Federal docket number: FDA-2015-N-3403
COUNCIL FOR RESPONSIBLE GENETICS’ RESPONSES TO REQUEST FOR INFORMATION PUBLISHED AT 80 FED. REG. 60,414 – 60,416 (Oct. 6, 2015):
“Clarifying Current Roles and Responsibilities Described in the Coordinated Framework for the Regulation of Biotechnology and Developing a Long-Term Strategy for the Regulation of the Products of Biotechnology”
The Council for Responsible Genetics (“CRG”) is a thirty-two year old science-based nonprofit whose mission is to represent the public interest and foster public debate about the social, ethical and environmental implications of genetic technologies. CRG welcomes the Obama Administration’s initiative to modernize the regulatory system for biotechnology products. As the White House’s July 2, 2015 Memorandum (“Memorandum”) correctly states, this regulatory system “must protect public health, welfare, safety and our environment....” Memorandum, p. 1 (emphasis added). CRG herewith submits its responses to the Notice of Request for Information, 80 Fed. Reg. 60,414 – 60,416 (Oct. 6, 2015) (“RFI”), within the context of this mandatory purpose of the regulatory system, and in light of CRG’s mission of fostering public understanding of, and democratic participation in, decisions concerning the uses and implications of genetic technologies.
These responses target each of the following facets of questions (“Q”) 1 - 5 (at 80 Fed. Reg. 60,416): (Q1 and Q2) the additional clarification that could and should be provided to the public regarding the biotechnology product areas that are within the statutory authority and responsibility of the FDA, USDA, and EPA, and the roles those agencies play in exercising such authority and responsibility; (Q3) how the Federal agencies can improve their communication to the public regarding the bases for their decision-making used to ensure the safety of the products of biotechnology; and (Q5) specific issues that should be addressed in the update of the Coordinated Framework or in the long-term strategy to ensure that the Federal regulatory system is equipped to assess efficiently the risks, if any, associated with future products of biotechnology while protecting health and the environment, maintaining public confidence in the regulatory process, and increasing transparency and predictability. In the course of these responses, we will refer to certain relevant data and information (Q4).
I. The government could and should clearly inform the public not just of the biotechnology product areas for which the Federal agencies have statutory authority and responsibility, but of the areas for which the agencies either do not have such authority and responsibility, or choose not to exercise it. (Response to Q1 and Q2)
A. Although the government asserts it has authority to regulate foods from genetically engineered plants, it does not do so.
The FDA publicly asserts that it “regulates the safety of food for humans and animals, including foods produced from genetically engineered (GE) plants;” and that, “[f]oods from GE plants must meet the same food safety requirements as foods derived from traditionally bred plants.” What the FDA could and should clearly state to the public is that,
1. because FDA considers foods produced from GE plants to be identical, or at least substantially equivalent, to foods derived from traditionally bred plants, FDA presumes that GE-plant derived food is safe;
2. because FDA presumes all GE-plant derived food is safe, FDA has chosen not to exercise its regulatory authority to require that any GE-plant derived food be proven to be safe prior to its introduction to the market;
3. because FDA has offered developers of GE-plant derived food the opportunity to voluntarily consult with FDA concerning the safety of such food, FDA has presumed—and has assured the public--that all such food has been subject to the consultation process, even though there is no legal consequence to developers for failing to consult with FDA;
4. the FDA does not make an independent pre-market determination of the safety of GE-plant derived food, and relies on the determination of safety made by the developer and based on the information the developer has decided to provide, or not provide, to the FDA during the voluntary consultation process if there is one;
5. the FDA has chosen to exercise its role in ensuring food safety and wholesomeness by relying on the producer’s legal duty to assure the quality of the food it brings to market; but
6. the FDA does no monitoring of or for any genetically engineered foods that have entered the market; and
7. the FDA has concluded that all genetically engineered foods on the market are safe because it has no evidence of adverse health effects suffered by consumers as a result of eating GE foods, even though (a) proof of food-related health effects is difficult, even when those effects are acute, but especially when they are sub-acute and due to long-term exposures, and (b) even if consumers or animals suffer such health effects, they would have difficulty linking them specifically to GE foods because the FDA has chosen not to require labeling of GE foods or foods containing GE ingredients.
