david glass regulatory presentation and case study bio pac rim conference december 2013

David J. Glass, Ph.D.

D. Glass Associates, Inc.

BIO Pacific Rim Summit

December 10, 2013

Presentation Overview

Overview: U.S. and international biotechnology regulation

EPA TSCA biotechnology regulation and its impact on biofuel and bio-based chemical production

Case Study: Joule Unlimited Technologies, Inc.: EPA review of Microbial Commercial Activity Notice (MCAN) for modified cyanobacteria for ethanol production


Overview of U.S. Biotechnology Regulation Environmental Protection Agency

Microbial pesticides, plant pesticides.

Engineered microorganisms used for other industrial purposes.

U.S. Department of Agriculture

Transgenic plants, plant-produced industrial products.

Food and Drug Administration

Foods, feed, food additives, pharmaceuticals


Modified microorganisms, algae for biofuel, bio-based chemical production

Transgenic feedstocks for fuel, chemical production

Microbial biomass used for animal feed

Overview: USDA Biotechnology Regulations Regulations issued in 1987 (7 CFR Part 340) cover environmental

uses, interstate movement of “potential plant pests”.

Historically, these rules have covered outdoor field trials or commercial growth of transgenic plants in agriculture and industrial/pharmaceutical production.

Numerous field trials of transgenic energy crops have also taken place under these regulations.

Major USDA decisions (e.g. commercial approvals) require environmental assessment for NEPA compliance.


USDA rules would apply to transgenic plants, and possibly open-pond uses of modified algae.

International Biotechnology Regulation

European Union. Applicable national government approval would be required under “Contained Use” Directive 2009/41/EC or “Environmental Release” Directive 2001/18/EC.

Canada. Industrial uses of modified organisms may fall under the New Substances Notification regulations under the Canadian Environmental Protection Act.

Australia. Under the Gene Technology Act and its regulations, both contained and non-contained uses of modified microorganisms would require a license from the government.

In many other countries, biotechnology laws are based on the principles of the Cartagena Protocol on Biosafety, part of the Convention on Biological Diversity.


International Biotechnology Regulation


Poster presented at ABS 2013: See my Advanced Biotechnology for Biofuels blog for more details on international regulations. (http://wp.me/pKTxe-8a)

EPA TSCA Biotechnology Rule:Overview Regulations under the Toxic Substances Control Act (TSCA) at 40

CFR Part 725 cover “new microorganisms” not regulated elsewhere in the federal government.

“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.

Most research and pilot projects are not regulated if suitably contained. Commercial use or importation requires 90 day advance notification to EPA.


EPA TSCA Biotechnology Rule:R&D (“Small Quantities”) Exemption R&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 applies to R&D by for-profit entities, usually including pilot plants.

Open-pond algae reactors may not be judged to be “contained structures”; non-contained uses may require EPA notification and review via TERA process prior to commencement.


EPA TSCA Biotechnology Rule:TSCA Experimental Release Applications TERA must be filed 60 days before proposed outdoor use.

There have been 25 TERAs submitted since 1997 for small-scale, outdoor R&D of engineered microorganisms. All but 3 have been approved.

These have included agricultural microorganisms, microbes to be used for bioremediation or for detection of hazardous contaminants in soil.

No TERAs to date for fuel or chemical processes.

TERAs would provide stepwise review for any proposed uses of modified algae in open ponds.


EPA TSCA Biotechnology Rule: Microbial Commercial Activity Notices (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 properties.

Potential health and environmental effects.

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 Over 50 MCANs reviewed since 1997, including:

Numerous MCANs for industrial enzymes (most using Trichoderma reesei as host organism).

Several MCANs for production of ethanol from species including E. coli, Klebsiella oxytoca, S. cerevisiae, Z. mobilis.

MCANs for production of various bio-based chemicals.

MCAN filing activity has significantly increased in the last several years: at least 6-8 filings per year in FY 2011, 2012, 2013.



A direct, continuous process with abundant inputs and valuable outputs

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Programmable Biocatalyst

Proprietary System

Efficient Process

Our “upstream” platform converts CO2 to liquid fuels and chemicals, avoiding the extreme costs and risks of oil E&P

Ethanol

Diesel

Jet Fuel

Gasoline

Chemicals

H2OCO2

©2013 Joule. Rights Reserved.


