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Contents

  1. Top of page
  2. Contents
  3. Introduction
  4. Animal Cloning
  5. Regulation of Genetic Engineered Animals – Statutory and Regulatory Authority
  6. FDA’s General Approach to Regulation of GE Animals
  7. FDA’s Approach for Food/Feed Safety Assessments Involving GE Animals
  8. Conflicts of interest
  9. References

Animal biotechnology represents one subset of tools among a larger set of technologies for potential use to meet increasing world demands for food. Assisted reproductive technologies (ART) such as artificial insemination and embryo transfer continue to make positive contributions in food animal production. The US Food and Drug Administration (FDA) performed a comprehensive risk assessment to identify potential food consumption or animal health risks associated with animal cloning, an emerging ART. At that time, FDA concluded that animal cloning posed no unique risks either to animal health or to food consumption, and food from animal clones and their sexually reproduced offspring required no additional federal regulation beyond that applicable to conventionally bred animals of the species examined. At this time, no new information has arisen that would necessitate a change in FDA’s conclusions on food from animal clones or their sexually reproduced offspring. Use of recombinant DNA technologies to produce genetically engineered (GE) animals represents another emerging technology with potential to impact food animal production. In its regulation of GE animals, FDA follows a cumulative, risk-based approach to address scientific questions related to the GE animals. FDA evaluates data and information on the safety, effectiveness and stability of the GE event. FDA carries out its review at several levels (e.g. molecular biology, animal safety, food safety, environmental safety and claim validation). GE animal sponsors provide data to address risk questions for each level. This manuscript discusses FDA’s role in evaluation of animal cloning and GE animals.


Introduction

  1. Top of page
  2. Contents
  3. Introduction
  4. Animal Cloning
  5. Regulation of Genetic Engineered Animals – Statutory and Regulatory Authority
  6. FDA’s General Approach to Regulation of GE Animals
  7. FDA’s Approach for Food/Feed Safety Assessments Involving GE Animals
  8. Conflicts of interest
  9. References

Increased worldwide demand for food is a consequence of the ongoing growth in world population. The Food and Agriculture Organization (FAO) of the United Nations projects the worldwide demand for food will nearly double in the first half of this century (FAO 2002, 2008, 2009). Similarly, the projected worldwide demand for meat and dairy products will increase by ∼70 and 50 per cent, respectively, during this time frame (FAO 2011). These increases need to occur while maintaining and improving food security (availability, accessibility, stability and safety of food) and most will need to be met through the use of existing and new technologies because of limited natural resources. Given these challenges, food security continues to be a topic of intense discussions at both domestic and international levels, as authorities grapple with the issues of population growth, climate change and changes in dietary patterns.

Animal biotechnology represents a potential set of tools within the larger body of technologies to help increase the supply of secure food. In the broadest sense, animal biotechnology can be considered technological application to animals or their derivatives to improve food production and enhance animal and human health. Less broadly, animal biotechnology may also be considered to include the array of assisted reproductive technologies (e.g. artificial insemination, in vitro fertilization, embryo transfer and animal cloning), or application of recombinant deoxyribonucleic acid (rDNA) techniques for the purposes of producing genetically engineered (GE) animals. In fact, the Codex Alimentarius Commission defines ‘modern biotechnology’ narrowly as meaning the application of in vitro rDNA techniques to create genetically engineered organisms (Codex Alimentarius 2009).

FDA’s role in the oversight of animal biotechnology is consistent with FDA’s public health mission by helping to define the pathway for introduction of products from safe and effective technologies to improve production of safe and secure food while enhancing human and animal health. These efforts nest well within broader efforts related to ‘One Health’ (One Health – One Medicine 2009). To date, FDA has been involved with risk assessment and/or regulation of animal cloning and GE animals. From a scientific perspective, FDA views animal cloning vs. GE animals as two distinct technologies based on potential risks they pose to the animals themselves or to humans and animals consuming the edible products derived from these animals. There are also legal reasons for the differences in how FDA regulates the products of these technologies.