In short, although the FDA asserts that it has the authority and responsibility to regulate GE-plant derived food for humans and animals, it has chosen not to do so either before or after that food goes to market. Rather, FDA relies on the lack of evidence that such food poses any short or long-term safety or nutritional problems, even though FDA neither exercises any regulatory authority to look for such evidence or require that it be submitted; nor provides consumers with any information based on which they and their doctors could readily identify potential problems.
B. Although the government asserts that it regulates genetically engineered plants based on the product and its intended use, and not on the process used to engineer the product, sometimes it does not regulate plants based only on the process used to engineer the product.
USDA does at least exercise some level of mandatory pre-market review of genetically engineered plants (as well as certain other organisms) pursuant to its statutory authority under the Plant Protection Act. For the plants it regulates, such review can be as little as notification to USDA regarding GE plants that the plant proponent contends meet eligibility criteria and performance standards established by USDA; to a petition seeking a determination by USDA that the GE plant be deregulated, and therefore not subject to further USDA regulatory authority; to a full-blown application for a USDA permit approving (potentially with conditions) the introduction of a GE plant that poses a plant pest risk. What the USDA could and should clearly state to the public is that,
1. the USDA limits the exercise of mandatory regulatory oversight to genetic engineering involving plants and other organisms that fall within the legal definition of a “plant pest;”
2. there are many genetic engineering processes applied to plants that involve methods and organisms that do not fall within the legal definition of a “plant pest,” such as the use of a “gene gun” to inject genetic material from a species that is not a “plant pest” into the cells of the target plant;
3. therefore, there have been and will be many GE plants that are not subject to any USDA regulatory oversight at all;
4. if these GE plants are not intended for use as human or animal food, they are not even subject to the FDA’s voluntary consultation process for GE plants.
In short, although the federal regulatory system for biotechnology products is often characterized as focusing on the “product not the process,” the determination whether many GE plants are subject to government regulation is in fact based on the genetic engineering process used to create the product.
C. Although the government asserts that it has the authority and responsibility to regulate genetic modification of all animals for safety, effectiveness, and environmental impact, FDA does not currently necessarily do so.
The FDA has asserted regulatory authority over all genetically engineered animals, without regard for the intended use of such animals, because it considers genetic engineering to involve the introduction of new DNA intended to affect the structure or function of the subject animal. The introduction of new DNA into an animal (“rDNA construct”) falls within FDA’s jurisdiction over “new animal drugs” (“NAD”).  As such, with certain limited exceptions, the law requires that a New Animal Drug Application (“NADA”) be submitted to and approved by FDA before a GE animal may be introduced in interstate commerce. Otherwise, applicable law mandates that the NAD (i.e., the rDNA construct) is deemed to be unsafe. As a condition of approval, the FDA can require that the NADA include all information and data concerning the rDNA construct’s safety and effectiveness, including an explanation of any omission of reports from any investigator to whom the rDNA construct was made available, and an environmental assessment. What the FDA could and should clearly state to the public is that,
1. notwithstanding the statutory provision that, except under limited circumstances, a GE animal must be submitted to FDA pre-market review and approval, the FDA reserves the discretion not to require this statutory review and approval process;
2. notwithstanding the statutory provision that mandates that a GE animal be deemed unsafe if it has not been the subject of an approved NADA, the FDA reserves the discretion to declare such an animal to pose no “clear risk to the public health” even though no NADA was even submitted, no less approved;
3. rather than requiring the proponent of an animal rDNA construct to provide affirmative evidence of the safety and degree of environmental risk of introducing the rDNA construct through the genetic engineering of an animal, the FDA has dispensed with regulatory oversight of a GE animal based on the lack of evidence that such an animal is unsafe or poses an environmental risk.
