable next-generation systems

• Standardization of next-generation biomeasurement systems that bridge historical and new data will be

needed as new methods emerge

EXECUTIVE

SUMMARY

EXECUTIVE

SUMMARY
Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 1

Importance of Measurement to the Biosciences 

The science of understanding how biological systems operate and interact with one another (the biosciences) 

is increasingly important to global prosperity and quality of life. As the world’s population grows, so will 

the need for more efficient and sustainable ways to grow food, keep people healthy, produce energy, and 

manufacture biological drugs, therapeutics, and chemicals. These advances can only be realized by gaining a 

deeper understanding of how biological systems operate—an understanding that depends on advancing the 

state of the art in biosciences measurement.

Despite major breakthroughs and discoveries in recent years, our understanding of biological systems still 

faces many challenges. Biology is an informational science that depends on accurate measurements and 

standards. Whether quantifying the amount of protein in a cancer cell or the rate at which an organism 

converts sugar to alcohol, measurements are the foundation for improving our understanding of biological 

systems. Future progress depends on our ability to measure key features, including the complex interplay of 

thousands of biochemicals that control living systems.

Conference Overview

Given the importance of measurement to the 

biosciences, the National Institute of Standards and 

Technology (NIST) and the University of Maryland 

Biotechnology Institute (UMBI) co-hosted an 

international conference, Accelerating Innovation in 

21st Century Biosciences: Identifying the Measurement 

Standards and Technological Challenges, on October 

19-22, 2008, in Gaithersburg, Maryland. This 

landmark event drew attendance of leading bioscience 

professionals from all over the world.

Speakers from industry, government, and national 

metrology institutes as well as academic scholars and 

researchers from the biosciences arena presented 

and discussed global measurement, standards, and 

technology concerns for 21st century biosciences. The 

conference was a first-time opportunity to identify 

and discuss the global measurement and standards 

challenges to biosciences innovation in a number of 

important areas (see Exhibit 1.1). If left unresolved, 

these impediments could prevent the realization 

of the benefits of important new discoveries in the 

biosciences. 

Exhibit 1.1 Conference Focus Areas

Agriculture - increasing yield, quality, and safety in 

the world’s food supply

Bioenergy - obtaining sustainable energy from 

biological sources

Environment - understanding our planet through 

linking molecules to ecosystems

Biopharmaceutical Manufacturing - obtaining 

higher quality products through better bioprocess 

measurements

Medicine - improving health through measurement of 

complex biological signatures

Hot Topics - unrecognized, overlooked, 

underestimated, and often ignored measurement 

needs in the biosciences, including

•	 Agriculture viability

•	 Antibiotic and antiviral drug resistance

•	 Environmental bioremediation

•	 Environmental bioterrorism monitoring

•	 Marine versus terrestrial sources of bioenergy

•	 Personalized medicine

•	 Stem cell therapy

•	 Synthetic biology

1.0 

introduction

1.0 

introduction
2 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

The conference provided an excellent venue for participants to meet with bioscience practitioners from all 

over the world, share the views of international policy makers, network, collaborate, exchange technical 

information, and build international relationships. The design and content of the conference was developed 

by a dedicated Biosciences Steering and Organizing Committee comprised of stakeholders from different 

areas of the biosciences and measurement communities (see Exhibit 1.2). The committee worked together 

to develop a broad-based conference format that would encourage information exchange and allow for 

the free flow of ideas. The conference format included an international plenary symposium with roundtable 

discussions, followed by visionary topical speakers in the primary conference focus areas. Two days were 

then devoted to technical panel sessions to identify and prioritize the critical measurement and standards 

challenges to innovation in biosciences.

Science Policy Roundtable

During the opening plenary session, a roundtable discussion 

was held to gain a global understanding of the challenges 

facing the biosciences and to exchange information on 

advances and opportunities. In a moderated format, forwardthinking leaders in different fields of the biosciences discussed 

their focus with respect to investments in biosciences and 

related policy. Roundtable participants are listed in Exhibit 1.3.

Exhibit 1.2 Conference Steering and Organizing Committee

Conference Co-Chairs

Willie E. May, National Institute of Standards and Technology (NIST)

Jennie Hunter-Cevera, University of Maryland Biotechnology Institute (UMBI) 

Steering and Organizing Committee

Clare Allocca, NIST

Michael Amos, NIST

Jason Boehm, NIST

Judy Britz, Principal at Britz Consulting

Gary Brooker, Johns Hopkins University (JHU)

William Heetderks, National Institutes of Health (NIH) 

Fred Holland, Hollings Marine Laboratory, National Oceanic 

 and Atmospheric Administration (NOAA) 

Craig Jackson, Consultant

Robert Kaarls, Secretary of International Committee for Weights 

 and Measures (CIPM)

George Klee, Mayo Clinic 

Helen Parkes, Laboratory of the Government Chemist, UK (LGC)

Jerry Parrott, Human Genome Sciences, Inc.

Terry Purkable, Applied Physics Lab (APL), JHU 

Sara Radcliffe, Biotechnology Industry Organization (BIO)

Fred Razzaghi, Consultant

Theodore Roumel, UMBI

James Serum, Scitek Ventures

Tamas Torok, Lawrence Berkeley National Laboratory (LBNL)

Keith Webber, Food and Drug Administration (FDA)

Exhibit 1.3 

Science Policy Roundtable

Moderated by Mitch Waldrop, Nature

•	 Laurence Besley, Department of Innovation, 

Industry, Science and Research, Australia

•	 Chavonda Jacobs-Young, White House Office 

of Science and Technology Policy, USA

•	 Timothy Hall, Directorate General for 

Research, European Commission

•	 João Alziro Herz da Jornada, Department 

of Development, Industry and Exterior 

Commerce, Brazil

INTRODUCTION
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 3

National Metrology Institutes Directors’ Roundtable

Directors from National Metrology Institutes (NMIs) around the world responded to topic questions of interest 

to the biosciences community and discussed the unique challenges facing their countries. They gave a 

brief summary of the history of their institution and what they are currently working on in the biosciences, 

including funding levels for measurement and standards activities. Roundtable participants are listed in Exhibit 

1.4.

Plenary Topical Presentations 

Following the roundtable discussions, leaders in each of 

the conference focus areas provided their views on the 

opportunities and challenges to innovation. Each plenary talk 

included a sector overview; importance of the area to society 

and the economy; the vision for the future, i.e., the future 

promise of biosciences and the industry; major technological 

impediments to innovation; and the impacts of failing to 

address challenges. Plenary speakers are shown in Exhibit 1.5. 

Presentations are available online at http://www.cstl.nist.gov/

Bioscience%20Conference/Material.html

Technical Panels

Two days of the conference were devoted to technical panel 

sessions covering each of the conference focus areas. Each technical panel was co-chaired by a Steering 

Committee member and an outside subject matter expert (see Exhibit 1.6). The technical panel members 

were chosen based on their expertise in the field of interest and ability to provide a broad perspective on 

future challenges. A complete list of technical panel members is provided in Appendix B.

In the facilitated sessions for each focus area, panel members worked to identify and prioritize the 

measurement and standards challenges that significantly impede innovation. A series of questions was asked 

in each session, relevant to each focus topic, as follows:

•	What are the characteristics and vision of the future?

•	What are the broad challenges to achieving the vision?

•	What do we need to measure to achieve the promise of biosciences, and why is it important?

•	What are the measurement and standards challenges limiting the potential technological innovations?

Exhibit 1.4 National Metrology Institutes Directors’ Roundtable 

Moderated by Robert Kaarls, Secretary of CIPM

•	 Kwang Hwa Chung, Korea Research Institute of Standards and Science (KRISS), Korea

•	 Patrick Gallagher, NIST, USA

•	 Alejandro Herrero Molina, Joint Research Centre, Institute for Reference Materials and Measurements 

(JRC-IRMM), European Commission (EC)

•	 Anna Hills, National Physical Laboratory (NPL), UK

•	 James McLaren, National Research Council, Institute for National Measurement Standards (NRC- INMS), Canada

•	 Marc Pieksma, Nederlands Meetinstituut (NMi), The Netherlands

Exhibit 1.5 

Plenary Symposium Speakers

Agriculture - Pamela Ronald and Raoul 

Adamchak, University of California at Davis, USA

Bioenergy - Anna Palmisano, U.S. Department 

of Energy (U.S. DOE), USA

Environment - Stephen Weisberg, 

Southern California Coastal Water Research 

Project Authority, USA

Biopharmaceutical Manufacturing - James 

Thomas, Amgen, USA

Medicine - Lee Hood, Institute for Systems 

Biology (ISB), USA

INTRODUCTION
4 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

The results of these discussions provide an excellent 

perspective on future potential and the challenges 

to be faced. A particularly important outcome is a 

prioritized list of challenges that could be used to 

guide future work at NIST and the measurement and 

standards community worldwide. 

The hot topics session diverged from the facilitated 

format and included short talks from industry, 

government, and academic experts in strategically 

important bioscience areas. Following the 

presentations, participants were permitted to submit 

questions for discussion and response by the panel 

members. Presentations are available online at http://

www.cstl.nist.gov/Bioscience%20Conference/Material.

html.

Organization of the Report

The remainder of this report is organized around the 

outcomes of the technical panel sessions for the five 

primary focus areas: agriculture, energy, environment, 

manufacturing, and medicine, as well as the hot topics 

section. To clarify that this report focuses on the biological aspects of these fields, in some cases the word 

"bio" is added to the titles of tables and charts (e.g., bioenergy, biomanufacturing). 

Each of the following chapters summarizes the responses of the technical panel to the topical questions that 

were posed, including a vision of the future, broad technological and non-technological challenges, the 

role of measurement in technological innovation, the measurements and standards challenges, and priority 

measurement topics to guide future decision making.

The appendices provide supporting information for the conference, including sponsor profiles, a list of 

technical panel participants, and a compilation of the acronyms used throughout this report.

Exhibit 1.6 Technical Panel Co-Leaders

Agriculture (1) Tamas Torok, Lawrence Berkeley 

National Laboratory; (2) Steven Britz, U.S. Department 

of Agriculture

Bioenergy (1) Terry Purkable, Johns Hopkins 

University Applied Physics Laboratory; (2) Hratch 

Semerjian, Council for Chemical Research 

Environment (1) Fred Holland, Hollings Marine 

Laboratory; (2) Hendrik Emons, European Commission 

Joint Research Center Institute for Reference Materials 

and Measurements (EC-JRC-IRMM); (3) Kevin Summers, 

U.S. Environmental Protection Agency

Biopharmaceutical Manufacturing (1) Fred 

Razzaghi, Consultant; (2) William Koch, U.S. 

Pharmacopeia; (3) Larry Mahan, MD Department of 

Business and Economic Development

Medicine (1) Judy Britz, Britz Consulting; (2) Paul J. 

Utz, Stanford School of Medicine

Hot Topics (1) Jennie Hunter-Cevera, University of 

Maryland Biotechnology Institute; (2) Craig Jackson, 

Consultant

INTRODUCTION
Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 5

As world population continues to increase, thousands of acres 

of arable land are lost to development each year. As a result, 

there is increased pressure on agriculture and aquaculture 

to provide affordable, safe, and nutritious foods. New and 

innovative technologies are being developed to improve 

crop productivity, enhance crop protection, and increase 

environmental stress tolerance to help meet growing demands 

on the agricultural/aquaculture industry. Developing and 

testing these technologies involves sophisticated measurements 

on complex biological systems, including plants, animals, and 

microorganisms. 

The agriculture technical panel and plenary focused on future 

opportunities and challenges facing this important sector 

of the biosciences. These discussions produced a potential vision of the future and the broad challenges 

to be addressed. An important outcome was identification and prioritization of the critical measurement 

and standards challenges to technology innovation in this field. Overcoming these challenges is critical to 

increasing the yield, quality, and safety of the world’s food supply.

Vision of the Future

In the future, technological advances could lead to significant improvements in the way we grow, produce, 

and protect our food supply. These will affect more than just the quantity and quality of food supplied. 

Improvements will be achieved in the nutritional makeup of food (healthier and safer food), the sustainability 

of food systems (ecological, societal, and environmental), and the scientific ability to design foods that are 

personalized for individual consumption. 

Exhibit 2.1 illustrates the concepts put forth to describe some of the future characteristics of agriculture 

and the food supply. These characteristics embody what could potentially be attained with continued and 

sustained progress in technological innovation.

Technical Panel on Agriculture

Increasing yield, quality, and 

safety in the world’s food supply

Technical Panel Co-Leaders:

(1) Tamas Torok, Lawrence Berkeley National 

Laboratory; (2) Steven Britz, U.S. Department 

of Agriculture

Plenary Speakers: Pamela Ronald and 

Raoul Adamchak, University of California, 

Davis

2.0 

AGRICULTURE

2.0 

AGRICULTURE
6 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

Broad Challenges

The broad technological challenges identified for agriculture are shown in Exhibit 2.2. These illustrate 

the importance of better understanding the biology of plants and animals, their interactions with the 

environment, and their value as sources of food. To improve the quality of the food supply, clarification 

and consensus is needed on the constituents that are most nutritious and valuable to human health. Other 

challenges arise in expanding the food supply through aquaculture, which will require a much greater 

understanding and control of aquatic resources. Promoting a sustainable food supply is a key thread 

throughout. Future challenges arise in the use of fertilizers, pesticides, and water resources, as well as 

reducing the carbon footprint and other impacts on air, land, and water.

AGRICULTURE AGRICULTURE

Exhibit 2.1 Characteristics of the Vision of the Future for Agriculture

Technological Advances

• Systems are in place for more rapid plant breeding (predation-free and disease-free crops, moisture- and salt-resistant crops)

• Rapid, accurate, complete phytochemical composition analysis is possible, from farm to fork

• Genetically engineered (GE) agricultural products and crops are readily available

• Food is engineered for particular nutrients or profiles of nutrients; nutrient intakes are personalized based on genomics,

proteomics, lipidomics, and metabolomics

• Multiparameter measurements in complex biological systems are possible

• Unmanned aerial vehicles (UAVs) with remote sensing of crop stressors have the ability to monitor potentially dangerous

products

• Leaf pigments/protein: remote monitoring of photosynthetic capacity and nutrient limitation; precision agriculture; production

capacity

Societal Aspects

• Technical advancements provide food for 10 billion people in 20, 30, 40 years

• By 2030, education is available to the public, including farmers and breeders, on the environmental, social, and economic

impacts of sustainable agriculture

• Use of antibiotics in animal agriculture is significantly reduced or eliminated

Global Markets and Products

• Multi-country standards are in use

• Value of crops is based on compositional characteristics; agriculture becomes more than just a commodity market

Sustainability

• Efficient, safe nutrients and pesticides are used

• Real-time monitoring and modeling on the ecosystem scale is possible

• Crops are available to cope with climate change and rising emissions of CO2

• Sustainable animal production systems are in use

• Social and environmental costs (economic, other) of production are considered in design and operation of agricultural systems

• Solar energy is used as an energy resource for farm systems

• Carbohydrate profile, structural (i.e., fiber) and non-structural: important to defining nutritionally available energy in human

foods and animals feeds; important to biofuel applications
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 7

Exhibit 2.2 Broad Technological Challenges for Agriculture

Understanding Plants and Their Environments

HIGH PRIORITY

•	 Bioinformatics bottlenecks (communication, controlling vocabulary, data integration, storage 

analysis, and access to information)

•	 Insufficient knowledge of plant biology and ecosystems at the molecular level 

•	 Inefficient water use

MEDIUM PRIORITY

•	 Need to increase "effective" yield: move from valuing mass to target components (how to 

measure effective yield)

•	 Dynamic, non-invasive, in situ measurements capable of detecting/monitoring reversible, 

temporal, and spatial interactions

" Unintended consequences of GE food or increased yield, such as food safety issues (toxins 

and microbes)

•	 Establishing "best" targets for plant breeders to focus on

Understanding Animals and Their Environments

MEDIUM PRIORITY •	 Improved status of animal production efficiency, health, and environmental impact

•	 Replacing antibiotics and antimicrobials in animal feed

Post Harvest (Identity Preservation)

MEDIUM PRIORITY •	 Packaging food in safer ways (fewer contaminants such as heavy metals and toxins)

Improved Nutritional Quality

HIGH PRIORITY •	 Lack of agreement on valuable nutrients (beyond proteins, carbohydrates, fats, vitamins)

MEDIUM PRIORITY

•	 Improved methods for measuring phytochemical composition

•	 Need to clarify and agree on meat and egg nutritional quality 

" Essential fatty acid (EFA) status altered by limited food intake

Expanded Aquaculture Capabilities

MEDIUM PRIORITY

•	 Improvement of fish nutrition and disease control

•	 Need to develop algae that satisfy nutrient needs while minimizing water, soil effects (i.e., 

fewer pesticides, minimized environmental damage)

•	 Accounting for problems with invasive species

Sustainability

HIGH PRIORITY

•	 Enabling and encouraging precision agricultural practices

•	 Lack of comprehensive monitoring and modeling: water and agricultural chemistry

•	 Need to reduce the carbon footprint of agriculture

MEDIUM PRIORITY

•	 Better understanding of diseases for the development of "selective" pesticides

•	 Need to quantify "local" hydrology (atmosphere, surface, subsurface)

•	 Addressing air quality associated with animal production facilities

AGRICULTURE AGRICULTURE
8 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

Exhibit 2.3 illustrates the broad non-technological challenges that can impede technological advances to 

improve the food supply. Appropriate policies, incentives, standards, and regulation can help accelerate and 

encourage technological advances as appropriate.

Communication to promote dissemination of accurate information to the public is a broad challenge that 

must be addressed. A better understanding of land allocation (and the various benefits and disadvantages) 

is a key aspect. Consumers need to be better informed about what constitutes a healthy diet, the risks 

associated with the food supply, and future challenges. 

Education is an important element. To expand and continue rapid breeding programs, for example, will 

require rebuilding the plant breeding work force. Due to breakthroughs in nanotechnology and other areas, 

agriculture and food are increasingly multi-disciplinary and will require greater input from disciplines not 

traditionally involved in this field.

Role of Measurement

Measurements and standards play a key role in the agricultural sector, from plant genetics to production and 

harvest. Exhibit 2.4 illustrates the measurement parameters of interest and why they are important to better 

understanding and improving agricultural systems.

Exhibit 2.3 Broad Non-Technological Challenges for Agriculture

Policies/Regulations

HIGH PRIORITY

•	 Policies needed for rapid plant and animal breeding:

" Smart regulation

" Consistent international policies

" Government incentives to reduce cost

•	 Clarify/identify appropriate standards

MEDIUM PRIORITY •	 Addressing identified concerns about achieving national food security

•	 Internalizing environmental costs

Communication

MEDIUM PRIORITY

•	 Lack of public participation in allocating land

" Competing considerations for food, energy, "nature", living space

•	 Public perception of risk

•	 Need for improved diet education 

•	 Increasing population and its implications 

•	 Inability of consumers to make fully informed decisions about food consumption

•	 Inadequate education and information about products

Education

MEDIUM PRIORITY •	 Need to rebuild plant breeding work force 

•	 Multi-disciplinary educational requirements for new technology

AGRICULTURE AGRICULTURE
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 9

Exhibit 2.4 Key Measurements to Support Technological 

Innovation in Agriculture

Understanding Plants and Their Environment

•	 Gene expression: important part of expanding necessary information on biological systems

•	 Stomatal conductance: supports primary production and remote monitoring of photosynthesis and water supply

•	 Genome plus environment, which equates to phenotype: relation between plant and environment, to predict plant response 

and pathogen geography (timely, effective, efficient treatment)

•	 Photosynthetic partitioning and yield, genetics, CO2, environment: biotic/abiotic stress

•	 Microbial community structure/activities: space and time, intimate part of plant environment, safety 

•	 Environmental microbial baseline: finding human pathogens among background microbiota

•	 Reversible short-time interactions of living systems (massively parallel): understand multi-tasking

•	 Remote sensing: sensors for quantifying specific stressors (nutrient, disease, weeds, etc.); ecosystem health assessment largerscale linkage

•	 Leaf pigments/protein: remote monitoring of photosynthetic capacity and nutrient limitation; precision agriculture; production 

capacity

Understanding Animals and Their Environment

•	 Fertility and reproduction in animals: improved food supply 

•	 Antibiotic resistance: safety and health of animals

Post Harvest (Identity Preservation)

•	 GE protein in food: analysis of food components

•	 Standardized database of food components (baseline, seasonal, geography): compare GE and traditional plants

•	 Toxicity of biomaterial: ensure food safety

•	 Microbiota: interactions between food-borne microbes and consumer

•	 Traceability of food, with rapid track back to origin of problems: food safety, quality

•	 Rapid mycotoxin analysis: critical to food safety

Improved Nutritional Quality

•	 Phytochemical composition in foodstuffs: relation to genetics, environmental impacts

•	 Effects of phytochemicals on humans: impacts on cells, organisms

•	 Lipid composition: fats and oils are approximately 1/3 of energy intake; nutritional quality/absorption is related to lipid class and 

fatty acid content

•	 Amino acid profile rapid analysis: building blocks of protein critical to growth and therefore important to formulating animal 

production feeds

•	 Seed composition: more details will enhance crop quality

•	 Blood proteins for efficacy: what’s good/bad, most non-invasive, multiple proteins

•	 Natural antioxidants: foods contain a host of antioxidants important for food stability; many are undefined, qualitative analysis is 

needed

•	 Carbohydrate profile, structural (i.e., fiber) and non-structural: important to defining nutritionally available energy in human 

foods and animal feeds; important to biofuel applications

Expanded Aquaculture Capabilities

•	 Metagenomics of water environment: proteomics

•	 Environmental sensitivities: viability of aquaculture

AGRICULTURE AGRICULTURE
10 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

Exhibit 2.5 illustrates some of the measurements that are important to sustainable agriculture and particularly 

to reducing or mitigating pollution from farms. In general, this area was recognized as a high priority for 

measurements. Sustainability is becoming a key challenge as the industry looks to increase yields, quality, and 

nutrients without increasing environmental and other detrimental impacts.

