David J. Glass, Ph.D.
D. Glass Associates, Inc.
BIO World Congress on Industrial Biotechnology
July 20, 2015
Advanced Biotechnology can
Improve Usefulness of Algae
 Enhance algal growth rate.
 Enhance or alter lipid biosynthesis.
 Enhance photosynthesis.
 Enable use of alternate food sources.
 Create new biosynthetic pathways;
enable production of new products.
 Enable secretion of lipids
to aid oil/water separation.
Rosenberg et al. 2008, Radakovits et al 2010,
Jones et al. 2012, Larkum et al. 2012, Work et al. 2013 (and others).
D. Glass Associates, Inc.
Overview of U.S. Biotechnology
Regulation Possible applicability to algae
Environmental Protection Agency
 Microbial pesticides, plant pesticides.
 Engineered microorganisms used for other industrial
purposes. TSCA biotech rule
U.S. Department of Agriculture
 Transgenic plants, potential plant pests.
 Plant-produced industrial products. USDA biotech rule
Food and Drug Administration
 Foods, food additives, pharmaceuticals.
Product –specific regulation
D. Glass Associates, Inc.
Regulatory Jurisdiction for
Engineered Algae
 Proposed use of engineered algae by Mera
Pharmaceuticals in pharmaceutical production in Hawaii
in 2005: no federal agency claimed jurisdiction, state law
and state courts ultimately determined outcome.
 2008 USDA opinion letter to Coastal BioMarine stated no
USDA oversight over engineered algal strain if no “plant
pest” sequences, and no oversight for smaller-scale use
in contained reactors.
 Can USDA, EPA work together on GM algae regulation,
with one agency designated as the lead?
D. Glass Associates, Inc.
EPA TSCA Biotechnology
Regulations (1)
 Regulations adopted in 1997 under the Toxic Substances
Control Act (TSCA) cover commercial uses of “new
microorganisms”.
 Regulations cover only those industrial uses not regulated
by other agencies as foods, drugs, cosmetics, pesticides.
 Among covered activities: industrial enzyme production,
bioremediation, biotreatment, manufacture of fuels,
chemicals.
 New microorganisms are defined as “intergeneric”:
containing deliberate combinations of coding nucleic acids
from more than one taxonomic genus.
D. Glass Associates, Inc.
EPA TSCA Biotechnology
Regulations (2)
EPA considers scope of coverage to include algae.
From the biotechnology rule:
“Microorganism” means an organism classified, using the 5-kingdom
classification system of Whittacker, in the kingdoms Monera (or
Procaryotae), Protista, Fungi, and the Chlorophyta and the
Rhodophyta of the Plantae, and a virus or virus-like particle.
From the rule’s preamble:
Therefore, this definition includes, but is not limited to, bacteria,
protozoa, fungi, mycoplasmas, mycoplasma-like organisms,
spiroplasmas, microphytoplanktons, green and red algae, viruses,
and virus-like particles (e.g., viroids, satellites, and virusoids).
D. Glass Associates, Inc.
EPA TSCA Biotechnology
Regulations (3)
 Commercial use or importation of intergeneric organism
requires 90 day advance notification to EPA, through
submission of a Microbial Commercial Activity Notice
(MCAN).
 Most research and pilot projects would not require EPA review
if conducted in suitably “contained” facilities, with procedures
for controlled access, inactivation of wastes, emission controls,
worker notification.
 R&D with intergeneric organisms under non-contained
conditions, such as open-pond algae reactors, would require
EPA review through submission of a TSCA Experimental
Release Application (TERA) 60 days in advance of proposed
activity.
D. Glass Associates, Inc.
EPA TSCA Biotechnology Rule:
TSCA Experimental Release Applications
 TERAs submitted to EPA 60 days in advance, describing
the organism, the proposed research, and the proposed
controls and monitoring procedures.
 EPA can approve or deny TERAs, or approve testing with
limitations or required monitoring.
 To date, 30 TERAs submitted, most for agricultural or
bioremediation microorganisms. All but three of these
have been approved.
 The 5 TERAs most recently filed and approved were from
Sapphire Energy, Inc., for open-pond research with
modified algae.
D. Glass Associates, Inc.
EPA TSCA Biotechnology Rule:
TSCA Experimental Release Applications
 Sapphire TERAs covered open-pond research at UCSD using
different modified strains of the photosynthetic green algae
Scenedesmus dimorphus.
 Goals: assess ecological impact; test field efficacy of strains
shown effective in laboratory.
 Among findings (J. Shurin, personal communication):
 Modified algae can disperse and spread up to 50 meters away from
the test site, but rate of dispersal declines with distance.
 Both modified and wild-type algae grew in water from nearby lakes.
 GM algae had no apparent effects on biomass, diversity, or native
algae species.
 GM Scenedesmus is ecologically indistinguishable from the wild-type
strains.
