Errata

The prepublication version of Preparing for Future Products of Biotechnology, released on March 9, 2017, was provided to the public to facilitate timely access to the report. Although the substance of the report is final, editorial changes were made throughout the text and citations were checked prior to final publication. The following factual and typographical errors in the prepublication version are corrected in the final text.

Page Number in
Prepublication
Report
Error Correction

p. 4, Table S-1

p. 5, Table S-2

p. 42, Figure 2-7

p. 43, Table 2-3

p. 49, Figure 2-8

p. 50, Table 2-4

Unclear term: On Market Correction: A footnote has been added to define “On Market” as equivalent to “in use”; thus, products that have received regulatory approval but are not in use were not considered by the committee to be “On Market.”

p. 4, Table S-1

p. 42, Figure 2-7

p. 43, Table 2-3

Incorrect term: Bioluminescent zebra fish Correction: Fluorescent zebra fish

p. 4, Table S-1

p. 43, Table 2-3

Typographical error: Genomically recorded organisms Correction: Genomically recoded organisms

p. 4, Table S-1

p. 43, Table 2-3

Error: Genome-edited crops marked as “On Market” Correction: Checkmark removed from “On Market” column for genome-edited crops

p. 5, Table S-2

p. 50, Table 2-4

Error: Bioluminescent microbes for home and landscape uses marked as “On Market” Correction: Checkmark removed from “On Market” column for bioluminescent microbes for home and landscape uses

p. 5, Table S-2

p. 50, Table 2-4

Typographical error: Genomically recorded organisms Correction: Genomically recoded organisms

p. 9, Figure S-2

p. 136, Figure 5-2

Error: “Assessment” encompasses “Unregulated” products Correction: “Assessment” redrawn to show that products deemed to be unregulated are not included in that step.
p. 21 Clarification needed in prepublication text: Depending on the familiarity and complexity of the new product, the agency may determine public participation concerning the technology, the benefits of the technology, and its potential implications would be helpful to inform the risk analyses. Revised sentences: Depending on the familiarity and complexity of the new product, the agency may determine in some instances that public participation concerning the technology, the benefits of the technology, and its potential implications would be helpful to inform the risk analyses.
p. 23 Clarification needed in prepublication text: As noted in Figure 1-2 (arrow B), the regulatory agencies may interact with other parties on issues related to implementing the Coordinated Framework. For example, the agencies may work with various global organizations (such as the Organisation for Economic Co-operation and Development) to develop international test guidelines for future biotechnology products. These collaborative efforts expand technical capability and can enhance efficiency in developing risk-analysis methods and also enhance efficiency and effectiveness for U.S. developers intending to export their products. Revised sentences: As noted in Figure 1-2 (arrow B), the regulatory agencies could interact with other parties on issues related to implementing the Coordinated Framework. For example, agencies could work with various global organizations (such as the Organisation for Economic Co-operation and Development) to develop international test guidelines for future biotechnology products. These collaborative efforts could expand technical capability and enhance efficiency in developing risk-analysis methods and also enhance efficiency and effectiveness in evaluating products intended for U.S. import.
p. 26, Figure 2-1 Incorrect figure label: The y-axis label “Basepair/$” is incorrect. Corrected figure label: Y-axis is corrected to ‘U.S. Dollars per Base Pair.”
p. 27 Clarification needed in prepublication text: Recombinant DNA insertions typically involve the transformation of plasmids—the insertion of circular rDNA molecules capable of replicating alongside the host’s genome—or direct insertion into the host’s genome using homologous recombination (the natural ability of cells to exchange DNA between similar DNA molecules of host genes and exogenous DNA). Revised sentence: Recombinant DNA insertions typically involve the transformation of plasmids—the insertion of circular rDNA molecules capable of replicating alongside the host’s genome—or direct insertion into the host’s genome using either the natural ability of cells to exchange DNA or by techniques that create double-stranded breaks in the genome, allowing incorporation of exogenous DNA).
p. 28 Clarification needed in prepublication text: Scientists have re-engineered the CRISPR-Cas9 system so that a single RNA (the guide RNA) can create the Cas9-mediated cut of a target sequence in a genome. Revised sentence: Scientists have re-engineered the CRISPR-Cas9 system so that a single RNA (the guide RNA) can direct the Cas9-mediated cut of a target sequence in a genome.
p. 39, Table 2-2 Updated source needed for Table 2-2 Table 2-2 has been updated with data from U.S. Department of Agriculture–Animal and Plant Health Inspection Service. 2017. Regulatory Impact Analysis & Initial Regulatory Flexibility Analysis, Proposed Rule, APHIS 2015-0057, RIN 0579-AE15; Importation, Interstate Movement, and Environmental Release of Organisms Produced through Genetic Engineering (7 CFR part 340). Available at https://www.regulations.gov/document?D=APHIS-2015-0057-0002.
p. 40 Clarification needed for Footnote 24 prepublication text: See Chapter 3 for more discussion of the roles and responsibilities of the regulatory agencies. Revised Footnote 24: See Chapter 3 for more discussion of the roles and responsibilities of the regulatory agencies and Appendix D for the Federal Food, Drug, and Cosmetic Act definition of food.
p. 44 Error: Drought tolerance in corn (Shi et al., 2017) and more healthful oil quality in soybean (Haun et al., 2014) were being demonstrated through genome editing as well, and canola with herbicide resistance introduce through genome editing was already on the market in the United States.

