Risk and Regulation Redux: Revisiting Regulatory Frameworks in Light of New Biotechnologies Emily Marden Sidley Austin LLP University of British Columbia Deepti Kulkarni

Agenda Existing product- and process-based regulatory frameworks Challenge for regulators posed by new technologies Emerging regulatory responses and extra regulatory issues Observations and expectations SIDLEY AUSTIN LLP

U.S. Coordinated Framework for Biotechnology Asilomar Conference Early U.S. lead in biotechnology Risk-based versus precautionary Concerns about tinkering with life Reflects Context of Period DNA technology on a spectrum with conventional breeding Products are subject of regulation, not process Existing statutes adequate to address risks Regimes would be refined based on experience and scientific developments Transparency important Key Presumptions 1986 1992 2017 Key Dates SIDLEY AUSTIN LLP

Resulting Regulation: Coordinated Framework USDA Plant pests, plants, seeds Animal biologics Meat and poultry FDA Food and feed Medical products GE Animals Cosmetics EPA Plant Pesticides Herbicides Chemicals, new microorganisms PPA, AHPA, FMIA, PPIA, EPIA, VSTA FDCA, PHSA FIFRA, TSCA, FDCA SIDLEY AUSTIN LLP

Labeling Trajectory is interesting because with focus on risk-based regulation, labeling debates became focus of many 1990-2000 Federal policy established and implemented Survives legal challenge 2001-2015 Uptick in state and local initiatives Vermont law survives preliminary legal challenge First GE animal approved for food use 2016-today Federal GE labeling law passed Federal regulations to be implemented by USDA Moving forward Full implementation of federal regulations Impact on consumers SIDLEY AUSTIN LLP

Relationship between regulation, uncertainty and risk Persisting Questions Relationship between regulation, uncertainty and risk Impacts on R&D, innovation, food security Value Lack of harmonization Regulatory complexity Social and ethical issues (e.g., ownership, alteration of life, transparency) Consumer understanding Role of government SIDLEY AUSTIN LLP

Novel Biotechnologies Gene editing, synthetic biology, genomics Enabling technologies with the potential for a large number of new end products Conventional methods: mutagenesis, polyploidy, protoplast Transgenesis/ recombinant DNA New biotechnologies: genomics, gene editing, synthetic biology SIDLEY AUSTIN LLP

Challenge for Regulators Scope of existing statutes Availability of regulatory triggers Ensuring any novel safety issues considered Ensuring appropriate risk-benefit balance Durability of current regulatory frameworks Proprietary issues Social/consumer issues Ethical issues Consideration of extra-regulatory issues Different national and international frameworks Harmonization SIDLEY AUSTIN LLP

Regulatory Reframing Modifying regulatory frameworks to address gene editing Goal is to set forth regulatory criteria to apply to new technologies e.g., USDA/APHIS proposed definition for “genetic engineering;” FDA/CVM proposed regulation of “intentionally altered genomic DNA” in animals Excluding low-risk actions based on agency experience Reflects regulatory experience with products and broader shifts in scientific understanding e.g., USDA/APHIS proposed exclusions for GE organisms; shift to “analyze first system” Narrowing regulatory scope to exclude modifications that could occur in nature Reflects evolution in scientific and policy perspectives Cements placement of biotechnology in spectrum of breeding techniques e.g., “bioengineering” defined in National Bioengineering Food Disclosure Standard; USDA/APHIS proposed exclusion for GE organisms SIDLEY AUSTIN LLP

Extra-Regulatory Issues Harmonization Moral and Ethical Issues Proprietary Issues Transparency SIDLEY AUSTIN LLP

Social/ethical Commentary Conclusions Path Forward Social/ethical Commentary Regulatory Law Stakeholder Comment Innovation SIDLEY AUSTIN LLP

BACK UP SIDLEY AUSTIN LLP

US: USDA Proposed Rules Refine definition of “genetically engineered” for purposes of regulations based to a greater degree on risk Move to an “analyze first” regulatory system Plant pest scope remains SIDLEY AUSTIN LLP

US: FDA and EPA FDA EPA Draft Guidance: GE Animals Broad and process-based “Intentionally altered” as trigger Request for data to assess risk Request for Information: Plant-based Foods Consulting on whether there are safety issues to be considered EPA Intends to clarify its approach consistent with Coordinated Framework TSCA model SIDLEY AUSTIN LLP

Regulatory Reframing on Genome 2016 National Bioengineered Food Disclosure Law The term ‘bioengineering’ . . . refers to a food that contains genetic material that has been modified through in vitro recombinant deoxyribonucleic acid (DNA) techniques; and for which the modification could not otherwise be obtained through conventional breeding or found in nature. USDA Revised Definition of “Genetically Engineered Organism” Specifically, for purposes of the revised regulations, an organism would not be considered a GE organism if: The genetic modification to the organism is solely a deletion of any size or a single base pair substitution which could otherwise be obtained through the use of chemical- or radiation-based mutagenesis. The genetic modification to the organism is solely introducing only naturally occurring nucleic acid sequences from a sexually compatible relative that could otherwise cross with the recipient organism and produce viable progeny through traditional breeding (including, but not limited to, marker-assisted breeding, as well as tissue culture and protoplast, cell, or embryo fusion). The organism is a “null segregant.” (Proposed Rule, “Importation, Interstate Movement, and Environmental Release of Certain Genetically Engineered Organisms, Jan. 19, 2017). Focus moves from the product as a whole to the genome with potential implications for extra-regulatory issues FDA, Genome Editing in New Plant Varieties Used for Foods; Request for Comments, Jan. 19, 2017) Recently, new technologies have emerged that are intended to alter the genomes of various organisms, including plants. FDA is aware that these technologies make it easier for plant developers to produce new plant varieties with targeted genetic modifications EPA (TSCA) – Final Rule, “Microbial Products of Biotechnology,” 1997. 40 CFR 725.3 Intergeneric: “microorganism is formed by the deliberate combination of genetic material originally isolated from organisms of different taxonomic genera.” SIDLEY AUSTIN LLP

Regulatory Reframing Represents a Significant Shift Exception to this is for GE animals This guidance addresses animals whose genomes have been intentionally altered using modern molecular technologies, which may include random or targeted DNA sequence changes including nucleotide insertions, substitutions, or deletions, or other technologies that introduce specific changes to the genome of the animal. This guidance applies to the intentionally altered genomic DNA in both the founder animal in which the initial alteration event occurred and the entire subsequent lineage of animals that contains the genomic alteration. Draft Guidance: Regulation of Intentionally Altered Genomic DNA in Animals, January 2017 SIDLEY AUSTIN LLP

Challenges Extra-regulatory Issues Regulatory Frameworks Agency mandates and resources mean certain issues are not addressed Potential for persistent unresolved issues May in turn affect acceptance Can spur legislative changes [Deepti + Emily] Of course the issue is that there is no predictable pathway for considering these issues within the regulatory process. Harmonization occurs at both an international and domestic level SIDLEY AUSTIN LLP