Impact of Government Biotechnology Regulations on Use of Genetically Modified or

Synthetic Algae in Biofuel Production

David J. Glass, Ph.D.D. Glass Associates, Inc.Algae Biomass Summit

September 28, 2010

Biotechnologies Applicable to BiofuelsClassical mutation and selectionPlant breedingRecombinant DNADirected evolutionDNA shufflingMetabolic engineeringSynthetic biology

Applications of Biotechnology to Clean Fuel ProductionEnhanced or engineered microorganisms for

fermentation of ethanol, butanol, other fuels.Enzymes for fuel production manufactured using

engineered microorganisms or plants.Selected or engineered plant species for use as

improved biofuel feedstocks.Improved algal strains for production of biodiesel, jet

fuel, ethanol, other fuels.

Genetic Engineering Strategies: AlgaeEnhance algal growth rate.Enhance or alter lipid biosynthesis.Enhance photosynthesis.Enable use of alternate food sources.Create new biosynthetic

pathways.Enable secretion of lipids

to aid oil/water separation.

Scientific Issues in the Regulation of Modified AlgaeLegitimate scientific issues need to be addressed for many projects involving modified algal strains. Stability of vector and introduced genes.Possible deleterious functions encoded by

transgene(s).Potential for horizontal gene transfer, crossing to

wild algae species.Potential for engineered strain to be transported

outside facility, survive and compete in environment.

Overview of U.S. Biotechnology Regulation Environmental Protection AgencyMicrobial pesticides, plant pesticides.Engineered microorganisms used for other industrial

purposes.

U.S. Department of AgricultureTransgenic plants, potential plant pests.Plant-produced industrial products.

Food and Drug AdministrationFoods, food additives, pharmaceuticals

TSCA biotech rule

USDA biotech rule

Product –specific regulation

Possible applicability to algae

Overview: EPA TSCA Biotechnology RegulationsRegulations under the Toxic Substances Control Act

(TSCA).Regulations cover industrial uses of “intergeneric”

microorganisms not regulated by other agencies; e.g. industrial enzyme production, bioprocessing.

Scope of coverage could include algae.Most research and pilot projects are not regulated if

suitably “contained”.Commercial use or importation requires 90 day advance

notification to EPA.

Overview: USDA Biotechnology RegulationsRegulations issued in 1987 cover environmental

uses, interstate movement of “potential plant pests”.Applicability to algae under current definitions not

clear.Rules have generally not covered “contained” use of

organisms in manufacturing.USDA has been considering revisions to the rule

since 2007.Regulatory program being challenged in the courts

over NEPA compliance.

Overview: FDA Biotechnology RegulationsEngineered algae used for food, food additive,

pharmaceutical production would be subject to FDA product-specific regulations.

These regulations focus more on safety, efficacy of end product, and less on risks of production organism.

Algae used for an FDA-regulated purpose would likely be exempt from EPA oversight under TSCA.

Regulatory Jurisdiction for Engineered AlgaeProposed use of engineered algae by Mera

Pharmaceuticals in pharmaceutical production in Hawaii in 2005 generated controversy, 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.

It is important to avoid jurisdictional disputes as the industry moves forward.

EPA TSCA Biotechnology Rule:“New Organism” Definition TSCA covers only “new chemicals”, so

Biotech Rule covers only “new microorganisms”.

“New microorganisms” defined as “intergeneric”: i.e., containing deliberate combinations of coding nucleic acids from more than one taxonomic genus.

Many recombinant microorganisms will not meet this definition, and not be covered by these rules.

EPA TSCA Biotechnology Rule:R&D (“Small Quantities”) ExemptionR&D uses of “new microorganisms” may qualify for

exemption, if used “solely for R&D” in a suitably “contained structure”.

Applicant must adopt procedures at the facility for controlled access, inactivation of wastes, emission controls, worker notification.

Exemption could apply to R&D by for-profit entities, including pilot plants.

Open-pond algae reactors may not be judged to be “contained structures”.

Non-contained uses may require EPA notification, review prior to commencement.

