On March 9, 2017, the National Academies of Sciences, Engineering, and Medicine (National Academies) published a report entitled Preparing for Future Products of Biotechnology, prepared by the Committee on Future Biotechnology Products and Opportunities to Enhance Capabilities of the Biotechnology Regulatory System (Committee). The Committee was asked to describe the possible future products of biotechnology that will arise over the next five to ten years, as well as provide some insights that can help shape the capabilities within the U.S. Environmental Protection Agency (EPA), the U.S. Food and Drug Administration (FDA), and the U.S. Department of Agriculture (USDA) as they move forward. According to the Committee, agencies may be overwhelmed by the number and diversity of new biotechnology products. The Committee states that the agencies should increase their scientific capabilities, tools, and expertise in key areas of expected growth. The report reflects the Committees deliberations regarding the future products of biotechnology that are likely to appear on the horizon, the challenges that the regulatory agencies might face, and the opportunities for enhancing the regulatory system to prepare for what might be coming. The Committee reached consensus on conclusions and recommendations that are based on extensive information gathering, Committee discussions, and input from a wide variety of communities interested in biotechnology. A copy of the slides used during a National Academies webinar on the report can be found on the National Academies website.

On July 2, 2015, the White House Office of Science and Technology Policy, the Office of Management and Budget, the U.S. Trade Representative, and the Council on Environmental Quality issued a memorandum, Modernizing the Regulatory System for Biotechnology Products, directing EPA, FDA, and USDA to update the Coordinated Framework for the Regulation of Biotechnology (Coordinated Framework). The Obama Administration asked the agencies to accomplish three tasks:

Clarify the current roles and responsibilities of the EPA, FDA, and USDA in the regulatory process;

Develop a long-term strategy to ensure that the federal regulatory system is equipped to assess efficiently the risks, if any, of the future products of biotechnology; and

Commission an expert analysis of the future landscape of biotechnology products.

As reported previously, on January 4, 2017, the White House announced the release of the 2017 Update to the Coordinated Framework for the Regulation of Biotechnology. The 2017 Update provides a comprehensive summary of the roles and responsibilities of EPA, FDA, and USDA with respect to regulating biotechnology products. Together with the National Strategy for Modernizing the Regulatory System for Biotechnology Products, published in September 2016, the 2017 Update offers a complete picture of a robust and flexible regulatory structure that provides appropriate oversight for all products of modern biotechnology. Within that regulatory structure, the federal agencies maintain high standards that, based on the best available science, protect health and the environment, while also establishing transparent, coordinated, predictable and efficient regulatory practices. More information is available in the White House blog item, Increasing the Transparency, Coordination, and Predictability of the Biotechnology Regulatory System.

The July 2, 2015, memorandum called for the commission of an external, independent analysis of the future landscape of biotechnology products. EPA, FDA, and USDA commissioned the National Academies to prepare an analysis to identify potential new risks and frameworks for risk assessment and areas in which the risks or lack of risks relating to the products of biotechnology are well understood. This analysis is presented in the report prepared by the Committee that was released on March 9, 2017.

The Committee was tasked to:

Describe the major advances and the potential new types of biotechnology products likely to emerge over the next five to ten years;

Describe the existing risk-analysis system for biotechnology products including, but perhaps not limited to, risk analyses developed and used by EPA, USDA, and FDA, and describe each agencys authorities as they pertain to the products of biotechnology;

Determine whether potential future products could pose different types of risks relative to existing products and organisms. Where appropriate, identify areas in which the risks or lack of risks relating to the products of biotechnology are well understood; and

Indicate what scientific capabilities, tools, and expertise may be useful to the regulatory agencies to support oversight of potential future products of biotechnology.

Human drugs and medical devices were not included in the purview of the study.

To address its statement of task, the Committee gathered information from a number of sources, and heard from over 70 speakers over the course of three in-person meetings and eight webinars. The Committee received responses to a request for information from a dozen federal agencies, and solicited statements and written comments from members for the public. According to the report, the Committee defined biotechnology products as products developed through genetic engineering or genome engineering (including products where the engineered DNA molecule is itself the product, as in an engineered molecule used as a DNA information-storage medium) or the targeted or in vitro manipulation of genetic information of organisms, including plants, animals, and microbes. The term also covers some products produced by such plants, animals, microbes, and cell-free systems or products derived from all of the above.