Measurement also plays a role in policy and regulation. For example, to assure the biosafety and acceptance 

of GE crops, relevant functional assays are needed to support regulation. The challenges to accomplishing 

this are very complex. 

Measurement is also essential to communication of information about the food supply to the public. 

Confidence in food-related measurement helps assuage public concerns about food safety and enables 

consumers to make well-informed decisions.

Measurements and Standards Challenges

The key challenges related to measurements and standards for agriculture are illustrated in Exhibit 2.6. While 

these are not comprehensive lists of the measurement needs facing agriculture, they provide a starting point 

for some of the key challenges from a biosciences perspective.

Standards and Standardized Methods. A central theme is assuring confidence and consistency in 

biological measurements of plant/animal systems and their ecological and environmental interactions. 

Consensus among users of measurements and analytical tools is a critical aspect. Current methodologies 

have considerable variability and inconsistency among laboratories and within the user community. As the 

global aspects of markets continue to increase, international standards will be important to assure worldwide 

product acceptance and understanding of key parameters.

Exhibit 2.5 Key Measurements to Support Sustainability in Agriculture

Mitigating Environmental Impacts from Farms

•	 Sustainability measurements: recognition of good practices in the marketplace and promotion of sustainable practices

•	 Carbon and greenhouse gas (GHG) emissions associated with organic and conventional production practices: accessible 

database for carbon offsets

•	 Preferential fluid dynamics: although active only a fraction of the time, this process is responsible for up to 90% of pesticides 

reaching ground water

•	 Rapid analysis of phytate phosphorous: animal nutrition and environmental effects

•	 Fast analysis of potential human pathogens in waste used for fertilizer or compost: safety of raw produce

•	 Manure nutrient profile: animal waste profiles and environmental impacts

•	 Animal feed conversion ratio: improved precision of feed formulations (less waste)

Land Use and Soil Sustainability

•	 Indirect land use change: assessment of environmental/societal/economic externalities

•	 Degraded land: identification of where and how improved land use is possible

•	 Rapid soil nutrient analysis: soil nutrient mapping and fertilizer application as part of a precision agriculture system

•	 Soil-water dynamics (surface and subsurface hydrology): water drives plant growth and chemical transport and behavior

AGRICULTURE AGRICULTURE
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 11

Exhibit 2.6 Measurement and Standards Challenges for Agriculture

Standards and Standardized Methods

HIGH PRIORITY

• Better sampling methods and sample processing methods robust enough for complex

samples (environmental, food, animal)

• Reference materials for field testing devices

• Acceptance of standard method, if developed, by those using independent or in-house

methods

• International standards for compounds: protein, microbe analysis (threshold, standard

method)

MEDIUM PRIORITY

• Resolution of analytical variation (actual lab-to-lab and within a lab), with practical value

• Achieving consensus among those who use analytical tools and make decisions based on the

values

• Lack of knowledge of where to "sense" an agricultural environment (where to sample and

reflect environmental risk)

Technological Improvements to Measurements/Methods

HIGH PRIORITY

• Fertility tests and standards, with knowledge transfer to industry to improve animal and plant

science

• "Shotgun" lipidomics as a quantitative tool

" Requires an array of stable-isotope labeled standards for various lipid class, molecular

species

• Ineffective existing methods for chemical composition—time consuming and often require

extraction, which may generate errors

• Methods to assess carbon flux in plants—real-time (e.g., carbon-11)

• High-throughput molecular breeding technology

• Classification and enumeration of high-complexity microbial communities

MEDIUM PRIORITY

• Remote estimates of soil moisture/chemistry are too uncertain to use for optimizing irrigation

• Prion screening

• Identification and classification of microorganisms; species concept and lateral gene transfer

• Robust remote quantitative sensor for canopy photosynthetic capacity (not normalized

difference vegetation index [NDVI]) to identify stress

• Quantified uncertainty and representative measurements that monitor the environment (soil

water dynamics, flow processes, etc.)

• Detection of multiple proteins in complex mixtures (cheap, rapid, sensitive)

• High-throughput fatty acid analysis including robotic derivatization (transmethylation),

columns/methods for ultra-fast gas chromatography (GC) analysis, and software for

automated data analysis

Measurement Innovation

HIGH PRIORITY • Remote quantitative sensor for plant water status

• Nanotechnology devices for rapid detection (field devices)

MEDIUM PRIORITY

• In vivo, real-time measurements in an intact system

• Measurement of reversible interactions in multi-tasking living systems

• Measurement of microbiota structure and function

• Quantification of subsoil stratigraphy

AGRICULTURE AGRICULTURE
12 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

Technological Improvements to Measurement Methods. Primary challenges appear to be the need 

for greater accuracy, broader capabilities, speed of measurements and analysis, and the ability to take 

measurements both in real time and remotely. Improvements to measurement methods could provide new 

insights on plant and animal breeding, the value and use of lipids and fats, and the complexities of microbial 

communities. Enhanced monitoring of the environmental interactions among plant and animal systems could 

increase the capability to identify stresses on the environment and produce new knowledge to enhance plant 

and animal science and engineering. 

Measurement Innovation. The complexity of the biological systems involved creates a unique challenge 

that will require innovation in measurement methods, particularly for measuring water in plants, structures 

of microbiota, and reversible interactions occurring among living systems. New technologies such as 

nanotechnology could potentially be applied to develop new measurement methods that may help answer 

some of the key questions pertaining to plant and animal systems.

Sustainable Agriculture. Exhibit 2.7 illustrates some of the key measurement challenges related to 

developing and promoting the use of sustainable agricultural practices. One of the major challenges is 

identifying and coming to consensus on the minimal set of data that is needed to define and monitor 

sustainability, as well as to examine the life-cycle impacts. There are also significant challenges in 

understanding and communicating the true costs of sustainability (as well as non-sustainability), and ensuring 

that sustainable practices are practical for farmers and livestock operators. This means sustainable practices 

must be easy to implement and use, require a low level of training, and give reproducible results.

Priority Measurement Topics

The measurement challenges illustrated in Exhibit 2.6 provide the foundation for a set of three priority 

measurement focus areas for agriculture that aim to address these challenges. Collectively, panel members 

determined: the importance of the focus area, objectives in addressing it, a potential approach, and 

stakeholder roles. They also rated the technological and commercial risks and the impacts of action in five 

categories. Their findings are reflected in Exhibits 2.7–2.9. 

These focus areas address some of the most critical challenges that have been identified for agriculture. Many 

focus on improved data processing and analysis, making accurate measurement and information accessibility 

essential to overcoming these challenges. The priorities also reflect a need for new measurement technologies 

and standards to support a new level of quality and functionality in next-generation agriculture.

Exhibit 2.6 Measurement and Standards Challenges (cont.)

Sustainable Agriculture

HIGH PRIORITY

• Identification of minimal metadata collection requirements

• Understanding cost of sustainability: time, capital vs. value realized, economic/commercial

value, social value

• Promoting sustainable agricultural applications:

" Ease of use

" Level of required training

" Repeatability

MEDIUM PRIORITY

• Complexities of measurements for carbon footprint

• Limited accessibility of remote sensing data from federal and military sources

• Lack of agreement/establishment of variables to include in life-cycle analysis (LCA) and

sustainability assessment

AGRICULTURE AGRICULTURE
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 13

AGRICULTURE AGRICULTURE

Adequate analytical tools and technologies are not available for effectively and accurately measuring 

chemical and biochemical composition in plants, animals, soils, water, and waste streams.

•	 Improved food quality 

and safety

•	 Improved and efficient utilization 

of resources

•	 Assurance of public confidence 

in food supply and agriculture

•	 Encourage joint or collaborative 

efforts of laboratories

•	 Involve multiple government 

agencies and state agricultural 

groups

•	 Robust tools for composition 

measurement

" Increased capability for

metabolomics, proteomics, etc.

" Increased speed, sensitivity, 

specificity, and ease of use

" Decreased cost and size

•	 Clearly defined standards for 

public health 

•	 Accessible information for 

all stakeholders

PRIORITY MEASUREMENT AND STANDARDS CHALLENGE

RATIONALE OBJECTIVES ELEMENTS OF 

APPROACH

STAKEHOLDERS AND ROLES

Government: USDA and NIST in a leadership role; EPA and FDA in 

supporting roles 

National laboratories: National laboratories as appropriate

Industry: Consumer and producer stakeholder groups

Other: State and regional agricultural groups

RISK

The cost of improving analytical 

technologies may be high, but the 

long-term payoff will be positive.

RELATIVE IMPACTS

Accelerates innovation *** New instrumentation and data analysis

Enhances competitiveness *** Improved markets

Provides societal benefits *** Improved food safety and quality

Supports environmental protection *** Increased detection of contaminants

Preserves/enhances energy security ** Potential improvements to bioenergy crops

Technical

Commercial

Analytical Tools and Technologies for 

Composition of Agricultural Systems

Exhibit 2.7 Priority Measurement Topic

*** (High)

Low High
14 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

AGRICULTURE AGRICULTURE

Management of data generation, handling, processing, and dissemination is not 

effective enough to maximize the benefit of bioinformatics.

•	 Bioinformatics are the foundation 

for biology-based technology 

innovation

•	 Better computational tools 

are essential to cope with the 

complexity of data analysis, 

management, representation, 

and visualization

•	 Encourage joint or collaborative 

efforts by laboratories

•	 Involve multiple government 

agencies and state agricultural 

groups

•	 Rapid and accurate analysis of 

data 

•	 Integration of data into relational 

models that answer biological 

questions with high confidence 

•	 Enhanced data-sharing capacity

PRIORITY MEASUREMENT AND STANDARDS CHALLENGE

RATIONALE OBJECTIVES ELEMENTS OF 

APPROACH

STAKEHOLDERS AND ROLES

Government: USDA, NIST 

National laboratories: As appropriate

Academia: Development of tools

Industry: Data inputs

RISK

RELATIVE IMPACTS

Accelerates innovation ***

Allows for modeling, validation, and testing; 

describes system inter-relationships

Enhances competitiveness ***

Faster, confident data analysis supports accurate 

models and rapid innovation

Provides societal benefits *** Improved food supply for global populations

Supports environmental protection ***

Decreased environmental impact, optimized 

agricultural activities

Preserves/enhances energy security ** Optimized energy use and resources

Technical

Commercial

Bioinformatics for Agriculture

Exhibit 2.8 Priority Measurement Topic

Low High

*** (High)

Complexity of data handling and 

coordination among many users creates 

high commercial risk.
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 15

AGRICULTURE AGRICULTURE

Real-time technologies are not adequate for the remote/non-invasive 

measurement of required state variables for agriculture.

•	 Improved resource use efficiency

•	 Reduced biotic stress

•	 Environmental protection

•	 Improved productivity/cost 

efficiency

•	 Encourage joint or collaborative 

efforts of laboratories

•	 Involve multiple government 

agencies and state agricultural 

groups

•	 Sensors for water and nutrient 

status, weeds, pathogens, 

pests, temperature, pesticide 

volatilization, and air quality

•	 Data processing systems for raw 

data

•	 Data processing systems for 

analysis and decision making

PRIORITY MEASUREMENT AND STANDARDS CHALLENGE

RATIONALE OBJECTIVES ELEMENTS OF 

APPROACH

STAKEHOLDERS AND ROLES

Government: USDA research centers, NIST 

National laboratories: As appropriate

Academia: Data collection and testing

Industry: Technology development, validation

Private research institutes: Data validation

RISK

RELATIVE IMPACTS

Accelerates innovation *** New technology developed

Enhances competitiveness *** Increased quality and productivity and reduce cost

Provides societal benefits *** Reduced unneeded inputs, pollution, run-off

Supports environmental protection *** See above

Preserves/enhances energy security ** Increased biomass of energy crops

Technical

Commercial

Real-Time Remote and Non-Invasive 

Measurements for Agriculture

Exhibit 2.9 Priority Measurement Topic

Low High

*** (High)

Time and cost associated with new 

technology development creates high risk.
16 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges
Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 17

Recent scientific scenarios and possible contributions to rising 

food prices have raised some questions about the sustainability 

of first-generation biofuels produced from food crops (e.g., 

corn-based ethanol) or using resources (land and water) 

necessary for growing food for humans and farm animals. 

The production of alternative fuels from renewable, nonfood biological feedstocks, therefore remains an important 

component of any future alternative energy strategy, and offers 

potential for addressing greenhouse gas (GHG) emissions. 

Biodiesel produced from oil-rich algae or the recombinant or 

synthetic biology-based production of next-generation biofuels 

are examples of more sustainable sources of bioenergy currently 

under development. Measurements and standards are a critical 

aspect of biofuels at every stage of development, from basic 

research in plant science and genetics, to the distribution and 

delivery of biofuels to consumers.

The energy technical panel and plenary focused on future opportunities and challenges for sustainable 

production of non-food-based biofuels. Group discussions produced a potential vision of the future and the 

broad challenges to be addressed. They then identified and prioritized the critical measurement and standards 

challenges to the development and use of next-generation biofuels. Overcoming these challenges will be 

critical to establishing and maintaining the feedstock production, conversion, and delivery infrastructure 

needed to ensure that renewable biomass is a viable energy supply option. 

Vision of the Future

It is expected that bioenergy, and particularly biofuels, will increasingly become an established part of the 

energy infrastructure. While today most biofuels are made from corn (ethanol) and soy beans (biodiesel), 

next-generation biofuels produced from non-food sources will dominate in the future. While biofuels will not 

be the only alternative transportation energy option, they will be an important component along with electric 

vehicles, hydrogen fuel-cell vehicles, and others.

Exhibit 3.1 illustrates the concepts and characteristics of the vision of the future for biofuels. Attaining this 

vision will depend highly on the development and deployment of new biochemical and thermochemical 

technologies to convert non-food biomass resources (e.g., cellulosic biomass, algae) into viable fuels, 

chemicals, and materials. It is envisioned that integrated biorefineries of the future will routinely produce 

a wide slate of products from a diversity of feedstocks such as perennial grasses, woody energy crops, 

agricultural and forestry residues, and even industrial and consumer wastes.

Technical Panel on Bioenergy

Obtaining sustainable energy from 

biological sources

Technical Panel Co-Leaders: (1) Terry 

Purkable, Johns Hopkins University Applied 

Physics Laboratory; (2) Hratch Semerjian, 

Council for Chemical Research

Plenary Speakers: Anna Palmisano, U.S. 

Department of Energy

3.0 BIOENERG ioENERGYY
18 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

Broad Challenges

The broad challenges identified for biofuels are shown in Exhibit 3.2. The most critical challenges relate 

to technology development, specifically solving the recalcitrance problems of cellulosic biomass. Effective, 

economical pretreatment and conversion technologies, both biochemical and thermochemical, will be 

needed to successfully use non-food biomass such as perennial grasses, crop residues, and wood. 

BIOENERGY BIOENERGY

Exhibit 3.1 Characteristics of the Vision of the Future for Bioenergy

Energy Security and Infrastructure

•	 A significant portion of transportation fuels are derived from sustainable, domestically produced biofuels

•	 75% of fossil fuels are replaced with bio-based sources via a variety of fuels and blends

•	 Biofuels provide a significant source of clean, long-distance, and heavy-duty transportation fuels

•	 A robust national infrastructure promotes expanded use of biofuels (and flex-fuel engines)

Technological Advances

•	 Engines have been modified to make better use of biofuels

•	 Oil/hydrocarbons are produced directly from plants

•	 Direct conversion of sunlight to bio-based energy is possible (e.g., via genetic engineering)

•	 Biocatalysis provides new routes to chemicals

•	 Integrated biorefineries use proven biochemical and thermochemical technologies and diverse feedstocks to produce a variety 

of products

Global Market and Products

•	 Advances in biomanufacturing and co-products create new markets and products

•	 Enzymes and bacteria for biochemical production of biofuels are traded as commodities; clear standards and certified reference 

materials (CRMs) are available to assess organism potency for production of biofuels

•	 Global biodiesel/ethanol standards independent of feedstock are in use

•	 Global production and use of liquid biofuels from optimized bio-refineries increase, and such refineries are responsive to 

regionally appropriate standards

•	 The cost of energy from renewable biomass is less than the cost of energy from oil and coal

•	 National laws on fuel quality and testing assure marketability

Societal Aspects

•	 Long-term public commitment to biofuels beyond economics is a primary driver of development and deployment

•	 Consumers have a wider choice of economic transportation fuels

Sustainability

•	 Life-cycle analyses are available for expanded uses and types of biofuels

•	 Bioenergy is integrated with other sectors (e.g., buildings) on a local basis to improve sustainability (e.g., lawn clippings into 

fuel)
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 19

Exhibit 3.2 Broad Technological Challenges for Bioenergy

Technology Development

HIGH PRIORITY

•	 Economical conversion technologies (enzymes, gasification, products) for processing cellulosic 

biomass

•	 Better catalysts for cellulosic biofuels 

•	 Genetic engineering for more efficient production

•	 Catalysts for chemical production from biomass residues

•	 Optimized, integrated biorefining systems

MEDIUM PRIORITY •	 New biology for more efficient use of solar energy and acreage (microbes and algae)

LOWER PRIORITY

•	 Addressing the energy-water nexus (water and biomass sources, biorefining)

•	 Optimizing energy inputs into process (e.g., fertilizer, process heat)

•	 Efficient separation technology for end products

Feedstock Production, Storage and Transport

MEDIUM PRIORITY •	 Land use—optimizing fuel/acre efficiency 

•	 Multi-feedstock plants

LOWER PRIORITY •	 Assurance of feedstock supply and storage

Distribution and Delivery Infrastructure

HIGH PRIORITY •	 Infrastructure to deploy biofuels (transporting, storing, blending, dispensing)

MEDIUM PRIORITY •	 Fleet availability (engine development)

LOWER PRIORITY

•	 Standards and regulations (logistics)

•	 Optimization of infrastructure, i.e., supplies, production, distribution, and utilization; including 

byproducts

Methods and Standards Infrastructure

MEDIUM PRIORITY

•	 Local production/utilization, transport costs, point-source pollution

•	 Global standards addressing regional and other barriers 

•	 Need for rapid, precise, and inexpensive methods and certified reference materials

LOWER PRIORITY •	 Harmonization of standards for different feedstocks

Sustainability

HIGH PRIORITY •	 Sustainability of bio-feedstocks, from dirt to delivery

•	 Robust LCA methodology to enable fair comparison with oil, agriculture, and cattle

MEDIUM PRIORITY

•	 Defining and measuring sustainability across all relevant areas 

•	 Yield sustainability—biomass replacement, water use, other resources

•	 Effects of urbanization on farmland and other indirect impacts on land

•	 Limits of recyclability of materials on manufacturing options for bioproducts

BIOENERGY BIOENERGY
20 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

Distribution and delivery infrastructure also presents a critical issue, particularly as the volume of biofuels 

begins to increase. The current infrastructure needs to be expanded and improved to handle large volumes of 

next-generation biofuels. The infrastructure for transporting and storing biomass feedstocks is also insufficient 

and needs to be upgraded. Standards are needed both upstream to identify the quality and specifications of 

perishable biomass feedstocks from production through transport and storage, and downstream to specify 

fuel quality from the plant gate to vehicle use. 

Exhibit 3.3 illustrates the broad non-technological challenges to achieving the promise of next-generation 

biofuels. Public perception is a key issue; strong science and education are needed to increase public 

understanding and dispel misperceptions about biofuels. Market push and pull continue to be a challenge for 

biofuels. Next-generation biofuels based on non-food biomass are not cost effective given today’s technology, 

and capital and operating costs are high. Price-enabled products are needed to trigger demand and ensure 

continued investments from the commercial sector. Loan guarantees and other incentives may help to push 

biofuels forward until new technology becomes more mature.

For the industry to become established, stable development infrastructure must be created and sustained 

over the long term. The presence of a stable, educated workforce; funding to support long-term R&D as well 

as near-term demonstration projects; and coordination of information and other efforts at the federal, state, 

and local levels are all important elements of the needed infrastructure. 

Even though substantial investments have already been made, continued investment by the public and 

private sectors will be needed to move next-generation technologies into the marketplace. While cellulosic 

ethanol technologies are on the immediate horizon, there will be a significant lag between construction and 

operation of the first-generation plants and optimized operation of integrated biorefineries.