Revision: Drought tolerance in corn (Shi et al., 2017) and more healthful oil quality in soybean (Haun et al., 2014) were being demonstrated through genome editing as well.28

28At the time the committee was writing its report, a canola variety with herbicide resistance had been commercialized by the company Cibus, which described the variety as developed using genome editing (Gocal, 2015). The resistance arose from a single nucleotide mutation in the BnAHAS1C gene selected for during an oligonucleotide-mediated genome-editing approach. However, Canadian regulatory documents note that, although the variety was developed using a genome-editing approach, Cibus “hypothesized that the single nucleotide mutation was the result of spontaneous somaclonal variation” rather than directly from the oligonucleotide-mediated editing. See Novel Food Information–Cibus Canola Event 5715 (Imidazolinone and Sulfonylurea Herbicide Tolerant). Available at http://www.hc-sc.gc.ca/fn-an/gmf-agm/appro/canola-5715-eng.php.

 

Gocal, G. 2015. Non-transgenic trait development in crop plants using oligo-directed mutagenesis: Cibus’ Rapid Trait Development System. Pp. 97–106 in NABC Report 26 New DNA-Editing Approaches: Methods, Applications, & Policy for Agriculture, A. Eaglesham and R.W.F. Hardy, eds. Ithaca, NY: North American Agricultural Biotechnology Council.

