INSIGHTS | POLICY FORUM
1564 24 DECEMBER 2021 • VOL 374 ISSUE 6575 science.org SCIENCE
through the formation of new companies or
licensing to existing companies.
Related to this is the potential to relax
restrictions on the involvement of principal
investigators from universities and national
laboratories in early stages of technology
transfer. Although conflict-of-interest con-
siderations exist, they could be mitigated
with appropriate oversight and coordination
among universities and funding agencies.
Policies vary among institutions but should
be reevaluated if found to create barriers to
translational efforts.
Other adjustments to existing funding
structures could help support the transla-
tion of emerging fields. There is a current
focus on large multi-institutional, interdis-
ciplinary center grants. In these funding ve-
hicles, disparate expertise is gathered to ad-
dress a complex problem. The basic premise
for justifying these center grants is that by
supporting a single center, they provide
conditions in which solutions to large inter-
disciplinary problems can be sought more
efficiently. It is our experience, however,
that this premise is often false. Priorities
and interests can be misaligned, with a sub-
set of stakeholders disinterested or poorly
engaged. For some translational projects,
intermediate-sized grants (~$0.75 million to
$1 million annually for 5 years) could allow
small interdisciplinary teams to function
with more flexibility, higher accountability,
and closer connection of principle investi-
gators to the goals of the program.
Further, such funding modifications
would increase the necessity of transla-
tional research and commercialization and
thus help create a culture of support and
recognition for innovative solutions to criti-
cal bottlenecks in the practical application
of new discoveries.
TECHNOLOGY AND INFRASTRUCTURE
An industrial biotechnology process com-
prises a biocatalyst (microbe or enzyme), a
bioprocess that produces the product, and
an appropriate downstream purification fa-
cility. Consider the diversity of biocatalysts
(cells or enzymes), process environments
(aerobic, microaerobic, or anaerobic),
modes of operation (batch, fed batch, or
continuous), and types of substrate (glu-
cose, glycerol, methane, or lignocellulosic
biomass). Successful scale-up of a biomanu-
facturing process means providing a bio-
process environment (exemplified in the
design and operation of bioprocess equip-
ment) ideally suited to the specific needs of
the biocatalyst. This is not a trivial process,
and failure to do so may waste an otherwise
excellent biocatalyst. Bioprocess develop-
ment is not straightforward, able to rise to
the requirements of any biocatalyst.
With respect to required infrastructure,
the greatest need is facilitated access to
and use of pilot-scale fermentation facili-
ties. Pilot-scale facilities are essential for
the risk-reduction process, particularly
for evaluation of biocatalyst performance
in scale-up environments, which present
challenges that are not found in laboratory-
scale studies. Several products have met
challenges in this process. Artemisinin
production has faced scale-up challenges,
with fermentation-based synthesis being
consistently more expensive than extrac-
tion from farmed plants ( 8 ). Astaxanthin
faced scale-up challenges after 2 years of
production in a toll manufacturing plant
( 9 ). Upon attempting to scale up to a facil-
ity that was four times larger, poor batch
performance required troubleshooting that
substantially delayed production. The defi-
cit of facilities and inability to reduce risk
are major contributors to the “valley of
death” between academic demonstration of
a technology and its commercial-scale de-
ployment. Reducing risk in scale-up studies
is expensive and requires equipment that
is not typically part of an academic setting.
In addition, it is considered too applied forgovernment support and too premature for
industrial investment.
As a first step, we have compiled a list of
pilot-scale (approximately 100- to 20,000-
liter units) facilities at universities and na-
tional laboratories in the United States (see
the table). Readily noticeable from this list is
their limited capacity, both max capacity at
any given site and overall capacity. However,
this list can provide a starting point for a
well-organized registry or system, such as
the EPP Network (www.eppnetwork.com)
and Pilots4U (https://biopilots4u.eu) in the
European Union. A second consideration for
these existing sites is their varied staffing,
downstream processing capabilities, modes
of operation, and user fees. With some excep-
tions, the primary functionality of these sites
is a contract manufacturing model, in which
the operations team is decoupled from and
not invested in proving out a biocatalyst. It
also provides minimal training and educa-
tion. Others have more of a biopharma focus,
such as those associated with the Advanced
Mammalian Biomanufacturing Innovation
Center, whose mission differs from that of
industrial biotechnology. The solution will
likely take a combination of greater pilot-List of academic pilot-scale facilities in the United States
FACILITY LOCATION MAX CAPACITY (LITERS
CSL Behring Fermentation Facility
(Huck Institutes of the Life Sciences,
Pennsylvania State University)University Park,
PA100Biological Process Development Facility
(University of Nebraska-Lincoln)Lincoln, NE 150Massachusetts Biomanufacturing Center
(University of Massachusetts-Lowell)Lowell, MA 200Biotechnology Scale-Up Facility
(University of Maryland)College Park, MD 250Advanced Biofuels Process Development
Unit (Lawrence Berkeley National Lab)Emeryville, CA 300Synthetic Biomanufacturing Facility
(Utah State University)North Logan, UT 400Bioexpression and Fermentation Facility
(University of Georgia)Athens, GA 750Cell and Cell Product Fermentation
Facility (Rutgers University)Piscataway, NJ 800Center for Biocatalysis and Bioprocessing
(University of Iowa)Coralville, IA 1000Fermentation Facility (Iowa State
University)Aimes, IA 1000Integrated Bioprocessing Research
Laboratory (University of Illinois
Urbana-Champaign)Urbana, IL 1500Bioeconomy Institute (Michigan
State University)Lansing, MI 3800Integrated Biorefinery Research Facility
(National Renewable Energy Lab)Golden, CO 9000National Corn-to-Ethanol Research Center
(Southern Illinois University-Edwardsville)Edwardsville, IL ~22,000