Exhibit 3.3 Broad Non-Technological Challenges for Bioenergy

Public Acceptance

HIGH PRIORITY •	 Improvement of public awareness of key issues through strong science

MEDIUM PRIORITY •	 Distribution of the correct message to a wide audience via multimedia

Economics

HIGH PRIORITY •	 Price-enabled products (trigger demand and sustain interest and production)

MEDIUM PRIORITY

•	 Large up-front capital costs

•	 Uncertainties in the price of oil and other economic factors (economic growth, commodities 

markets, cost of raw materials and resources)

LOWER PRIORITY •	 Identification of value-added components in feedstock and process

Development Infrastructure

HIGH PRIORITY •	 Basic infrastructure (stable workforce, adequate funding, coordination)

MEDIUM PRIORITY •	 Educated workforce (scientists, engineers, multi-disciplinary researchers)

Public and Private Investment

HIGH PRIORITY

•	 Long-term commitment to biofuels and funding for technology and infrastructure

•	 Long-term public and private commitment and funding for R&D and next-generation 

technologies

MEDIUM PRIORITY •	 Stronger national coordination of effort

•	 Economic incentives for farmers and technology originators

BIOENERGY BIOENERGY
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 21

Role of Measurement

Measurements and standards are vital to development and deployment of next-generation biofuels on a 

large scale. As illustrated in Exhibit 3.4, metrology is needed to support all aspects of the supply chain, 

from feedstock production and harvesting, to biomass conversion processes and eventual consumer use in 

vehicles.

Exhibit 3.4 Key Measurements to Support Technological Innovation in Bioenergy

Sustainability

•	 Input variables that comprise sustainability: land/water, infrastructure, demand, costs

•	 Consensus on sustainability and GHGs from land use: methods and standards for all alternate inputs related to current 

production and future production required by renewable fuel standards (RFS)

•	 Sustainability of biomass resources: available biomass resources compared to traditional sources they replace

•	 Land use carbon and change: land use change parameters will be important to land use class (LUC) values

Finished Fuel Properties

•	 Characterization of biofuels/material interactions: corrosion, surface friction 

" Inexpensive and accurate methods to work in the field, and assurance of biofuels quality, especially ethanol and biodiesel, at 

customer levels

" Internationally accepted standards, certified reference materials, and methods to facilitate use in global market are 

fundamental for robust use

•	 Renewable content: retail enforcement of mandates, regulations

•	 Toxicity of byproducts and biofuels: impacts on health and safety

•	 Characterization of combustion products: characterization of next-generation biofuel engines

Thermochemical and Physical Properties

•	 Feedstock and fuel properties: critical to quality control 

•	 Properties of critical substances and reactions: alcohol, structure, thermodynamics, reaction kinetics and transport properties 

(equilibrium constants), enzyme activity; certified reference materials and analytical methods, standard reference data

" Enables process design and process optimization; measurement/monitoring of process variables; supports computation 

and modeling

•	 Fundamental thermophysical properties: heat of combustion, vapor pressure, vapor-liquid equilibrium (VLE), liquid-liquid 

equilibrium (LLE), and viscosity to enable rational design and optimization

•	 Energy efficiency: energy inputs, process energy, energy outputs to enable technology comparison

Process Monitoring

•	 Feedstocks characteristics: impact of feedstocks on processes

•	 Chemical composition of feedstocks: enable process parameter modification/feedback in biorefineries

•	 Online/automated analysis of complex process streams: better control, optimization, ultimately higher yield, 

efficiency, and profit

•	 Online chemical composition of bioproduct and co-products: enable tight quality control

•	 Conversion of biomass to sugar: better understanding of a critical process step, assessment of phases

•	 Metabolic "traffic monitor" in organisms: understand mechanisms of industrial organisms

•	 Quality assurance: new measurement methods, procedures, and CRMs to support high quality in biofuels production, 

especially second-generation enzymes

•	 Remote sensing of crop readiness and water use: enable large-scale production planning

BIOENERGY BIOENERGY
22 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

Measurement and Standards Challenges

The key challenges related to measurements and standards for bioenergy are illustrated in Exhibit 3.5. 

These are not intended to be all-inclusive of the measurement needs that must be addressed for bioenergy. 

However, they provide a starting point for identifying some of the key challenges facing the emerging 

biofuels industry.

Exhibit 3.5 Measurement and Standards Challenges for Bioenergy

Analytical Measurements

HIGH PRIORITY

•	 Characterization of various forms of biomass and fundamental biochemical substances 

(e.g., xylose, cellulose)

•	 Fast test methods and devices for field enforcement; faster, simpler, cheaper field techniques 

to measure product characteristics

•	 Lack of understanding and inadequate measurement of future biofuels (e.g., biodiesel, other 

next-generation fuels)

MEDIUM PRIORITY

•	 Carbon dating to identify renewable fraction of biofuels

•	 Robust, sound methods for monitoring production of next-generation biofuels, especially 

enzymatic processes

•	 Method to determine origin of biofuels (e.g., feedstock source)

•	 Difficulty in testing toxicity in humans

LOWER PRIORITY •	 Lack of measurement technology to address thermal instability of long-chain compounds

Documentary Standards

HIGH PRIORITY •	 Standards based on performance measurements that are independent of feedstock

•	 Consensus metrics for greenhouse gases, definition of sustainability of biofuels production

MEDIUM PRIORITY

•	 Standards to enable stable, quantifiable fluorescence (biomarkers, microarray, gene chip) for 

online sampling/monitoring

•	 Standardization of highly complex feedstocks (e.g., oils composed of many types 

of triglycerides)

Harmonization of Measurements and Standards

HIGH PRIORITY

•	 Extensive infrastructure of measurements and associated techniques: reference materials, 

cheap field methods; accredited laboratories; certification schemes

•	 Harmonized test methods and units between countries to enable comparison of results

MEDIUM PRIORITY

•	 International harmonization of measurements of key parameters; involvement of national 

metrology institutes for CRM, protocols, and sustainability measurements

•	 Preemptive federal laws covering various biofuels metrics

LOWER PRIORITY •	 Alignment of state/local standards with national standards

BIOENERGY BIOENERGY
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 23

Analytical Measurements. There is an immediate need to improve characterization methods for various 

forms of biomass in terms of composition, reliability, quality, and enzyme activity, particularly for nextgeneration biofuels. Methods are needed to monitor the characteristics of biomass in production and 

harvesting; during conversion processes; and after storage, transport, and delivery. In the long term, it would 

be desirable to be able to understand and monitor issues related to toxicity, reliably identify the renewable 

fraction of a biofuel in situ, and identify the originating feedstock.

Documentary Standards. Standards are needed to establish the performance and sustainability of biofuels, 

regardless of the type of feedstock used. Sustainability is an issue that should be addressed in the near term, 

particularly by defining sustainability parameters. Defining sustainability for both the biofuels already in the 

marketplace and next-generation biofuels continues to be a challenge worldwide. The standardization of 

highly complex mixtures, such as oils containing a variety of triglycerides, is problematic because of the many 

combinations possible, although this could potentially be addressed via development of standards using 

surrogate mixtures. 

Harmonization of Measurements and Standards. Ensuring consistent measurements and standards 

across the biofuels supply chain requires an extensive network of measurement methods and techniques. 

While portions of this network are already in place, new components will need to be developed, particularly 

for biomass production and quality assurance. The measurement infrastructure also needs to accommodate 

next-generation biofuels as they begin to enter the market. With the global market for biofuels steadily 

increasing, a high priority is to establish a measurement and standards framework and infrastructure that are 

harmonious across nations. This will ensure that the United States can potentially export and import biofuels 

and bioproducts as well as biomass feedstocks. 

Priority Measurement Topics

The measurement challenges illustrated in Exhibit 3.5 provide the foundation for a set of five priority 

measurement focus areas for bioenergy that aim to address these challenges. Collectively, panel members 

determined: the importance of the focus area, objectives in addressing it, a potential approach, and 

stakeholder roles. They also rated the technological and commercial risks and the impacts of action in five 

categories. Their findings are reflected in Exhibits 3.6–3.10. 

These focus areas address some of the most critical challenges that have been identified for bioenergy. Many 

concentrate on standards and references, making compatibility and consensus essential to overcoming these 

challenges. The priorities also reflect a need for new measurement technologies to support a new level of 

quality and functionality in next-generation bioenergy.

BIOENERGY BIOENERGY
24 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

BIOENERGY BIOENERGY

Exhibit 3.6 Priority Measurement Topic

The lack of standard reference data for bioenergy process design, optimization, and policy is slowing 

development of these technologies. Without certified reference materials as the basis for reliable 

measures, bioenergy technology cannot achieve its full potential.

•	 Improved effectiveness of process 

design, optimization, and policy

•	 Fundamental for measurements 

and biofuels infrastructure 

•	 Enabled understanding of 

biotechnological processes

•	 Coordination on a global 

scale

•	 Skilled people to evaluate data

•	 Adequate and long-term 

funding for efforts

•	 Find data gaps, fill with new 

experiments and computations

•	 Involve full production chain

•	 Gain user inputs on priorities

•	 Acceptance and comparability of 

measurement results

" Customer bases for 

acceptance

" Legal bases for commerce

" Quality assurance (e.g., 

proficiency of performance)

•	 Comprehensive and reliable 

tables of biofuels property data

" Consensus data of 

importance

PRIORITY MEASUREMENT AND STANDARDS CHALLENGE

RATIONALE OBJECTIVES ELEMENTS OF 

APPROACH

STAKEHOLDERS AND ROLES

Government: Funding support; NIST (leadership on measurement 

infrastructure)

Industry: Trade groups 

Private research institutes: Test and validation

Standardization bodies: Standards

RISK

RELATIVE IMPACTS

Accelerates innovation *** New bioenergy technologies

Enhances competitiveness *** Lowered cost, proven performance and quality, 

enhanced global marketability

Provides societal benefits *** Accelerated use of renewable energy options

Supports environmental protection ** Optimized energy requirements for processing 

and distribution

Preserves/enhances energy security *** Commercial use of biofuels as alternatives to oil

Technical

Commercial

Standard Reference Data and 

Certified Reference Materials for 

Bioenergy Technologies

Good data is necessary at an early 

stage for commercial development. The 

reference material may be obsolete by the 

time it reaches the market, posing some 

commercial risk.

Low High

*** (High)
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 25

BIOENERGY BIOENERGY

A gap exists between emerging definitions of sustainability and the potential to move toward 

sustainable practices; consensus metrics and documentary standards will enable a consistent 

approach to sustainability.

•	 An objective approach allows 

for marketplace acceptance, 

business and development 

planning, land management 

decisions, and public policy 

development

•	 U.S. government works with 

other governments to create a 

standards framework

•	 Focus on regionally appropriate, 

measurable sustainability 

standards

•	 Objective, measurable approach 

to sustainability to help improve 

the process

•	 Utilization of consensus metrics 

in the development of biofuels

PRIORITY MEASUREMENT AND STANDARDS CHALLENGE

RATIONALE OBJECTIVES ELEMENTS OF 

APPROACH

RISK

RELATIVE IMPACTS

Accelerates innovation ** Better understanding of sustainability of new 

biofuels products

Enhances competitiveness *** Helps demonstrate balance of sustainability and 

performance, enables global marketability

Provides societal benefits *** Ensures greater sustainability in product 

development and use

Supports environmental protection *** Provides consistent approach to sustainability with 

fewer environmental impacts

Preserves/enhances energy security *** Sustainable alternative to imported fuels

Technical

Commercial

Consensus Metrics for Greenhouse 

Gases, Land Use, and Sustainability

The cost of improving analytical 

technologies may be high, but the payoff 

will be positive in the long term.

Government: Open process with many research initiatives and stakeholders, 

including agriculture, biofuel producers, international agricultural research 

groups, and non-governmental organizations

STAKEHOLDERS AND ROLES

Exhibit 3.7 Priority Measurement Topic

Low High

*** (High)
26 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

BIOENERGY BIOENERGY

Molecular events associated with the breakdown of cellulosic materials to sugars (an extremely difficult 

process that is key to the conversion and use of cellulosic biomass) are not well understood.

•	 Enhanced production of biofuels 

from cellulosic materials

•	 Improved processes that are 

more cost effective and faster 

(potentially increasing yield)

•	 Industry partnership with NIST

•	 Set up benchmarks for plant 

material science

•	 Enable determination of

" The structure of cellulose and 

hemicellulose in different types 

of feedstocks and the impact of 

different types on pre-treatment 

of structure

" How enzymes interact with 

pretreatment products/

individual trial enzymes

•	 Improved understanding of 

the various mechanisms and 

interactions of lignocellulose 

with enzymes

•	 Better model of lignocellulosic 

structure 

" Computational chemistry

PRIORITY MEASUREMENT AND STANDARDS CHALLENGE

RATIONALE OBJECTIVES ELEMENTS OF 

APPROACH

STAKEHOLDERS AND ROLES

Government: Policy, standards support, funding 

National laboratories: Techniques/fundamental data or materials

Academia: Basic research/engineering

Industry: Validator feedback

Private research institutes: Basic research/engineering

RISK

RELATIVE IMPACTS

Accelerates innovation *** Accelerated technology development for use of 

cellulosic materials for biofuels

Enhances competitiveness ** Cost-effective pathways for biomass pretreatment 

and conversion

Provides societal benefits ** Use of non-food biomass resources

Supports environmental protection ** Fewer environmental impacts and greenhouse 

gases from cellulosic biofuels

Preserves/enhances energy security *** Use of abundant, domestic biomass as fuel source

Technical

Commercial

Breakdown Mechanisms of 

Cellulosic Materials

Technical and commercial risk is relatively 

high until the technology is proven.

Exhibit 3.8 Priority Measurement Topic

Low High

*** (High)
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 27

BIOENERGY BIOENERGY

Lack of field inspection test kits that are accurate, affordable, and accompanied by timely lab results 

increases product cost and decreases consumer protection.

•	 More timely inspection for 

compliance will improve 

consumer protection and 

economics

•	 Develop

" The device, (sensitivity of test, 

test methods for content, firmly 

established tolerance limits)

" Reference materials (accuracy/

reliability)

" ASTM standards for emerging 

biomass and finished fuel

•	 Technology transfer to 

manufacturer/distributors

•	 A screening device that is faster, 

simpler, and cheaper

•	 Results within minutes that 

would test for compliance with 

ASTM standards

PRIORITY MEASUREMENT AND STANDARDS CHALLENGE

RATIONALE OBJECTIVES ELEMENTS OF 

APPROACH

RISK

RELATIVE IMPACTS

Accelerates innovation * Indirect advanced fuels development

Enhances competitiveness * Increased consumer confidence and marketability

Provides societal benefits *** Consumer protection with new fuels, enables 

cheaper fuels

Supports environmental protection ** More consistent fuels, inspection tests to reduce 

environmental impacts

Preserves/enhances energy security *** Confident use of new renewable energy resource

Technical

Commercial

Fuel Compliance Inspection Tools 

for Retail Products

Near-term, inexpensive technology with 

low technical and commercial risk and 

high probability for acceptance.

STAKEHOLDERS AND ROLES

Industry (including trade groups and standards 

organizations): Form a task force of automotive engineers, 

consumers, developers, regulators, manufacturers, and the fuel industry to 

address issues

Exhibit 3.9 Priority Measurement Topic

Low High

*** (High)
28 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

BIOENERGY BIOENERGY

Lack of compatible test methods and units between countries increases cost and hampers 

biofuels development, use, and global trading.

•	 Trade facilitation

•	 Comparison of fuel technologies

•	 Guaranteed quality and fuel 

performance

•	 Utilize and work with existing 

international consortia/

organizations

•	 Identify criteria for comparison 

that is globally acceptable

•	 Comparability of fuel 

properties to support 

international trade 

(export and import)

•	 Compatible infrastructure design

•	 Assurance of engine 

compatibility

PRIORITY MEASUREMENT AND STANDARDS CHALLENGE

RATIONALE OBJECTIVES ELEMENTS OF 

APPROACH

RISK

RELATIVE IMPACTS

Accelerates innovation * Indirect support for new, advanced biofuels

Enhances competitiveness *** International trade and marketability support

Provides societal benefits ** Consumer confidence in renewable transportation 

fuels

Supports environmental protection *** Global comparability and acceptance for 

sustainability

Preserves/enhances energy security *** Global acceptance, use of biofuels

Technical

Commercial

International Compatibility 

of Biofuels

Low technical and commercial risk for 

standards and test methods; global 

support for new methods.

STAKEHOLDERS AND ROLES

Government: U.S. and other countries, NIST and other NMIs

Academia: Data collection

Industry: Test and validation

Trade groups: International trade and standards organizations

Exhibit 3.10 Priority Measurement Topic

Low High

*** (High)
Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 29

Technological advances in commerce, healthcare, agriculture, 

and energy production in the 21st century will profoundly 

affect the condition of the environment and the ecosystems 

that compose it in many unanticipated ways. For example, 

introduction of "new" pollutants (e.g., prescription drugs and 

metabolites, new-generation pesticides, and flame retardants) 

may impair natural processes and degrade environmental 

quality. These unintended consequences of environmental 

alterations on global ecosystems have the potential to 

adversely affect human well-being, including public health, 

economic sustainability, and the resilience of communities 

and cultures. It is critical that early warning systems to 

assess the status and trends of the environment and identify 

potential threats to ecosystems and human well-being be 

established at local, regional, national, and global scales before 

irreparable harm ensues. To mitigate these risks, identification 

of environmental quality and public health indicators, and 

development of new measurement and testing technologies and methods, including sampling procedures 

and sensor systems, will be required. 

The environment technical panel and plenary focused on exploring the potential measurement, standards, 

and technological challenges that must be overcome to establish and implement the required early warning 

systems. The panel identified the technological advances required to distinguish natural environmental 

changes from those resulting from anthropogenic activities. The following sections describe the results of 

the technical panel discussions, including a potential vision of the future and broad challenges that need 

to be addressed. The prioritized critical measurement and standards challenges to technology innovation 

identified by the committee must be overcome to create and sustain environmental early warning systems 

that contribute to sustaining healthy ecosystems and human well-being.

Vision of the Future

In the future, it is envisioned that systems for monitoring and tracking the state of the environment will 

quantitatively measure ecosystem health in near real time through advances in technology and measurement 

methods. Interoperable and networked information management systems and models will translate the 

complex data obtained into information valued by other sectors and environmental decision makers. It is 

possible that a "P4 medicine" approach, described by Dr. Leroy Hood in his Medicine plenary lecture, could 

be achieved for the environment (predictive, preventive, place-specific, and participatory) where information 

from environmental early warning systems is combined with the prognosis and treatment of potentially 

endangered ecosystems. 

Exhibit 4.1 illustrates some of the characteristics of the future of the environment that could help sustain early 

warning systems. Measurement technologies—new and improved—play a key role in all of the concepts 

shown. 

Technical Panel on Environment

Understanding our planet through 

linking molecules to ecosystems

Technical Panel Co-Leaders: (1) Fred 

Holland, Former Director, Hollings Marine 

Laboratory; and (2) Hendrik Emons, Head 

of Reference Materials Unit, Institute for 

Reference Materials and Measurements 

(IRMM)/JRC European Commission

Plenary Speakers: Stephen Weisberg, 

Southern California Coastal Water Research 

Project Authority, USA

4.0 

ENVIRONMENT

4.0 

ENVIRONMENT
30 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

Broad Challenges

The broad challenges identified for environment are shown in Exhibit 4.2. Some of the greatest challenges 

relate to our lack of a mechanistic understanding of the linkages between human activities, environmental 

threat, ecosystem processes, and human well-being. Currently, there is little agreement on what to measure 

and how to measure it to characterize environmental health. New tools and methods are needed to increase 

knowledge and understanding of complex ecosystems and how they interact to sustain human wellbeing. The impacts of anthropogenic activity on the environment can be significant, and ideally should be 

predicted and understood in advance, rather than addressed retrospectively. Another critical challenge is 

effectively assimilating and integrating the large amounts of multi-disciplinary data required for a reliable early 

warning system. The complexity of ecosystems and resulting information presents considerable challenges 

if the data are to be used for decision-making in a timely way. Communication of information in general is 

an issue, particularly among different disciplines, scientific communities, and with the public and private 

sectors. Overall, the non-linear, dynamic state of the environment and ecosystems represents an overarching 

challenge that adds to the complexity of forecasting potential issues and impacts before they occur.

