Rationale for updated guidelines for determining whether a plant is regulated under Part V of the Seeds Regulations (Directive 2009-09)

May 3 2023

On this page

• 1.0 Purpose
• 2.0 Introduction
• 3.0 Regulatory basis for updated guidance
• 4.0 Plant breeding practices that support environmental safety
• 5.0 Gene editing technologies and plant breeding
• 6.0 Regulatory alignment
• 7.0 Practical approaches to clarifying regulatory triggers
  • 7.1 Environmental assessment criteria
  • 7.2 Plants with a new commercially-viable herbicide tolerance trait (but no inclusion of foreign DNA) always require authorization
  • 7.3 Plants containing foreign DNA always require authorization
  • 7.4 New crop species (including trees) and new uses are outside the scope of this guidance
• 8.0 Ongoing monitoring and guidance updates

1.0 Purpose

This document describes the scientific and regulatory factors considered by the Canadian Food Inspection Agency (CFIA) for the 2023 update to guidance for plants with novel traits.

2.0 Introduction

The CFIA administers Canada's Seeds Regulations, Part V – Release of Seed, which came into force in 1996. These regulations focus on the release of seed into the Canadian environment in terms of safety for the environment and human health. Seed that is novel requires an authorization prior to release. Part V also recognizes that plant breeding can result in seed that is not novel. This approach to oversight allows CFIA to concentrate our resources on the assessment of novel products, while allowing plant breeders to develop improved lines within a scientifically-justified regulatory framework.

Technologies available for use in plant breeding have advanced since 1996, and plant breeders have expressed a need for updated guidance so that they understand how the regulations apply to new technologies. CFIA agrees that updates to our guidance and programming to adapt to new developments are needed. Updated guidance helps to enable innovators to make use of new technologies, and is aligned with CFIA's mandate to protect Canada's plant resource base while enhancing the prosperity of the Canadian agricultural sector.

Gene editing can be used to develop plants that could have also been developed through conventional breeding. An update to guidance is needed to explain how edited plant lines are regulated. As outlined in section 4, plant breeding is a time-consuming and labour-intensive process. Breeders can use gene editing to combine useful characteristics by design rather than by relying on chance and multiple breeding cycles. They are anticipating that gene editing tools will help them continue to develop plant lines to meet present and future challenges facing agriculture, including climate change, predictable crop yields, and a stable and nutritious food supply. Breeders anticipate that these technologies will hold great benefits for Canadian farmers, consumers, the Canadian economy, and the environment by making the good use of our agricultural lands to reliably grow quality crops.

In light of these new technologies for plant breeding, the CFIA has updated our Directive 2009-09 guidance for determining whether a plant is subject to Part V of the Seeds Regulations. This update clarifies which products of plant breeding require an authorization prior to release. To develop the updated guidance, the CFIA:

• reviewed literature on gene editing technologies (example references listed in section 9)
• organized webinars with plant breeding experts (for example, researchers and plant breeders)
• participated in expert panels with industry and public research representatives
• engaged with domestic and international regulatory counterparts
• reviewed comments from a public consultation held from May 2021 to September 2021.
• reviewed Health Canada's Scientific opinion on the regulation of gene-edited plant products within the context of Division 28 of the Food and Drug Regulations (Novel Foods) and references therein
• reviewed the Canadian Biotechnology Action Network's report entitled "Unintended effects caused by techniques of new genetic engineering create a new quality of hazards and risks" and references therein^Footnote 1
• reviewed reports prepared by international regulatory counterparts regarding the use and safety of gene editing technologies in plant breeding, and references therein^{Footnote 2Footnote 3}
• engaged with key stakeholders through multiple in-depth technical discussions held before and after the 2021 public consultation, including:
  • non-governmental advocacy organizations
  • industry associations representing the organic sector
  • industry associations representing the seed and grain value chain
  • industry associations representing seed breeders using gene editing
  • academic and public sector plant breeders

Throughout these information-gathering and engagement activities, the CFIA reviewed:

• how plant breeding practices and the overall seed value chain work to ensure the safety and quality of all new plant lines
• CFIA's 30 years of experience with novel plants, and comparison to the experiences of international regulators under their respective regulatory frameworks
• how gene editing technologies work in principle and specifically in the context of their use in plant breeding
• how plant lines developed using gene editing compare to lines developed using other methods of plant breeding
• how gene-edited seed fits within the CFIA's regulatory framework for seed
• whether the updated guidance is worded in a way that will be clearly understood and practical to implement

Based on the activities and analysis outlined above, the CFIA developed updated guidance for novel seed. The remainder of this document provides greater detail on the CFIA's rationale.

There were some comments from the public consultation and other technical discussions with stakeholders that fell outside of the CFIA's scope of determining environmental safety (for example, market access, information for seed buyers, economic considerations, standards for purity and quality of seed and grain, food safety, intellectual property rights, etc.). These have been shared with relevant groups within the Government of Canada and are being addressed through different mechanisms.