The Committee grouped future products into three major classes:

Open-release products: The open-release products that the Committee saw on the horizon include plants, animals, microbes, and synthetic organisms that have been engineered for deliberate release in an open environment. According to the report, the ability to sustain existence in the environment with little or no human intervention is a key change between existing products of biotechnology and some of the future ones anticipated in this class. The report states that the Committee thought that future open-release products would be developed for familiar uses, such as agricultural crops, but would also likely be developed for uses such as cleaning up contaminated sites with engineered microbes, replacing animal-derived meat with meat cultured from animal cells, and controlling invasive species through gene drives;

Contained products: The Committee concluded that future biotechnology products that are produced in contained environments are more likely to be microbial based or synthetically based rather than based on an animal or plant host. According to the report, organisms of many genera are used in fermenters to produce commodity chemicals, fuels, specialty chemicals or intermediates, enzymes, polymers, food additives, and flavors. When considering the laboratory as a contained environment, the report states that many examples of transgenic animals from vendors are widely used today for research and development. Because performing biotechnology in contained environments allows higher control over the choice of host organism, systems with advanced molecular toolboxes are already in high use; and

Platforms: Biotechnology platforms are tools that are used in the creation of other biotechnology products, according to the report, including products that are traditionally characterized as wet lab, such as DNA/RNA, enzymes, vectors, cloning kits, cells, library prep kits, and sequencing prep kits, and products that are dry lab, such as vector drawing software, computer-aided design software, primer calculation software, and informatics tools. The report states that these two categories continue to meld as newer approaches are published or commercialized.

The report notes that there are a variety of technical, economic, and social trends that drive and will continue to drive the types of biotechnology products developed in the next decade. Technical and economic trends in the biological sciences and biological engineering are accelerating the rate at which new product ideas are formulated and the number of actors who are involved in product development. The report states that with regard to social trends, it was evident to the Committee that there are many competing interests, risks, and benefits regarding future biotechnology products. According to the report, it was clear that the U.S. and international regulatory systems will need to achieve a balance among these competing aspects when considering how to manage the development and use of new biotechnology products.

The Committee found that the Coordinated Framework appears to have considerable flexibility in statutory authority to cover a wide range of biotechnology products. The jurisdictions of EPA, FDA, and USDA are defined in ways that may leave gaps or redundancies in regulatory oversight, however. According to the report, even when jurisdiction exists, the available legal authorities may not be ideally tailored to new and emerging biotechnology products. Other agencies will likely have responsibilities to regulate some future biotechnology products, and their roles are not well specified in the Coordinated Framework.

The report states that the Committee found that the complexity of the existing biotechnology regulatory system, which could appear fragmented, results in a system that is difficult for product developers -- including individuals, nontraditional organizations, and small enterprises, as well as consumers, product users, and interested members of the public to navigate. The complexity can cause uncertainty and a lack of predictability for developers of future biotechnology products and creates the potential for loss of public confidence in oversight of future biotechnology products.

According to the report, the increased rate of new product ideas means that the types and number of biotechnology products in the next five to ten years may be significantly larger than the current rate of product introduction. The report cautions EPA, FDA, USDA, and other relevant agencies to prepare for this potential increase, including finding effective means of evaluation that maintains public safety, protects the environment, and satisfies the statutory requirements appropriate for each agency. The increased number of actors involved in product development means that the regulatory agencies will need to be prepared to provide information regarding the regulatory process to groups that may have little familiarity with the Coordinated Framework.

According to the report, advances in biotechnology are leading to products that involve the transformation of less familiar host organisms, have multiple engineered pathways, are comprised of DNA from multiple organisms, or are made from entirely synthetic DNA. Such products may have few or no comparators to existing nonbiotechnology products, which function as the baseline of comparison in current regulatory risk assessments of biotechnology products.