ENVIRONMENT ENVIRONMENT

Exhibit 4.1 Characteristics of the Vision of the Future for Environment

Measurement Science and Technology

•	 Analytical methods for assessing environmental health that are quantitative, specific, and standardized are available for 

application for a range of spatial and temporal scales

•	 Broadly applicable, rapid molecular biology tools are used to measure toxins, pathogens, biodiversity (microbes to communities), 

and organism health

•	 Networked real-time sensors feed information about toxins, pathogens, biodiversity, and ecosystem processes into web-based 

databases where reliable models convert the complex data into information useful for environmental decision-making 

•	 Advanced databases and IT systems support for centralized knowledge and information exchange

Predictive Modeling and Simulation

•	 Models that describe structure-property-function relations and connectivity from molecules and ecosystems are developed and 

used to identify key environmental quality indicators and measurements

•	 New modeling approaches improve capabilities for forecasting and hindcasting changes in environmental conditions

Ecosystem Health Services and Products

•	 Rapid, accurate, qualitative, objective measures of ecosystems enable P4 (predictive, preventive, place-specific, participatory) 

management of ecosystems 

•	 The connectivity between a healthy environment and human well-being and quality of life is understood and valued by society
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 31

Exhibit 4.2 Broad Technological Challenges for Environment

Defining Complex Ecosystems and Health

HIGH PRIORITY

•	 Rapid and reliable real-time results for key environmental quality indicators that bridge 

historical and new measurement approaches 

•	 Lack of reference materials for key environmental quality indicators (toxins, strains, genetic 

sequences) 

•	 Difficulties in making new technologies user-friendly (kits, dipsticks, indices) from local to 

global scales 

•	 Lack of reliable and rapid methods for assessing pathogen risks and virulence

MEDIUM PRIORITY

•	 Accepted and standardized procedure for validation of new measurement methods at 

multiple spatial and temporal scales with fewer false positives 

•	 Standardized sample processing (concentrating, extracting, purifying) for molecular level 

indicators

LOWER PRIORITY •	 Lack of fast, cheap approaches or tools for measuring ecosystem health, including biodiversity

Impacts of Commercial Activity

HIGH PRIORITY

•	 Technology transfer to client communities (commerce, government, management, public at 

large) 

•	 Prevention/prediction of environmental problems before they occur

•	 Non-linearity/dynamic state of ecosystems

MEDIUM PRIORITY

•	 Addressing potential issues early on, during development stages (research to application); 

enacting regulations in advance using forecasting tools

•	 Adoption of new approaches and methods at local scales/field level

LOWER PRIORITY

•	 Understanding of new product performance and prediction of unintended impact on 

environment

•	 Forecasting and addressing climate change (highest priority in Organisation for Economic 

Cooperation and Development/Working Party on Biotechnology [OECD/WPB])

Complex Data Integration/Processing

HIGH PRIORITY

•	 Interdisciplinary environmental measurements represent multiple spatial and temporal scales 

and are difficult to integrate 

•	 Reliable forecasting tools and predictive models for environmental stresses do not exist and 

modes of action are poorly understood for many stressors

MEDIUM PRIORITY •	 Difficulty measuring the non-linearity and dynamic nature of ecosystems

Communications

HIGH PRIORITY

•	 The perception that environmental health is not important and is antithetical to the economy 

and human well-being 

•	 Inadequate mechanisms and systems for communicating environmental data across sectors 

and disciplines

MEDIUM PRIORITY •	 Engagement of the commercial sector to become proactive in protecting ecosystem health 

and services

LOWER PRIORITY •	 Interdisciplinary communications require a common language/terminology

ENVIRONMENT ENVIRONMENT
32 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

Role of Measurement

Exhibit 4.3 illustrates the measurements that are important to building early warning systems for the 

environment, particularly those relevant to system properties and ecosystem health. Important measurement 

areas include (1) explanatory variables and external drivers that provide information about the environmental 

setting and the external environmental and socio-economic factors that affect ecosystem characteristics 

(climate change, land and resource use, extreme events such as hurricanes, and the degree and type of 

pollution); (2) biomarkers, diagnostics, and exposure measures that provide information about threats or 

factors that affect environmental condition and health; and (3) broader system properties (biodiversity, food, 

and biomass/fiber production) that are critical to sustaining ecosystem functions and services and support 

human well-being. Identification of system properties was particularly problematic because no generally 

accepted definition of ecosystem health exists and many ecosystem services are undervalued by society 

(waste processing, food and biomass/fiber production, climate and flood control).

Exhibit 4.3 Key Ecosystem Measurements for Environmental Early Warning Systems

Explanatory Variables and External Drivers

•	 Identification and characterization of stressors: resource and land use, pollution, extreme events, invasive species, and climate 

change

•	 External drivers and inputs: atmospheric and hydrographic processes, inputs of key materials

•	 Bulk physical and chemical properties: temperature, oxygen levels, and other environmental quality parameters

•	 Full life-cycle carbon budget: cradle-to-grave understanding of interactions with climate

•	 Historical and current data: retrospective analysis, evaluation of trends

Biomarkers/Diagnostics/Exposure Measures

•	 Degree of environmental contamination and stress: levels of chemical pollutants, toxins, and pathogens in the environment 

•	 Contaminant fate and effects: threshold values for new and emerging pollutants, mixtures of pollutants, pathogen abundance 

and virulence

•	 Identification of threshold values and limits for exposures: pollutant concentrations that affect critical biological functions 

•	 Abundance and genetic profiles of key pathogens and other toxin-producing organisms: improved assessment of risk and 

virulence, genetic markets of toxicity and virulence

•	 Species identification and organism identity: microbes to higher taxa (group in class of organisms) 

•	 Genetic profiles of pathogens and other microbes: presence of virulence or toxin-producing genes

•	 Extreme and unanticipated occurrences or events: extreme wildlife mortalities, persistent toxic algae blooms, and presence of 

invasive organisms

•	 Human exposures and health effects: contaminant levels in food products and recreational waters

System Properties

•	 Biodiversity at multiple levels: community, specific taxa, and molecular 

•	 Health of sentinel organisms: population and disease status, physiological state, metabolic signatures, and reproductive 

condition

•	 Rates of key processes: food and fiber production, material transformations and processing

•	 Change in ecosystem services that affects human well-being: flood control, food or fiber harvest levels, and human illness and 

disease

ENVIRONMENT ENVIRONMENT
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 33

Supporting or explanatory measurements provide important ancillary information for developing 

preventive and remediation strategies and identify external drivers and factors that affect ecosystem health 

that are well beyond the immediate system boundaries and sphere of influence. Biomarkers and other 

diagnostic indicators are important to identification, characterization, prevention, and treatment of adverse 

environmental changes. For example, biomarkers can be used to identify potential for disease, determine 

the virulence and fate of harmful organisms or pathogens, and assess the potential for toxic releases. 

Exposure measurements provide information about the actual degree of contamination and other stresses 

the biological components of an ecosystem experience. Evaluating system responses to multiple stressors, 

such as complex mixtures of chemical pollutants, is important because synergistic interactions often result in 

effects which far exceed the additive effects of the substances composing the mixture. Information about the 

effects of multiple stressors provides input to models that improve predictions of potential impacts on health, 

safety, and environmental condition. Overall system measurements are those ecosystem attributes that are 

most directly connected to ecosystem attributes and services that affect human health and well-being. For 

example, the health of sentinel species, like fish and marine mammals, may provide early warning and better 

understanding of potential threats to human health and well-being.

Measurements and Standards Challenges

The key challenges related to measurements and standards for environmental early warning systems are 

illustrated in Exhibits 4.4 and 4.5. These are not intended to be all-inclusive for the measurement needs 

that must be addressed for this important field. However, they provide a starting point for identifying and 

prioritizing some of the key challenges that must be addressed.

Explanatory Variables. The major challenge to incorporating broad perspective variables (e.g., resource 

and land use, air and water transport, global patterns) will depend on effective integration of a diversity of 

data at different scales, from the molecular to ecosystem levels. This will require an array of measurement 

technologies ranging from DNA probes to satellites, geographic information systems, and others. Collecting 

and integrating multi-disciplinary data at these scales will require a significant investment for research, 

development, demonstration and deployment of new technologies, data gathering, and modeling.

Exposures and Stressors. Greater understanding of the linkages among external drivers and stressors 

affecting ecosystem health, environmental exposures, and system-level responses is needed as an underlying 

foundation for an environmental early warning system. Gaining this knowledge is impeded by the growing 

magnitude and diversity of toxins, chemicals, hazardous compounds, pathogens, diseases, and other stressors 

released into water, air, land, and living systems. The impacts of multiple stressors and complex mixtures is 

particularly problematic and must be measured and understood to forecast and effectively remediate system 

responses and sustain ecosystem services critical to human well-being. New measurements and standards, 

including sampling methods, could be required for toxins, pathogens, and other stressors.

Biomarkers. Standardized, validated methods for the development and use of biomarkers are currently 

lacking and are critical for the proper incorporation of biosciences into early warning systems. Issues such 

as natural variability, specificity of biomarkers, variability across environmental conditions, accountability for 

regional differences within and among species, and other challenges which impede standardization have to 

be addressed.

System Indicators and Properties. Priority challenges for obtaining system properties involve first 

defining what constitutes the ecosystem, determining the measures of system health, and identifying 

the indicators that provide early warning of changes in ecosystem health, or services that are important 

to sustaining ecosystem health and human well-being. Once defined, a variety of challenges remain in 

obtaining the system-level measurements needed, such as characterization of biodiversity at the molecular 

level, assessment of the health status of sentinel organisms, effective utilization of remote sensing systems, 

ENVIRONMENT ENVIRONMENT
34 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

Exhibit 4.4 Measurement and Standards Challenges 

for Environment Early Warning Systems

System Properties

HIGH PRIORITY

•	 Definition of the components and indicators of ecosystem health and services 

•	 Species definition from a molecular perspective: appropriate level of similarity 

•	 Assurance of temporal/geographic stability of indicator or diagnostic responses

MEDIUM PRIORITY

•	 The non-steady state, non-linear aspects of ecosystems and environment

•	 Remote-sensing technology to provide molecular- to system-scale measurements—requires technology 

development and ability to interpret hyperspectral signatures

•	 Availability of repositories for cells, tissues, and cultures

•	 Reproducibility of measurement results across researchers, platforms, and users

•	 Establishment of a standard and supplemental catalog for biologic component identification at all 

levels (molecular-ecosystem/biomedical)

•	 Difficulty with biological sample stability and archiving when compared to chemicals 

•	 Handling natural bio-variability in protein characterization and single nucleotide polymorphisms (SNP)/

post-translational modifications (PTM)

System Indicators

HIGH PRIORITY

•	 Characterization and quantification of a "healthy" ecosystem, community, or organism

•	 Lack of accepted measures of sentinel organism health

•	 Difficulty validating metagenomic analysis

•	 Identification of crucial system-level parameter(s)

MEDIUM PRIORITY •	 Net carbon sequestration or emissions by natural or managed ecosystems 

•	 Availability of inexpensive, reliable, non-satellite-based remote sensing technologies

LOWER PRIORITY •	 Effective method for identifying reliable sentinel organisms

Biomarkers

HIGH PRIORITY

•	 Difficulties with biomarkers (e.g., some are species-specific; current standards and reference 

materials may not apply; regional differences may exist within species)

•	 Validated methods for multiple biomarkers (metabolite patterns) for stress and disease

MEDIUM PRIORITY

•	 Poor comparability of proteomics measurements 

•	 Missing reference materials for quality assurance/calibration

•	 Lack of reliable generic biomarkers for organism "stress", including disease

Explanatory Variables

MEDIUM PRIORITY

•	 Data integration from molecular to system level—technology ranging from DNA probe to satellite 

imagery

•	 Sufficient investment in technology

Exposures and Stressors

LOWER PRIORITY

•	 Availability of more certified toxin standards

•	 Pathogen concentration/extraction from environmental samples

•	 Validation of cell-line culture viability/virulence during archival for use in later response studies

•	 Predicting emerging pathogens arising from climate change

•	 Methods for measuring emerging contaminants/metabolites in water, sediment, and tissues, given a 

continuously changing compound list

•	 Limited data and methods for toxicity of mixed and new chemicals

•	 Lack of methods/standards for many harmful algal bloom (HAB)-related toxins

ENVIRONMENT ENVIRONMENT
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 35

attainment of accurate measurements, and assurance of the integrity and fitness-for-purpose of biological 

samples. Development of system-scale indicators and property measurements will be a mid- to long-term 

endeavor due to the complexity of ecosystems. 

As Exhibit 4.5 illustrates, there are a number of critical crosscutting measurement and standards 

challenges that should be addressed to enable the development of environmental early warning systems. 

Standardization of methods and measurements is a key aspect. One of the most important issues to be 

resolved is reconciling differences between old and new measurements and developing new standards 

where they are needed. Other key challenges involve handling the large amounts of information required at 

different scales, ensuring validity of data, coordinating with existing efforts in different disciplines/agencies, 

and building a foundation of widely applicable molecular-level measurement tools such as biomarkers, 

genetic probes, and microarrays. Other challenges arise in the comparability of measurement results, and the 

effective linking of different environmental parameters to enable appropriate decision-making.

ENVIRONMENT ENVIRONMENT

Exhibit 4.5 Crosscutting Measurement and Standards Challenges 

for Environmental Early Warning Systems

HIGH PRIORITY

• Reconciling differences between new and old measurements and developing additional standards and

methods where needed

• Identification of appropriate genetic markers for biological groups of interest

• Securing the needed resources for personnel, funding, and technological advances

• Building/maintenance of a repository of certified reference genetic probes for species, certified nucleic

acid probes, polymerase chain reaction (PCR) primers

• Greater coordination/synergy among bioinformatics initiatives and related efforts

• Reliability and consistency of measurement results over broad spatial and temporal scales: from pipette

to biome, from microseconds to centuries

MEDIUM PRIORITY

• Comparability of measurement results for toxins, pathogens, diseases, and molecular tools

• Measurement bias—amplification and inhibition of specific properties

• Education/training on measurement data quality from local to global scales

• Understanding linkages of environmental parameters: pathogen presence, appropriate genotype and

virulence, risk of disease

• Failure to exploit advances in other fields (weather, climate) and apply to environmental measurements

and forecasting (leveraging IT advances, intelligence/knowledge sharing)

LOWER PRIORITY

• Lack of disease definitions/descriptions and ways to disseminate disease data

• Building/sharing of authenticated sequence libraries

• Large number of anthropogenic chemicals being recognized as "emerging contaminants"

• Economical methods for bulk toxin production and purification
36 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

ENVIRONMENT ENVIRONMENT

Priority Measurement Topics

The measurement challenges illustrated in Exhibits 4.4 and 4.5 provide the foundation for a set of three 

priority measurement focus areas for environmental early warning systems that aim to address these 

challenges. Collectively, panel members determined: the importance of the focus area, objectives in 

addressing it, a potential approach, and stakeholder roles. They also rated the technological and commercial 

risks and the impacts of action in five categories. Their findings are reflected in Exhibits 4.6–4.8. 

These focus areas address some of the most critical challenges that have been identified for environmental 

early warning systems. They cover a spectrum of measurements needed to support the availability of 

ecosystem health indicators and the quantification and integration of complex environmental data. The 

priorities also reflect a need for new measurement technologies and standards to support a new level of 

quality and functionality in next-generation environmental early warning systems.
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 37

ENVIRONMENT ENVIRONMENT

Validated biomarkers are lacking for evaluation of the status of earth’s ecosystems; appropriate biomarkers could provide important 

diagnostic information on ecosystem health and system indicators, and could help identify and remediate possible threats.

•	 Early warning and forecasting 

to improve public health 

and well-being, food safety, 

environmental protection and 

remediation, and to determine 

safety of actions

•	 Better diagnostic tools 

and therapies: rapid assay 

development, enhanced 

bioremediation, preventive 

technologies

•	 Encourage joint or collaborative 

efforts of laboratories

•	 Involve multiple government 

agencies from local to 

international level

•	 Robust tools for composition 

measurement

" Increased capability for 

metabolomics, proteomics, 

etc.

" Increased speed, sensitivity, 

specificity, and ease of use

" Decreased cost and size

•	 Clearly defined standards for 

public health

•	 Accessible information for all 

stakeholders

PRIORITY MEASUREMENT AND STANDARDS CHALLENGE

RATIONALE OBJECTIVES ELEMENTS OF 

APPROACH

RISK

RELATIVE IMPACTS

Accelerates innovation ** Development of early warning systems

Enhances competitiveness *** Enhancements in food safety, human health, and 

ecosystem health

Provides societal benefits *** Safer environment, better health, industrial 

protection; sustains critical ecosystem services

Supports environmental protection *** Rapid detection of perturbation and trends for 

ecosystem assessment and risks

Preserves/enhances energy security *** Sustainable alternative energy development

Technical

Commercial

Biomarkers and Indicators for 

Assessing the Health of Ecosystems

Near-term risk is moderate in early stages; 

risk is high over the long term, as systems 

development become more costly and 

complex.

STAKEHOLDERS AND ROLES

Government: Steering/coordination, funding, international collaboration, 

use of system, public information, research support; EPA, NOAA, USGS, NIST 

(reference materials), CDC, NASA, DOE, DOI, NSF, NIH 

National laboratories: Reference laboratories as appropriate

Academia: Discovery, integration, measurements, and tools; research 

universities

Industry (vendors, suppliers, etc.): Tools, supplies; biotechnology, food, 

environmental, NGOs

Trade groups: Acceptance, public awareness, communication

Exhibit 4.6 Priority Measurement Topic

Low High

*** (High)
38 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

ENVIRONMENT ENVIRONMENT

Identifying, understanding, and quantifying what to measure is difficult. Challenges arise in translating 

traditional versus molecular definitions, and determining operational definitions of species. 

•	 Tools for management of 

populations

•	 A standardized measurement of 

biodiversity

•	 Identification of accidental 

releases/invasive species

•	 Use a coordinating entity to 

spearhead activity

•	 Select six target groups/taxa 

representing the diversity of life 

•	 Reference combining and 

traditional taxonomy; determine 

standardized genes of target 

groups/taxa 

•	 Compare across the six groups/

taxa to identify shared and 

unique markers

•	 Protocols for quantitative 

assessment of similarity: 

roadmap to reference methods 

and standards that answer 

specific questions

•	 Standard for what constitutes 

a biological species from a 

molecular perspective (contextdependent) and selection of 

metrics for quantification

•	 Process for determining the 

definition of a molecular species

PRIORITY MEASUREMENT AND STANDARDS CHALLENGE

RATIONALE OBJECTIVES ELEMENTS OF 

APPROACH

RISK

RELATIVE IMPACTS

Accelerates innovation *** Foundation for creation of early warning systems

Enhances competitiveness *** Reduced cost of environment, health, and safety

Provides societal benefits *** Enhanced quality of life

Supports environmental protection *** Advanced systems for protecting environment, 

health, and safety

Preserves/enhances energy security *** Adaptation of biofuels based on properties

Technical

Commercial

Definition of System Properties 

from Molecular Properties

STAKEHOLDERS AND ROLES

Government: Steering/coordination, funding, international collaboration, 

use of system, public information, research support; EPA, NOAA, USGS, NIST 

(reference materials), CDC, NASA, DOE, DOI, NSF, NIH 

National laboratories: Reference laboratories

Academia: Discovery, integration, measurements, and tools; research 

universities

Industry (vendors, suppliers, etc.): Tools, supplies; biotechnology, food, 

environmental, NGOs

Trade groups: Acceptance, public awareness, communication

Exhibit 4.7 Priority Measurement Topic

Low High

*** (High)

Technical risk is moderate. Commercial risk 

is uncertain until development work begins 

to yield results.
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 39

ENVIRONMENT ENVIRONMENT

Challenges include data interoperability, biological/biomedical ontologies, bioinformatics (analytical models 

performance and comparability), and lack of an environmental registry/ontology (species, awareness, concepts).

•	 More reliable information for 

timely decision making on 

complex environmental problems

•	 Standardized repository of 

information promotes data 

comparability and quality, 

enhances synthesis, and reduces 

uncertainties

•	 Include systems biology/complex 

systems analysis and data 

interoperability standards

•	 Integrate with GEOSS

•	 An enterprise architecture that 

enables timely and efficient data 

integration and analysis with 

results of known quality

•	 Greater coordination of data 

and tools among bioinformatics 

initiatives and other efforts

PRIORITY MEASUREMENT AND STANDARDS CHALLENGE

RATIONALE OBJECTIVES ELEMENTS OF 

APPROACH

RISK

RELATIVE IMPACTS

Accelerates innovation *** Foundation for creation of early warning systems

Enhances competitiveness *** Cost reduction of decision making

Provides societal benefits *** Enhanced protection of health and safety

Supports environmental protection *** Better understanding and mitigation of 

environmental impacts, adverse incidents

Preserves/enhances energy security ** Understanding of environmental impacts of 

biofuels

Technical

Commercial

Reliable Integration of Complex 

Environmental Data for Decision Making

STAKEHOLDERS AND ROLES

Government: Steering/coordination, funding, international collaboration, 

use of system, public information, research support; EPA, NOAA, USGS, NIST 

(reference materials), CDC, NASA, DOE, DOI, NSF, NIH 

National laboratories: Reference laboratories

Academia: Discovery, integration, measurements, and tools; research 

universities

Industry (vendors, suppliers, etc.): Tools, supplies; biotechnology, food, 

environmental, NGOs

Trade groups: Acceptance, public awareness, communication

Exhibit 4.8 Priority Measurement Topic

Low High

*** (High)

High technical and commercial risk 

associated with developing and managing 

highly diverse, complex data frameworks.
40 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges
Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 41

As the world enters the 21st century, biological manufacturing 

science is touching on nearly every aspect of human life—

from processing starting materials into finished products, 

to processing waste into energy—and is creating economic 

value at each step along the way. While technological 

advances and scientific discoveries are accelerating change 

and driving innovation in the commercial biomanufacturing 

sector, the manufacture of many biological products depends 

on technologies that have remained the same for years. 

Keeping pace with societal demands for therapeutics, 

energy, and other biobased goods and services will require 

innovative approaches that in turn depend on the availability 

of transformative tools for product characterization and 

measurement, manufacturing engineering, and knowledge management. 

The biopharmaceutical manufacturing technical panel and plenary focused on identifying critical capabilities 

for biomanufacturing. Participants sought to highlight where new or novel metrology methods, standards, 

and technologies are needed to help blaze the path to 21st century biomanufacturing systems that are riskbased, efficient, agile (high-throughput), flexible, and focused on quality.

Panel discussions produced a potential vision of the future and the broad challenges to be addressed. 

An important outcome was identification and prioritization of the critical measurement and standards 

challenges to technology innovation in this field. Overcoming these challenges will be critical to ensuring 

that measurement technology is available to keep pace with and support technological innovations in 

biomanufacturing.