In short, although the FDA asserts that all GE animals are subject to a mandatory NADA submittal and approval process, FDA reserves the discretion to circumvent that process, and has in fact done so.
D. Although the government has the authority to monitor the safety and environmental impact of genetically engineered plants, animals, and other organisms, it has no regular program in place to do so.
In its 1992 policy statement regarding foods derived from GE plants, the FDA stated that it is the food producer’s “clear legal duty...to assure the safety of foods they offer to consumers...,” and that this duty “is backed up by [FDA’s] strong enforcement powers....” Where, as with GE-derived foods, the food is not subject to a mandatory pre-market safety review and approval process, FDA’s food safety regulatory authority is basically limited to its “post-market authority of section 402(a)(1) of the [FFDCA] (21 U.S.C. 342(a)(1)).” Under this section, which defines as “adulterated” any food that contains a poisonous or deleterious substance in such quantity as to make the food injurious to health, the FDA can remove unsafe foods from the market. Food producers can also be subject to criminal sanctions and civil liability for having marketed such unsafe foods. Hence, the food producer theoretically has strong legal and economic incentives to assure the safety of the food brought to market.
The problem with this model of food system safety is that there is virtually no government post-market monitoring to determine whether the producer of GE-derived foods is complying with its duty, even where that compliance can be easily determined. For example, the federal government does little or no post-market food safety monitoring of the crops that have been engineered to be “herbicide tolerant” (“HT”), and which have been found by independent studies to have higher levels of herbicidal residue than non-GE crops; or of the crops that have been engineered to generate, and which themselves contain, a variant form of the insecticidal Bacillus thuringiensis (“Bt”)., Yet, these constitute the overwhelming majority of genetically engineered plants and GE-derived food, and have, after years of unmonitored use, resulted in, among other things, the evolution of herbicide resistant weeds and Bt resistant insects. And, because there has been absolutely no meaningful monitoring of GE-derived foods, it will be difficult for the government, no less the people who have been consuming these foods, to draw conclusions about possible health impacts legally sufficient to impose on the food producers any post-market accountability for possible detrimental health impacts from these foods. Without such accountability, there is no meaningful incentive for developers and producers of genetically engineered foods to assure that their products are not compromising food safety.
With respect to GE animals, the FDA likewise has no plans to institute a post-market monitoring program. Rather, with respect to the safety and effectiveness of new rDNA constructs in animals, the FDA intends to rely exclusively on the NADA’s predictive accuracy of stability in the animal over time. There is apparently no plan to monitor the effectiveness of containment measures, the inadvertent introduction of GE animals into the food system, or the ecological impact of any release (accidental or intentional) of a GE animal into the environment.
II. The government should establish a single information clearinghouse for biotechnology products. (Response to Q3)
The present federal regulatory system for biotechnology products is a confusing mix of roles and responsibilities which is neither legally straightforward nor intuitively clear. Regulatory authority is asserted by FDA over GE plants insofar as they are intended for use as food. The USDA exercises regulatory authority over genetic engineering of plants and organisms only insofar as legally defined “plant pests” are involved. EPA has authority with respect to GE products under FIFRA only insofar as pesticides may be applied to them or generated by them, but not with respect to the products themselves; and under TSCA, only with respect to legally defined “new” microorganisms. With respect to GE animals, FDA asserts authority based on the characterization of genetic engineering as a “new drug” affecting the structure or function of the subject animal. In some cases, the government asserts that its focus is on the “product not process,” while in other cases (e.g., USDA’s “plant pest” authority; FDA’s “new drug” authority), the process plays a clear role in the agency’s approach to regulation. And, as discussed above, although the government asserts regulatory authority over biotechnology products as a matter of law, the reality is that many biotechnology products are not subject to legally required government review and approval as a matter of fact.
