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David Glass Regulatory Presentation and Case Study BIO Pac Rim Conference December 2013


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Presentation from BIO Pacific Rim Conference December 2013, providing an overview of regulations affecting industrial biotechnology, and presenting a case study of an MCAN successfully submitted to the EPA for a genetically modified cyanobacterium for production of ethanol.

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David Glass Regulatory Presentation and Case Study BIO Pac Rim Conference December 2013

  1. 1. David J. Glass, Ph.D. D. Glass Associates, Inc. BIO Pacific Rim Summit December 10, 2013
  2. 2. 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 D. Glass Associates, Inc.
  3. 3. Overview of U.S. Biotechnology Regulation Environmental Protection Agency  Microbial pesticides, plant pesticides.  Engineered microorganisms used for other industrial purposes.  Modified microorganisms, algae for biofuel, bio-based chemical production U.S. Department of Agriculture  Transgenic plants, plant-produced industrial products.  Transgenic feedstocks for fuel, chemical production Food and Drug Administration  Foods, feed, food additives, pharmaceuticals  Microbial biomass used for animal feed D. Glass Associates, Inc.
  4. 4. 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. D. Glass Associates, Inc.
  5. 5. 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. D. Glass Associates, Inc.
  6. 6. International Biotechnology Regulation Poster presented at ABS 2013: See my Advanced Biotechnology for Biofuels blog for more details on international regulations. ( pKTxe-8a) D. Glass Associates, Inc.
  7. 7. 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. D. Glass Associates, Inc.
  8. 8. 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. D. Glass Associates, Inc.
  9. 9. 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. D. Glass Associates, Inc.
  10. 10. 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. D. Glass Associates, Inc.
  11. 11. 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. D. Glass Associates, Inc.
  12. 12. A Novel Gas-to-Liquid Platform Powered by Sunlight, Fed by CO2, and Tailored for Valuable Products ©2013 Joule. Rights Reserved. Proprietary & Confidential.
  13. 13. A direct, continuous process with abundant inputs and valuable outputs Our “upstream” platform converts CO2 to liquid fuels and chemicals, avoiding the extreme costs and risks of oil E&P Programmable Biocatalyst H2O CO2 Ethanol Diesel Jet Fuel Proprietary System Gasoline Efficient Process ©2013 Joule. Rights Reserved. Proprietary & Confidential. ©2013 Joule. Rights Reserved. Chemicals 16
  14. 14. Our CO2 gas-to-liquids platform The biocatalyst, production unit and infrastructure are engineered for high productivity and scalability Programmable Biocatalyst Novel Production Unit Infrastructure  The biocatalyst requires minimal days of growth before diverting its energy to fuel production  Waste CO2 is biocatalytically converted to targeted molecules via photosynthesis ©2013 Joule. Rights Reserved. Proprietary & Confidential. ©2013 Joule. Rights Reserved.  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 17  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
  15. 15. Joule SunSpringsTM Hobbs: Where the vision becomes reality Biocatalyst Prep Production Unit  Commissioned in September 2012 to test and demonstrate the platform at increasingly larger scale Central Plant  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 ©2013 Joule. Rights Reserved. Proprietary & Confidential. ©2013 Joule. Rights Reserved. 18
  16. 16. 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 cyanobacterium Synechococcus 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. ©2013 Joule. Rights Reserved. Proprietary & Confidential. ©2013 Joule. Rights Reserved. 19
  17. 17. 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. ©2013 Joule. Rights Reserved. Proprietary & Confidential. ©2013 Joule. Rights Reserved. 20
  18. 18. 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. ©2013 Joule. Rights Reserved. Proprietary & Confidential. ©2013 Joule. Rights Reserved. 21
  19. 19. 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. ©2013 Joule. Rights Reserved. Proprietary & Confidential. ©2013 Joule. Rights Reserved. 22
  20. 20. 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 EPAapproved 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. ©2013 Joule. Rights Reserved. Proprietary & Confidential. ©2013 Joule. Rights Reserved. 23
  21. 21. 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. ©2013 Joule. Rights Reserved. Proprietary & Confidential. ©2013 Joule. Rights Reserved. 24
  22. 22. Thank you very much David J. Glass, Ph.D. D. Glass Associates, Inc. 124 Bird Street Needham, MA 02492 Phone 617-653-9945 D. Glass Associates, Inc.