D. Glass Associates, Inc.
EPA TSCA Biotechnology Rule: Microbial
Commercial Activity Notifications (MCANs)
 MCAN reporting required at least 90 days before
commencing commercialization or importing a “new
microorganism” for a TSCA purpose.
 MCAN requires submission of data to EPA.
 Microorganism identity, construction and its properties
 Potential health and environmental impacts.
 Information about the industrial process,
control/containment measures, worker exposure, possible
environmental release.
 EPA review, clearance of MCAN authorizes commercial
use for any purpose.
D. Glass Associates, Inc.
EPA TSCA Biotechnology Rule:
Biofuel, Bio-Based Chemical MCANs
 Approx. 85 MCANs filed since 1997. Number and
frequency have increased in last 4-5 years.
 Most early MCANs covered GMOs for production of
industrial enzymes.
 18 MCANs for S. cerevisiae, 3 for Zymomonas
mobilis, all for ethanol production.
 Joule, Algenol have filed MCANs for cyanobacteria;
Solazyme has filed 4 MCANs for modified microalgae.
 Complete list available at
www.epa.gov/biotech_rule/pubs/submiss.htm.
D. Glass Associates, Inc.
MCANs Submitted to EPA by Fiscal Year
25
20
15
Number
of
MCANs
10
5
0
1998
1999
2000
D. Glass Associates, Inc.
2001
2002
2003
2004
2005 2006
Fiscal Year
2007
2008
2009
2010
2011
2012
2013
2014
EPA TSCA Biotechnology Rule:
Summary
 Algae and cyanobacteria covered under the rule;
EPA has recent experience with MCANs and TERAs
for algae and cyanobacteria.
 MCAN reviews for contained manufacturing have
been straightforward; EPA has recent track record
reviewing microorganisms for use in biofuels, biobased chemical production.
 The TERA process provides a stepwise approach to
regulation and risk assessment of outdoor uses.
D. Glass Associates, Inc.
USDA Biotechnology
Regulations (1)
 Regulations issued in 1987, administered by USDA
Animal and Plant Health Inspection Service (APHIS).
 Regulations cover environmental uses or interstate
movement of organisms considered to be “potential plant
pests”.
 Potential plant pest status is based on presence of DNA
sequences from listed potential plant pests. Inclusion of
Agrobacterium on the list has captured most transgenic
plants.
 Most submissions have been for transgenic plants, some
for modified agricultural microorganisms.
D. Glass Associates, Inc.
USDA Biotechnology
Regulations (2)
 Rules have generally not covered “contained” use of
organisms in manufacturing, but could cover openpond uses.
 Applicability to algae under current definitions not
clear; most algae strains would not be covered
unless engineered to contain DNA from potential
plant pest.
D. Glass Associates, Inc.
USDA Biotechnology Regulation:
Oversight over R&D
 R&D use covered only if in open environment.
 Notifications: 30 day advance notice.
 Permits: submit application 120 days in advance.
 Permits generally required for industrial uses.
 Submissions require:
 Description of host organism and genetic
modifications.
 Description of field test; proposed procedures and
controls.
 Assess environmental impact of field use.
D. Glass Associates, Inc.
USDA Biotechnology Regulation:
Approvals for Commercial Use
 Approval for commercial use and sale through
“petitions for nonregulated status”.
 Since early 1990s, USDA has approved over
100 petitions to allow commercial sale of
engineered crop plants.
 Commercial approvals can take 1-4 years,
and require USDA to prepare Environmental
Impact Statements.
D. Glass Associates, Inc.
USDA Biotechnology Regulation:
Summary
 Tens of thousands of transgenic plant field tests
approved under these regulations, over 100
modified crop varieties approved for commercial
sale – no approvals for algae?
 Limited experience with R&D permits for novel
biofuel feedstocks, no commercial approvals.
 USDA likely to have scientific expertise to review
biology of photosynthetic algae, but applicability
under existing definitions unclear.
D. Glass Associates, Inc.
International Biotechnology
Regulation
 Most countries around the world have biotechnology
regulations, in most cases based on principles of the
Cartagena Protocol on Biosafety.
 Many countries differ from the U.S. in having unified
laws and regulations that cover all genetically
modified organisms: no jurisdictional issues for
algae.
 However, principles of risk assessments for algae
and microorganisms should be similar throughout
the world.
D. Glass Associates, Inc.
Pathway for approval:
Contained Use of GM Algae
D. Glass Associates, Inc.
Pathway for approval:
Open-Pond Use of GM Algae
D. Glass Associates, Inc.
Industrial Biotechnology,
April 2015
Volume 11, Number 2
Pages 71-83
DOI: 10.1089/ind.2015.1503
Additional information
available at our blog,
Advanced Biotechnology
for Biofuels
(dglassassociates.wordpress.com)
D. Glass Associates, Inc.
Thank you very much
David J. Glass, Ph.D.
D. Glass Associates, Inc.
124 Bird Street
Needham, MA 02492
Phone 617-653-9945
[email protected]
www.dglassassociates.com
D. Glass Associates, Inc.