Although the various relevant agencies make an effort to communicate to the public regarding the bases for their decisionmaking regarding biotechnology products, one has to navigate from one website to another, and within websites, to try to determine what if any responsibility for and action concerning a biotechnology product or product area the government will take or has taken. Furthermore, readily available information regarding some of the most pressing questions with which the public is concerned is often opaque. For example, regarding the safety of foods derived from GE plants, “Are foods from GE plants safe to eat?”, the FDA says simply, “Yes. Credible evidence has demonstrated that foods from GE plant varieties marketed to date are as safe as comparable, non-GE foods.” There is no identification of what this evidence is, or its pertinence to any particular GE plants or derived foods, nor a reference to where such information may be found. Is the evidence that GE plants are safe to eat based on general principles or based on a specific review of the foreign gene constructs, the review of micronutrients before and after the genetic modification, and the review of any pleotropic effects from gene-gene interactions from the promoters?
The patchwork regulatory framework, spread among multiple agencies multiplied by numerous statutory provisions and differing agency approaches taken to products and areas of products, promotes public confusion and lack of confidence. Clear, accurate, and accessible communication with the public would therefore greatly benefit from establishment of a single clearinghouse of information regarding such products. The clearinghouse should be staffed by knowledgeable scientific, legal, policy, and communications professionals who can help the public navigate government actions concerning the science, law, and policy relevant to biotechnology products. Such information should be made available through a website devoted exclusively to biotechnology products. Transparency of the regulatory process will go a long way to reducing false impressions about what is and what is not reviewed.
III. The government should plug the regulatory gaps that presently exist as a consequence of how the agencies have implemented the Coordinated Framework, while working, in the long-term, to overhaul the Coordinated Framework in favor of a unitary Federal approach to the regulation of the products of genetic engineering. (Response to Q5)
A. The FDA should implement mandatory review of genetically engineered foods, and require that all GE foods and foods containing genetically engineered ingredients be labeled.
With respect to biotechnology products in our food system, one of the fundamental failures in the existing regulatory system was identified by the FDA itself almost fifteen years ago. In January, 2001, FDA proposed a rule that would have, for the first time, legally required pre-market notification and data submission to FDA with respect to new plant-derived bioengineered foods. Since the implementation of the Coordinated Framework, there has been only a voluntary process that encourages biotech developers to “consult” with FDA regarding the safety of new plant-derived bioengineered foods. That voluntary process involves the GMO developer’s submittal of a summary of the results of the developer’s own research in support of the developer’s conclusion that the plant or food is safe. FDA is relegated to review of the summary and expression of any questions or reservations concerning the developer’s conclusion based on the summary submitted. The FDA does not independently reach its own determination whether the food is safe or unsafe. Nor does the FDA have authority to require that all research conducted by the developer be submitted, in its complete form. Nor is there public input into the review process. And, since the consultation process is voluntary, a GMO developer can legally introduce the food into the market without going through the process at all. The public can have no confidence that such a process ensures the safety of these products in the food system. Indeed, the public cannot even have confidence in the FDA’s oft-repeated assertion that no biotech food product has entered the food system without having completed the consultation process, since the process itself is voluntary, and the FDA does no monitoring whatsoever of foods on the market for genetic modification.
At a minimum, the 2001 FDA Proposed Rule should be immediately promulgated. Among other things, that rule would require that: FDA is notified of bioengineered food that will enter commercial distribution, including affirmation that the food is safe; the intended use of the food complies with FFDCA; relevant data will be made available to FDA on request; affirmation that the notification is a representative and balanced submission that includes both favorable and unfavorable information pertinent to evaluation of safety, nutritional, or other regulatory issues associated with the food; a list of the identities and sources of introduced genetic material; expected significant changes in the composition or characteristic properties of food derived from the plant as a result of the transformation event, regardless of whether the changes result from insertion of new genes or from modification in the expression of endogenous genes; full description of the transformation method, including information on unintended proteins that could be expressed; an estimate of the dietary exposure to substances introduced in, or modified in, the food, or an explanation of the basis for any conclusion that an estimate of dietary exposure is not needed to support a conclusion of safety.