Vision of the Future

In the future, it is envisioned that technological advances could lead to a range of improvements in 

biomanufacturing and enable production of biological products more cost effectively and reliably. Greater 

understanding of biological properties, the manufacturing process, and product variables will enable 

greater process control, the use of standardized platforms, and more flexibility in processing and products. 

Innovations such as cell-free manufacturing, seamless scale-up of new product lines, standardized platform 

technologies (bioreactors, cell lines), and new methods for manufacturing regenerative medicine products 

(e.g., stem cell therapies) will enable faster realization of emerging concepts such as personalized/niche drugs 

and customized biotherapies.

Technical Panel on 

Biopharmaceutical Manufacturing

Obtaining higher quality products 

through better bioprocess measurements

Technical Panel Co-Leaders: (1) Fred 

Razzaghi, Consultant; (2) William Koch, U.S. 

Pharmacopeia; (3) Larry Mahan, MD DBED

Plenary Speakers: James Thomas, Amgen

5.0

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42 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

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Exhibit 5.1 Characteristics of the Vision of the Future for 

Biopharmaceutical Manufacturing

Technological Advances

•	 Stem cells are differentiated into cellular, tissue, or organ-based regenerative therapies

•	 Manufacturing processes using and/or producing biological materials are well-controlled to maximize yield of the most desired 

molecular or cellular product forms

•	 Standardized platform technologies are in place for perfusion systems in biopharmaceutical production: bioreactors, cell lines 

and expression construction, and control systems

•	 Scale-up is seamless: yield, purity, identity, and ability to scale up readily

•	 Process and product are transparent

•	 Manufacturing, safety, and protective response to vaccines are known and incorporated into design

•	 Sampling of bioreactors is possible

•	 Cell-free manufacturing enables:

" Proof of measurements to support characteristics—design input and process control

" Controlling/understanding variations—quality, systems biology for the future

" Design control of available characteristics

•	 Long-term product-process correlation prediction enables the understanding of:

" Impacts of raw materials

" How to model product and process

" Quality 

" Structure-function relationships

" Each stage and end-size

" Performance

" Knowledge-based design

Societal Aspects

•	 Biotherapeutics are personalized in terms of design, development, and delivery

•	 Customized niche drugs can be made for individual patients in small quantities

•	 Products are manufactured in safer, more environmentally-friendly ways using "green" biological methods

•	 New, more predictable manufacturing methods will facilitate "follow-on biologics," making expensive drugs more affordable 

and available

Global Markets and Products

•	 Biomanufactured products are cost-competitive

•	 Product/process modifications both in development and licensed manufacture are faster

•	 Companies can cooperate on all but profit centers

•	 Flexible, continuous bioprocessing has a short-turnaround demand flow process

•	 Building universal platforms for cell manufacturing is well-understood

•	 Systemic methods are available for process, product, and evaluation

Sustainability

•	 Standardized cleanup process is possible for biofuels/biorefineries

•	 More green processes are possible
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 43

Broad Challenges

The broad technological challenges identified for biomanufacturing are shown in Exhibit 5.2. These illustrate 

the need for better understanding of the manufacturing process. Today this is largely an iterative, slow 

process that involves trial and error and then feedback to incorporate improvements. The inherent uncertainty 

of biological processes sometimes makes it difficult to predict or control processing outcomes and product 

quality, and to scaleup new processes. 

The quality-assurance tools available to other types of manufacturing (e.g., chemicals, food) are practically 

nonexistent for biological manufacturing processes. Tools that measure performance, diagnose quality issues, 

and evaluate products are needed to enable better, more cost-effective biological manufacturing.

Another critical challenge is knowledge-based and stems from a generally limited understanding of 

systems biology and end-use pathways, in vivo mechanisms, and the variability and/or relevance of 

material attributes. Better understanding of these technical areas could provide the knowledge to improve 

biomanufacturing reliability and reduce some of the uncertainties in today’s processes.

Exhibit 5.2 Broad Technological Challenges for Biopharmaceutical Manufacturing

Manufacturing Innovation Drivers

HIGH PRIORITY •	 Lack of understanding of the manufacturing process; slow steps to understanding what 

works (analytics, clinical trials, feedback to implement changes)

MEDIUM PRIORITY

•	 Difficulty of biomanufacturing process

" Uncertainty (e.g., cells can mutate)

" Scale-up sometimes not possible or changes product

" The biologic produces a desired product in low concentration

•	 Requirement for biological system to produce a product, not just chemistry

Enabling Technologies

HIGH PRIORITY •	 Insufficient in-process and end-product measurements (e.g., functionality)

MEDIUM PRIORITY

•	 Insufficient measurement tools

" Inadequate tools to predict performance

" Diagnostic tools are not sharp enough for robust point stratification

LOWER PRIORITY

•	 Availability of rapid protein and carbohydrate analyses to support process analytical 

technology (PAT)

•	 Improved pre-clinical models to enable better clinical predictability

Fundamental Systems Biology

HIGH PRIORITY

•	 Inadequate systems biology knowledge and end-use pathways

" Difficulty of bio-processes, e.g., in vivo mechanisms of action are not well understood

" Understanding the impact or relevance of the variability of material attributes, e.g., if one 

pathway is altered, what effects occur downstream on multiple organ systems and the 

organism?

MEDIUM PRIORITY •	 Lack of manufacturing science knowledge, especially for industrial pharmacy, pushes 

biomanufacturing down the value chain

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44 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

Exhibit 5.3 illustrates the broad non-technological challenges for biomanufacturing. A key challenge is the 

high cost and risk of R&D. Current investments in R&D, education, and other infrastructure are insufficient to 

keep pace with the increasing size and global nature of biomanufacturing. Solving some of the challenges 

requires an interdisciplinary approach, which can be impeded by an inability to communicate in the same 

technical "language". Conflicts in collaboration can lead to a fracturing of effort between industry and 

academia, taking longer or making it difficult to find solutions. 

Policy and regulation are other key areas that can inadvertently impede progress in some cases. Biological 

systems are inherently uncertain. As a result, biologics must often undergo continuous process improvement 

and change in an iterative manner, with efficacy being determined after the product has been manufactured 

(since the outcome cannot always be predicted).

Exhibit 5.3 Broad Non-Technological Challenges for 

Biopharmaceutical Manufacturing

Costs, Culture, Communications

HIGH PRIORITY

•	 Costs to implement new technology and cost of high-risk research

" Risk of contamination requires sterile production

" Multiple complex products increase risk and cost

•	 Insufficient investment, education/research, regulatory structure, and capacity given the size 

and global nature of the challenge 

•	 Problems of interdisciplinary communication

MEDIUM PRIORITY

•	 Pros and cons of fractured efforts involving industry, academia, and others 

•	 Communication of the value proposition

" Concerns over regulatory and approval process

" Certain obstacles to making changes

Education and Fundamental Knowledge

MEDIUM PRIORITY •	 Lack of experienced bioengineers with broad training 

•	 Field is cutting edge and lacks historical knowledge base

Policies/Regulation

HIGH PRIORITY

•	 Lack of guaranteed continuous improvement

" Conflicting paradigm—once a product is made, it is perfect 

" Flexibility to learn and improve/understand risk 

•	 Variability in personalized products (cell therapies, bioreactors)

" Poor understanding of test methods and limitations

•	 Poorly understood boundaries of complex biological products

" Iterative process in producing and improving products

MEDIUM PRIORITY

•	 Difficulty of standardization for cutting edge technology

" Gaps in basic knowledge 

" Lack of standards for emerging technologies

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 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 45

Exhibit 5.4 Key Measurements to Support Technological 

Innovation in Biopharmaceutical Manufacturing

Biopharmaceutical Production

•	 Properties: biochemical composition, biophysical attributes, biologic attributes, and material attributes to provide data on 

functionality, reliability, and performance

•	 Identification of product attributes: purity, quality, safety (rapid microbiology, molecular biology), efficacy/strength, formulation, 

stability, and use assurance indices to provide measures of product quality assurance

•	 Characterization of raw materials: optimization of materials use through measures of impact of feedstock variation on organism 

growth, feedstock components, product impurities, and ancillary products (e.g., catalysts)

•	 Protein identification measures: simple, low-cost, rapid measures enable process understanding through data on specific proteins 

and concentrations

•	 Protein aggregation and causes: better measurements enable process understanding and optimization

•	 Online potency: enables process development and manufacturing

•	 Material process: measurement and data analysis to provide feedback on processing

•	 Limits of variability: understanding of all acceptable limits

•	 Complex profiles or spectra/consistency: enable comparison when data sets have changed

Biopharmaceutical Safety and Use

•	 Biological state of patient: treatment efficacy

•	 Function: fitness for use, safety, and potency

•	 Function in man: immunogenicity (+/-), protection

Enabling Regulatory Decisions

•	 Consensus standards for product definitions/quality: economic impact of availability of information

•	 Production (and nutrient) level in the bioreactor: process and quality control

•	 Genotypic/phenotype drift of manufacturing platform (e.g., microbe, algae, etc.): product reliability and control

•	 Rapid glycol profiling of therapeutic proteins: safety and effectiveness

•	 Product purification characteristics: efficiency of purification/cleanup and impact on molecule of interest

•	 Purity/concentration of feed streams: control and understanding

•	 Production attributes: understanding of starting material and process 

•	 In-process measurement without negative effect: control/monitoring of cell growth/viability and tissue engineering structure 

•	 Scale-up parameters (bioreactor parameters, chemical, physical, thermochemical): effective scale-up of medical material transfer 

system (MMTS) from lab- to large-scale

•	 Bio-process mass balance: decrease of reactants and/or increase in products (in-line with feedback)

Lifecycle Sustainability

•	 Measurands: better understand what to measure

•	 Process byproducts/wastes: fate of solid and liquid wastes and waste gases

•	 Reproducible quality: better control of quality and product

•	 Lifecycle economics: determination of cost-benefits and profit-benefits

•	 Real-time measurements: acceleration, improvement, and optimization of process; create continuity; improve models

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46 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

Role of Measurement

Measurements and standards play an important role in biomanufacturing in biopharmaceutical production 

processes, to ensure safety during processing and use, and from a lifecycle perspective (sustainability). 

Measurements and standards are also critical to support the regulatory process, particularly as it pertains 

to approval of new biological products and innovations, as well as the environmental impacts of biological 

processes. Exhibit 5.4 illustrates the key measurements in this field and why they are important.

Measurement and Standards Challenges

The key challenges related to measurements and standards for biomanufacturing are illustrated in Exhibit 

5.5. These challenges represent the measurement needs that must be addressed in this field, but are not allinclusive. They provide a good starting point for understanding some of the urgent measurement challenges 

facing this unique and rapidly growing industry.

Biomanufacturing Processes. Biological manufacturing processes, which work with living cells, have 

a high degree of uncertainty in both processing methods and in reliably obtaining the desired product 

attributes; they are difficult to control and monitor. The ability to make measurements in complex matrices in 

a process environment, and obtaining samples online and in-process, remains a significant challenge. When 

data is available, it is difficult to determine how that data can be used to improve the process. The variability 

in different product platforms creates a barrier in a number of ways, but particularly in designing generic 

processing tools and methods that can be applied across platforms.

Products. Variability in biological products is difficult both to measure and predict with any reliability 

(e.g., what creates variability?), mostly due to the inherently dynamic nature of living systems. Without 

understanding the mechanisms behind product variability, obtaining the desired attributes becomes an 

iterative rather than straightforward process. In many cases, measurements of product attributes are driven 

by the need to meet regulatory requirements or approvals. Such measurements do not necessarily provide 

any useful information about manufacturing performance or other factors that impact product attributes and 

functionality. Finding simpler ways to mimic complex systems (e.g., immune system assay), more accurate 

bioassays, and how to measure product changes in vivo could provide tools for understanding and improving 

pathways to reliable product attributes.

Lack of Fundamental Knowledge. Developing a better understanding and analysis of the risk factors 

for product efficacy is a high priority. The lack of efficacy is often determined by different processes and 

procedures in use. These are not necessarily matched to criteria of acceptability within the manufacturing 

process. As a result, risk analysis is not rational, but rather drug-related or tied to doctor error.

Tools/Methods. New tools are needed to measure proteins/biomarkers in complex fluids, particularly 

alternatives to mass spectrometry. An enhanced understanding of structure-function relationships, for 

example, could enable improved quality, consistency, safety, effectiveness, and yield of biological products. 

Tools for measuring structural properties, aggregation, oxidation, and other system properties will 

ultimately pave the way for predictive biotechnology and product development. A key issue is the current 

level of sensitivity, specificity, and objectivity of measurements for biological systems in the manufacturing 

environment.

Other. The high cost of measurement is an impediment in today’s biomanufacturing environment. Cost 

decisions are complicated by whether tools are permanent or disposable technology, and if processes must be 

retrofitted. Add-on technologies can require process redesign at significant cost, and the ultimate cost-benefit 

ratios must be demonstrated to justify the investment. Another challenge in developing and implementing 

new measurement technology is the sometimes diverse nature of the user and desired outcomes, which can 

range from physicians to regulators to equipment suppliers.

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 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 47

Exhibit 5.5 Measurement and Standards Challenges for 

Biopharmaceutical Manufacturing

Biomanufacturing Processes

HIGH PRIORITY

•	 Specific measurements in complex matrices, compounded by interference in in-process 

environments

•	 Lack of cross-platform compatibility and comparable methodologies

•	 Lack of clarity on how to use the data to improve the process

•	 Obtaining representative samples online

Products

MEDIUM PRIORITY

•	 Inadequate understanding of sources of product variability

•	 Mimicking complex systems (e.g., immune system assay) in simpler ways 

•	 Prevalence of regulatory-driven measurements versus those driven by characteristics for 

manufacturing performance and function

LOWER PRIORITY •	 Accurate bioassays (potency) in the face of inherent variability of biological systems

•	 Measuring product changes in vivo (difficult to measure function ex vivo)

Lack of Fundamental Knowledge

HIGH PRIORITY

•	 Irrational risk analysis caused by determination of efficacy by different processes and 

procedures that are not necessarily matched to criteria of acceptability within manufacturing 

process

Tools/Methods

HIGH PRIORITY

•	 Lack of alternatives to mass spectrometry (MS) as a measurement tool for proteins/biomarkers 

in complex fluids

•	 Sensitivity, specificity, and objectivity of measurements

MEDIUM PRIORITY •	 Lack of generally applicable data pre-processing tools to incorporate more information into 

models

Other

HIGH PRIORITY

•	 Cost of measurement 

" Permanent versus disposable technology

" Add-on technology and redesign implications

MEDIUM PRIORITY

•	 Measurement challenges created by diverse users 

" Innovator/copier

" Regulatory (U.S. vs. other country)

" End-user (physician/patient/hospital/NGO) 

•	 High level of skill required to install the equipment in-process

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48 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

Priority Measurement Topics

The measurement challenges illustrated in Exhibit 5.5 provide the foundation for a set of four priority 

measurement focus areas for biomanufacturing that aim to address these challenges. Collectively, panel 

members determined: the importance of the focus area, objectives in addressing it, a potential approach, and 

stakeholder roles. They also rated the technological and commercial risks and the impacts of action in a set of 

categories. Their findings are reflected in Exhibits 5.6–5.9. 

These focus areas address some of the most critical challenges that have been identified for 

biomanufacturing. Many are data- and knowledge-based, making improved data-gathering and analytical 

tools essential to overcoming these challenges. The priorities also reflect a need for new measurement 

technologies and standards to support a new level of quality and functionality in next-generation 

manufacturing and bioproducts.

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A lack of comparable measurements inhibits understanding of process/product correlation. Written standards for 

process performance, final products, and input materials are lacking; these standards also require industry acceptance.

•	 Enhanced, predictable, biological 

manufacturing processes will 

enable lower costs and greater 

user benefits

•	 Increase cross-disciplinary 

collaboration with USP, PDA/

regulators worldwide, MBSC, 

industry (instrument and product 

manufacturers), academia, and 

NIH/other funding agencies

•	 Obtain stakeholder input 

(regulators, standard-setters, 

industry, general interest/industry) 

into prioritization of needs leading 

to infrastructure development, 

partnerships

•	 Standards to improve processes 

that accelerate delivery of good 

medical products to end-users

•	 Reduced measurement 

uncertainty resulting in reduced 

manufacturing cost, higher 

product consistency and 

manufacturing predictability, 

reduced manufacturing failures, 

and better product safety

PRIORITY MEASUREMENT AND STANDARDS CHALLENGE

RATIONALE OBJECTIVES ELEMENTS OF 

APPROACH

RISK

RELATIVE IMPACTS

Accelerates innovation *** Easier path for new products

Enhances competitiveness ** Enhances global/regional market acceptability

Provides societal benefits *** Better medicines faster

Supports environmental protection *** Better prediction of outcomes

Preserves/enhances energy security * Support for bioenergy products

Technical

Commercial

Standard Reference Data 

for Biotechnologies

Inappropriate standards can slow 

biopharmaceutical manufacturing and 

undermine standard-setter credibility; lack 

of standards is costly and limiting.

STAKEHOLDERS AND ROLES

Government: FDA, funding agencies, NIST and international equivalents, 

intergovernmental agencies (e.g., WHO) 

Academia: Collaborators, innovators, independent evaluators

Industry: Involved

Standards developers: USP and others in a coordination role—forum or 

similar mechanism

Standards development is low-risk, but 

applicability may be too late.

Exhibit 5.6 Priority Measurement Topic

Low High

*** (High)
50 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

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MANUFACTURING

BIOPHARMACEUTICAL

MANUFACTURING

Obtaining representative samples without negatively impacting the biological process is difficult; 

in situ sampling is ideal, but appropriate sensors are lacking.

•	 Improved quality assurance

•	 Optimization provides enhanced 

flexibility

•	 Greater process control

•	 Develop pre-competitive sampling 

approaches where possible

•	 Conduct R&D for in situ

approaches, such as non-fouling 

sensing, inferential sensing, stable 

systems for measurements

•	 Pursue collaborative approaches

•	 Full characterization of reactor 

performance

•	 Optimized design criteria

" Representative sample size

" Sample presentation

" Sterility requirements

" Utility considerations

" Disposal considerations

" Liquid versus vapor

PRIORITY MEASUREMENT AND STANDARDS CHALLENGE

RATIONALE OBJECTIVES ELEMENTS OF 

APPROACH

RISK

RELATIVE IMPACTS

Accelerates innovation ** High impact on in-process development, low 

impact on manufacturing

Enhances competitiveness ** High impact if data used for optimization, low 

impact if used for monitoring quality

Technical

Commercial

Optimized Sampling Approaches for 

Biological Manufacturing Processes

Technical risk is high for in situ methods, 

low for sampling; adoption of technology 

may be slow.

STAKEHOLDERS AND ROLES

Government: Broad government consortia; supporting roles for all 

stakeholders; NIST (measurement infrastructure)

Industry: Involved

Exhibit 5.7 Priority Measurement Topic

Low High

*** (High)
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 51

BIOPHARMACEUTICAL

MANUFACTURING

BIOPHARMACEUTICAL

MANUFACTURING

Complexity with content management systems (CMS); stability (comparability, portability) 

of existing tools; understanding of system biology.

•	 Enables predictive biotechnology 

•	 Improved quality, consistency, 

safety, effectiveness, and yield of 

biological products

•	 Develop academia/industry/

NIST/measurement community 

partnerships

•	 Research infrastructure, conduct 

other basic research

•	 Establish pilot plant

•	 Develop new funding models, 

information exchange

•	 An orthogonal method for 

determination and characterization 

of glycosylation, aggregation, 

oxidation, and other relevant 

aspects

•	 Understanding of structurefunction relationships in 

biological systems

•	 Tools to determine what aspects 

are relevant 

•	 Comparability of methods 

and determination of what to 

measure

•	 Data and multivariant analysis 

for performance: sensitivity, 

specificity, and objectivity

PRIORITY MEASUREMENT AND STANDARDS CHALLENGE

RATIONALE OBJECTIVES ELEMENTS OF 

APPROACH

RISK

RELATIVE IMPACTS

Accelerates innovation *** Better prediction of performance

Enhances competitiveness *** Cost-effective manufacturing

Provides societal benefits *** Safer, more effective products

Supports environmental protection ** Understanding potential byproducts, wastes

Technical

Commercial

Next-Generation 

Biomanufacturing Tools

Natural development so technical risk is 

low; low return on investment increases 

commercial risk.

STAKEHOLDERS AND ROLES

Government: Collaborative partnerships, NIST (measurement infrastructure)

National laboratories: As appropriate

Academia: Research infrastructure

Industry: Collaborative partnerships

Exhibit 5.8 Priority Measurement Topic

Low High

*** (High)
52 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

BIOPHARMACEUTICAL

MANUFACTURING

BIOPHARMACEUTICAL

MANUFACTURING

There are a lack of accepted process and production cell-culture standards in which to test systems and biology 

characterizations, which are needed to enable development of effective measurement methods.

•	 Ability to assess the relevance 

and process risk of new 

measurement tools and enable 

identification of sources and 

effects of variability

•	 Enhanced fundamental 

understanding of the systems 

biology of production platforms, 

leading to better predictive 

outcomes and product quality 

assurance

•	 Establish industry/NIST/FDA/NGO 

partners (UMBI CARB, ATCC, USP, 

etc.) consortium for consensus 

platforms and production 

methods of "standard" products

•	 Identify site(s) of R&D activities 

(the UL labs) and repositories for 

cells, standards, etc.

