By Lauren M. Graham, Ph.D.
On November 7, 2017, the U.S. Department of Agriculture’s (USDA) Animal and Plant Health Inspection Service (APHIS) issued a notice in the Federal Register announcing that it was withdrawing its proposed rule that would have revised the importation, interstate movement, and environmental release of certain genetically engineered (GE) organisms. The proposed rule, which was issued on January 19, 2017, aimed to “update the regulations in response to advances in genetic engineering and understanding of the plant pest and noxious weed risk posed by [GE] organisms, thereby reducing burden for regulated entities whose organisms pose no plant pest or noxious weed risks.” After reviewing public comments on the proposed rule, USDA decided to re-engage with stakeholders and explore alternative policy approaches. More specific comments from USDA and the reasons supporting its decision are set forth in the notice.
While it appears that some in industry may welcome the withdrawal, most would agree that all stakeholders should work collaboratively and quickly to develop a new framework to speed the process to market, and to ensure the regulatory landscape is more efficient and clearer than it currently is. USDA and pertinent others should immediately begin another process to enable the regrouping to begin.
By Lauren M. Graham, Ph.D.
On August 21, 2017, the National Academies of Sciences, Engineering, and Medicine (NAS) released their interim report titled A Proposed Framework for Identifying Potential Biodefense Vulnerabilities Posed by Synthetic Biology. The U.S. Department of Defense (DOD) asked NAS to develop the framework to:
- Guide an assessment of the security concerns related to advances in synthetic biology;
- Assess the level of concern warranted for various advances and identify areas of vulnerability; and
- Prioritize options to address these vulnerabilities.
The report provides an overview of the categories of synthetic biology and a set of initial questions aimed at guiding the assessment of concern related to the technologies and applications of the field. The framework outlines factors for assessing the levels of concern that each technology and application presents in terms of malicious use, as well as factors for assessing the capability for mitigation. The final report will use the framework to provide DOD with an assessment of concerns and mitigation options by developing informed answers to the questions posed in the interim report.
On November 9, 2016, Inside EPA published “ New TSCA Requirements Raise Challenges To EPA Biotech Review Staff” (subscription required), outlining what EPA has done to adapt to revised Toxic Substances Control Act (TSCA) requirements for engineered microorganisms. Richard E. Engler, Ph.D., Senior Chemist with Bergeson & Campbell, P.C. (B&C®), was quoted in the article discussing what to expect from approaching biotechnology regulations:
Richard Engler, a former EPA toxics official now a senior chemist with environmental law firm Bergeson & Campbell, attended the [Second Public Meeting and Opportunity for Public Comment on EPA's Draft Algae Guidance for the Preparation of TSCA Biotech Submissions] and said in a Nov. 3 interview with Risk Policy Report, "I think EPA's still figuring out what 'reasonably foreseeable' means. It's a challenge for chemicals as well as microorganisms.
Noting that the Lautenberg Chemical Safety Act, which reformed TSCA, "is silent on microorganisms," Engler adds that the "effect of Lautenberg is parallel for chemicals and microorganisms." A key change in the updated law, Engler says, is the new requirement that EPA make an affirmative decision on whether new chemicals or microorganisms meet TSCA's risk standard of "will not present an unreasonable risk of injury to health or the environment," which is "true for chemicals and microorganisms."
One difference that Engler notes is that if a newly submitted chemical "is a new microbe, it increases the data need for EPA to show not likely to present" unreasonable risk.
Engler said that what Segal described is "what [significant new use rules (SNURs)] do. They limit releases of substances or an organism so the commercial activity in the notice is permitted but if another company wanted to use [it] in a different manner a significant new use notice is required."
As an example, Engler said that "if a [microbial commercial activity notices (MCAN)] submitter had a contained use [of a microorganism] with complete destruction of the organism but if EPA was unsure . . . they might place a SNUR on the microorganism that the submitter or anyone else would have to abide by."
In this example, as in other cases, Engler said, EPA would treat a new organism and the decision on whether to place a SNUR on other uses of that microorganism as it would a new chemical. "It's the same rules," he said. "The hazards are different, there are other risks because they're living organisms. There are concerns about gene transfer between the MCAN organism and whatever's in the wild. But the criteria is the same and the regulatory tools they use to contain are the same."
One change that Engler noticed is that all SNURs will now be accompanied by a consent order. "EPA said that their interpretation of Lautenberg is that if they make a 'may present' finding, they must also impose a Section 5(e) consent order. In the past we could do a non 5(e) SNUR."
"Their new interpretation is they have to do a consent order" with a SNUR," Engler said. "The effect depends on what the consent order says. It may say, 'SNUR is in effect until the SNUR is published'" once the commercial activity commences. "In the past, [5e orders] were typically used to impose testing" requirements.
Like other elements of changes to TSCA, Engler said that the consent order changes will apply equally to chemicals and microorganisms. "With TSCA reform in place, I'm not sure what consent orders will look like," he said. "But that will be the same for chemicals and microbes."
