Coordinated Framework and EPA Oversight of Biotechnology

Transcription

1 Coordinated Framework and EPA Oversight of Biotechnology Mark Segal, Ph. D. FACILITATING SAFE AND SECURE SCIENCE Practical Approaches for IBCs June 16-19, 2013 Seattle, WA 1

2 The Coordinated Framework The Coordinated Framework for the Regulation of Biotechnology (1986) is a set of policy statements organized by the White House Office of Science and Technology Policy and issued by five government units with responsibilities for biotechnology Food and Drug Administration Environmental Protection Agency U.S. Department of Agriculture Occupational Safety and Health Administration National Institutes of Health 2

3 What the Coordinated Framework Did Acknowledged that existing law was sufficient to permit oversight of biotechnology Permitted each agency with oversight responsibility to describe how it implements its regulations in this area Established lead (but not exclusive) roles for identified uses of biotechnology Recognized that some overlap of authority existed and established coordination among agencies that had overlapping responsibilities. 3

4 Toxic Substances Control Act (TSCA) and Genetically Engineered Microorganisms TSCA Authority Under TSCA, EPA has the authority to regulate the manufacture, use, distribution in commerce, and disposal of chemical substances and mixtures. Through the Coordinated Framework policy statement and 1997 Rule, certain microorganisms, were included as substances within this authority TSCA requires premanufacturing notification of all 'new' substances not otherwise excluded or exempted TSCA covers chemical substances (typically used in environmental, industrial, or consumer products) that are not specifically excluded Substances Specifically Excluded from TSCA Regulation Pesticides, but not pesticide intermediates (EPA/OPP FIFRA) Food, food additives, drugs, cosmetics, and their intermediates, and substances used as medical devices Tobacco and tobacco products Nuclear materials 4

5 TSCA Biotech Rule (1997) Rule established procedures for premanufacturing review of new microorganisms. Rule retained EPA s interpretation of new (intergeneric) microorganisms as stated in the 1986 Coordinated Framework Policy Statement. For clarity, EPA consolidated all requirements and procedures into one part of the Code of Federal Regulations (40 CFR 725). Applies to new microorganisms that are manufactured, imported, or processed for commercial activities, including R&D activities. 5

6 Rule Definition of Microorganism Definitions 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 Rhodophyta of the Plantae, and a virus or virus-like particle. Preamble states, Therefore, this definition includes, but is not limited to, bacteria, protozoa, fungi, mycoplasmas, mycoplama-like organisms, spiroplasmas, microphytoplanktons, green and red algae, viruses, and virus-like particles. Should new categories of microoganisms within the Monera, Protista, Fungi, and the Chlorophyta and Rhodophyta of the Plantae be identified, these would also be considered microorganisms under this definition. 6

7 New Microorganisms Subject to TSCA Section 5 New microorganisms are : those formed by deliberate combinations of genetic material from organisms classified in different taxonomic genera (intergeneric) constructed with synthetic genes that are not identical to DNA that would be derived from the same genus as the recipient cell are not listed on TSCA Inventory used in TSCA applications Exclusions naturally occurring microorganisms genetically engineered microorganisms other than intergeneric intergeneric microorganisms resulting only from the addition of well-characterized, non-coding regulatory regions 7

8 TSCA Inventory an existing chemical substance is one that is listed on the TSCA Chemical Substance Inventory as being manufactured or imported in the U.S. a new chemical substance is one that does not appear on the TSCA Chemical Substance Inventory 8

9 Reporting Under TSCA Biotech Rule Rule established mechanisms for reporting to EPA, including a number of specific exemptions MCAN - Any manufacturer, importer, or processor must file a Microbial Commercial Activity Notice (MCAN) 90 days prior to initiating manufacture/import (unless the activity is eligible for an exemption). TERA - Persons who wish to introduce a new microorganism into the environment for commercial R&D purposes must submit a TSCA Experimental Release Application (TERA) (similar to an abbreviated MCAN submission) 60 days prior to initiation of the field test. Tier I and Tier II Exemptions - Exemptions from MCAN filing are available for closed system commercial activities utilizing approved recipient organisms (40 CFR ), meeting certain criteria for the introduced genetic material, and specific containment/control technologies. 9