Our CO2 gas-to-liquids platform

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Novel Production Unit

Infrastructure

The biocatalyst, production unit and infrastructure are engineered for high productivity and scalability

Programmable Biocatalyst

The biocatalyst requires minimal days of growth before diverting its energy to fuel production

Waste CO2 is biocatalytically converted to targeted molecules via photosynthesis

The process inputs are abundant, and the outputs can be tailored by switching the product-specific biocatalyst

Production is readily scalable via simple replication of modular units

The facility supports an integrated production process, from biocatalyst construction to product creation, separation and storage

The CO2 gas-to-liquid process is direct and continuous



Joule SunSpringsTM Hobbs: Where the vision becomes reality

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Production Unit

Central Plant

Commissioned in September 2012 to test and demonstrate the platform at increasingly larger scale

Core production unit and infrastructure in place to advance to full process demonstration

Achieving progress on numerous variables, e.g. productivity, process efficiency

Sustained Sunflow®-E ethanol production, with other products to follow

Facility and processes will become the blueprint for future commercial plants

Biocatalyst Prep



EPA Jurisdiction over Joule’s production organisms

Joule’s modified biocatalysts for ethanol production are considered “new microorganisms” under EPA’s TSCA biotechnology regulations (40 CFR Part 725):

The modified organisms include coding sequences from outside the Synechococcus genus and are considered “intergeneric”.

The intended commercial use is for a purpose not regulated by any other federal agency.

First biocatalyst: modified strain of the cyanobacteriumSynechococcus for ethanol production.

Laboratory, pilot and some demo plant activities qualify for the “contained structure” (R&D) exemption.

Commercial use requires filing a Microbial Commercial Activity Notice (MCAN) at least 90 days before commercial use.

19©2013 Joule. Rights Reserved.


Joule Regulatory Strategy and Timeline

Plan was to file first MCAN well in advance of anticipated start of commercial use.

Early presubmission meeting with EPA staff (2011).

First MCAN for commercial ethanol production strain (MCAN Number J12-0006) filed July 2012.

Short-term goal was to gain approval to use this strain commercially at Joule’s Demonstration Plant in Hobbs, New Mexico.

EPA completed its review Fall 2012, began drafting Consent Order that would allow use of strain at Hobbs under specified conditions.

Consent Order signed July 2013.



Data Included in MCAN

In the MCAN, Joule provided all available information to enable a risk assessment for the MCAN biocatalyst strain, including:

Description of strain construction.

Biological characteristics of the MCAN strain.

Genomic analysis and literature review to establish lack of evidence that the Joule host strain has any toxic, infectious, or pathogenic properties.

Review of literature data on natural habitats and environmental incidence of the host strain.

Discussion of ecology, geology of Hobbs site as they relate to environmental impacts: e.g. local wildlife and flora, depth of aquifer.

Data on survival/persistence in Hobbs soil.

Description of Joule’s bioreactors, production process and containment features.



EPA Conclusions

Use of the strain at Hobbs is unlikely to present unreasonable risk.

Minimal concerns for adverse human health effects, and minimal concerns for ecological effects from use in ethanol production.

The introduced genes are not inherently hazardous; probability of horizontal gene transfer is expected to be low.

Survival of the MCAN strain in Hobbs soil is expected to be low in the event of breach of containment.

However, these findings cannot (yet) be extended to locations other than Hobbs, e.g. pending data on MCAN strain survival in other environments; so EPA required Joule to enter into a Consent Order limiting approved uses to Hobbs.

Certain testing and data are required to allow an assessment of commercial use at sites other than Hobbs.



Summary: Consent Order Requirements

Commercial Use of MCAN Strain at Hobbs is allowed, subject to terms of the Consent Order.

Soil Survival Testing. Conduct additional studies of the survivability of the MCAN strain in Hobbs soil, using an EPA-approved protocol within one year of commencing commercial use of the MCAN strain at Hobbs.

Validation of Waste Inactivation. During first year of use of the MCAN strain, monitor the efficacy of the waste inactivation system, using EPA-approved protocol, to show 6-log reduction.

Monitoring of Capsule Failures. Required to keep appropriate records of capsule breaches and accidental spills, and to keep records documenting how these releases were cleaned up. Records to be available for EPA review upon request.



Summary

Joule’s goal achieved to enable use of the MCAN strain at Hobbs.

First MCAN established that EPA had minimal concerns over potential health or safety impact of Joule’s production organisms.

EPA review identified key data and information to include in future MCAN submissions; particularly data needed to support use at facilities other than Hobbs.

Joule has developed a productive relationship with EPA staff.

Reviews of future Joule MCANs for additional ethanol production organisms should be quicker, more straightforward.

Successful EPA review of first MCAN may be useful in dealings with regulatory bodies in other countries.


Thank you very much

David J. Glass, Ph.D.D. Glass Associates, Inc.124 Bird StreetNeedham, MA 02492Phone [email protected]


david glass regulatory presentation and case study bio pac rim conference december 2013

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