In addition, FDA should develop standardized protocols for testing bioengineered food, for both acute and possible sub-acute health impacts. Tests submitted by food developers should be reviewed for consistency with those protocols. And, if a developer asserts that its product qualifies for the GRAS (“generally recognized as safe”) exemption for food additives, the FDA should require that such assertion be supported by studies published by refereed journals, with greater weight given to studies conducted by scientists without a conflict of interest such as receipt of funding from the developer or other product proponent. All studies relied on as the basis for GRAS status, including the underlying data, should be available to the public.
Finally, FDA should define what it means for food to contain genetically modified or foreign (not natural to its species) genes and require that all GE foods, and foods containing genetically engineered or foreign genetic ingredients, be labeled as such. The lack of mandatory FDA review of all such GE food products, FDA’s failure to legally mandate that it be informed of all studies conducted by or with the knowledge of the food developer and not just those studies the developer chooses to submit in support of its safety evaluation, the lack of readily available information from the FDA concerning what foods consist of genetically engineered products, and the lack of readily available information concerning the basis for FDA’s continued assertions that GE food products on the market are safe (although FDA refuses to issue such a determination with respect to any such product that has been through the voluntary consultation process), have all undermined confidence in the safety of such foods among a significant percentage of the public. Furthermore, FDA takes the position that it is unaware of any safety issues arising from the consumption of GE food products, despite the fact that the cause of many foodborne illnesses are difficult to trace, and the ability to trace them to the GE constituents in food is virtually impossible when such foods are unmarked.
B. The USDA should exercise its authority under the Plant Protection Act to extend its mandatory regulatory requirements to all GE plants, not just genetic engineering involving “plant pests,” and should implement all of the USDA-OIG’s 2005 recommendations for increased information to be obtained prior to and during field testing of GE crops.
Under the Plant Protection Act, 7 U.S.C. § 7712(a), the USDA has the authority to regulate "any plant, plant product, biological control organism, noxious weed, article, or means of conveyance ... [where] the prohibition or restriction is necessary to prevent the introduction into the United States or the dissemination of a plant pest or noxious weed within the United States." (emphasis added) A “noxious weed” is defined as “any plant or plant product that can directly or indirectly injure or cause damage to crops..., livestock, poultry, or other interests of agriculture, irrigation, navigation, the natural resources of the United States, the public health, or the environment.” To date, the USDA has chosen to regulate GE-plants only under its “plant pest” authority, creating a gaping regulatory hole for any genetic modification that does not involve a “plant pest” as statutorily defined and limited. See, I.B. and fn. 4, above. The definition of “noxious weed” is clearly broad enough to encompass any genetically engineered plant, unless that plant is determined not to pose a threat to agriculture or natural resources. To plug the gaping regulatory hole created by the USDA’s cramped exercise of its authority, the USDA should immediately extend its mandatory regulatory requirements to all GE plants so it can assess any threat posed to U.S. agricultural interests and natural resources before such plants are released to the environment, and should assure that the 2005 recommendations of the USDA-OIG have been fully implemented for all GE plants.
C. The FDA should subject all GE animals with heritable rDNA constructs to the mandatory NADA submittal and approval process unless they meet the limited statutory exceptions provided under 21 U.S.C. § 360b(a).
Under the FFDCA, a new animal drug (“NAD”) must go through the pre-market NADA submittal and approval process unless it meets the limited statutory exceptions provided under 21 U.S.C. § 360b(a). Notwithstanding the clear statutory mandate, FDA has announced that, in its discretion, it will not require such review and approval for non-food animals in certain circumstances, including (i) when the GE animal is intended to be raised and used in contained and controlled conditions, and (ii) based on FDA’s informal evaluation of risk, such as the one made with respect to the Glofish intended to be sold as an aquarium pet. Not only is such exercise of discretion contrary to the law and policy underlying the FFDCA’s approach to NAD’s, experience has shown it to be unwise to base the decision to deregulate heritable genetic traits on intended use.