10 (a) and Research Exemption TSCA section 5 only applies to microorganisms that are manufactured, imported, or processed for commercial purposes. EPA has defined manufacture or process for commercial purposes as manufacture or process for purposes of obtaining an immediate or eventual commercial advantage as determined by indicia of commercial intent. Commercial purposes for research and development means that the activities are conducted with the purpose of obtaining an immediate or eventual commercial advantage for the researcher: R&D funded directly by a commercial entity regardless of who is actually conducting the research: (i) A commercial entity contracts directly with a university or researcher (ii) A commercial entity gives a conditional grant (the commercial entity holds patent or licensing rights (iii) Any other situation in which the commercial entity intends to obtain an immediate or eventual commercial advantage for the commercial entity and/or the researcher. R&D not funded directly by a commercial entity, if the researcher intends to obtain an immediate or eventual commercial advantage. (i) Research to improve of a product already on the market (ii) The researcher seeks commercial funding for the purpose of developing a commercial application; (iii) The researcher or university seeks a patent to protect a commercial application which the research is developing (iv) Other evidence that the researcher is aware of a commercial application for the research. 10

11 Activities subject to the jurisdiction of other Federal programs or agencies. The research is exempt from reporting if the research meets all of the following conditions 1 : The microorganism is manufactured, imported, or processed solely for research and development activities. There is no intentional testing of a microorganism outside of a structure The research is funded by another Federal agency contingent on compliance with the relevant portions of the NIH Guidelines or the Federal agency imposes legally binding requirements that the research is to be conducted in accordance with the NIH Guidelines 1. Paraphrased from 40 CFR Part (a) to (c) 11

12 Research Exemption for Contained Use Activities conducted inside a structure. A person who manufactures, imports, or processes a microorganism is not subject to the reporting requirements under subpart D of this part if all of the following conditions are met: (a) The microorganism is manufactured, imported, or processed solely for research and development activities. (b) The microorganism is used by, or directly under the supervision of, a technically qualified individual, as defined in The technically qualified individual must maintain documentation of the procedures selected to comply with paragraph (d) of this section and must ensure that the procedures are used. (c) There is no intentional testing of a microorganism outside of a structure, as structure is defined in (d) Containment and/or inactivation controls. Accounts for survival, release and transfer Approved by authorizing official Records are maintained 12

13 Research Exemption for Contained Use In Structure is defined Structure means a building or vessel which effectively surrounds and encloses the microorganism and includes features designed to restrict the microorganism from leaving 13

14 Possible Regulatory Decisions when MCAN Reporting is Required Sufficient information to determine no unreasonable risk for any potential use no regulatory action taken company may commence manufacture after the 90 days after receive Notice of Commencement, listed on the TSCA Inventory Sufficient information to determine no unreasonable risk for the intended use but not all potential uses Section 5(a)(2) Significant New Use Rule (SNUR) company may commence manufacture after the 90 days after receipt of Notice of Commencement, is listed on the TSCA Inventory Sufficient information to determine unreasonable risk Section 5(f) or 6(a) prohibit or restrict use Insufficient information to determine effects, but possibility exists for unreasonable risk and/or substantial/significant exposure Section 5(e) negotiate Consent Order to restrict use & specify data needs to lift Consent Order 14 Section 5(a)(2) Significant New Use Rule (SNUR)

15 Risk Assessment Components Risk = Hazard x Exposure Microbial Identification Product characterization, genetic construction analysis Human Health Hazard Assessment Ecological Hazard Assessment Construct Hazard Analysis (hazard consequences of genetic construction) Engineering Report (worker exposure, releases from facility) Exposure Report (environmental and general population exposures) Economic Analysis TSCA is a Risk/Benefit Statute 15

16 Data Needs for MCANs or TERAs Points to Consider Guidance Document Elements taxonomic descriptions of the recipient and donor microorganisms detailed construction of the submission microorganism human health effects information on the submission microorganism environmental effects information on submission microorganism by-products, production volume, and use information worker exposure and environmental releases/containment environmental release protocols expected survival/dispersal - environmental exposures emergency/contingency protocols 16

17 DIY-iGEM Issues for Consideration Some DIY projects might have commercial indicia Commercial DIY projects may not have containment conditions that qualify for TSCA exemption from review, even if they use exempt organisms Contained research Much academic research done within a structure would qualify for exemption, but researchers and IBCs need to make sure it complies with all the qualifications for exemption. 17

18 Office of Pollution Prevention and Toxics Microbial Products of Biotechnology; Final Regulation Under the Toxic Substances Control Act; Final Rule 40 CFR Parts 700, 720, 721, 723, and 725 Points to Consider in the Preparation of TSCA Biotechnology Submissions for Microorganisms 18