Animal cloning represents an assisted reproductive technology (ART) in which there is the potential for more rapid distribution of naturally occurring, desirable traits in breeding stock. In contrast, genetic engineering relates to the application of rDNA techniques to introduce new genes or modify existing ones to introduce new traits in animals. FDA’s Guidance for Industry #187 clarifies the authority of FDA to regulate an rDNA construct in a GE animal as ‘an article (other than food) intended to affect the structure or any function of the body of man or other animals’ under the new animal drug provisions of the Federal Food, Drug and Cosmetic Act (FDA 2009). FDA considers genetically engineered animals that are propagated using animal cloning to be genetically engineered for the purposes of regulation.

This manuscript describes FDA processes related to evaluation of animal cloning and GE animals. For the latter animal biotechnology, particular focus is on food safety risk assessment within the context of the overall process for regulation of GE animals.

Animal Cloning

  1. Top of page
  2. Contents
  3. Introduction
  4. Animal Cloning
  5. Regulation of Genetic Engineered Animals – Statutory and Regulatory Authority
  6. FDA’s General Approach to Regulation of GE Animals
  7. FDA’s Approach for Food/Feed Safety Assessments Involving GE Animals
  8. Conflicts of interest
  9. References

ARTs have been used in animal agriculture for an extended period of time to improve performance of resulting offspring. ARTs range from minimal assistance to animals engaged in natural service through the more recent development of somatic cell nuclear transfer (SCNT), colloquially referred to as ‘cloning’ (Rudenko et al. 2004; Rudenko and Matheson 2007). Based on discussions with companies planning to clone livestock and recommendations from the National Academy of Sciences’ National Research Council (NRC 2002), FDA conducted a risk assessment for animal cloning (FDA 2008a). Following the conclusion of an extended risk assessment process in which animal health and food safety were evaluated, FDA concluded that food from clones and their sexually reproduced offspring was as safe to eat as food derived from animals resulting from conventional breeding. In addition, FDA found that animal health risks were qualitatively the same as those noted for other ARTs; though, they were generally noted at an increased frequency compared with frequency seen for other ARTs when they were introduced (FDA 2008a). Guidelines for health assessment of, and care for, animal clones, prepared by an international body of scientists (through the International Embryo Transfer Society, IETS), provided a framework for animal health risk management for animal cloning (IETS 2008). Based on its risk assessment, the FDA concluded that there were no further scientific concerns in need of addressing, and food from clones and their sexually produced offspring need not be subject to further regulation beyond that applicable to food from conventionally bred animals of the species that were examined (FDA 2008b). Given no new information has arisen to alter these conclusions, at this time, FDA feels these conclusions are still appropriate. FDA continues to monitor scientific literature to keep abreast of recent developments with the technology and provides technical assistance to government agencies within and outside the US on the scientific issues association with cloning.

FDA’s scientific findings are generally consistent with findings of authorities from other countries (Food Standards Australia New Zealand 2003, 2010; New Zealand Food Safety Authority, undated; European Food Safety Authority 2008; Japan: Watanabe 2011 & Ito and Watanabe 2011). Recently, officials from Argentina, Brazil, Paraguay, New Zealand and the United States signed a document in support of the scientific findings of these comprehensive risk assessments on animal cloning (USDA Foreign Agricultural Service 2011).

Regulation of Genetic Engineered Animals – Statutory and Regulatory Authority

  1. Top of page
  2. Contents
  3. Introduction
  4. Animal Cloning
  5. Regulation of Genetic Engineered Animals – Statutory and Regulatory Authority
  6. FDA’s General Approach to Regulation of GE Animals
  7. FDA’s Approach for Food/Feed Safety Assessments Involving GE Animals
  8. Conflicts of interest
  9. References

Genetic engineering is a process in which rDNA technology is used to introduce desirable traits into organisms. FDA defines a GE animal as one that contains an rDNA construct to introduce new traits. Although more conventional breeding methods have long been used to propagate desirable traits in animals, genetic engineering is a much more targeted and powerful method of introducing traits into animals.