p. 44 Clarification needed in prepublication text: RNAi technology had already been used to reduce browning the flesh of apples and potatoes (NASEM, 2016b), and these products had cleared U.S. regulatory requirements. Scientists were using RNAi to create virus resistance in cassava, a staple crop in many African countries (Taylor et al., 2012). RNAi was also being used as a way different from rDNA to introduce insect resistance into corn; this product was deregulated by USDA–APHIS in 2015. Revision: RNAi technology had already been used to introduce traits, including the reduction of browning in the flesh of apples and potatoes (NASEM, 2016b), and such products had cleared U.S. regulatory requirements. Scientists were using RNAi to create virus resistance in cassava, a staple crop in many African countries (Taylor et al., 2012). RNAi was also being used as a way different from rDNA-mediated toxin expression to introduce insect resistance into corn; this product was deregulated by USDA–APHIS in 2015.
p. 45 Incorrect term: Engineered bioluminescent zebra fish have been on the market since 2003. Correction: Engineered fluorescent zebra fish have been on the market since 2003.
p. 49, Figure 2-8 Error: Bioluminescent microbes for home and landscape uses marked as “On Market” Correction: Bioluminescent microbes for home and landscape uses shown as “Under Development” and “Early-Stage Concept.”
p. 74, Table 3-2,
New Animal Drug,
Premarket Risk
Assessment column
Clarification needed in prepublication text: New animal drugs cannot be marketed until FDA affirmatively approves them. The burden of proof is on the manufacturer to show that the drug is safe and effective for the animal and—for drugs used in animals used as food—that the drug will not place humans at risk by leaving residues in edible tissues. Revision: New animal drugs cannot be marketed until FDA affirmatively approves them. The burden of proof is on the manufacturer to show that the drug is safe and effective for the animal and—for drugs used in food-producing animals—that food products derived from treated animals are safe for consumption.
p. 74, Table 3-2,
New Animal Drug,
Post-market Risk
Assessment column
Clarification needed in prepublication text: FDA performs inspections and encourages veterinarians and animal owners to report emerging safety problems with approved animal drugs. Revision: FDA performs inspections and requires reporting of certain safety problems by sponsors and manufacturers as well as encouraging reporting by veterinarians and animal owners of safety problems with approved animal drugs.
p. 75 Clarification needed in prepublication text: Future biotechnology products may include an additional array of new products that may not fit within existing policies. Examples would be synthesized foodstuffs produced directly in industrial and fermentation facilities without the intermediation of plants or animals (such as egg-white protein produced from GE yeast) or cultured food products like yogurt containing GE microorganisms. This discussion examines the flexibility of FDA’s statutes to cope with such products. Revision: Future biotechnology products may include an additional array of new products, for example, synthesized foodstuffs produced directly in industrial and fermentation facilities without the intermediation of plants or animals (such as egg-white protein produced from GE yeast) or cultured food products like yogurt containing GE microorganisms. Some of these future foodstuffs may fit within FDA’s existing policies, but other may present challenges. This discussion examines the flexibility of FDA’s statutes to cope with such products.
p. 78 Incorrect and missing agencies: The trends identified in Chapter 2 present challenges and counsel a need to ensure that FDA’s Center for Food Science and Applied Nutrition receives adequate resources for the task ahead. Correction: The trends identified in Chapter 2 present challenges and counsel a need to ensure that FDA’s Center for Food Safety and Applied Nutrition and Center for Veterinary Medicine receive adequate resources for the task ahead.
p. 78 Clarification needed in prepublication text: FDA’s new animal drug risk assessment considers a drug’s safety and effectiveness to the animal and, in the case of animals used for food, whether the change creates risks to humans through residues or other impacts on the animal’s edible tissues. Revision: FDA’s new animal drug risk assessment considers a drug’s safety and effectiveness to the animal and, in the case of food-producing animals, whether food derived from the animal is safe for consumption.
p. 78 Clarification needed in prepublication text: Biotechnology-altered animals of the future may include nonfood animals, such as pets or species brought back from extinction. In addition to environmental risks, these animals may pose consumer-safety risks. For example, a biotechnology-altered pet could have altered susceptibility to zoonotic diseases or aggressive traits that pose injury risks to humans. FDA’s new animal drug authorities do not allow the agency to address these risks. Revision: Biotechnology-altered animals of the future may include nonfood animals, such as pets or species brought back from extinction. In addition to environmental risks, these animals may pose consumer-safety risks. For example, a biotechnology-altered pet could have altered susceptibility to zoonotic diseases or aggressive traits that pose injury risks to humans. According to the FDCA, the term safe, as used in the new animal drug provisions, “has reference to the health of man or animal.” While this is sometimes conceived as an authority merely to ensure the safety of foods derived from food-producing animals, it actually carries a broader authority to consider human-safety impacts of new animal drugs. Thus, if an alteration to an animal results in human risks that go beyond food-safety risks, FDA has authority to take these other risks into account as part of a user-safety evaluation.
p. 85, Table 3-3, USDA–APHIS Authority column Clarification needed in prepublication text: Products are regulated by USDA–APHIS while under experimentation and can subsequently be deregulated for commercial release. Revision: Products are regulated by USDA–APHIS while under experimentation and can subsequently be deregulated for unconfined release, which for many types of products is a necessary practical step for commercial use.
p. 87 Clarification needed in prepublication text: As of 2016, USDA authority over GE insects has been exercised under the PPA but no under the AHPA. Revision: As of 2016, USDA authority over GE insects that are plant pests has been exercised under the PPA but the AHPA authority has not been exercised over GE insects that are animal pests.
p. 88 Incorrect sentence: Because of the use of a plant pest to transform an organism has been a key feature in the authority grant to USDA–APHIS to oversee products of biotechnology, the agency typically has not regulated biotechnology plants that are not engineered using a plant-pest vector or those plants that do not contain any plant-pest DNA. Correction: Because the use of a plant pest to transform an organism has been a key feature of the regulations used by USDA–APHIS since 1987 to oversee products of biotechnology, the agency typically has not regulated biotechnology plants that are not engineered using a plant-pest vector or those plants that do not contain any plant-pest DNA.
p. 88 Clarification needed in prepublication text: As of 2016, USDA–APHIS had considered several cases of crops engineered with genome-editing technology to cause directed insertions or deletions of one to several bases with no evidence that the genetic sequences used to introduce deletions contained any material from a plant pest. Revision: As of 2016, USDA–APHIS had considered several cases of crops engineered with genome-editing technology to cause directed insertions or deletions of one to several bases.
p. 90 Clarification needed in prepublication text: Under the proposal, GE crops and plants submitted to USDA–APHIS would be considered regulated articles only if the agency had not evaluated previously the plant-pest risk or noxious-weed risk posed by the submitted trait–crop combination or if the trait–crop combination has received DNA from a donor organism in a taxon known to contain plant pests and the introduced DNA was sufficient to produce a plant-disease property in the trait–crop combination. Revision: Under this proposal, GE crops and plants would be subject to a mandatory regulatory status evaluation by USDA–APHIS only if the agency had not evaluated previously the plant-pest risk or noxious-week risk posed by the submitted trait–crop combination or if the trait–crop combination has received DNA from a donor organism in a taxon known to contain plant pests and the introduced DNA was sufficient to produce a plant-disease property in the trait–crop combination.
p. 91, Box 3-4 Clarification needed in prepublication text: When NEPA is triggered, product developers must submit an environmental assessment to USDA–APHIS before the permit can be granted or the product regulated. Revision: When NEPA is triggered, USDA–APHIS must determine its appropriate response under NEPA regulations before a permit can be granted or the product deregulated.
p. 91, Box 3-4 Clarification needed in prepublication text: For FDA’s oversight of biotechnology-altered animals, NEPA can be triggered when the agency considers a field trial (which the agency sees as analogous to clinical trials of an “investigational new animal drug”) and again when the animal is approved for commercial use. Revision: For FDA’s oversight of biotechnology-altered animals, NEPA can be triggered for major federal actions, which include FDA’s approval of an investigational new animal drug application (for example, an application to commence a field trial) and FDA’s approval of a new animal drug application to commence commercial use.
p. 92, Box 3-4 Incorrect sentence: The Oxitec mosquitoes (engineered to produce sterile offspring) were the first biotechnology-altered animals to undergo a NEPA assessment for a field release, although the GE salmon also received a NEPA analysis for transport of the food into the United States. Correction: The Oxitec mosquitoes (engineered to produce sterile offspring) were the first biotechnology-altered animals to undergo a NEPA assessment for a field release.
p. 92, Box 3-4 Incorrect sentence: It reviewed a zebra fish genetically engineered to glow before the agency put in place its GE animal policy in 2009; the agency determined it would not regulate the zebra fish because the fish would not be sold as food. Correction: It reviewed a zebra fish genetically engineered to fluoresce before the agency put in place its GE animal policy in 2009; the agency decided not to enforce the approval requirement for the zebra fish based on an evaluation of risk factors, including whether it posed a human, animal, or environmental risk.
p. 92, Box 3-4 Missing source Source added: SOURCE: Based on a white paper prepared for the committee by S. Carter, Science Policy Consulting, 2016, which is available upon request from the National Academies’ Public Access Records Office at PARO@nas.edu.
p. 93, Box 3-5 Incorrect statement: With respect to biotechnology products, the regulatory agencies have limited experience with the ESA. USDA–APHIs has generally made a “no effect” determination in its decisions, and so has limited experience with the ESA and consultation with FWS and NMFS. Similarly, EPA and FDA have found “no effect” for all of their biotechnology products. Revision: With respect to biotechnology products, the regulatory agencies have limited experience undertaking ESA Section 7(a)(2) consultations. At the time the committee was writing its report, EPA, FDA, and USDA–APHIS have typically made “no effect” determinations for their regulatory actions.
p. 93, Box 3-5

