NCC Comments on FDA Genome Editing Proposal

June 19, 2017

Division of Dockets Management (HFA-305)
Food and Drug Administration
5630 Fishers Lane
Room 1061
Rockville, MD  20852

Jason Dietz
Center for Food Safety and Applied Nutrition (HFS-205),
Food and Drug Administration
5001 Campus Dr.
College Park, MD 20740

RE: Docket ID No. FDA-2016-N-4389-0274. Genome Editing in New Plant Varieties Used For Foods; Request for Comments

Dear Mr. Dietz,

The National Cotton Council (NCC) appreciates the opportunity to provide input on the Food and Drug Administration’s (FDA) notice for a request for comments on “Genome Editing in New Plant Varieties Used for Foods”.

The NCC is the central organization of the United States cotton industry.  Its members include producers, ginners, cottonseed processors and merchandisers, merchants, cooperatives, warehousers and textile manufacturers.  A majority of the industry is concentrated in 17 cotton-producing states stretching from California to Virginia. U.S. cotton producers cultivate between 9 and 12 million acres of cotton with production averaging 12 to 18 million 480-lb bales annually. The downstream manufacturers of cotton apparel and home furnishings are located in virtually every state. Farms and businesses directly involved in the production, distribution and processing of cotton employ more than 125,000 workers and produce direct business revenue of more than $21 billion.  Annual cotton production is valued at more than $5.5 billion at the farm gate, the point at which the producer markets the crop.  Accounting for the ripple effect of cotton through the broader economy, direct and indirect employment surpasses 280,000 workers with economic activity of almost $100 billion. In addition to the cotton fiber, cottonseed products are used for livestock feed, and cottonseed oil is used as an ingredient in food products as well as being a premium cooking oil.

With new technologies and plant varieties continuously emerging, it is critical that the process in place to regulate genome edited products be clear and predictable for researchers and industry and is based on sound science.  In order for this to happen, FDA, USDA, and EPA must work closely with one another to coordinate their activities to ensure there is a consistent regulatory approach across the U.S. government. Currently, USDA has proposed to exclude certain applications of genome editing from pre-market regulatory review because they are low risk.  These products have small genetic differences that can also occur naturally or through long-standing breeding methods and remain within the plant’s gene pool. Our following comments focus on these applications of genome editing methods.

1. In what ways are the food safety risks associated with human and animal foods from genome edited plants the same as or different from those associated with other plant development methods (e.g., hybridization, chemical or radiation-induced mutagenesis and non-targeted genetic modifications using in vitro recombinant DNA technologies)? Please provide data and/or information to support your view.

• To what extent is the scientific knowledge of and experience with current new plant varieties (such as those developed with in vitro recombinant DNA technologies that have gone through the voluntary consultation process) relevant to the safety assessment and regulatory status of food from new plant varieties produced using genome editing? Is there additional scientific knowledge that would be relevant specifically to the safety assessment and regulatory status of new plant varieties produced using genome editing? Please provide data and/or information to support your view.

The FDA 1992 policy statement on new plant varieties [1] recognized that plant breeding methods represent a continuum, from traditional crossing of two varieties to using molecular methods to introduce genes from other species into a plant. In fact, spontaneous genetic changes can also result in deletions, insertions, and inversions as well as small and large chromosomal rearrangements. In recent years, cotton producers have come to rely upon expanding knowledge of plant genomes and biological diversity to develop new varieties.

Unlike the use of rDNA methods and the creation of transgenes, the genome editing applications described in these comments create genetic diversity though changes in endogenous gene sequence and function that are in principle also possible to create using more traditional methods of breeding (e.g., spontaneous/induced mutagenesis and cross-breeding). 

Additionally, the plant varieties developed through these genome editing methods may well be indistinguishable at the DNA sequence level form from those plant varieties developed through alternative methods such as cross-breeding and spontaneous/induced mutagenesis. In contrast, plant varieties produced through rDNA techniques and transgenic varieties produced through genome-editing, may result in novel functional gene(s) that could not be introduced through the more traditional breeding methods.

2. Are there categories of genome edited plant varieties for which there are scientific bases to conclude that foods from such categories are unlikely to present food safety risks different from or greater than those for traditional plant breeding? Similarly, are there categories of genome edited plant varieties for which the regulatory status of the food derived from such plant varieties can be said to be no different from that of traditionally-bred plants? If there are such categories, is there a basis upon which to determine that there would be no reason to include them in any voluntary premarket consultation process? If so, please describe the characteristics of such categories (including, for example, information about the types of phenotypes and modifications (insertions, deletions or substitutions) achieved through genome editing) and provide data and/or information for why plant varieties in these categories are unlikely to present food safety risks or regulatory status questions. Regulatory status questions may include, for example, whether food from the new plant variety contains an unapproved food or color additive such that premarket review and approval is required (see sections 409 and 721 of the FD&C Act). As another example, if food from the new plant variety has a different nutritional profile from food from traditionally-bred plants, then certain labeling may be required to disclose a material change in the food.