FDA regulates GE animals under the new animal drug provisions of the Federal Food, Drug and Cosmetic Act (FD&C Act), and the National Environmental Policy Act (NEPA). The FD&C Act defines drugs as ‘articles (other than food) intended to affect the structure or any function of the body of man or other animals’. The rDNA construct in the resulting GE animal is thus a regulated article that meets the drug definition; the GE animal itself is not a drug. As a shorthand, the agency sometimes refers to regulating the GE animal (FDA 2009).

Generally, under the FD&C Act, a new animal drug is ‘deemed unsafe’ unless FDA has approved a new animal drug application (NADA) for that particular use, unless the drug is only for investigational use and conforms to an Investigational New Animal Drug (INAD) exemption under the FD&C Act and implementing regulations. FDA regulations concerning NADA approval are codified at section 514 of the Code of Federal Regulations (21 CFR 514). FDA regulations concerning exemptions for investigational use of new animal drugs are codified at 21 CFR 511.1. Among other things, INAD regulations cover shipments in interstate commerce of new animal drugs for tests in vitro and in laboratory research animals (21 CFR 511.1(a)) and for clinical investigation in animals (21 CFR 511.1(b)). The INAD requirements in 21 CFR 511.1(b) apply to investigational GE animals. Further, the development of GE animals constitutes clinical investigation, because it involves studying the effectiveness of the drug in the target species and the effects of the rDNA construct, including those of its expression product(s), on the animal containing it. GE animal sponsors carry out their investigation towards NADA approval under an INAD exemption.

In January 2009, the FDA issued a final guidance for industry on the regulation of GE animals (FDA 2009). In this guidance, FDA defined ‘GE animals’ as those animals modified by rDNA techniques, including all progeny that contain the modification. The term GE animal can refer both to animals with a heritable rDNA construct and to an animal with a non-heritable rDNA construct (e.g. a construct intended as therapy for a disease in that animal). The guidance explains further FDA’s statutory and regulatory authority with respect to GE animals, investigational use of GE animals, and NADA approval of GE animals. The guidance places into context recommended processes for GE animal sponsors and how the processes overlay on the general statutory and regulatory requirements for NADA approval.

Though all GE animals are subject to FDA regulation, FDA may exercise enforcement discretion with regard to INAD or NADA requirements for certain GE animals, based on the risk(s) these animals pose (FDA 2009). These consider non-food species of animals and may include: (i) GE animals subject to regulation by other government agencies or entities; (ii) GE animals raised and used in contained and controlled conditions such as GE laboratory animals used in research institutions; and (iii) GE animals intended for commercialization, depending on evaluation of factors related to human, animal or environmental risks. FDA asks the following questions when considering whether to exercise enforcement discretion: (i) Is there anything about the article itself that poses human, animal or environmental risks? (ii) In the event of environmental release, does the GE animal pose any more of an environmental risk than its non-GE counterpart? (iii) Are there concerns over the disposition of GE animals that could pose human, animal or environmental risks? and (iv) Are there any other safety questions not adequately addressed by the GE animal sponsor?

Below is a description of FDA’s approach to regulating GE animals, first as a brief overview of the process, then a more in-depth description to the approach for evaluating food safety for GE animals. Enforcement discretion is not discussed further, given food animals are not subject to this process.

FDA’s General Approach to Regulation of GE Animals

  1. Top of page
  2. Contents
  3. Introduction
  4. Animal Cloning
  5. Regulation of Genetic Engineered Animals – Statutory and Regulatory Authority
  6. FDA’s General Approach to Regulation of GE Animals
  7. FDA’s Approach for Food/Feed Safety Assessments Involving GE Animals
  8. Conflicts of interest
  9. References

Risk-based approach to assessing GE animals

FDA developed a hierarchical risk-based approach to assess GE animals and their edible products (Fig. 1). The general types of data and information considered to address risk questions specific to each step in the hierarchical pathway are outlined in Table 1. This approach does not rely on a single ‘critical’ study, but rather on the cumulative weight-of-evidence provided by all of the steps in the review. It is risk-based because it examines both the potential hazards (i.e. components that may cause an adverse outcome) identified at each step and the likelihood of harm among the receptor populations (i.e. those individuals or populations exposed to the GE animal(s) or their products). Each step addresses not only risk questions specific to that particular step, but also characterizes hazards for subsequent steps in the process. Even though the risk assessments are presented as discrete steps in the hierarchy, some steps have an overlap of required data and information such that sponsors and FDA compile and review data and information of multiple steps concurrently.