•	 Convene a NIST-driven conference 

to initiate working committee(s) 

and gain buy-in

•	 A commonly available, fully 

described set of cell-culture 

reference systems to allow 

development of measurement 

tools, standards, criteria, and 

objectives

PRIORITY MEASUREMENT AND STANDARDS CHALLENGE

RATIONALE OBJECTIVES ELEMENTS OF 

APPROACH

RISK

RELATIVE IMPACTS

Accelerates innovation ***

UL concept for biomanufacturing; common 

standard platform lowers variability, increases 

potential acceptance by end-user

Enhances competitiveness ** High impact on new technologies in manufacturing; 

medium impact on product acceptance

Provides societal benefits *** Expedited process, lower development and 

production cost, understanding of product quality

Supports environmental protection ** Increased production efficiencies (less waste, 

contaminants, etc.)

Preserves/enhances energy security **

Increased potential to incorporate "given 

technologies" in manufacturing; increased 

sustainability

Technical

Commercial

In-Process and End-Product 

Measurements

STAKEHOLDERS AND ROLES

Government: NIST, FDA, NIH 

National laboratories: Various

Academia: University biotechnology centers

Industry: Biopharma

Private research institutes: ATCC, USP

Trade groups: BIO, PhRMA (supportive role)

Exhibit 5.9 Priority Measurement Topic

Low High

*** (High)

Low risk to develop with positive benefits 

to many stakeholders.
Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 53

6.0 MEDICINE MEDICINE

The future of biology and medicine depends on the 

development of technologies and research approaches 

that embrace the high degree of complexity in biological 

systems. Therapeutic or preventative interventions will be 

based on "disease signatures"—unique descriptors that are 

definitive markers of health status. These signatures will be 

derived from the integration of quantitative and qualitative 

measurements (biochemical, biophysical, and bioelectronic) of 

hundreds to thousands of biomolecules and/or intermolecular 

and cellular interactions. Likewise, the next generation of 

health assessment diagnostic tests will be based on multiplex 

determinations constituting a unique complex signature, 

rather than single markers of biological activities. The shift to signature analysis in diagnostics will help enable 

routine health status monitoring that uses each person’s own signatures of wellness and disease as the 

controls against which to detect pathologic changes. This new focus will enable a comprehensive, integrated 

approach to wellness that includes prevention of disease, early detection of disease risk, and individualized 

treatment plans for each patient. In turn, this new approach to wellness may help control the rising cost of 

healthcare, for which spending now consumes nearly one-fifth of the U.S. gross national product. 

The medicine technical panel and plenary focused on the current needs and future opportunities related 

to innovative areas of medicine. These discussions emphasized identifying potential challenges impeding 

innovation in biomeasurements, clinical trial design, and the information processing and visualization 

technologies required to make disease signature analysis translatable into clinical practice. Panel participants 

identified a potential vision for the future, the broad technological challenges that need to be addressed, and 

the critical measurement and standards challenges that must be overcome to achieve technology innovation 

in the field of medicine. 

Vision of the Future

In the future, it is envisioned that revolutions in medicine will dramatically change the way patients are 

diagnosed and treated. As shown in Exhibit 6.1, technological advances, greater understanding of the 

correlation of disease to phenotype, ability to test the underlying etiology, and more sophisticated tests 

and assays will all contribute to improving diagnoses. Biomarkers will be well developed and more robust, 

enabling their use in guiding treatment decisions. Increased knowledge in many areas, combined with new 

predictive tools, will allow for the better identification and understanding of the characteristics and pathways 

of disease, enabling more effective therapies to be developed more quickly.

Standardization will play an important role in optimizing sample and data collection, improving the 

understanding and mining of information from journals worldwide, and providing the infrastructure for 

new medical tools, such as the use of disease signatures. Modeling capabilities will improve with a greater 

range of capabilities for assessing current status as well as future disease risks. These advances will support 

the movement toward health-based and preventive medicine, in addition to providing support for improved 

diagnosis and treatment.

Technical Panel on Medicine

Improving health through measurement 

of complex biological signatures

Technical Panel Co-Leaders: (1) Judy 

Britz, Britz Consulting; (2) Paul J. Utz, Stanford 

School of Medicine

Plenary Speaker: Lee Hood, Institute for 

Systems Biology
54 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

Personalized medicine, where diagnosis, prevention, and treatment are tailored to individuals, is envisioned 

as a future reality. The groundwork for customized medicine is now being laid, although significant 

challenges must first be overcome. As Exhibit 6.2 illustrates, substantial advances in our knowledge of the 

genome and genotypes, phenotypes, and establishment of disease signatures will contribute to the creation 

of truly personalized medicine. These will enable the connection of diagnosis and treatment, as well as the 

identification of potentially risky outcomes with individual patient characteristics. 

In the future, preventing disease and poor health, rather than reactively diagnosing and treating disease, will 

become the greater focus of medical practice. Emphasis will be placed on maintaining and improving good 

health, enabled by better, less-invasive health testing and monitoring methods, as well as safer therapies.

The business of healthcare will evolve to keep pace with the new demands placed on it by the move 

toward personalization and preventive, health-based medicine. This will require a substantial change and 

improvement in the way medical records and data are collected, stored, updated, and used. Medical records 

will need to be easily updatable in real time and transferable across different medical disciplines. Massive 

sets of patient information with many layers of detail will need to be combined with data on the etiology 

and genetics of disease to enable interpretation of health conditions as well as identification of preventive 

measures.

MEDICINE MEDICINE

Exhibit 6.1 Characteristics of the Vision of the Future for Medicine: 

Technological Advances Supporting Treatment and Diagnosis

Diagnosis

•	 More accurate diagnoses translate to more efficacious treatments; physicians can order multiplexed assays for disease groups 

(e.g., autoimmunity) and obtain readily interpretable, numerical scores defining relative risk

•	 Normal pathway correlation to phenotype is understood; measurement of aberrant signaling to identify therapeutic responses 

that correlate with genomic/protein expression profiles is possible

•	 Evidence-based lab medicine replaces intuitive test interpretation 

•	 Underlying disease etiology is evaluated, rather than a complex array of symptoms and pathways

•	 Standards guide collection of samples and data, as well as how disease signatures are characterized

Treatment

•	 The major cellular/molecular subtypes of disease can be identified, with robust biomarkers used in guiding treatment decisions

•	 Therapies are developed faster, based on more comprehensive understanding of biomolecular systems and more powerful tools 

for molecular engineering, and guided by companion diagnostics

Fundamental Knowledge

•	 Biomarkers and diagnostic clinical trials are integrated, and diagnostic clinical trials exist—sensitivity, specificity, predictive values 

are assessed

•	 Standard language and terminology enable harvesting the full benefit from published research literature

•	 Modeling capabilities range from proactive to reactive, and optimize treatment based on assessment of current status as well as 

risk for future events

•	 Statistical interpretations as well as mechanistic models are used as complementary information
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 55

Broad Challenges

The broad technological challenges to achieving the vision for medicine are shown in Exhibit 6.3. These 

reflect the growing movement toward revolutionary new ways of practicing medicine that are based on 

a deeper understanding of disease, the susceptibility of individuals to disease, and the efficacy and safety 

of treatments. Critical challenges are evident in a lack of adequate standards and measures; handling and 

effectively using massive amounts of information related to patient care and disease; and building the 

necessary science, technology, and knowledge foundation to support a new level of customized medicine 

tools.

The current regulatory environment, policies impacting privacy, lack of economic incentives, and inadequate 

communication all constitute broad, non-technological challenges to personalized medicine and advanced 

medical practices, as shown in Exhibit 6.4. The regulatory process will have to adjust to accommodate the 

changes inherent in personalized treatment where the patient has greater control over treatment options. 

New paradigms in diagnostics may require new regulatory approaches. 

Privacy issues will also arise, due to the larger and more detailed quantities of personal information needed 

for customized medical practice. As the sharing and transfer of information across practitioners and medical 

disciplines becomes more automated and routine, more complex issues related to the protection of patient 

information could emerge. 

MEDICINE MEDICINE

Exhibit 6.2 Characteristics of the Vision of the Future for Medicine: 

Personalized, Health-Based Medicine and New Business Models

Personalized Medicine

•	 Personalized medicine is a reality—physicians are able to integrate the individual’s genotype, phenotype, diagnosis, and disease 

based on a signature; develop a patient profile; and select type, drug, and monitoring needs accordingly. Treatment is predictive 

and personalized:

" Whole genome sequence is known per person

" Therapy is targeted based on genome, gene expression, and pathways

" Success of treatment is precisely monitored

" Individuals at risk for poor outcomes are identified through screening tests (blood, imaging, etc.) 

" Shared databases enable characterization of a patient against the larger population 

" Massive datasets/patient information (longitudinal and heterogeneous) are available; genetic data is essential for 

interpretation—together leading to health/disease signatures and P4 medicine (predictive, preventive, personalized, 

participatory)

" Medical records are useful to and usable by all practitioners; patient records are available and can be updated in real time with 

point-of-contact measurements, enabling monitoring of patient health/wellness

Health-Based Medicine

•	 Prevention is the focus: reactive medicine is transformed into proactive medicine

" Prevention/early treatment are enabled by testing multiple biomarkers and pathways

" Non-invasive and less-invasive methods make it easier to profile and monitor health 

" Public policy/government resources are directed to available, preventive medicine

" Insurance pays for preventive screenings; this is more cost-effective than treating disease

•	 Medicine is more focused on wellness 

" Intervention is targeted for maximum therapeutic efficacy with minimal toxicity

" The heterogeneity of disease is recognized, enabling new terminology to differenciate between healthy and unhealthy

" Markers to define health, rather than disease, are identified
56 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

MEDICINE MEDICINE

Exhibit 6.3 Broad Technological Challenges for Medicine

Information/Data Management

HIGH PRIORITY

•	 Management challenges resulting from computational barriers created by massive quantities 

of non-comparable data 

•	 Phenotype data entry and categorization 

•	 Standardization of clinical information

•	 Effective and useful collection and storage of data

LOWER PRIORITY •	 Flow of research data from journals to databases and IT resources

Products

HIGH PRIORITY

•	 Lack of standardized units of measure ("gold standard") for comparing, compiling, and 

analyzing across interface structures and input technologies, platforms, etc.

•	 Lack of standardized testing across different technologies

•	 Portable standards/reference materials for all medical tests 

•	 Technical/reference standards for samples, assays, protocols, data, validating assays

•	 Lack of standards to compare results of measurements on animal models (e.g., enzyme 

activity, structural and functional difference detection) by different laboratories and instrument 

manufacturers

•	 Need for derived reference standards for many assays

MEDIUM PRIORITY

•	 Standard method for sample acquisition and processing of blood cells, tissue, and biopsy 

specimens; internal controls to monitor proper sample handling

•	 Standardization of assays for proactive tests and methodology

Lack of Fundamental Knowledge

HIGH PRIORITY

•	 Lack of accepted "standard phenotypic" description of disease and normal populations

" Disease subtype and heterogeneity

" Clinical trial outcomes

" Histology/pathology

•	 Establishment of reliable clinical diagnoses (eliminating diagnostic inaccuracy) 

•	 Identifying assays for testing health or disease and salient differences (i.e., what are the 

irrelevant parameters and changes)

•	 Biological validation of biomarkers in clinical trials 

•	 Lack of data linking personalized medicine test results to improved patient outcomes 

(defining disease outcomes)

MEDIUM PRIORITY

•	 Lack of predictive tools to guide molecular-level engineering to develop new therapies and 

expand/accelerate the therapy/drug pipeline

•	 Barriers created by heterogeneity make it difficult to develop drugs and diagnoses

LOWER PRIORITY •	 Protein measurements: poor capture agents and sample uniformity

•	 Computation challenges: analysis of heterogeneity
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 57

MEDICINE MEDICINE

Additionally, the cost of healthcare is high and continues to increase. Personalized therapeutics could increase 

costs further in the short term, particularly in the early phases of development and use. Economic incentives 

may be needed to induce greater investments in preventive and predictive or health-based medical practice. 

Role of Measurement

Measurements have played an important role in medicine from its earliest beginnings, and today are 

an integral foundation of medical research, diagnostics, and treatment. Exhibit 6.5 illustrates the key 

measurements needed to support continued technological innovations in this crucial field and why they are 

necessary.

Exhibit 6.4 Broad Non-Technological Challenges for Medicine

Regulatory

MEDIUM PRIORITY •	 Validation and regulatory challenge inherent in "patient as own control" and expense of 

outcomes research

LOWER PRIORITY •	 Lack of clinical understanding in regulatory bodies (ability to prioritize parameters)

•	 Regulatory classification of diagnostic tests

Health Care Policy

HIGH PRIORITY •	 Privacy issues and consensus, public and private

LOWER PRIORITY •	 Ways to evaluate and improve practices with real patients

Economics and Incentives

HIGH PRIORITY •	 Lack of funding/funding prioritization and the existence of competing priorities, such as 

science, economics, and social objectives

MEDIUM PRIORITY

•	 Rising healthcare costs (imaging, high costs of customized therapies, overall costs)

•	 High cost of diagnostic trials 

•	 Economic incentives for preventative and predictive medicine

" Competing business incentives in personalized medicine/companion diagnostics

Economics and Incentives

HIGH PRIORITY

•	 Cultural attitudes around sharing (work toward common standards and goals) 

•	 Lack of collaboration between industry and academia overall

•	 Communication/collaboration between industry, academia, and government agencies

MEDIUM PRIORITY

•	 Education for: 

" Patients (pros/cons)

" Providers (interpret pros/cons)

" Payers (preventive and proactive, bulk versus niche)

" Individuals (participate as own control)
58 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

MEDICINE MEDICINE

Measurement is a key enabler of improved diagnostics. Genetic measurements aid in the understanding of 

disease pathways and signatures, are critical to the use of biomarkers and genetic markers for disease, and 

can provide information for early treatment and disease recognition.

Measurements are also crucial to understanding and subsequently improving the outcomes of medical 

treatments, as illustrated in Exhibit 6.5. Measures of morbidity, mortality, and quality-of-life parameters can 

reveal a lot about the efficacy of treatments and their long-term impacts. Outcome measures that evaluate 

how well new treatment paradigms are working compared with traditional approaches can be invaluable in 

guiding and refining innovative medical procedures or therapies. 

Exhibit 6.5 Key Measurements to Support Technological Innovation in Medicine

Diagnostics

•	 Scatter, absorption, and fluorescence of single cells with different metabolites: impact on cell functionality

•	 Interoperable data features for complete phenotype descriptions (physical, labs); robust, reproducible, platform-independent, 

and implementable with minimal training: standardization and best practices

•	 Relationships between measurement and phenotype: disease pathways

•	 All "-omics" (genomics, proteomics, glycomics, metabolomics, cellomics, lipomics): standards and reference materials needed for 

all potential biomarkers 

•	 Concentrations (free and bound) of low-abundance gene products, metabolites, etc., in biological specimens: enables new 

diagnostics

•	 Antibodies: measurement of epitopes

•	 Intact proteins in biological sample: accurate, reproducible measures are essential; intact proteins are important to understanding 

sample

•	 Post-translational modifications: changes in activity

•	 Rare- and single-cell state analysis of circulation, surface markers in circulatory blood cells, circulating microRNA: diagnosis and 

treatment, circulation of medications

•	 Single nucleotide polymorphism (SNP) studies, all genetic variations, epigenetics: disease signatures, early treatment, and disease 

recognition

•	 Antibody/antigen expression (protein expression): understanding disease pathways

•	 Living cell assays (antigen-specific, X-ray/MRI/CT/imaging): vaccines and infection, clinical outcomes

•	 Genotype and eliminating interference pattern (EIP)-genetic DNA, RNA (expression and regulatory species, protein, form and 

structure of cell, organ, and organism): understanding disease pathways, genetic markers for disease

•	 Carbohydrate analysis: relationships to changes in half-life and detection

Biomarkers

•	 Biomarkers of pharmacodynamics (proteins, peptides, pharmacogenomics [PGx]): prediction or establishment of drug efficacy

•	 Biomarkers of pharmacokinetics (drug levels, PGx): guide to dosing

•	 Circulating antibodies: markers of disease exposure and presence of autoimmune disease

•	 Tissue markers and measures of tissue at the cellular level, via molecular imaging: inclusion of normal and pathological states

•	 Biologically validated markers: aid decision making

Dynamic Measurements Over Time (longitudinal)

•	 Longitudinal data (biomarkers and clinical information): better characterization of patient populations

•	 Platform-specific standards: comparability of results over space and time

•	 Snapshot of serum/plasma protein, transcription, and serum versus tissue: non-invasive samples of disease phenotype

•	 Molecular structure and dynamics at resolutions beyond current technologies: enable molecular engineering of 

new therapeutics
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 59

MEDICINE MEDICINE

Consistent, accurate, validated information is crucial today but will be even more so in a personalized 

medicine environment. Common, standardized ways of reporting and making measurements, as well as 

consistency in the type of patient data that is entered into the medical information system, are essential for 

effective diagnosis and treatment. In some cases, simply defining the attributes that must be measured (i.e., 

measurands) to assess disease and health is important. Standards, which specify how measurements should 

be made, are necessary to ensure that physicians are consistently informed about critical medical variables, 

tests, treatments, and protocols. 

Measurement and Standards Challenges

The key challenges related to measurements and standards that were identified for medicine are illustrated 

in Exhibit 6.6. These are not intended to be all-inclusive of the measurement needs in medicine, but rather 

describe some of the challenges that need to be addressed to support personalized, health-based medicine. 

Standardization is a key theme that runs throughout the challenges shown here; it impacts the effective 

collection and handling of samples, is critical to the use of clinical phenotypes, and plays a key role in 

diagnostics and treatment.

Exhibit 6.5 Key Measurements to Support Technological Innovation in Medicine (cont.)

Measuring Outcomes and Effectiveness

•	 Morbidity/mortality, quality of life: measure of outcomes based on comparable inputs

•	 Histology—disease phenotype (gold standard): early detection and prediction of disease

•	 Quantitative measures of clinical phenotypes: ensure efficacy and utility of diagnostic test 

•	 Detailed clinical phenotype and medication history, effects of medications: impacts effectiveness of diagnosis and treatment

•	 Clinical phenotype/outcome measures versus biology and imaging: disease treatment paradigms

•	 Disease definitions, indices, outcome measures: disease treatment paradigms

•	 Long-term outcomes of defined phenotypes with accompanying sample banks: validation of biomarkers

•	 Biomarkers and outcomes data: better links with actual patient symptoms

Validation/Standardization of Measurement

•	 Common quantitative units across measurement platforms: consistency in measurement

•	 Defined measurement(s) that best distinguish disease from health (stable, unique, platform- and antibody-independent 

measurements): based on forms that are optimal discriminators or predictors, rather than what is available or easy to measure

•	 Consistency measures for input information: patient history, phenotypes (age, race, sex), social factors, diet, environment provide 

data for retrospective analysis

•	 Sample integrity measures: ensures quality of sample banks

•	 Process integrity and quality: informs best-practice decisions

•	 Statistical international standards: enable correct inferences, global consensus

•	 Variables that are not machine-dependent: markers that are stable over time

•	 Standard reference particles with defined refractive index, size, concentration, and fluorescence load: objective, deviceindependent standard

•	 Positron emission tomography with fluoride tracers (F-PET) sample integrity, suitability for immunohistochemistry (IHC), gene 

expression, other analysis: lowering of cost and time and improvement of data integrity

•	 Extension of CDISC standards to biomarkers and platform-independent data standards: enables integration and comparison of 

data across platforms
60 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

MEDICINE MEDICINE

Exhibit 6.6 Measurement and Standards Challenges for Medicine

Sample Integrity and Preparation

HIGH PRIORITY

•	 Standards and protocols for proper handling and treatment of samples

" Cells: Lack of validated method for processing, freezing/thawing cells; poor reproducibility 

of samples, lack of standards for fluorescence-activated cell sorting (FACS)

" Variation in formalin-fixed, paraffin-embedded tissue with positron emission tomography 

(FFPET) preparation; lack of standardization, standard integrity tests

" Similar initial samples for consistent analysis

" Lack of solid tissue standards and consensus on standard procedures

" Lack of standards for labeled measurands—synthetic standards are feasible but not 

adequate, and there are no means to determine sample integrity

•	 Collection of relevant samples in a manner that provides meaningful results in real-world 

settings

•	 Standardization of diverse instrument platforms

" Reconciling different types of assays used for the same measurand; technology exists, 

but impetus to accomplish may not be strong

" Data and assay interoperability/comparability

" Comparability between technologies and technology-independent standards

•	 Sharing of best practices and creating standard processes and methods requires better 

communication and process integrity 

" Limited number of technologies to measure process integrity 

•	 Traceability of biological measurements to an absolute or relative reference (functionality, 

dynamics, definition of environmental information)

•	 Intact stabilized cellular standards—characterized, qualitative cell lines for all signal 

pathways, NCI cell lines

MEDIUM PRIORITY •	 Definition of a "normal," "healthy" reference value and range when patient is in control

LOWER PRIORITY

•	 Standardization of data collection and quality controls to ensure data and sample integrity

" Inadequate technology and sample collection methods

" Collection sites that are poorly equipped and have poorly trained personnel

•	 Fluorochrome reference standards for all relevant detection systems are needed but require 

funding and dedicated expertise (e.g., FITC RM8640, SRM1932)

" Standardization of methods for small molecules (near-term) is hindered by various combinations 

of pre-analytical and analytical components, although technology exists to solve this

•	 Standards for rate measurements are lacking and not a priority for standards organizations; 

must be developed and validated independently

•	 Standardization of PGx results (e.g., warfarin) and lack of agreement on what clinical 

scenarios and equations to use

" Outcome endpoint definitions have prevented agreement

" Data for equation development is limited
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 61

MEDICINE MEDICINE

Sample Integrity and Preparation. Developing standards and protocols for the proper processing, 

handling, and treatment of cells, tissues, and other biological samples is a priority challenge. Without 

standard methods, the result is questionable sample integrity, poor reproducibility of results, and difficulty 

performing credible analysis. One objective is the ability to collect relevant samples in a way that is 

reproducible, accurate, and provides meaningful results in practical, real-world settings.

