• Updating The Biotechnology Mission For The Bioeconomy
  • April 14, 2016
  • Law Firm: Keller and Heckman LLP - Washington Office
  • What is the bioeconomy? The February 2016 Federal Activities Report on the Bioeconomy describes it as a loose-knit, diverse group of commercial activities with their common frame of reference being the deployment of renewable resources — plants, trees and vegetation — to make useful products, create jobs in rural areas, improve national energy security and help to lower our carbon footprint.[1] This useful and ambitious report was announced at the Advanced Bioeconomy Leadership Conference by Dr. Catherine Woteki, undersecretary for the U.S. Department of Agriculture’s Research, Education and Economics (REE) mission area and the department's chief scientist. The central theme of the report is its Billion Ton Bioeconomy Vision, transforming the United States into the world’s leading bioeconomy by producing one billion tons of biomass to power the development of nonfood products sustainably by 2030. A billion tons is a lot of biomass for growing the industrial manufacturing base, but it’s modest compared to the massive bioeconomy represented by food, and achievable without compromising food security.

    There are key strategic aspects to bringing about this transformation, like building the necessary infrastructure and scientific advances that will improve conversion efficiencies. To realize this vision also requires a clear understanding of the system and principles by which the products of biotechnology processes are regulated and the removal of certain regulatory barriers to expanding sustainable products. One of the main challenges is regulatory uncertainty stemming from concerns over environmental issues associated with growing the bioeconomy. For example, the report calls for rapid expansion of biofuels and bioproducts industries to achieve a target of 30 percent utilization of biomass carbon into the U.S. transportation sector. To achieve this target would require a reasonable amount of confidence in the Renewable Fuel Standard (RFS) program, which has been undermined by an aggressive litigation strategy that has been able to capitalize on the program’s unrealistic planning assumptions. It will also require streamlining redundant Toxic Substances Control Act (TSCA) premanufacture notification requirements, a process currently driven by an unintelligible set of rules that require identical chemical substances to have different names.

    The industrial sector of the bioeconomy — referred to here as industrial biotechnology — draws on genetic engineering techniques to improve the natural ability of organisms such as yeast and algae to create familiar substances, such as ethanol. In addition to the traditional enzyme manufacturing base, commercial operations mainly involve the use of contained large scale fermentation facilities (both new and retrofitted) that are manufacturing oils, lubricants, specialty chemicals, dietary supplement and cosmetic ingredients. A few commercial, open pond algae systems are operating as well. Both the production organisms and the output of these processes are subject to regulation. Certain activities that have been found to be low risk may qualify for exemptions from regulation. To the extent the chemical substances being produced are drop in replacements for existing chemicals and have a definite chemical structure, commercialization may proceed based on a similarity determination or in the case of substances regulated by the U.S. Food and Drug Administration, that the substances are generally recognized as safe. However, many of the chemical substances being produced through industrial biotechnology are considered new to some extent and regulatory obstacles need to be addressed before they may move beyond the research and development stage.

    Due to the wide range of products and uses that are available through the use of industrial biotechnology today, there is no single regulatory pathway to facilitate the marketing of commodity chemical substances in the United States. Each regulatory agency that participates in regulating the bioeconomy has particularly deep knowledge and expertise in the uses under its jurisdiction stemming from the existing use-based/agency specific statutes. The unique and defining feature of these programs is their flexibility, which permits the agencies to accept and consider applications for new innovations without having to entirely redesign their approach. The agencies encourage preconsultation to discuss the manner in which new product review requirements apply and the data needed to support these reviews. These programs touch the future, while ensuring that comprehensive safety reviews are conducted for the intended uses. While each agency needs the same core information about a new product, there is not an excessive amount of redundancy since each agency has a different point of focus. Regulatory determinations on whether organisms and products they produce are covered by existing clearances or require new ones are approached on a case-by-case basis by applying the same rules that apply to traditional products. In some, but not all cases, preconsultation with the regulating agency may be advisable to confirm that the selected approach is acceptable.

    For those seeking clarity and a better understanding of the current roles and responsibilities of the agencies that regulate the products of industrial biotechnology, an excellent starting point is the 1986 Coordinated Framework on Federal Regulation of Biotechnology.[2] The Coordinated Framework describes how existing statutes provide adequate federal authority over both research and commercialization of biotechnology products to ensure reasonable safeguards for the public and the environment. It does not create new authorities for the regulatory agencies involved, but rather provides a system for using existing authorities in a coordinated manner. The main guiding principles of the Coordinated Framework are that agency reviews should be of comparable rigor, with a focus on the products of genetic engineering rather than the techniques or processes themselves, and that the traditional risk-based approach to product regulation should be retained. The principles in the Coordinated Framework recognize that appropriate oversight of unreasonable risks, such as restrictions on the introduction of dangerous pathogens, is needed, and that a more limited oversight role is appropriate for lower-risk commercial activities, such as the traditional breeding of farm animals and plants.