EPA TSCA Biotechnology Rule: Microbial Commercial Activity Notifications (MCANs)Commercial use or importation of “new

microorganisms” requires MCAN reporting at least 90 days before commencing commercialization or importing microbe.

MCAN requires submission of data to EPA.Microorganism identity, construction and its properties.Information about the industrial process,

control/containment measures, worker exposure, possible environmental release.

EPA review, clearance of MCAN authorizes commercial use.

EPA TSCA Biotechnology Rule:Biofuel, Bio-Based Chemical MCANs 29 MCANs reviewed since 1997, including:Numerous MCANs for industrial enzymes.Modified E. coli and Klebsiella oxytoca for the

conversion of lignocellulosic biomass sugars to ethanol (Verenium, 2008, 2010).

“Biopolymer producing organism” for the industrial manufacture of a biopolymer (Company Confidential, 2008).

Modified Zymomonas mobilis for cellulosic ethanol production (DuPont, 2009).

EPA TSCA Biotechnology Rule:SummaryMost R&D would be exempt if “contained”.Commercial uses require 90 day advance notice.EPA has a track record in recent years reviewing

microorganisms for use in biofuels, bio-based chemical production.

EPA review considers risks and benefits.MCAN review clears the way for commercial use.EPA review is generally considered to meet

requirements under NEPA, so Environmental Impact Statement not needed.

USDA Biotechnology Regulation:Scope of CoverageUSDA Biotech Regulations administered by

Animal and Plant Health Inspection Service (APHIS).

Rules cover organisms that are potential plant pests, generally based on presence of DNA sequences from potential plant pests.

Rules cover environmental use or interstate movement of potential plant pest organisms.

Most submissions have been for transgenic plants, some for modified agricultural microorganisms.

USDA Biotechnology Regulation:Oversight over R&DR&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.

USDA Biotechnology Regulation:Approvals for Commercial UseApproval for commercial use and sale

through “petitions for nonregulated status”. Since early 1990s, USDA has approved 78

petitions to allow commercial sale of engineered crop plants.

Approvals can take 1-4 years.Recent court cases have ruled that these

approvals may require Environmental Impact Statements.

USDA Biotechnology Regulation:SummaryTens of thousands of field tests approved under

these regulations – 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.

Uncertain future for these regulations, due to ongoing rulemaking and court decisions regarding NEPA compliance.

Environmental Impact Statements?National Environmental Policy Act (NEPA) requires

Environmental Assessments, Environmental Impact Statements, for “major federal actions”.

Courts have ruled that product approvals under USDA biotech regulation require EIS’s.

EPA actions under most of its regulations considered to inherently comply with NEPA requirements.

Recent calls for DOE to conduct EIS for its program supporting algal biofuel research.

Question: are EIS’s needed, and if so, when?

ABO Technical Standards Committee: Goals Published in Initial DraftSet the terms of the debate; encourage responsible,

science-based regulation.Distinguish between different biotechnologies used

to create organisms.Develop standards for data submission,

performance of production facilities, organism containment.

Develop a “road map” for regulatory approval of industrial uses of modified algae.

Influence public perception.

ABO Technical Standards Committee: Challenges to Achieving GoalsBiotech regulations use longstanding definitions to

define which organisms are covered; would be difficult to introduce new classification schemes.

Regulations differ in performance standards, data requirements and review procedures; standardization would be easier if one agency had sole jurisdiction.

Growth of GM algae in open ponds.Public perception is critical. Although not as bad as

the 1980s, there are still many vocal critics out there.

Impact of Biotechnology RegulationsEfforts to promote standardization, interagency

cooperation are important to ensure a science-based regulatory framework.

However, the existing biotech regulatory framework provides a straightforward path to commercial approval, with many prior successes in agricultural, industrial biotechnology.

The regulatory process can be successfully managed with proper advance planning.

Thank you very muchDavid J. Glass, Ph.D.

D. Glass Associates, Inc.

124 Bird Street

Needham, MA 02492

Phone 617-653-9945

DGlassAssc@aol.com

www.dglassassociates.com

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