Clinical Phenotype and Outcomes. Definitions and standards for phenotype data are a high-priority 

challenge and are needed to help identify, characterize, and predict disease pathways and activity levels, and 

understand disease and treatment outcomes. The standardization of phenotypes is impeded by their inherent 

complexity, data that is mostly subjective in nature, and a lack of agreement on how to best characterize the 

data.

Standards and Preferences. The standardization of data and assays across a large number of biological 

platforms is a major challenge in medicine. Existing platforms are diverse and lack interoperability and 

comparability, and the technology needed to address these issues is not available. The inconsistencies 

inherent in tracing biological measurements to a well-defined reference point also make standardization 

challenging, as do a number of non-technical issues, including a lack of information-sharing and an 

unwillingness to undertake potentially costly efforts to develop cross-platform standards.

Exhibit 6.6 Measurement and Standards Challenges for Medicine (cont.)

Clinical Phenotype and Outcomes

HIGH PRIORITY

•	 Different standards/definitions for phenotype data

" Lack of agreement, complexity, subjective data

" Outcomes and phenotypes (e.g., disease activity indices)

" Inhibitive information-sharing and policies

" Phenotype inconsistency and lack of consensus 

" Definition of disease categories; tie to treatment plan, models, causes and outcomes, 

pathway perturbation

LOWER PRIORITY

•	 Standards for dynamic disease symptoms/characteristics (rather than approximation): looking 

at changes over time (active point) and underlying mechanisms

•	 Lack of models to generate and test hypotheses (now and to improve future processes)

•	 Information standards for encoding patient outcomes

" Cost challenges, limited incentives, few dedicated efforts 

" Availability of natural language processing technologies to encode free text 

" Need for well-characterized patient records to train and evaluate technologies

•	 Lack of agreement on metadata structure relevant to interchange of image and associated metadata

•	 Information management standards for biomarkers data

Simplifying Technologies

MEDIUM PRIORITY •	 Point-of-care device—reference material and control, robustness, operational/logistical 

issues
62 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

MEDICINE MEDICINE

Priority Measurement Topics

The measurement challenges illustrated in Exhibit 6.6 provide the foundation for a set of four priority 

measurement focus areas for medicine that aim to address these challenges. Collectively, panel members 

determined: the importance of the focus area, objectives in addressing it, a potential approach, and 

stakeholder roles. They also rated the technological and commercial risks and the impacts of action in a set of 

categories. Their findings are reflected in Exhibits 6.7–6.10. 

These focus areas address some of the most critical challenges that have been identified for emerging 

innovations in medicine. Many are related to the development of new standards and protocols that are 

essential to overcoming these challenges. Standardization will be critical to developing consistent frameworks 

for clinical data that can be used to better understand, monitor, predict, and control next-generation 

treatment and disease outcomes.
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 63

MEDICINE MEDICINE

A lack of consensus regarding the best approach(es) to sample preparation as well as a lack of 

markers of sample integrity are impeding progress toward the goal of personalized medicine. 

Sample integrity is key to reproducibility of results and credible analysis.

•	 Quality results to help 

achieve long-term benefits of 

personalized medicine

" Integrity markers

" Automated annotation of time, 

temperature, etc.

" Clinical data integration tools

•	 Identify markers of sample 

integrity for different sample types

•	 Improve methods of sample 

preparation for various 

applications

•	 Define guidelines and the 

regulatory environment and 

provide training (governmentsponsored consortium)

•	 Consistent sample collection and 

storage to provide samples that:

" Can be used across platforms

" Maintain integrity over time

" Provide for traceability

" Provide meaningful results

PRIORITY MEASUREMENT AND STANDARDS CHALLENGE

RATIONALE OBJECTIVES ELEMENTS OF 

APPROACH

RISK

RELATIVE IMPACTS

Accelerates innovation *** Supports goals for personalized medicine

Enhances competitiveness *** More cost-effective sampling

Provides societal benefits *** Prevention and control of disease

Technical

Commercial

Consensus Approaches and 

Markers for Sample Integrity

STAKEHOLDERS AND ROLES

Government: Broad consortium; NIST (reference materials)

National laboratories: As appropriate

Academia: Supporting role

Industry: Involved

Professional associations: AACC, IFCC, others

Private research groups: Supporting role

Technical risks include identification of 

sample integrity markers for different 

sample types and improving methods of 

sample preparation.

Exhibit 6.7 Priority Measurement Topic

Low High

*** (High)
64 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

MEDICINE MEDICINE

There is a lack of understanding of clinical and biological phenotypes 

needed to achieve the goal of personalized medicine.

•	 Understanding phenotypes 

is essential to achieve the 

long-term goal of personalized 

medicine

•	 Identify path forward for 

establishing and working in 

consortia

•	 Develop relevant pre-clinical 

models (animal, in vitro, and in 

silico models)

•	 Facilitate collaborations 

between government, industry, 

and academia (national and 

international)

•	 Better understanding of 

pathobiology

•	 Identification of targets for 

therapy 

•	 Improved trial design, endpoints, 

and outcomes

•	 Improved marketability: cheaper, 

tastes better, etc.

PRIORITY MEASUREMENT AND STANDARDS CHALLENGE

RATIONALE OBJECTIVES ELEMENTS OF 

APPROACH

RISK

RELATIVE IMPACTS

Accelerates innovation *** Supports goals for personalized medicine

Enhances competitiveness *** Cost-effective therapies

Provides societal benefits *** Enhanced human health

Technical

Commercial

Understanding Clinical and Biological 

Phenotypes for Therapeutics

STAKEHOLDERS AND ROLES

Moderate technical and commercial 

risk associated with paths to improve 

understanding of phenotypes, with 

positive outcomes for personalized 

medicine.

Government: NIST (involved)

National laboratories: As appropriate

Professional associations: Medical profession; broad consensus on 

phenotype nomenclature

Exhibit 6.8 Priority Measurement Topic

Low High

*** (High)
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 65

MEDICINE MEDICINE

Standardization of phenotypes is lacking; different standards and definitions result in disagreement 

on outcomes, phenotype inconsistency, and other limiting factors.

•	 Correlation between phenotype 

and underlying pathways and 

biological mechanisms

•	 Improved disease identification 

and management

•	 Develop informatics infrastructure, 

biorepositories, provision of 

standards

•	 Create new communication 

networks

•	 Consider impact on U.S. and 

foreign policy and regulation

•	 Improve interactions between 

FDA, NIST, NIH, IFCC, DARPA, 

DOD, and professional societies

•	 Definition of what the 

phenotype means

" Disease signature or indices

" Perturbed or normal pathways

" Biologic correlates of 

descriptive characteristics

" Severity

" Changes over time in disease 

activity

" Environmental or therapeutic 

outcomes in phenotypes

PRIORITY MEASUREMENT AND STANDARDS CHALLENGE

RATIONALE OBJECTIVES ELEMENTS OF 

APPROACH

RISK

RELATIVE IMPACTS

Accelerates innovation *** New paradigms in treatment of disease

Enhances competitiveness *** Economic benefits of better disease management

Provides societal benefits *** Prevention and control of disease

Technical

Commercial

Phenotype Standardization, Outcomes, 

Disease Definitions, and Disease Activity

STAKEHOLDERS AND ROLES

Standardization provides consistency and 

improves understanding with moderate 

technical and commercial risk.

Government: FDA, DOD, DARPA, NIST

National laboratories: As appropriate

Academia: Input to approach

Industry: Biotech, pharmaceuticals

Professional associations: Medical

Private research institutes: ISB, others

Trade groups: BIO, PhRMA

Other: Insurers, health maintenance organizations (HMOs)

Exhibit 6.9 Priority Measurement Topic

Low High

*** (High)
66 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

MEDICINE MEDICINE

Measurement is not standardized across platforms, which can produce misleading results and interpretation.

•	 Cross-validation of methods and 

platforms

•	 Confidence in biological 

measurements

•	 Process-based standard aids in 

process management, assay 

characterization

•	 Develop independent 

reference material, which is not 

changed and cannot change, 

as a surrogate for biological 

parameters

•	 Comparison of data across 

platforms using platformindependent reference material 

with

" Equivalency of data 

interpretation across 

technologies and platforms

" Relative unit of measure with 

traceability to an independent 

standard

PRIORITY MEASUREMENT AND STANDARDS CHALLENGE

RATIONALE OBJECTIVES ELEMENTS OF 

APPROACH

RISK

RELATIVE IMPACTS

Accelerates innovation *** Facilitates medical innovations

Enhances competitiveness *** Global compatibility, marketability

Provides societal benefits *** Confidence in test results

Technical

Commercial

Reference Materials and 

Standardization Across Platforms

STAKEHOLDERS AND ROLES

Commercial risk is high as standardization 

across platforms may be difficult, but 

outcomes would improve confidence.

Government: NIST

National laboratories: Various

Professional associations: AACC, CAP, IFCC

Standards organizations: Supporting role

Exhibit 6.10 Priority Measurement Topic

Low High

*** (High)
Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 67

Science today tends to be driven by what is considered 

“fundable” according to popularity in the field, sometimes 

leading scientists down a path before they question the 

value of the topic and the validity of their methodology. 

However, there are less “popular” bioscience areas and 

programs that should be considered hot topics by the 

measurement community. The Hot Topics technical panel 

session identified these overlooked areas that require better 

measurement technologies and standards to advance R&D in 

the biosciences. 

The hot topics panel session followed a different format than the technical panel sessions, with short 

presentations by industry, academic, and government experts in the fields of medicine, energy, agriculture, 

environment, and homeland security/forensics. The focus of presentations was on questions and challenges 

that may have been unrecognized, overlooked, underestimated, or ignored. Emphasis was placed on 

challenges not addressed during plenary discussions or technical panel sessions. Attendees with insights and 

personal experience in relevant areas were encouraged to submit questions for the panel. Topics included: 

7.0 HOT TOPICS 7.0 HOT TOPICS

Technical Panel on Hot Topics

Addressing Unrecognized, Overlooked, 

Underestimated, and Ignored 

Measurement Needs in the Biosciences

Technical Panel Co-Leaders: (1) Jennie 

Hunter-Cevera, UMBI; (2) Craig Jackson, 

Consultant

Session Speakers (in order of presentations)

Keith R. Yamamoto, UCSF: "Quantification and Integration in Biomedical Research: Measurements and Standards—

Emerging, Needed, Overlooked, Resisted" 

Kathy Hudson, Johns Hopkins University: "Genetic Testing: Measurement Standards & Technological Challenges"

Ann Reid, The National Academies: "Measuring the Microbial World"

Renee A. Reijo Pera, Stanford University School of Medicine: "Stem Cells and Therapies"

Gregory Petsko, Brandeis University: "Unintended Consequences in Biological Systems"

George E. Pierce, Georgia State University: "Environment—Drinking Water, Drinking Water Disinfection, and 

Bioremediation" and "Biomanufacturing—Scale-up of Vaccines and Biologics"

Feng Chen, University of Maryland Biotechnology Institute: "Algae for Biofuels and Clean Coal"

Bob Wall, USDA: "Closing the Gap: Unrecognized, Overlooked, Underestimated, and Ignored Challenges"

Joe Spence, USDA: "Food and Agriculture Detection and Measurement"
68 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

HOT TOPICS HOT TOPICS

Agriculture Viability. What is the hard evidence for risk of transgenic plants? What systems are we 

employing technically in assuring that transgenic plants can become more acceptable? What are the quality 

assurance measures for animals that are being used to produce pharmaceuticals today? What is the downside 

to use of antibiotics and steroids in animal production with respect to their own metabolism and cost savings? 

How can metagenomics play a role in improving crop yield through bio-inoculants? Are certain crops better 

for addressing the mitigation of global climate change than others and how does one measure this over time 

with respect to soil nutrient depletion? 

Antibiotic and Antiviral Drug Resistance. Is the evidence compelling that resistance stems from using 

antibiotics as growth stimulants? What will it take to find a new class of antibiotics—or, better yet, a really 

broad class of antibiotics that would even work against "trojan horses" with respect to biothreats? What new 

technologies and paradigms are needed to predict, detect, and manage emerging antibiotic-resistant strains 

that might result in epidemics? 

Environmental Bioremediation. How cost-effective is bioremediation? Does the benefit of 

bioremediation differ depending upon the pollutant being remediated? How should resources be allocated 

for bioremediation when benefits are not definable? Are there biotechnologies or nanotechnologies being 

developed to deal with "cleaning up" nuclear contamination? 

Environmental Bioterrorism Monitoring. Do we now have the right tools to distinguish environmental 

terrorism from natural phenomena? How sensitive is "sensitive enough" for finding biothreats released into 

the environment? 

Marine Versus Terrestrial Sources of Bioenergy. What are the advantages and disadvantages of 

tapping these sources? Can we engineer optimal enzyme functions within various organisms that are 

envisioned as energy producers? What are the anticipated limits that will constrain the use of bioenergy? 

What advances have been made that improve production rates from various forms of bioenergy to make the 

cost economical without subsidizing the operation? Are there predictive measurements and or models for 

prediction of conservation and sustainability issues? 

Personalized Medicine. What do we need if we are to realize 

the benefits of comparing changes within an individual rather 

than with respect to assumed "healthy" populations? How 

might personalized medicine balance genomic information with 

phenotypic information? Are our technologies, analytical methods, 

and standards adequate for making the long-term comparisons 

implied by personalized medicine and making inferences from 

changes? Will population comparisons become irrelevant to 

personalized medicine or require better definitions of populations 

and sub-populations? 

Stem Cell Therapy. What barriers do we still face in 

understanding potential tumor formation? How do you stop the 

cells from proliferating once inserted into the patient? When stem 

cells become therapeutics, do we have the capability, capacity, and 

know-how required to produce them in the quantities necessary? 

Will therapeutic stem cells originate from the patient in whom they 

will be transplanted to a different tissue? 
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 69

Synthetic Biology. How far have we 

come and how far do we still have to 

go? Can engineered pathways in these 

new life forms really survive and function 

as they were "created" to? What are the 

concerns regarding alterations in the 

biosphere that should be considered 

when practicing synthetic biology? More 

simply put, could new life forms thrive at 

the expense of unrecognizably important 

life forms in the biosphere?

Common Measurement 

Challenges in Biological Science 

Investigation and Application

A number of measurement challenges that 

cut across different sectors of the biosciences were identified. These are summarized below.

Information and Data Exchange. Inadequacies in our ability to conveniently share information across 

disciplines resulting from database structural incompatibilities were commonly cited as serious challenges 

to information exchange. The absence of interoperability in respect to data transfer between instrument 

platforms is one example of such inadequacy. Another example is the inflexibility of data structures to 

accommodate new information or previously overlooked information that needs to be incorporated into 

existing databases. Inadequacies in data and information availability and in the formats in which the data are 

stored pose serious, even threatening, risks when the data are intended to be used for making decisions. 

Education in Principles of Measurement. A general lack of familiarity of the importance of measurement 

science for the quality assurance of laboratory measurement results was observed, indicating a need for 

education in the principles of measurement. Some measurement concepts and fundamentals are relatively 

unknown outside the metrology community. 

Quality Assurance of Data and Tests. The absence of reference materials suitable for use in biological 

measurements limits confidence in the quality of data upon which decisions and recommendations can be 

made. This issue is wide ranging, extending from assessment of water quality to genetic markers for disease. 

Quality assurance procedures outside the current regulatory structure for genetic marker tests used in medical 

diagnosis, for example, create a situation that does not provide confidence in the comparability or accuracy 

of these tests. Test quality has not kept pace with new developments to the extent that confidence in 

measurement results can be deemed satisfactory. 

In Situ Measurement. Measurements that ignore the environment or milieu in which biological processes 

and reactions occur can provide data that mislead rather than inform. This is a consequence of the need for 

measurements that can be made in situ with the same accuracy of measurements previously made only after 

preparation of samples which destroy the information that is only available in situ. 

Non-Invasive Measurement. The need for non-invasive measurements, particularly for cells, was noted 

in several contexts. MRI, CAT, and PET scanning are technologies that might be adaptable to measurements 

of single cells. Examples of applicability are in embryogenesis and single-cell toxicology studies. A lack of 

technologies suitable for non-invasive measurement of embryonic systems and development severely impede 

progress in assessing the likelihood of successful in vitro fertilization. Similarly, technologies capable of acting 

like global positioning systems for intracellular structures could provide advantages for evaluating the effects 

HOT TOPICS HOT TOPICS
70 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

HOT TOPICS HOT TOPICS

of both toxic substances and potential therapeutic drugs on cells. If such technologies were to be developed, 

many of the impediments now identified with animal testing and limited traditional methods could potentially 

be overcome.

Cross-Discipline Transfer of Technology. Technologies that have been developed and are currently used 

in medical diagnostic testing environments need to be made available to laboratories in which more routine 

biological testing is employed; examples are water quality and soils testing. Some of the impediments are 

economic, but others result from the absence of methods and reference materials suitable for use in these 

application areas. Testing for microbial contamination of water is too frequently performed by methods that 

are not usable in real time (e.g., the water may have been safe when it was tested, but the test was two days 

ago). 

Ineffective Animal Models for Drug Testing. The traditional uses of animal models for assessment 

of risk and efficacy in the evaluation of new drugs are unsatisfactory, particularly when more specifically 

targeted therapeutic agents are being evaluated. Misleading results may arise from inadequate specificity of 

conventional methods and may result in risks not being identified or efficacy missed. Single-cell procedures 

that can be more suitable are hampered by inadequate sensitivity or the absence of calibration materials to 

assure the validity of such measurements. 

Understanding Measurement Needs. Technological advances are limited conceptually by measurement 

of what we know how to measure, rather than what we believe could be more informative. The challenge 

is being able to measure the attribute with the specificity and accuracy needed to form a sound basis for 

recommendations and decisions.
Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 71

8.0 UNIVERSAL 

IDEAS AND 

OBSERVATIONS

8.0 UNIVERSAL 

IDEAS AND 

OBSERVATIONS

Universal Ideas

As the preceding sections have illustrated, measurement challenges have been identified that are relevant 

to the unique requirements of individual sectors (e.g., agriculture, medicine). However, a number of critical 

measurement needs have emerged that are common to many areas of the biosciences. This is notable 

because solutions for these common measurement problems could thus have wide applicability and support 

innovation in more than one area. The universal, crosscutting needs identified for the biosciences are:

•	Better methodologies and practices for sample handling (ensures sample integrity, reproducibility of results, 

and traceability)

•	More robust protein measurements (enables broader understanding of disease and treatment)

•	High-throughput multiplexed measurements (enables rapid analysis of performance and functionality, and 

supports an accelerated discovery process)

•	Improved tools and standards for bioinformatics (enhances the reliability, accessibility, and utility of critical 

information exchange systems)

•	Improved measurement tools and standards (ensures confidence in data and enables comparability across 

platforms)

Observations

Based on the roundtable and plenary presentations, and discussions among the various technical panels, 

a number of overarching observations emerged. These emphasize the importance of biosciences to our 

economic future and quality of life, as well as the importance of measurement to achieving the future promise 

of biosciences. It is clear that, more sophisticated, highly reliable, and standardized measurement methods 

will be necessary to support and accelerate technological innovation in this important field. As rapid advances 

in the biosciences continue to emerge, measurements and standards will need to advance as well. Failure 

to do so could not only stifle innovation and discovery, but impede some of the new concepts that will be 

critical to our future economic security and quality of life. 

Overarching observations about the biosciences include the following:

•	Improvements in the biosciences are a key to global economic security and quality of life in the future.

•	A much deeper understanding of complex biological systems is needed.

•	Highly sophisticated measurements are needed in order to study the relevant changes that occur in 

complex biomolecular networks. 

•	Major measurement challenges exist that are stifling innovation in the biosciences.

•	Current technology is inadequate due to a very limited measurement infrastructure that allows scientists to 

have confidence in only a very small percentage of the biomeasurements being conducted.
72 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

•	New multiplex, multiparametric measurement technologies will need to be invented and developed. 

•	These new measurement systems will heavily rely upon the accuracy and comparability of the data 

obtained from current technologies to build the new systems.

•	Standardization of current measurement technologies will be needed to enable next-generation systems.

•	Standardization of next-generation biomeasurement systems that bridge historical and new data will be 

needed as new methods emerge.

UNIVERSAL 

IDEAS AND 

OBSERVATIONS

UNIVERSAL 

IDEAS AND 

OBSERVATIONS
Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 73

APPENDIX A:

SPONSOR PROFILES

APPENDIX A:

SPONSOR PROFILES

The National Institute of Standards and Technology (NIST)

www.nist.gov

From automated teller machines and atomic clocks to mammograms and semiconductors, innumerable 

products and services rely in some way on technology, measurement, and standards provided by the National 

Institute of Standards and Technology. 