A similar decision was made with respect to StarLink (TM) corn, genetically engineered to express the Bt toxin. Because EPA could not rule it out as a potential human allergen, EPA permitted its release only for sale as animal feed or for industrial purposes, i.e., it was not intended for use as human food. Despite this limitation on intended use, residues from StarLink(TM) corn were later found to have entered the human food supply, with subsequent reports of allergic reactions and determination by EPA scientists that no Bt tolerance level could be set that would be adequately protective of the public health.
Similarly with heritable rDNA constructs in animals, FDA should not presume that just because such animals are not intended for use as human or animal food, or are intended for use only in a contained environment, that animals with the construct will not escape and/or be used in ways not intended. For example, the USDA-OIG has reported that between 2001 and 2003, 386 pigs which were the offspring of pigs genetically modified with cattle and human genes were released into the human food supply, contrary to the protocols for the study of these pigs. The government did not discover the unintended release until up to two years after the fact. Furthermore, dispensing with the NADA submittal process also means dispensing with the evaluation of the impact of the genetic modification on the welfare of the subject animal—an element of the safety analysis that FDA states should be part of the NADA approval process.
D. The FDA and USDA should implement a monitoring program intended to determine whether the pre-market safety and environmental assessments, and conditions of use, that form the basis of approval and/or deregulation of biotechnology products are borne out by experience, and to identify any unintended adverse consequences or benefits resulting from the use of the products.
There remains significant controversy among reputable scientists and health professionals about the safety of consuming the products of genetic engineering as food. Safety concerns include the possible health effects of the intended modification of the food in question, such as the pesticide-related traits for which most commercially available GE-derived foods have been engineered. In addition, concerns extend beyond those raised by the intended effects of genetic engineering, to encompass the unknown and unintended effects on the modified organism caused by (i) the modification technologies themselves, and (ii) the interaction between the altered gene, the entire genome of the organism, and the larger environment, all of which may affect how the modified gene expresses itself and how the modification affects the entire organism. Even the FDA has opined that the processes of genetic engineering can create unintended effects that draw into question the presumption that the resulting food product is not materially different from its unmodified precursor. It goes without saying that if the government is not conducting post-market monitoring of the presence, dietary intake, and potential health effects of intended genetically engineered traits, it certainly is not conducting such monitoring of unintended effects of genetically engineered foods.
In addition, monitoring is necessary to identify environmental impacts that may result from the way biotechnology products are handled once they are in the hands of the intended users, or are released to the environment. For example, a thoughtfully designed monitoring program would likely have led to earlier notification of the now rampant problems of glyphosate resistance among weeds, and glyphosate and AMPA incidence in surface water, groundwater, and precipitation. Use modification measures could have been implemented that would have mitigated these impacts.
The inadequacy of present monitoring, and reporting of what is and is not monitored, has been the subject of repeated reports of the Government Accountability Office, USDA Office of the Inspector General, and the National Academy of Sciences. The recommendations of those bodies should be immediately implemented and extended as necessary to assure early discovery of unintended consequences of genetic engineering, and monitoring planning and implementation included for each new biotechnology product that is approved for release.
Thank you for your consideration of these comments.
/s/ Martin E. Levin, Esq.
Council for Responsible Genetics
See, National Academy of Sciences, National Research Council, “Environmental Effects of Transgenic Plants: The Scope and Adequacy of Regulation,” pp. 192 – 219 (National Academy Press 2002); USDA Office of Inspector General, “Animal and Plant Health Inspection Service Controls Over Issuance of Genetically Engineered Organism Release Permits,” Audit Report 50601-8-Te, pp. 28-40 (Dec. 2005). United States Government Accountability Office, GAO-09-60, “Genetically Engineered Crops,” pp. 45 - 49 (Nov. 2008); USDA Office of Inspector General, “Controls Over Genetically Engineered Animal and Insect Research,” Audit Report 50601-16-Te, pp. 14-16 (May 2011). United States Government Accountability Office, GAO-15-38, “Food Safety: FDA and USDA Should Strengthen Pesticide Residue Monitoring Programs and Further Disclose Monitoring Limitations,” pp. 57-58 (Oct. 2014).