Preparing for Future Products of Biotechnology (2017) / Chapter Skim
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5 Opportunities to Enhance the Capabilities of the Biotechnology Regulatory System
5 Opportunities to Enhance the Capabilities of the Biotechnology Regulatory System
Pages 137-170
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From page 137... ...
As technologies and basic knowledge advance, a regulatory system should be able to adapt to new risks of future biotechnology products and also to adjust to well-established categories of products as their level and types of risk become better understood. As discussed in Chapters 2, 3, and 4, the scope, scale, complexity, and tempo of future products is expected to increase rapidly, and this increase has the potential to overwhelm the existing regulatory system.
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From page 138... ...
Oversight can include codes of conduct, voluntary data-sharing programs, and public–private partnerships for certification standards as well as regulations. Risk analysis for future products of biotechnology can occur within a formal statute-based regulatory system or outside of one.
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From page 139... ...
Complexity refers to the number of traits that may be involved in a single product and the interactions between the various elements in a product. Increased scope and complexity are key components of future products that may have fewer or no comparators to nonbiotechnology products or no similar existing biotechnology products and thus little or no familiarity within the regulatory system.
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From page 140... ...
Although these examples do not represent new risk-assessment endpoints, they may require more sophisticated risk analyses, with consideration of increasingly complex interactions. As noted in Recommendation 6-3 of the National Academies report on gene drives (NASEM, 2016a:128)
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From page 141... ...
In this section, the committee provides some insights on how these topics might be addressed for the types of products that are anticipated in the next 5–10 years. As described in Chapter 3, the statutory authorities that apply to some of the future products of biotechnology can be confusing and better coordination among the agencies would be beneficial so that risk analyses cover the impacts of biotechnology products more comprehensively in some cases or avoid duplication of data submissions in others.
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An evaluation of the product's familiarity to regulatory agencies and its complexity in terms of risk analyses as compared to existing biotechnology products would be ascertained (red bins)
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Rather, for products that are familiar and not complex, the developer's and agency's risk assessors and managers and interested and affected parties can draw upon existing information and risk analyses for similar products, which should facilitate the efficiency of the regulatory decision even if a complex risk analysis is required. For products that are unfamiliar or complex or unfamiliar and complex, the risk-analysis processes may need to be developed based on limited information and experience and may perhaps require a de novo approach.
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From page 144... ...
Descriptions were given in the National Strategy for multiple online resources maintained by each of EPA, FDA, and USDA, though these were not yet integrated at the time the committee's report was written and hence product developers and other interested parties had to navigate multiple sites that reflect the complexity of the regulatory system and the agencies' jurisdictions. There are examples from the European Union that collect together various product types into a single point of entry and provide a means for public consultation in the context of allergenicity assessment.3 A similar system for the U.S.
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Peer review and engagement by external parties on potential future products could also be initiated by the regulatory agencies based on horizon scanning. Undertaking such proactive, pilot projects will increase preparedness.
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In looking at the products of biotechnology that are likely to emerge in the next 5–10 years, Chapter 2 describes some of the features of future products that will challenge the system and Chapter 4 articulates some of the challenges in applying the Coordinated Framework. In moving from products that are in columns B and C to those in column D of Figure 2-6, it will be important for agencies to be prepared for products that involve substantial internal complexity, complex interactions with the environment, relatively few or no comparators to nonbiotechnology products for use in risk analysis, and have little similarity with existing biotechnology products.
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. As indicated already above, it is likely that future products of biotechnology could be controversial due to their complex interactions with the environment and society, and the committee anticipates that additional concern from the public will be a common feature of many future biotechnology products.
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. These concerns need to be addressed in an advisory process, and the committee suggests the agencies consider the program-management and conduct-of-practices principles provided in the 2008 National Research Council report Public Participation in Environmental Assessment and Decision Making, which include 1.
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are approximately $60,000 higher.b EPA indi ates that its use of the SAP is for when scientific data for a decision are complex. EPA further notes c that it often seeks technical advice from the Scientific Advisory Panel on risks that pesticides pose to wildlife, farm workers, pesticide applicators, nontarget species, as well as insect resistance, and novel scientific issues sur rounding new technologies (emphasis added)
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. Implementation of Probabilistic Risk Analyses Associated with Future Products of Biotechnology As discussed in Chapter 4, probabilistic risk analysis has not been widely used in the regulation of biotechnology products.
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Private standard set ting could be employed for future consumer products and food additives, to establish testing methods for data needed to support risk assessments, and for establishing information knowledge bases and metadata requirements to support developers and agency risk assessors. aSee, for example, Flavor & Extract Manufacturers Association, About the FEMA GRAS™ Program.
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From page 152... ...
The committee believes that the risk analyses customarily conducted in environmental assessments and environmental impact statements required by NEPA may be inadequate to characterize the risks of certain future products of biotechnology. The committee found no statutory restriction that precludes the regulatory agencies from conducting quantitative risk assessments.
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Future products of biotechnology designed for open release in minimally managed or unmanaged environments will introduce an increasing diversity of potential environmental stressors that will necessitate improved ecological risk assessment to forecast potential effects with a view toward understanding and managing ecological services at the landscape level. The limitations of species-specific modeling and measurement in landscapes 5Incident Reporting by Pesticide Manufacturers/Registrants.
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From page 154... ...