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Figure 1.  Review hierarchy for FDA’s risk assessment for GE animals

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Table 1.   Data considered in FDA’s review process for GE animals
Review levelData and information examined
Product definitionCommon name, genus and species; name of GE animal lineage; name of rDNA construct, ploidy and zygosity, number of copies and location; claim, use conditions and restrictions
Molecular characterization – constructPurpose of GE event; source of DNA, details on how construct assembled; function(s) and sequence of introduced DNA; purity prior to initial introduction into cell or animal
Molecular characterization – animalMethod used to introduce rDNA into initial GE animal; whether animal is chimeric; breeding strategy to produce lineage progenitor (from which animals intended for commercialization are derived); genomic location(s) of rDNA insertion; flanking sequences and whether rDNA insertion is in active transcriptional region; final stabilized structure of the rDNA construct(s); copy number
Phenotypic characterizationintroduced trait(s); toxicity; animal observations (e.g. health, veterinary, therapy, growth, lactation, reproduction and behaviour); physiological status (e.g. blood chemistry, haematology, gross and histological pathology
Durability planConsistently inherited DNA construct and expressed trait over multiple generations; plan for maintaining equivalence of the marketed product with genotype and phenotype of approved GE animal; basis for post-approval reporting requirement (e.g., quantity of GE animals produced, adverse events, changes made to GE animal)
Environmental safetyGenotype/phenotype/general biology of GE animal; potential for escape/release and spread of GE animal; physical/biological confinement (if any); potential accessible ecosystems and characteristics
Food/Feed safetyAnimal health/physiology; toxicity/allergenicity of new substances present in edible products; key compositional parameters of edible products; analytical method
Claim validationData/studies on expressed trait(s) to support ‘effectiveness’ of rDNA construct

The hierarchical, risk-based approach is, in general, ‘event-based.’ An event can be defined as the result of an insertion(s) of an rDNA construct following the specific introduction of the rDNA into a target cell or organism. Animals derived from different events, even if they are based on the previously approved construct(s), require separate evaluations.

Approaches using ‘weight-of-evidence’ have been previously described in various other fields of study (Hill 1965; Krimsky 2005; Daly et al. 2007). In the weight-of-evidence evaluation of GE animals, FDA employs an adaptation of the Hill Criteria (Hill 1965) and draws on data from a number of sources (Table 2). These include the following, listed in rank order (from highest to lowest) of importance in the overall weight-of-evidence evaluation: (i) controlled studies conducted on the specific animals being considered for approval; (ii) other non-controlled studies on these same animals; (iii) historical records and data for these animals; and (iv) studies reported in the scientific literature investigating these same animals or their relatives. Each source, in turn, is given appropriate deference with respect to its relevance to the risk or hazard identification question under consideration. Irrespective of the source or order of deference given to a given data set, all of the data and information are evaluated in the context of basic scientific principles and external validity.