On October 17, 2016, the Industrial Biotechnology Innovation Centre (IBioIC) announced over £3 million in investments over six synthetic biology projects. IBioIC was founded by Ingenza Ltd, GlaxoSmithKline plc (GSK), and INEOS to connect academic expertise in synthetic biology with industrial capabilities from businesses in the area. IBioIC focuses on biotechnology in health, industrial, agriculture, and marine areas. Recipients of the £3 million in funding are:
|“Synpromics with University of Edinburgh to enable better gene therapy;
|Lucite International with University of St Andrews to increase the sustainability of acrylic glass;
|Unilever with University of Edinburgh to create “greener” skin cleansers;
|Ingenza Ltd with University of Glasgow to develop advanced metrology (measurements) for biotechnology;
|Twist Bioscience with University of Edinburgh to develop tools to engineer yeast strains for fuels and pharmaceuticals; and
||Nissan Chemicals with University of Glasgow for new tools for bio-production of pharmaceuticals, nutraceuticals, cosmetics.
On June 22, 2016, DOE released the detailed agenda for the Biotechnology for Clean Vehicles: Harnessing Synthetic Biology To Enable Next-Generation Biomaterials And Biofuels session at the Sustainable Transportation Summit. The session is hosted by DOE's Office of Energy Efficiency and Renewable Energy (EERE) and will focus on how novel biomaterials and renewable fuels can be used to improve vehicle efficiency and sustainability. The session will also discus the role of synthetic biology in enabling renewable fuels and materials. The Biotechnology for Clean Vehicles session will be held from 8:00 a.m. to 12:00 p.m. (ET) on July 12, 2016, during the Sustainable Transportation Summit in Washington D.C.
On October 15, 2015, Bergeson & Campbell, P.C. (B&C®) and the Woodrow Wilson International Center for Scholars (Wilson Center) hosted “Leveraging Synthetic Biology’s Promise and Managing Potential Risk,” a panel discussion featuring Lynn L. Bergeson, Sheryl Lindros Dolan, and Richard E. Engler, Ph.D., of B&C, and Todd Kuiken, Ph.D., Senior Program Associate, Synthetic Biology Project, Wilson Center.
The event coincided with the release of “The DNA of the U.S. Regulatory System: Are We Getting It Right For Synthetic Biology?,” authored by the legal experts, scientists, and policy specialists of B&C and released through the Wilson Center’s Synthetic Biology Project. Panelists discussed how synthetic biology applications would be regulated by the U.S. Coordinated Framework for Regulation of Biotechnology, how this would affect the market pathway of these applications, and whether the existing framework will protect human health and the environment. The webcast was recorded and is viewable online.
Panelists spoke of the many challenges facing synthetic biology innovations. More government resources are needed to regulate efficiently these innovative products in a timely fashion, and greater clarity is needed to inform innovators as to the government oversight that these products will be subject prior to commercialization. The public’s understanding of the products and the regulatory process to which they are subject as a predicate to commercialization also needs enhancement to ensure public confidence in the oversight system.
Bergeson stated that B&C welcomed this opportunity to educate the public about synthetic biology through this collaborative report. The report contains several “teachable moments” that will help those in positions of decision-making to identify gaps and disconnects in regulation and communication and to be better able to anticipate challenges. Synthetic biology innovations are coming into the market at a fast pace. It is difficult for government regulators to keep up with the pace of these innovations due to jurisdictional ambiguities and limited federal resources.
Another challenge is inter-agency communication. Federal families are often not on the same page in terms of how they manage and address products of synthetic biology. There needs to be a “conscious effort” to communicate and the public needs to become more educated as to the regulatory process. Bergeson reminded attendees of the current opportunity to do so with the White House Office of Science and Technology Policy (OSTP) October 6, 2015, Request for Information (RFI) to solicit relevant data and information, including case studies that may assist in the development of the proposed update to the Coordinated Framework for the Regulation of Biotechnology (responses due November 13, 2015). More information on the RFI is available in B&C’s memorandum: Biotechnology: OSTP Seeks Comment on Clarifying Current Roles and Responsibilities Described in the Coordinated Framework for the Regulation of Biotechnology.
On September 16, 2015, the Woodrow Wilson International Center for Scholars (Wilson Center) released a funding report on U.S. Trends in Synthetic Biology Research Funding. The Wilson Center found that the U.S. invested approximately $820 million in synthetic biology research between 2008 and 2014, with nearly 60 percent of the funding coming from the Defense Advanced Research Projects Agency (DARPA). The National Science Foundation (NSF) has also been funding synthetic biology research, investing $138 million since 2008, but is winding down funding in anticipation of the conclusion of the Synthetic Biology Engineering Research Center (SynBERC) in 2016. Of all U.S. funding for synthetic biology research, less than one percent is focused on risk research with a similar amount focused on ethical, legal, and social issues. This funding report was released as an update to the 2010 brief Trends in Synthetic Biology Research Funding in the United States and Europe, an assessment of the funding resources provided by U.S. and European governments for synthetic biology research.