The above section "Consistent, Efficient, Effective DecisionMaking Processes for Future Products of Biotechnology" also raises the need for assessing similarities and differences among biotechnology products and anticipates a stratified assessment process that in some cases will be highly reliant on access to existing risk-analysis data or data summaries for biotechnology products already in the market. To this end, a suite of publicly available physical and computational models and methodologies that can be accessed for risk assessments with different degrees of complexity would be helpful.
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From page 155... ...
Therefore, the idea of "comparator" may need to expand to include similar existing biotechnology products with which regulatory agencies already have experience. Methods to quantitatively compare products will be needed for determining which bin is appropriate for a new product; selecting data from other product data sets for screening-level risk assessments or problem formulation; selecting data to use in effects or exposure analysis steps in a risk assessment; and selecting data to generate a risk characterization of a new product and/or place a characterization of a new product in context with an existing, similar product.
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From page 156... ...
In addition to comparators, research on phenotypic characterization is also needed to advance understanding of trait function and potential ecological consequences over the short and long term as well as understanding on how environmental context can affect phenotypic expression. Gene Fitness, Genetic Stability, and Horizontal Gene Transfer Engineered organisms that reproduce can suffer mutations that affect the physiology of the organism, leading to the potential for "instability" in the genome (engineered genetic constructs mutating in ways that could cause loss of function)
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In instances where products enter the marketplace through a notice to the appropriate regulatory agency, post-market monitoring or surveillance may be used to determine if future risk analyses and potential risk mitigation may be needed following use of the products (for example, cosmetics)
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. The 2016 National Academies report on gene drives articulated a phased testing approach for gene drives that includes research preparation, laboratory research, field research, staged environmental release, and post-release surveillance to gather information to support risk assessments and risk-mitigation measures to reduce potential nontarget effects (NASEM, 2016a)
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From page 159... ...
The risk estimates and descriptions in human health and ecological risk assessments for existing biotechnology products are typically qualitative in nature; however, certain portions of an assessment may be quantitative, such as for estimates of human dietary exposure assessment or determining nontarget species sensitivity. The current assessments may provide a limited discussion of the uncertainties associated with risk estimates with the overall risk-assessment conclusion based on the perspective that assumptions used in a risk assessment will provide an adequate margin of safety.
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. Molecular Characterization as a Preliminary Assessment Tool Molecular characterization of biotechnology products can provide important precursor information that can guide the direction and extent of human health and ecological risk assessments necessary for regulatory decisions (Corrigan-Curay et al., 2015)
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From page 161... ...
Three examples are • Allergen Online, a peer-reviewed allergen list and sequence-searchable database intended for the identification of proteins that may present a potential risk of allergenic cross reactivity curated by the University of Nebraska.10 • The International Life Sciences Institute crop composition database, which summarizes ranges in nutrient, toxicant, and antinutrient content of crops for use in substantial equivalence comparisons.11 • The CRISPR Genome Analysis Tool curated by Iowa State University and used for design and analysis of guide RNA for minimization of off-target genome edits.12 Given the large amounts of data that will be generated to support modeling and monitoring efforts, some degree of standardized methodologies and information systems will be required. Issues that will require attention include standardizing notation; standardizing testing procedures and assessment paradigms; characterizing the potential impacts of similar testing protocols on risk assessments; and approaches for collecting and integrating data from existing and future risk assessments and environmental impact statements, without compromising product developers' data compensation rights when specified under a relevant statute.
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From page 162... ...
. Another example of multiparty input in horizon scanning of potential future products which considered future regulatory needs was the Woodrow Wilson Center report Creating a Research Agenda for the Ecological Implications of Synthetic Biology, which identified several priority research areas (Drinkwater et al., 2014)
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From page 163... ...
Currently such tools are heavily deployed on enabling early-stage discovery or development. The adaptation of these tools to the task of predictive modeling on environmental openrelease scenarios would benefit later-stage risk assessment but can inform release scenario design, and possibly point to new opportunities to design, monitor, or enhance features of future products destined for deliberate release.
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From page 164... ...
SUMMARY AND CONCLUSIONS As technologies and basic knowledge advance, the regulatory system needs to be able to adapt to new risks of future biotechnology products and also to adjust to well-established categories of products as their level and types of risk become better understood. A regulatory system with a greater emphasis on stratified approaches that prioritize the regulatory agencies' familiarity with a product, the complexity of the risk assessment for the product, and the anticipated risk associated with the product (that is, proportionate oversight)
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From page 165... ...
Defined mechanisms and avenues for such engagement should be built into the risk assessment and decision-making processes from the beginning. Conclusion 5-4: Ecological risk assessment provides a methodology for more quantitative risk assessments for future biotechnology products and their release scenarios but will require more emphasis on measurement and modeling of effects on populations, com munities, and ecosystems.
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, contribute to utilizing proportional efforts in risk analyses. Conclusion 5-5: There are many opportunities for enhancing the capabilities, expertise, and tools available to regulatory agencies in areas that are likely to see increased emphasis and complexity in future products of biotechnology.
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1998. Guidelines for Ecological Risk Assessment.
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2012-05: A Set of Scientific Issues Being Considered by the Environmental Protection Agency Regarding: Problem Formulation for the Reassessment of Ecological Risks from the Use of Atrazine. Available at https://www.epa.gov/sites/production/files/2015-06/documents/061212minutes.pdf.
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Risk Analysis 26(3)
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Webinar presentation to the National Academies of Sciences, Engineering, and Medicine Committee on Future Biotechnology Products and Opportunities to Enhance Capabilities of the Biotechnology Regulatory System, July 29. Schein, C.H., O
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