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Genetically Modified Organisms and TSCA

The Technology

Biotechnology’s role in sustainable environmentConcern: novel behaviors, in some instances, may present a risk to human health or the environmentCertain uses assessed under TSCA

The Technology

Traditional mutation techniques inefficient, difficult to target to specific traits

Traits that enhance production or quality in other species can be identified and transferred through biotechnology

Yield increased, greater efficiency

Leads to new and improved end products

source: EPA (Aug. 2003)

Categories of Biotechnology(for regulatory purposes)

Microorganisms have been employed by business, universities, and government to meet certain R&D and commercial needs for years

Majority of these applications are outside TSCA’s jurisdiction

Regulatory Categories

Specifically excluded from TSCA -Foods and beveragesMedical applicationsPesticides

source: EPA (Aug. 2003)N

ew P

rodu

cts

1995 2000 2005 2010

Agronomic Traits

Feed Processing

Chemicals

Health

TSCA Regulated Uses

TSCA § 3(2)(A) definition of “chemical substance” includes microorganisms

“Any organic or inorganic substance of a particular molecular identity. . . ”

About 10 percent of the overall market (source: EPA Reg. Impact Anal. (1997))

TSCA Regulated Uses

Enzyme production, other chemicals in contained fermentation systems

Key monomers in polyestersPolymer-grade acrylamideEPA view - High fructose corn syrup industry created by use of these enzymes

Polylactic acid

Other TSCA Uses

Treatment of biological waste

Field application to enhance nitrogen fixation on crops (soybeans, alfalfa)

Bioethanol, biodiesel

Bioethanol

The Third Wave source – EPA (Aug. 2003)

TSCA Rules

New, intergenetic microorganisms 40 C.F.R. Part 725; 62 Fed. Reg. 17909 (April 11, 1997) commercial uses and commercial R&Dsome old, some new, exemptionssignificant new use rules (none yet)

Must also establish TSCA status forOther feedstocksReaction product (e.g., the polymer)

Defined terms: Microorganism

Organism in the kingdoms of Monera (Procaryotae), Protista, Fungi, the Chlorophyta and Rhodophyta of the Plantae, and a virus or virus-like particles

Includes bacteria Does not include

cell cultures of human cells.

Defined terms: Intergeneric

Formed by deliberately combining genetic material first isolated in a different taxonomic genusDeliberate combination of certain mobile genetic elements (DNA)Does not include well-characterized, noncoding regulatory regions from another genusIf not intergeneric – on the TSCA Inventory

Defined terms: Noncoding Region

A segment of introduced genetic material for which

The regulatory region and any inserted flanking nucleotides do not code for a protein, peptide, or functional ribonucleic acid molecules and The regulatory region solely control the activity of other regions

Operators, promoters, terminators, etc.

Defined terms: Mobil genetic element

An element of genetic material that has the ability to move genetic material within and between organisms, including plasmids, viruses, insertion sequences

Microbial Commercial Activity Notice (MCAN) – 90 day review

Requirementsrecipient and new miccroorganismGenetic constructionPhenotypic and ecological characteristics (e.g., habitat, distribution, source)ByproductsProduction volume, use, worker exposureExisting data

Need to file NOC to place on Inventory“Upfront" CBI substantiation

Traditional Exemptions

FFDCA, FIFRA regulated usesMixtures (components not exempt)Manufactured and processed solely for export and labeled accordingly

Non-commercial R&D Exempt

Microorganisms manufactured, imported, or processed for noncommercial purposes, e.g., solely for academic research

40 C.F.R. § 725.205

Non-commercial R&D Exempt

Commercial indicators –

company contracts directly with a researcher

company gives a conditional grant where the company holds patent rights, or establishes a joint venture where the company has the patent or licensing rights

Non-commercial R&D Exempt

Commercial if the researcher is not funded directly, but intends to obtain an immediate or eventual commercial advantage, e.g. –

developing a commercially viable improvement of a product on the market

has sought or is seeking commercial funding for commercial development

has sought or is seeking a patent

Commercial R&D Exemptions

Contained structure exemption (§ 725.234)National Institutes of Health Guidelines for Research Involving Recombinant DNA Molecules ("NIH Guidelines") (§ 725.232)Outside a structure/2 strains (§ 725.238)

Rhizobium melilotiBradyrhizobium japonicum

TSCA Experimental Release Application (TERA) for other releases (§ 725.250)

TERA - 60 day review

Organizations manufacturing, importing, or processing "new" microorganisms intended for use in commercial R&D in the environment

Identity of organismPhenotypic and ecological characteristicsDescription of R&D includes # organisms released, target organismsAll available dataRecords must be kept 3 years Report to EPA w/in 1 year

Exemptions for Commercial Use Beyond R&D

Test Market – Same as Traditional (45 day review)

§ 725.300Contained Structure/Well-Characterized Microorganisms

Tier I Tier II§ 725.400

Well-characterized

The function of the genetic material has been determined. Includes -

Acetobacter aceti Aspergillus niger Asplergillus oryzaeBacillus lichenformisBacillus subtilisClostridium acetobutylicumEscherichia coli K-12Penicillium roqueforti, Saccharomyces cerevisiaeSaccharomyces uvarum

Well-characterized

Limited in the genetic material that can be introduced (e.g., regulatory sequence permitting the expression of solely the genes of interest) Poorly mobilizable Free of encoding sequence for polypeptides that contribute to a toxic effect (list of prohibited sequences)

Other Conditions

Tier I § 725.424 – No filing required . . .SO LONG AS containment meets EPA specifications

system designed to contain organismscontrolled accesswritten, published, an implemented safety proceduresinactivation procedures steps to minimize release through aerosols and exhaust, other routesemergency clean up

Other Conditions

Tier II § 725.428 – 45 Day ReviewAffirmative request submitted to EPAIf different containment is used

SUMMARY

Not many MCAN filings so farMany activities qualify for the exemptionsNon-confidential MCANsAnd TERAshttp://www.epa.gov/biotech_rule/submiss.htm