Table 2.   Weight-of-evidence evaluation for GE animals
General considerations for evaluating all evidence
Basic principles of science (biological plausibility)
External validity
Order of deferenceDescriptionConsiderationsExample
1Controlled studies Final structure of rDNA Construct Same animal lineage Internal validityStudy quality Generation of animals Relevance of endpoint to risk questionLarge double blind Use of ‘Good Study Practices’ Full data set Agreed study design
2Non-controlled studies Same animal lineage Same rDNA constructStudy size/duration Study quality Generation HusbandryPilot study Very small study Different endpoint Summary data only No study design or design not followed
3Historical data Same lineage animal Same rDNA construct ‘Epidemiology’ studyGeneration HusbandryNot ‘formal study’ Laboratory/cage records Incomplete records
4Studies on similar or related animals or constructs Different rDNA copy number/eventDegree of similarity Related article Related animalDifferent species Different gene confers same phenotype Other regulatory elements in rDNA construct

Team-based review

The assessment of an application for approval by FDA is performed by an interdisciplinary team of agency subject-matter experts drawn from across the Centre. In general, these teams include molecular biologists, animal scientists, veterinarians, toxicologists, chemists, statisticians, risk assessors and other specialists, as required by the technical nature of each component of the hierarchical review process and embraces/is consistent with aspects of an interdisciplinary approach recommended in ‘New Biology’ (NRC 2009). In general, this interdisciplinary team is assembled as sponsors begin their interactions with FDA. Depending on the nature of the submission, in-depth reviewers (at least two) are assigned to each submission, each of whom prepares an initial individual evaluation of the data and information. For example, the components that address the characterization of the construct generally have molecular biologists acting as in-depth reviewers, while the phenotypic characterizations could have veterinarians, animal scientists and statisticians as in-depth reviewers. The evaluations performed by the in-depth reviewers are presented to the full team; the entire team acts as a peer-review panel for the in-depth reviewers’ evaluations. Following discussion, the in-depth reviewers prepare a written review, again subject to peer review.

Real-time, entire life cycle review

FDA’s approach for review of GE animal applications over the entire life cycle of the particular application involves real-time review of supporting data and information. Review over the entire life cycle means that the interdisciplinary team assigned to the application continues to be involved in data review during all pre- and post-approval regulatory activities. ‘Real-time’ review means that data and information are evaluated by FDA early in the development process for the product. This often occurs as soon as data are collected to address the risk questions for a particular step of the overall review process, as opposed to submission of data late in the process that may occur for more traditional new animal drug applications. For real-time review to be most effective, GE animal sponsors and FDA actively engage in discussions on the appropriate scientific questions to address for a particular section of the application, and how best to address these questions as sponsors build their data packages for FDA review. This often represents an iterative process of communications during development, submission and review of a particular data package. Although appearing to have the initial effect of lengthening the duration and affecting the predictability of the review outcome, FDA expects to develop a more efficient review process by ensuring that the appropriate data are generated as the GE animals are developed, rather than needing to reprise studies or identify new issues late in the process.

FDA’s Approach for Food/Feed Safety Assessments Involving GE Animals

  1. Top of page
  2. Contents
  3. Introduction
  4. Animal Cloning
  5. Regulation of Genetic Engineered Animals – Statutory and Regulatory Authority
  6. FDA’s General Approach to Regulation of GE Animals
  7. FDA’s Approach for Food/Feed Safety Assessments Involving GE Animals
  8. Conflicts of interest
  9. References

For animal species traditionally used as food, FDA assesses risk to address the issue of whether food or feed from the GE animal poses additional risks to humans or animals consuming edible products from GE animals vs appropriate non-GE comparators. This applies to GE animal applications related to food (agriculture) and non-food (e.g. biomedical) uses of the various food animal species. The food/feed safety assessments are different for GE animals based on whether the animals themselves are intended for food or non-food uses. In general, non-food use risk assessments rely heavily on the degree of containment the sponsor has in place to ensure that the GE animals will not enter the food supply.

Subsequent discussion on food/feed safety evaluation focuses on GE animals whose edible products are intended for introduction into the human food or animal feed supply. Multiple steps in the hierarchical pathway serve to identify and characterize hazards to animals, humans or the environment. For example, the molecular characterization steps serve to identify potential toxins or allergens for consideration in the food/feed safety assessment. However, to focus the remainder of this manuscript, particular attention in subsequent sections is placed on relationship of animal health (phenotypic characterization) and food/feed safety, as well as on the food/feed safety risk assessment process itself.