The U.S. Environmental Protection Agency (EPA) announced last week that it is developing a project intended to support public dialog concerning the development and use of synthetic biology (Synbio) algae. EPA has oversight responsibility for the production and use of intergeneric microorganisms, including cyanobacteria, eukaryotic microalgae (genetically modified (GM) algae), and their products by application of genetic engineering approaches, including those called Synbio. EPA's recently posted document, US Environmental Protection Agency GM/Synbio Algae Project, states that it is focusing its project around GM/Synbio algae applications.
EPA intends to facilitate the development of the GM/Synbio algae project by holding an expert workshop, open to the public on September 30, 2015. While the workshop will focus on the technical questions that EPA believes are important to its development of a GM/Synbio algae considerations document, EPA states that it will also provide an opportunity to stakeholders and the general public to comment on any aspects of GM/Synbio algae that they believe are relevant to EPA's mission.
EPA's posting of the GM/Synbio algae project is hugely important for the industrial biotechnology and synthetic biology communities. EPA's announcement suggests a broader Agency initiative is underway, and is best read in the context of other relevant developments. Full details on this announcement and related developments are available in Biobased and Renewable Products Advocacy Group (BRAG®) affiliate Bergeson & Campbell P.C. (B&C®)'s memorandum EPA Posts Information on GM/Synbio Algae Project.
With little fanfare or advanced notice to the general public, on July 2, 2015, the White House Office of Science and Technology Policy (OSTP), the Office of Management and Budget (OMB), the U.S. Trade Representative, and the Council on Environmental Quality issued a memorandum directing the U.S. Environmental Protection Agency (EPA), the U.S. Food and Drug Administration (FDA), and the U.S. Department of Agriculture (USDA) to update the Coordinated Framework for the Regulation of Biotechnology. Last updated in 1992 and first rolled out in 1986, the Coordinated Framework outlines a comprehensive federal regulatory policy for products of biotechnology. The memorandum directs the federal agencies to develop a long-term strategy to ensure that the regulatory system for biotechnology products is prepared for future products, and commissions an expert analysis of the future landscape of biotechnology products. A July 2, 2015, OSTP blog item entitled "Improving Transparency and Ensuring Continued Safety in Biotechnology" notes that the complexity of the array of regulations and guidance documents developed by EPA, FDA, and USDA "can make it difficult for the public to understand how the safety of biotechnology products is evaluated, and navigating the regulatory process for these products can be unduly challenging, especially for small companies." The memorandum states that the objectives "are to ensure public confidence in the regulatory system and to prevent unnecessary barriers to future innovation and competitiveness by improving the transparency, coordination, predictability, and efficiency of the regulation of biotechnology products while continuing to protect health and the environment."
The Coordinated Framework describes the federal regulatory policy intended to ensure the safety of biotechnology products. The 1992 update to the Coordinated Framework "sets forth a risk-based, scientifically sound basis for the oversight of activities that introduce biotechnology products into the environment." According to the memorandum, the update affirmed that federal oversight should focus on the characteristics of the product and the environment into which it is being introduced, rather than the process by which the product is created.
The memorandum states that federal agencies regulating biotechnology products "should continually strive to improve predictability, increase efficiency, and reduce uncertainty in their regulatory processes and requirements." Improvements must:
- Maintain high standards that are based on the best available science and that deliver appropriate health and environmental protection;
- Establish transparent, coordinated, predictable, and efficient regulatory practices across agencies with overlapping jurisdiction; and
- Promote public confidence in the oversight of the products of biotechnology through clear and transparent public engagement.
BRAG affiliate Bergeson & Campbell, P.C.'s (B&C®) full memorandum, "Biotechnology: White House Directs EPA, FDA, and USDA to Update the Coordinated Framework for the Regulation of Biotechnology," is available online.
The October 2014 issue of Industrial Biotechnology features the article Creative Adaptation: Enhancing Oversight of Synthetic Biology Under the Toxic Substances Control Act (TSCA), written by Lynn L. Bergeson, Of Counsel with the Biobased and Renewable Products Advocacy Group (BRAG®), Charles M. Auer, former Director of the U.S. Environmental Protection Agency's (EPA) Office of Pollution Prevention and Toxics (OPPT), and Oscar Hernandez, former Director of the Risk Assessment Division (RAD) of EPA OPPT.
Synthetic Biology is delivering on its promise as an emerging scientific field providing society with effective new sustainable products in diverse areas including renewable energy, contamination remediation, and medical applications, among others. As is the case with any rapidly evolving technology, the pace of technological innovation challenges regulators' ability to identify and address adequately the substantial uncertainties they confront when discharging their legal obligations under controlling laws to ensure human and environmental safety. This article provides a brief description of Synthetic Biology, discusses the current domestic regulatory framework that governs the regulation of products of Synthetic Biology, and focuses narrowly on options and opportunities EPA, innovators in the area of Synthetic Biology, and the TSCA-regulated community at large may wish to consider to enhance TSCA's core adaptive capacity to identify and address potential health and environmental risk implications posed by the commercialization of products of Synthetic Biology.