    The last time the Coordinated Framework was reviewed was in 1992. Like the original framework, the 1992 update continued to acknowledge the value that the focus on products rather than processes has for creating as few obstacles as possible for biotechnology developments. Since then, while there have been significant changes in the shape of the biotechnology product landscape, we think the output-based approach remains critical to maintain a level playing field with competing products produced by more traditional means. On July 2, 2015, under the direction of the White House Office of Science and Technology Policy (OSTP), the primary agencies that regulate the products of biotech­nology — the U.S. Environmental Protection Agency, FDA and USDA — began a new update of the Coordinated Framework, aimed at developing a long-term strategy to ensure that the federal biotech regulatory system is prepared for the future products of biotechnology.[3] The agencies have decided that there is a need to undertake clarification of their current roles and responsibilities and develop a long term strategy for assessing the risks of future products of biotechnology. The National Academies of Science, Engineering and Medicine has been commissioned to conduct an analysis of the future shape of the biotechnology product landscape.

    One aspect that is naturally under review is synthetic biology. Synthetic biology is improving the accuracy and speed at which new products of biotechnology can be created. A powerful tool called the CRISPR-Cas9 genome editing technique is the poster child of the power of these new techniques. Using CRISPR, the University of California, Irvine, has re-engineered a mosquito that does not transmit malaria and passes on this trait to 99.5 percent of its offspring. It is possible to similarly envision the eradication of the Zika virus more quickly than was possible in the past. CRISPR technology is a game changer, and after our ability to map the genome itself, it is one of the most significant advances in genetic engineering. The technique has the ability to precisely target and change a DNA sequence. It will be interesting to see whether and to what extent the use of CRISPR-editing in microorganisms and plants will be regulated, because in many cases its use will not be distinguishable from the results of a spontaneous mutation. Indeed, is a CRISPR modified crop is genetically engineered if all you have done is use the technology to force DNA breaks at a well-chosen spot and then rely upon the organism to naturally repair the damage? Infrequently, there is an error in the repair and a stray bit of genetic material will be incorporated. If that natural repair yields a commercially significant benefit, it is the plant that did the recombinant engineering, not the scientist. There is often no distinguishable change at the molecular level, and no introduction into the genome of foreign DNA sequences is involved. Effectively, all you have done is accelerate the occurrence of mutations that eventually would have occurred under conditions where they can be recognized and nurtured.

    Unlike other systems, the regulatory framework of the United States anticipates future scientific developments like these. By comparison, the European system’s definition of a genetically modified organism is technology and process-based. As illustrated by European Directive 2001/18/EC, genetic engineering techniques are listed as exempt or subject to regulation, with the default assumption that any technique not specifically referenced is subject to precommercial notification requirements. There are several difficulties associated with this kind of an approach, which stem in part from the Cartagena Protocol on Biosafety, an international agreement which aims to ensure the safe handling, transport and use of living modified organisms resulting from modern biotechnology that may have adverse effects on biological diversity, taking also into account risks to human health. In these prescriptive systems, regulations will always lag emerging technology developments, making it more difficult to seamlessly facilitate their introduction. The techniques under development, like CRISPR, may result in small changes in an amino acid sequence at critical sites within a protein that provide large, beneficial improvements in performance and operational yield. The main advantage to these techniques is their precision, eliminating inadvertent insertional effects and leading to fewer unintended effects. Today, even the smallest of changes are likely to trigger the need for full blown regulatory review.

    These and other important developments are under consideration as the federal government seeks to coordinate the development of the bioeconomy in the United States between now and 2030. Market restrictions and labeling have made the bioeconomy landscape increasingly more complicated as international regulations evolve and diverge. Historically, the US and EU have been at opposing ends of the spectrum while the rest of the world tends to gravitate toward either pole. More recent U.S. legislative initiatives in a handful of states like Vermont have spurred some to propose national and uniform requirements for food. DNA-sequencing technology, while facilitating advances in productivity, and other aspects such as disease control, triggers biosecurity restrictions on the distribution of synthetic biology sequences and export controls.

    Since it represents yet another ambitious regulatory and policy challenge, the federal commitment to the Bioeconomy Vision should be addressed as part of updating the Coordinated Framework. It is clear that the Billion Ton Vision is a USDA goal, and the Bioeconomy Report has been timed to underscore its importance and specifically influence the framework review. The flexibility envisioned by the original framework is essential to achieve the Billion Ton Goal, and the agencies should avoid being drawn into more process-oriented issues. These two important planning activities crucial to the U.S. bioeconomy are taking place concurrently, and if regulatory flexibility prevails, each will incorporate an element of coordination with the other. However, unless all of the agencies that are part of the Coordinated Framework raise their sights and embrace the challenge, regulation may become the main impediment to achieving the Billion Ton Vision, as the USDA is the only agency participating in updating the Coordinated Framework with a promotional, in addition to a regulatory, mission.

    [1] Biomass Research and Development Board. Federal Activities Report on the Bioeconomy. USDA February 2016.

    [2] Executive Office of the President, Office of Science and Technology Policy. Coordinated Framework for Regulation of Biotechnology, Announcement of policy; notice for public comment. 51 Fed. Reg. 23302

    (June 26, 1986); updated at 57 Fed. Reg. 6753 (Oct. 28, 1992).

    [3] https://www.whitehouse.gov/blog/2015/07/02/improving-transparency-and-ensuring-continued-safety-biotechnology