For future biotechnology products in all degrees of complexity and novelty, the Committee considered the risk assessment endpoints related to human health or environmental outcomes, such as illness, injury, death, or loss of ecosystems function. The Committee concluded that these endpoints are not new, but the intermediate steps along the path to those endpoints may be more complex, more ambiguous, and less well characterized than those for existing biotechnology products. According to the report, the scope, scale, complexity, and tempo of biotechnology products likely to enter the regulatory system in the next five to ten years have the potential to critically stress EPA, FDA, and USDA, both in terms of capacity and expertise.

At a high level, the Committee found that there are existing frameworks, tools, and processes for risk analyses and public engagement that can be used to address the issues likely to arise in future biotechnology products in a way that balances competing issues and concerns. Given the profusion of biotechnology products that are on the horizon, however, there is a risk that the capacity of the regulatory agencies may not be able to provide efficiently the quantity and quality of risk assessments that will be needed. The report states that an important approach for dealing with the increase in the products will be the increased use of stratified approaches to regulation, where new and potentially more complex risk analysis methods will need to be developed for some products, while established risk analysis methods can be applied or modified to address products that are familiar or that require less complex risk analysis. To help articulate what capabilities, tools, and expertise might be useful to meet these objectives, the Committee created a conceptual map for decision-making aimed to assess and manage product risk, streamline regulation requirements, and increase transparency.

The Committee identified the following broad themes regarding future opportunities for enhancement of the U.S. biotechnology regulatory system:

The bioeconomy is growing rapidly and the U.S. regulatory system needs to provide a balanced approach for consideration of the many competing interests in the face of this expansion;

The profusion of biotechnology products over the next five to ten years has the potential to overwhelm the U.S. regulatory system, which may be exacerbated by a disconnect between research in regulatory science and expected uses of future biotechnology products;

Regulators will face difficult challenges as they grapple with a broad array of new types of biotechnology products -- for example, cosmetics, toys, pets, and office supplies -- that go beyond contained industrial uses and traditional environmental release (for example, Bacillus thuringiensis (Bt) or herbicide-resistant crops);

The safe use of new biotechnology products requires rigorous, predictable, and transparent risk-analysis processes whose comprehensiveness, depth, and throughput mirror the scope, scale, complexity, and tempo of future biotechnology applications; and

In addition to the conclusions and recommendations from this report, EPA, FDA, USDA, and other agencies involved in regulation of future biotechnology products would benefit from adopting recommendations made by previous National Academies committees related to future products of biotechnology that are consistent with the findings and recommendations in this report.

On the basis of its conclusions, the Committee developed a number of detailed recommendations regarding actions that can be taken to enhance the capabilities of the biotechnology regulatory system to be prepared for anticipated future products of biotechnology.

EPA, FDA, USDA, and other agencies involved in regulation of future biotechnology products should increase scientific capabilities, tools, expertise, and horizon scanning in key areas of expected growth of biotechnology, including natural, regulatory, and social sciences;

EPA, FDA, and USDA should increase their use of pilot projects to advance understanding and use of ecological risk assessments and benefit analyses for future biotechnology products that are unfamiliar and complex and to prototype new approaches for iterative risk analyses that incorporate external peer review and public participation; and

The National Science Foundation, the Department of Defense, the Department of Energy, the National Institute of Standards and Technology, and other agencies that fund biotechnology research with the potential to lead to new biotechnology products should increase their investments in regulatory science and link research and education activities to regulatory-science activities.

The report is well written and contains a significant amount of new and valuable information on the types of new biotechnology products being innovated and coming into commerce, trends of note regarding future products, and regulatory gaps and redundancies that need to be addressed. This background information is clearly presented and supports well the conclusions that are essential to understand, and the recommendations that are in urgent need of response.

That the federal agencies tasked with regulating biotechnology products need increased funding and organizational retooling to address the challenges eloquently and convincingly described in the report are truths beyond dispute. In this political climate, and under this Administration, meeting these needs will be challenging. Shareholders of all sorts in the biotechnology area -- businesses, innovators, environmental and public health activists -- are urged to weigh in and express support for the allocation of resources needed to fulfill the reports recommendations. Future generations of biotechnology products are on the line and at risk if these recommendations fall on deaf ears.

2017 Bergeson & Campbell, P.C.

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National Academies Report Finds Future Biotechnology Products May Overwhelm Agencies - The National Law Review