1. If such categories exist, how do plant developers ensure the safety of foods from new plant varieties in these categories? For example, how are safety assessments of foods from these varieties accomplished, and what data and information are or should be considered in such assessments?
2. If certain categories of genome edited plants do not raise questions of safety or regulatory status, should there nevertheless be a mechanism separate from the voluntary premarket consultation process through which plant developers may voluntarily notify FDA about their intent to market a food derived from a genome edited new plant variety that falls within these categories? If so, what process should plant developers use to notify FDA? What kind of information should be included in such a notification to FDA?
3. Given that genome editing techniques can give rise to a broad range of plant modifications, from simple gene deletions to totally novel genes, and that some such modifications can be achieved through traditional breeding, please discuss the basis upon which to determine that there would or would not be a reason to include, in any voluntary premarket consultation process, foods from genome edited crops with modifications that could have been achieved through traditional breeding.

As stated previously, the FDA 1992 policy statement on new plant varieties [2] recognized that plant breeding methods represent a continuum, from traditional crossing of two varieties to using molecular methods to introduce genes from other species into a plant.  Gene editing is a continuum with different applications. Certain genome editing applications could be accomplished though more traditional plant breeding methods such as mutation breeding or crossing a commercial variety with a wild relative or traditional cross breeding. Other genome editing applications, such as introducing a gene from an unrelated species are similar to those new plant varieties that currently go through the FDA consultation process. 

It is important to view any food safety issues in this context. New plant varieties developed using applications of genome editing, which are essentially a more precise way of cross-breeding or inducing mutagenesis, should be considered the same as those new plant varieties developed through more traditional breeding methods.  The 1992 policy statement is as relevant for new plant varieties developed today as it was in 1992, particularly given the advances in plant genetics.

There is no scientific or risk-based reason that new plant varieties developed through applications of genome editing that could be achieved through more traditional methods of plant breeding should be treated differently from a regulatory perspective than those new plant varieties developed through more traditional plant breeding.  Thus, targeted mutations through genome editing should not be treated any differently with respect to the FDA consultation process as are spontaneous or induced mutations.  Likewise, new varieties developed using genome editing to precisely change endogenous DNA sequence and function should not be treated differently than new varieties developed using cross-breeding to change endogenous DNA sequence and function.  

The FDA 1992 policy statement acknowledged that plant breeders undergo well-established quality and testing processes regardless of the plant breeding method employed to develop a new variety.  The basis for the 1992 FDA guidance on new plant varieties is the existing practices of plant breeders to assess the safety and nutritional value of a new plant variety prior to that variety entering the market. FDA stated that they did not intend to alter these long established practices nor did they intend to create new regulatory obligations for them.  Any developer of a new plant variety can—and should—use the guidance in the 1992 policy statement to determine if a consultation with FDA is appropriate. 

Regarding a possible notification to FDA before a new plant variety is introduced into the market, it is unclear what value this would bring to the Agency and under what authority these notifications would be provided to the Agency.  We would also note that for applications of genome editing, the Agency should not use, as the baseline, the number of crops and consultations that have been conducted for new plant varieties developed through rDNA methods. Genome editing applications such as targeted mutations can potentially be utilized across a broad range of crops and by a range of developers—if overly burdensome and unnecessarily expensive regulatory policies are not implemented. It is therefore unclear how the agency would handle notifications mentioned in question 2. 

3. Are there categories of genome edited plant varieties for which there are scientific bases to conclude that foods from these categories are more likely than traditionally-bred plants to present food safety risks? If so, please describe the characteristics of these categories (including, for example, information about the types of phenotypes and modifications (insertions, deletions or substitutions) achieved through genome editing) and provide data and/or information to support why plant varieties in these categories are more likely to present food safety risks than traditionally-bred plants.

Plant varieties produced through rDNA techniques and transgenic varieties produced through genome-editing, may result in novel functional gene(s) that could not be introduced through the more traditional breeding methods. These applications could potentially present food safety issues. However, after 20 plus years of voluntary consultations with FDA, these potential concerns have not manifested into actual risks due to the widely adopted processes used by the public and private sector for introduction of new plant varieties.

4. What steps can we take to help small firms, including those who may be considering using genome editing to produce new plant varieties for use in human or animal food, to engage with FDA about any questions related to food safety or the regulatory status of foods from their new plant varieties? Please provide supporting data and other information to support your comments and responses to this question.

In summary, the FDA 1992 policy statement is as relevant for new plant varieties developed today as it was in 1992, particularly given the advances in plant genetics.  Any developer of a new plant variety can—and should—use the guidance in the 1992 policy statement to determine if a consultation with FDA is appropriate. For the most part, small firms and public sector researchers have not yet developed new plant varieties that would have gone through the voluntary consultation process.  Therefore, FDA should provide clear guidance to these entities, including restoring to the FDA website the flow chart associated with the 1992 guidance, and conducting webinars and seminars on the 1992 policy statement.  Educational outreach should be done in collaboration with USDA and EPA.

The NCC appreciates this opportunity to provide comments concerning a technology so important to the U.S. cotton industry.  Please do not hesitate to contact us with any questions or concerns.

Respectfully submitted,

Steve Hensley

Senior Scientist, Regulatory and Environmental Issues