Phenotypic characterization of the GE animal

Several steps in the hierarchical pathway may serve to identify and characterize potential food/feed safety hazards. Because of the reliance of food safety on animal health, the assessment of animal health is an integral part of FDA’s food/feed safety risk assessment in GE animals. A critical prerequisite to safe food/feed from edible products of food animals is that those animals be healthy. As such, the phenotypic characterization of the GE animal provides important information to identify and characterize potential hazards to consider during food/feed safety evaluation of the GE animal.

A critical component of this analysis is the identification of the actual lineage of GE animals being evaluated. Part of FDA’s process is the identification of the lineage progenitor, and the identification and characterization of the stabilized rDNA construct in the lineage of animals being considered. This is critical because other lineages derived from the initial GE animal may be discarded as part of the development process. These ‘discarded’ animals may have different phenotypes from the ones considered for approval (and subsequent commercialization should approval be granted), which are not germane to the potential risks that may be present in the commercialized lineage.

In the phenotypic characterization step, FDA seeks to determine whether production of the lineage of GE animals intended for commercialization poses any public health risks, including food/feed safety. It does so by evaluating the expression of the introduced trait and its effect(s) on the resulting GE animal. First evaluated are the data that characterize whether the rDNA construct or its expression product(s) cause direct toxicity – that is, whether there are adverse effects attributable to the intrinsic toxicity of the construct or its expression product(s). Indirect effects are also evaluated (indirect effects are those that may be caused by perturbation of physiological systems by the construct or its expression product(s) (e.g. the expression product may change the expression level of another protein). In general, FDA recommends that sponsors compile and submit data and information addressing the health of the GE animals, including veterinary and treatment records, growth rates, lactation, reproductive function and behaviour. In addition, FDA recommends that data on the physiological status of the GE animals, including clinical chemistry, haematology, histopathology and gross pathology be submitted for evaluation.

Food/Feed safety risk assessment

As part of the food/feed safety risk assessment of GE animals, FDA takes into consideration potential food/feed safety hazards identified and characterized in other steps of the hierarchical pathway, for example, animal health evaluation as part of phenotypic characterization. Assuming that the GE animals are healthy, FDA focuses the food/feed safety assessment on the safety of new substance(s) present in food and a compositional analysis of edible products from GE animals. FDA’s approach to assessing food/feed safety is consistent with international standards for food safety assessment for foods from GE animals (Codex Alimentarius 2009).

Given the FD&C Act defines food in part as ‘articles used for food or drink for man or other animals’, FDA standards for food safety apply similarly to human food and animal feed. FDA’s standard for food safety – reasonable certainty of no harm – applies equally to food from animals or plants. Thus, the same safety standard applies whether an evaluation is conducted by the Centre for Food Safety and Applied Nutrition under the food additive provisions of the FD&C Act or by the Centre for Veterinary Medicine under the new animal drug provisions of the FD&C Act. It is important to understand that the safety of any food, including foods derived from GE animals, cannot be established with absolute certainty. Foods derived from GE animals are assessed by evaluating relevant similarities and differences between the edible products from GE animals and appropriate non-GE comparators. By comparing relevant safety and nutritional parameters, FDA draws a conclusion as to whether the edible products from the GE animal are as safe as those derived from conventionally bred animals currently safely consumed.

Food/feed safety risk questions can be divided into two overall categories. The first asks whether there is any direct toxicity, including allergenicity, via food or feed consumption associated with the expression product of the construct or components of the construct. The second category of questions addresses potential indirect toxicity associated with both the rDNA construct and its expressed product (e.g. will expression of the rDNA construct affect physiological processes in the resulting animal such that unintended food/feed consumption hazards are created, or existing food/feed consumption risks are increased). Potential adverse outcomes via the food/feed exposure pathway can be identified by (i) determining whether there are any biologically relevant changes to the physiology of the animal evaluated in part during phenotypic characterization and (ii) whether reasons for food safety concerns (e.g. nutritional or toxicological) are suggested by any biologically relevant changes in the key compositional parameters of edible products from the GE animal compared with those from the appropriate non-GE comparator.