Clarification needed in prepublication text: However, FWS has not been intimately involved in the regulation of GE animals, and FWS personnel have criticized FDA’s environmental assessments and decision-making processes for GE animals like the AquAdvantage Salmon (as summarized in Earthjustice and CFS, 2013).

 

Revision: However, FWS has not been intimately involved in the regulation of GE animals, and FWS personnel have criticized FDA’s environmental assessments and decision-making processes for the AquAdvantage Salmon (as summarized in Earthjustice and CFS, 2013).

 

p. 94, Box 3-5 Missing source Source added: SOURCE: Based on a white paper prepared for the committee by S. Carter, Science Policy Consulting, 2016, which is available upon request from the National Academies’ Public Access Records Office at PARO@nas.edu.
p. 96 Clarification needed in prepublication text: Jurisdiction redundancy also exists; for example, all three agencies receive composition and agronomic performance data for GE crops. Revision: Jurisdiction redundancy also exists; for example, all three agencies can receive composition and agronomic performance data for GE crops.
p. 106 Clarification needed in prepublication text: There may be regulatory gaps associated with these types of products. For example, if USDA determines that a product is not regulated by virtue of the mechanism used to insert the genetic modification or the source of the genetic material, then the agency may have no authority to do a National Environmental Policy Assessment. Revision: There may also be regulatory gaps associated with these types of products. For example, if USDA determines that a product is not regulated by virtue of the mechanism used to insert the genetic modification or the source of the genetic material, and that product may be a plant pest or weedy species, there would not be oversight when oversight is warranted.
p. 116, Figure 4-5 Incorrect data Correction: Figure 4-5 has been updated with correct data.
p. 123, Figure 4-8 Incorrect data in “Control of organismal traits” Correction: Figure 4-8 has been updated with correct data for that area of research.
p. 180, Glossary Incorrect definition: Definition of trait limited to only plants. Correction: The definition of trait has been revised.
p. 196 Incorrect term and meaning: animal feed Correction: The term animal feed has been replaced with animal food and the meaning has been revised.