Founded in 1901, NIST is a non-regulatory federal agency within the U.S. Department of Commerce. NIST’s 

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. NIST 

carries out its mission in four cooperative programs:

•	The NIST Laboratories, conducting research that advances the nation’s technology infrastructure and is 

needed by U.S. industry to continually improve products and services

•	The Baldrige National Quality Program, which promotes performance excellence among U.S. 

manufacturers, service companies, educational institutions, healthcare providers, and non-profit 

organizations; conducts outreach programs; and manages the annual Malcolm Baldridge National Quality 

Award, which recognizes performance excellence and quality achievement

•	The Hollings Manufacturing Extension Partnership, a nationwide network of local centers offering technical 

and business assistance to smaller manufacturers 

•	The Technology Innovation Program, which provides cost-shared awards to industry, universities, and 

consortia for research on potentially revolutionary technologies that address critical national and societal 

needs.

The University of Maryland Biotechnology Institute (UMBI)

www.umbi.org

The University of Maryland Biotechnology Institute is a hub of intensive study into the applied science 

of biotechnology and its application to human health, the marine environment, agriculture, and protein 

engineering/structural biology. 

Established in 1985 by the state of Maryland, UMBI’s four centers conduct research and training that provide 

a core of expertise and facilities to advance the state’s scientific and economic development.

UMBI emphasizes collaboration with industry, other research institutions, and federal laboratories and 

sponsors training workshops, short courses, symposia, and seminars throughout the year.

UMBI’s mission is to conduct groundbreaking research in key areas of biotechnology, make fundamental 

discoveries, generate innovative solutions to practical problems, and develop new technologies for 

commercial application. UMBI is committed to providing an exceptional environment for specialized training 

and mentoring tomorrow’s biotechnology workforce while promoting economic growth.
74 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

SPONSOR 

PROFILES

SPONSOR 

PROFILES

American Autoimmune Related Diseases 

Association, Inc. (AARDA)

www.aarda.org

The American Autoimmune Related Diseases Association is dedicated to the eradication 

of autoimmune diseases and the alleviation of suffering and the socioeconomic impact of autoimmunity 

through fostering and facilitating collaboration in the areas of education, public awareness, research, and 

patient services in an effective, ethical, and efficient manner. The AARDA is the only national non-profit 

health agency dedicated to bringing a national focus to autoimmunity, the major cause of serious chronic 

diseases. Approximately 50 million Americans—20% of the population, or one in five people—suffer from 

autoimmune diseases. Women are more likely than men to be affected; some estimates say that 75% of those 

affected—some 30 million people—-are women. Still, with these statistics, autoimmunity is rarely discussed as 

a women’s health issue.

Aspen Technology, Inc. (AspenTech)

www.aspentech.com

AspenTech is the world’s leading supplier of software that optimizes process manufacturing. From our MIT and 

U.S. Department of Energy roots in the early 1980s, to the groundbreaking release of aspenONE V7 in 2008, 

AspenTech has always been at the forefront of innovation in the process industries. 

With integrated AspenTech solutions, process manufacturers can implement best practices for optimizing their 

engineering, manufacturing, and supply chains. As a result, AspenTech customers are better able to achieve 

their operational excellence goals—increasing capacity, improving margins, reducing costs, and becoming 

more energy efficient. 

Today, AspenTech solutions are used by virtually every leading company in the process manufacturing 

industry. More than 75,000 users at over 1,500 companies rely on AspenTech. For more than 25 years, 

AspenTech customers have achieved hundreds of millions of dollars in cost savings and performance 

improvements. 

The culmination of that industry leadership and experience was manifested in the release of aspenONE V7 in 

2008. It represents best practices for process optimization. It redefines ease-of-use in software for the process 

industries. It makes operational excellence achievable and—even in the face of today’s market challenges—

easier than you think.

Energetics Incorporated 

www.energetics.com 

Energetics, Incorporated is a full-service technical and management consulting company. 

We provide our clients with support to help research, develop, and commercialize new technologies to meet 

the nation’s need for cost-effective, efficient, and environmentally-friendly sources of energy. In addition, we 

provide technical and management support to clients responsible for the protection of the U.S. infrastructure 

related to energy assurance and homeland security. 

Our special strengths include an in-depth knowledge of:

•	Energy supply and generation technologies 

•	Electric utility industry/technologies 
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 75

SPONSOR 

PROFILES

SPONSOR 

PROFILES

•	Federal energy and environmental regulation 

•	Advanced transportation and industrial technologies 

•	Process and manufacturing industries 

•	Building energy technology 

•	Energy assurance and security

IEEE-USA

www.ieeeusa.org

IEEE-USA is an organizational unit of the Institute of Electrical and Electronics Engineers, Inc. created in 1973 

to support the career and public policy interests of IEEE’s U.S. members. IEEE-USA is primarily supported by an 

annual assessment paid by U.S. IEEE members. 

IEEE-USA’s mission as outlined in the IEEE bylaws is to recommend policies and implement programs 

specifically intended to serve and benefit the members, the profession, and the public in the United States in 

appropriate professional areas of economic, ethical, legislative, social, and technology policy concern. 

Our vision is to serve IEEE U.S. members by being the technical professional’s best resource for achieving 

lifelong career vitality and by providing an effective voice on policies that promote U.S. prosperity.

Johns Hopkins University (JHU)

www.jhu.edu

The mission of The Johns Hopkins University is to educate its students and cultivate their capacity for life-long 

learning, to foster independent and original research, and to bring the benefits of discovery to the world. 

Further, JHU strives to create an interactive community of educators, students, researchers, corporations, and 

government representatives whose collaborative thinking and discovery expand academic and technological 

boundaries and advance economic development.

Human Genome Sciences (HGS)

www.hgsi.com

The mission of Human Genome Sciences is to apply great science and great medicine to bring innovative 

drugs to patients with unmet medical needs. 

We are poised for the market with a clinical pipeline that includes three novel products in late-stage 

development: Albuferon in Phase 3 trials for hepatitis C, LymphoStat-B in Phase 3 trials for systemic lupus, and 

ABthrax in late-stage development for inhalation anthrax. 

Both Albuferon and LymphoStat-B have the therapeutic potential to change and save lives and the 

commercial potential to become blockbusters in the marketplace. Each is being co-developed and 

commercialized in collaboration with a world leader in the pharmaceutical industry—Novartis for Albuferon 

and GlaxoSmithKline for LymphoStat-B. 

ABthrax is being developed under a contract with the U.S. Government and represents a new way to address 

the threat of inhalation anthrax. The pivotal efficacy studies have demonstrated a dramatic and significant 
76 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

survival benefit. In January 2009, HGS began the delivery of 20,000 doses of ABthrax to the U.S. Strategic 

National Stockpile. Right behind these three late-stage products is a high-potential mid-stage pipeline led by 

our TRAIL receptor antibodies for cancer—and including a number of products to which HGS has substantial 

financial rights in the GSK pipeline. 

Our manufacturing capability represents a significant strategic advantage. HGS is able to produce and 

purify multiple protein and antibody drugs in two state-of-the-art process development and manufacturing 

facilities—totaling approximately 400,000 square feet and offering both small-scale and large-scale 

production. 

HGS has built a strong cash position that allows us to focus on advancing our lead products toward 

commercialization as rapidly as possible, while at the same time investing in our early- and mid-stage pipeline. 

U.S. Pharmacopeia (USP)

www.usp.org

The United States Pharmacopeia (USP) is an official public standards-setting authority for all 

prescription and over-the-counter medicines and other healthcare products manufactured or 

sold in the United States. USP also sets widely recognized standards for food ingredients and 

dietary supplements. USP sets standards for the quality, purity, strength, and consistency of these products—

critical to the public health. 

USP’s standards are recognized and used in more than 130 countries around the globe. These standards have 

helped to ensure public health throughout the world for close to 200 years. 

USP is a non-governmental, not-for-profit public health organization whose independent, volunteer experts 

work under strict conflict-of-interest rules to set its scientific standards. USP’s contributions to public health are 

enriched by the participation and oversight of volunteers representing pharmacy, medicine, and other health 

care professions as well as academia, government, the pharmaceutical and food industries, health plans, and 

consumer organizations. 

USP’s mission is to improve the health of people around the world through public standards and related 

programs that help ensure the quality, safety, and benefit of medicines and foods.

Waters Corporation

www.waters.com

For fifty years, Waters Corporation has developed innovative analytical science 

solutions to support customer discoveries, operations, performance, and regulatory compliance. 

Waters holds worldwide leading positions in complementary analytical technologies—liquid chromatography, 

mass spectrometry, rheometry, and microcalorimetry. These markets account for approximately $5 billion of 

the estimated $20-$25 billion worldwide analytical instrumentation market.

Specifically, the company designs, manufactures, sells, and services ultra-performance liquid chromatography 

(UPLC), high-performance liquid chromatography (HPLC), chromatography columns and chemistry products, 

mass spectrometry (MS) systems, thermal analysis, and rheometry instruments. Waters operates in two 

divisions: Waters Division and TA Instruments.

SPONSOR 

PROFILES

SPONSOR 

PROFILES
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 77

Montgomery County Department of Economic Development

www.montgomerycountymd.gov

Montgomery County, Maryland, is your gateway to the Mid-Atlantic’s robust business 

community. Centrally located at the epicenter of the region’s federal and advanced 

technology marketplace, it is next door to the nation’s capital and home to: 

•	More than 200 biotech companies 

•	The highest concentration of PhDs in the nation 

•	More than 100,000 advanced technology workers 

•	19 federal research and regulatory agencies 

•	More entrepreneurs than any other jurisdiction in the nation 

•	The largest number of woman- and Asian-owned businesses in Maryland 

•	Half of all Hispanic-owned businesses in Maryland 

•	The second largest and fastest growing number of African American-owned businesses in Maryland 

Federal agencies including the NIH, FDA, and NIST are all located in Montgomery County. Industry leaders 

are also located here, including Discovery Communications, Hughes Network Systems, Human Genome 

Sciences, Lockheed Martin, Marriott International, and MedImmune. 

Montgomery County encourages business and economic development in a number of ways. The highlysuccessful Business Innovation Network nurtures and grows young entrepreneurs into thriving county 

employers. Its nationally renowned 93,000-acre Agricultural Reserve helps protect, promote, and support 

diverse agribusinesses. The award-winning Small Business Mentorship Program pairs new business owners 

with successful business leaders. A Local Small Business Reserve Program helps ensure that local businesses 

get their share of county procurement contracts.

SPONSOR 

PROFILES

SPONSOR 

PROFILES
78 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges
Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 79

APPENDIX B:

TECHNICAL PANEL 

PARTICIPANTS

APPENDIX B:

TECHNICAL PANEL 

PARTICIPANTS

*See glossary for list of acronyms

Lakshmi Amaravadi, Biogen Idec

Michael Ambrose, USP

Jeff Amthor, U.S. DOE

Don Archer, NIST

Nick Bajjalieh, United Soybean Board

Paul Becker, NIST

Judy Britz, Britz Consulting

Steve Britz, USDA

Mark Brukhardt, USGS

Kenneth Butcher, NIST

Ray Chrisman, CPAC

Bill Clarke, Johns Hopkins University Hospital

Chuck Corr, Archer Daniels Midland

Jeff Cossman, Critical Path Institute

Jon Deeds, FDA

Anthony DeStefano, USP

John Duguid, Genzyme

Hendrik Emons, EC-JRC-IRMM

Matthew Frome, Solazyme

David Galas, Institute for Systems Biology

Timothy Gish, USDA-ARS

Robert Goldberg, NIST

Steven Gutman, U.S. FDA

Timothy Hall, EC Research Directorate General

Bill Heetderks, NIBIB

John Heissenbuttel, Council on Sustainable 

Biomass Production

Anna Hills, NPL

Fred Holland, NOAA

Tomoshige Hori, JBA

David Hussong, OPS/CDER/FDA

Steve Hutcheson, Zymetis

Chris Jones, NIBSC

Joao Jornada, INMETRO

Lisa Karam, NIST

George Klee, Mayo Clinic

Andy Klein, NIST

Bill Koch, USP

Dan Kuebbing, UMBI

Anne-Francoise Lamblin, NSF

Maureen Lanan, Biogen Idec

Albert Lee, NIH

Hsien-Chen MA, ITRI

Larry Mahan, MD DBED
80 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

Robert Mandrell, USDA-ARS, WRRC

Elizabeth Mansfield, CDRH/FDA

Jeremy Melanson, NRC-Canada

Anthony Micheals, Proteus Environmental

Technologies

Peter Miller, UCSC, SCCWRP

Barbara Mittleman, NIH

Pallavi Nithyanandan, USP

David Parmelee, USP

Terry Purkable, JHU-APL

Norman Purvis, Nodality, Inc.

Fred Razzaghi, Consultant

Westley Reeves, University of Florida

Dean Ripple, NIST

Bodo Roemer, Abbott

Teri Rowles, NOAA-NMFS

Norman Salem, Jr., Martek Biosciences

Marc Salit, NIST

Paul Sandifer, NOAA-NOS

Dean Schroer, Roche

Lori Schwacke, NOAA/NCCOS

Hratch Semerjian, CCR

David E. Smith, Luminex

Jill Stewart, UNC-CH

Mark Strom, NOAA-NMFS

Michael Tarlov, NIST

Harold Thistle, USDA Forest Service

Tamas Torok, LBNL

Michael Townsend, Genentech

Paul J. "PJ" Utz, Stanford University

Sudha Visvanthan, Centocor

Nam Sun Wang, University of Maryland

Suphat Watanasiri, Aspen Technology

Keith Webber, OPS/CDER/FDA

Steve Weisberg, SCCWRP

James Whetstone, NIST

Tom Wiggins, NIST

Judy Wilber, XDx

James Witter, NIH-NIAMS

Steve Young, U.S. EPA

TECHNICAL PANEL

PARTICIPANTS

TECHNICAL PANEL

PARTICIPANTS
Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 81

APPENDIX C:

list of acronyms

APPENDIX C:

list of acronyms

AACC American Association for Clinical Chemistry

AARDA American Autoimmune Related Diseases Association, Inc.

APL Applied Physics Lab

ASTM American Society for Testing and Materials, now ASTM International

ATCC Association Tunisienne de lutte contre le Cancer (Tunisian Association for Fighting 

Against Cancer)

BIO Biotechnology Industry Organization

CAP College of American Pathologists

CARB Center for Advanced Research in Biotechnology

CAT computerized axial tomography

CCQM Consultative Committee for Amount of Substance, Bureau International des Poids et 

Mesures

CCR Council for Chemical Research

CDC Centers for Disease Control and Prevention

CDISC Clinical Data Interchange Standards Consortium

CDRH/FDA Center for Devices and Radiological Health/Food and Drug Administration 

CIPM International Committee for Weights and Measures (Comité International des Poids et 

Mesures)

CMS Centers for Medicare & Medicaid Services

CO2 carbon dioxide

CPAC Center for Process Analytical Chemistry 

CRM certified reference material

CT computed tomography

DARPA Defense Advanced Research Projects Agency

DBED Department of Business and Economic Development
82 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

DNA deoxyribonucleic acid

DOD U.S. Department of Defense

DOE U.S. Department of Energy

DOI U.S. Department of the Interior

EC European Commission

EC-JRC-IRMM European Commission, Joint Research Center Institute for Reference Materials and 

Measurements

EFA essential fatty acid

EIP eliminating interference pattern

EPA U.S. Environmental Protection Agency

EPI epigenetic

FACE Free Air CO2 Enrichment

FACS fluorescence-activated cell sorting

FDA Food and Drug Administration

FDA-CDER-OPS Food and Drug Administration, Center for Drug Evaluation and Research Office of 

Pharmaceutical Science 

FDA-CDRH Food and Drug Administration, Center for Devices and Radiological Health

FITC fluorescein conjugation of antibodies 

F-PET positron emission tomography with fluoride tracers

FFPET formalin-fixed, paraffin-embedded tissue with positron emission tomography

GC gas chromatography

GE General Electric

GE genetic engineering

GEOSS Global Earth Observation System of Systems 

GHG greenhouse gas

GIS geographic information system

GSK Glaxo SmithKline

HAB harmful algal bloom

HGS Human Genome Sciences

HMO health maintenance organization

LIST OF

ACRONYMS

LIST OF

ACRONYMS
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 83

IEAA Institute of Electrical and Electronics Engineers

IFCC International Federation of Clinical Chemistry and Laboratory Medicine

IHC immunohistochemistry

INMETRO National Institute of Metrology, Standardization, and Industrial Quality (Instituto 

Nacional de Metrologia, Normalização e Qualidade Industrial)

INMS Institute for National Measurement Standards (Canada)

ISB Institute for Systems Biology

IT information technology

ITRI Industrial Technologies Research Institute

JBA Japan Bioindustry Association

JCVI J. Craig Venter Institute

JGI Joint Genome Institute

JHU Johns Hopkins University

JHU-APL Johns Hopkins University, Applied Physics Laboratory

KRISS Korea Research Institute of Standards and Science

LBNL Lawrence Berkeley National Laboratory

LCA life-cycle analysis

LGC UK designated national measurement institute for chemical and biochemical analysis

LLE liquid-liquid equilibrium

LT long-term

LUC land use class

MBSC Medical Board of the State of California

MD DBED Maryland Department of Business and Economic Development

MMTS medical material transfer system

MRI magnetic resonance imaging

MS mass spectroscopy

MT mid-term

NASA National Aeronautics and Space Administration

NCI National Cancer Institute

NDVI normalized difference vegetation index

LIST OF

ACRONYMS

LIST OF

ACRONYMS
84 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

NGOs non-government organizations

NIBIB National Institutes of Health, National Institute of Biomedical Imaging and 

BioEngineering

NIBSC National Institute for Biological Standards and Control

NIH National Institutes of Health

NIH-NIAMS National Institutes of Health, National Institute of Arthritis, Musculoskeletal and Skin 

Diseases

NIST National Institute of Standards and Technology

NIST-TIP National Institute of Standards and Technology, Technology Innovation Program

NMI National Metrology Institute

NMi Nederlands Meetinstituut

NOAA National Oceanic and Atmospheric Administration

NOAA-NCCOS National Oceanic and Atmospheric Administration, National Centers for Coastal 

Ocean Science

NOAA-NMFS National Oceanic and Atmospheric Administration, National Marine Fisheries Service

NOAA-NOS National Oceanic and Atmospheric Administration, National Ocean Service

NPL National Physical Laboratory

NRC National Research Council, USA

NRC-INMS National Research Council, Institute for National Measurement Standards (Canada) 

NSF National Science Foundation

NT near-term

OECD Organisation for Economic Co-operation and Development

OECD/WPB OECD, Working Party on Biotechnology

-omics

general term for a broad discipline of science and engineering for analyzing the 

interactions of biological information objects in various omes, such as genome, 

proteome, metabolome, expressome, and interactome. 

FDA-OPS-CDER Food and Drug Administration, Office of Pharmaceutical Science, Center for Drug 

Evaluation and Research 

OSTP Office of Science and Technology Policy

P4 predictive, preventive, personalized, and participatory

PAT process analytical technology

PCR polymerase chain reaction

LIST OF

ACRONYMS

LIST OF

ACRONYMS
 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges 85

PDA Parenteral Drug Association

PET positron emission tomography

PGx Pharmacogenomics (an individual’s genetic variation effects on therapeutic responses 

or adverse events) 

PhRMA Pharmaceutical Research and Manufacturers of America

PLT platelet count

PTM post-translational modifications

PURMA Public Utilities Risk Management Association

R&D research and development

RBC red blood cell

RFS renewable fuels standard

RNA ribonucleic acid

SCCWRP Southern California Coastal Water Research Project

SNP single nucleotide polymorphism

SRM Standard Reference Material®

UAV unmanned aerial vehicle or unmanned aircraft vehicle systems (UAVs) 

UCSC University of California, Santa Cruz

UCSF University of California, San Francisco

UK United Kingdom

UL Underwriters Laboratory

UMBI University of Maryland, Biotechnology Institute

UNC-CH University of North Carolina at Chapel Hill

USDA U.S. Department of Agriculture

USDA-ARS U.S. Department of Agriculture, Agricultural Research Service

USDA-WRRC U.S. Department of Agriculture, Western Regional Research Center

USGS U.S. Geological Survey

USP United States Pharmacopeia 

VLE vapor-liquid equilibrium

WBC white blood cell

WHO World Health Organization

LIST OF

ACRONYMS

LIST OF

ACRONYMS
86 Accelerating Innovation in 21st Century Biosciences: Identifying the Measurement, Standards, and Technological Challenges

XDx Molecular diagnostics company 

LIST OF

ACRONYMS

LIST OF

ACRONYMS
The Steering Committee wishes to thank the following members of the 

NIST Biovision Executive Team who contributed to the planning of this conference:

Willie E. May, Chair

Michael D. Amos, Bioscience Advisor

George W. Arnold, Technology Services

Jason Boehm, NIST Program Office

Marcus T. Cicerone, Materials Science and Engineering Laboratory

John A. Dagata, Manufacturing Engineering Laboratory

Laurie E. Locascio, Chemical Science and Technology Laboratory

Dan A. Neumann, NIST Center for Neutron Research

James K. Olthoff, Electronics and Electrical Engineering Laboratory

William R. Ott, Physics Laboratory

James A. St. Pierre, Information Technology Laboratory

Lloyd J. Whitman, Center for Nanoscale Science and Technology