As part of the food/feed safety assessment, regulatory method(s) are developed for the GE animals in question. A regulatory method is an analytical method that enables determination of the residues of the article regulated as a new animal drug in food-producing animals. In general, an analytical method is developed by a GE animal sponsor, and the FDA performs its own validation of the method. Following approval, the FDA-validated method serves as the regulatory method for that GE animal. The predominant regulatory method for GE animals is one of identity, but in some cases a regulatory method may be needed to assure that a residue is below an FDA-established tolerance level. When developing regulatory methods for identity, GE animal sponsors consider the ability of the method to: (i) identify the rDNA construct in the approved GE animal (or its edible products) in a mixed population of animals; (ii) discriminate the approved GE animal from a ‘knockoff’, that is, a GE animal that may bear similarities to the approved one, but does not contain the approved rDNA construct at the approved integration site; (iii) detect changes in the stability of the rDNA construct as inserted in the animal to demonstrate stability over time – FDA may need to revisit previous findings relative to food/feed safety if changes occur that present new food/feed safety hazards; and (iv) be robust in nature such that their use at multiple regulatory laboratories does not require additional specialized training or equipment. To date, analytical methods proposed by sponsors have employed molecular biological techniques such as polymerase chain reaction.

Challenges/Future considerations

Animal biotechnology has considerable potential to help meet future worldwide demands for secure food. With this promise, are several challenges that need to be addressed from all sectors involved with the development, regulation and dissemination of products resulting from this technology. A key issue for many new technologies subject to regulation is that there is a lag between the initial implementation of the technology and the development of regulatory frameworks to evaluate those technologies. This is not surprising given that developing a risk-based framework for all of the products of that technology is difficult, and the extent to which such a framework would be suitable for any particular application is unclear. Thus, regulatory review of the first (or first few) products is often protracted and causes uncertainty for the sponsor, investors, the public and other stakeholders. Another major challenge is the need for regulatory bodies to focus on the actual risk(s) that may be posed by the GE animals intended for commercialization rather than on issues that are of importance for understanding the underlying science but are not relevant to questions of regulatory approval.

Additionally, the FD&C Act states that a new animal drug is ‘deemed unsafe’ unless FDA has approved a new animal drug application (NADA) for that particular use. Although this provides the legal basis to compel GE animal sponsors to develop data packages relevant for obtaining NADA approval, this provision should not be used to make the assumption that products derived from this technology (or any technology) are inherently unsafe or dangerous. In other words, regulators are best served when implementing this part of the statute by proceeding from a ‘neutral’ position on safety when formulating relevant, science-based risk questions for safety evaluation. By making the distinction between the statutory definition of ‘unsafe’ and the lack of demonstration of safety via sponsor-generated data to address relevant safety/risk questions, FDA can most effectively communicate that FDA’s regulatory framework permits approval of safe and effective products of animal biotechnology (when the data so supports such a decision), and allay concerns and bolster confidence from the public.

Communication is also crucial at many levels as animal biotechnology evolves and becomes assimilated into food production systems. The scientific community and sponsors of the technology have traditionally communicated with federal regulatory bodies to determine whether and how a particular technology is to be regulated. This sort of communication is essential if the agency is to be aware of new developments so as to be prepared to evaluate them. Communicating with the public, however, presents a different set of challenges. In their roles as neutral arbiters of the product(s) of any technology, regulatory agencies need to emphasize their roles as competent interpreters of the underlying science and rigorous evaluators of potential risks to foster public confidence in the regulatory process without being seen as promoters of the products they regulate.

References

  1. Top of page
  2. Contents
  3. Introduction
  4. Animal Cloning
  5. Regulation of Genetic Engineered Animals – Statutory and Regulatory Authority
  6. FDA’s General Approach to Regulation of GE Animals
  7. FDA’s Approach for Food/Feed Safety Assessments Involving GE Animals
  8. Conflicts of interest
  9. References