As a regulator, CFIA is focused on topics that relate to health and environmental safety. Agriculture and Agri-Food Canada is focused on the related economic considerations and support for farmers. Both organizations met with stakeholder groups during the development of CFIA's guidance. The purpose of these meetings was to develop strategies for managing the introduction of gene-edited crops, including strategies for providing seed buyers with enhanced information about how a particular seed variety was developed. Transparent information about the use of gene editing will help to support diverse farming practices.

3.0 Regulatory basis for updated guidance

Part V of the Seeds Regulations describes the programming and requirements for releasing novel seed in Canada. CFIA's programs for novel seed are 1 part of Canada's overall regulatory system for plant agriculture. There are additional requirements depending on the end use of the agricultural product, which may include:

• pre-market safety assessment programs for novel animal feeds (CFIA) and novel foods (Health Canada)
• requirements relating to seed production such as seed certification and variety registration
• labelling requirements related to mandatory safety and nutrition information
• standards to be met to qualify for voluntary marketing claims

In keeping with Canada's approach to regulated activities, it is the individual's responsibility to understand and follow their regulatory obligations. It is the CFIA's role to provide guidance that assists individuals in understanding the regulations, to provide regulatory programming, and to verify that the regulations are being followed. Regulations carry the force of law, while guidance explains how a regulation is applied. Guidance cannot extend the regulator's authority beyond what is provided in the regulation, and likewise does not allow for regulated activities to bypass regulation.

All plant breeders have a responsibility to understand how the plant lines they are developing interact with the Canadian environment. Breeders must not release a plant line that would have a significant negative impact on the environment or human health. This guidance update does not change that fundamental responsibility.

Over the past 30 years, the CFIA has advanced knowledge of the assessment of novel plants and established a history of decisions of which plants are novel versus which plants are not. The CFIA has assessed and authorized over 120 plant products for release into the environment as crops. This has included plants developed using conventional breeding methods such as mutagenesis, as well as plants developed by inserting foreign DNA. Likewise, the CFIA's field trials program has reviewed over 2200 unique lines for use in field testing. The CFIA has also provided advice to multiple plant breeders in cases where the plant was not novel. In these cases where the plants were not considered novel, there was no need for the CFIA to perform a pre-market assessment or to authorize the release.

Taken together, this body of experience in assessing novel plants and providing advice on cases where a plant is not novel has provided CFIA with a substantial understanding of the types of traits that are being developed using a range of technologies. Along with this, CFIA has also established which types of traits are novel in the context of environmental release.

This guidance update took into account the CFIA's experience with determining novelty and assessing novel plants. Based on this experience, CFIA has identified the kinds of products where an authorization to release is needed. This includes products with foreign DNA and products with commercially-viable herbicide tolerance traits. Breeders also continue to have the responsibility to inform CFIA of any other trait that could have a significant negative impact on the environment.

4.0 Plant breeding practices that support environmental safety

A key consideration in the development of this guidance was the overall context of plant breeding practices. In developing this guidance update, the CFIA took into account the rigorous breeding techniques that are used in developing a new variety, and how this is supported by technology.

Plant breeding is a competitive and highly-developed field. Domesticated crop species are already very advanced, and breeders are often seeking to make incremental improvements on elite breeding lines, without losing the performance gains achieved over decades of breeding and selection. To be successful, breeders must understand the genetic potential of their crop species, identify additional sources of genetic diversity (such as spontaneous mutations, wild relatives, heritage lines), plan their breeding and selection strategy, and monitor all aspects of their new lines at every step of the breeding process and throughout their commercial lifespans.

For a finished variety to reach a commercial marketplace of farmers purchasing seed, the quality of the variety must be demonstrated at many stages. This includes collaborations with other breeders, documenting the pedigree of the lines, meticulous handling and screening to maintain genetic purity, and well-documented trials that demonstrate quality and performance of the line. All of this information serves to inform decisions about whether the line will be recommended for variety registration (if applicable), granting of breeders rights, whether seed growers will produce seed, and ultimately whether a seed buyer will decide to purchase the seed and continue to use it on their farm to meet the demands of the marketplace.

In-depth product characterization provides confidence in how the line will perform in the field (maturity, disease resistance, uniformity, fertilization needs, stress tolerance, etc.) and for its end uses (storage, processing, cooking, nutritional value, etc.). This high degree of planning and observation also limits the possibility that plants would have unintended negative environmental or health impacts (for example, invasiveness, host a plant pest, or produce an allergen). Breeders discard any material that does not perform up to these high standards. It is common for a product pipeline to start with 8,000 to 12,000 plants and end with 2 to 4 elite lines that hold potential as finished varieties. For elite lines with potential, field trials are performed in diverse environments to evaluate agronomic performance and plant quality.^{Footnote 4Footnote 5}

These principles of crossing, selection, characterization, and long-term monitoring have always been a part of plant breeding practices, regardless of the methods used to develop a new plant. This guidance does not change the responsibility of breeders to analyze or characterize their product, nor their responsibility to ensure that their products are safe for environmental release.

With the rigour of this breeding context, and based on a history of safe use of plant breeding domestically and internationally, the CFIA foresees that plants derived through conventional breeding will generally be substantially equivalent to other populations of the same species in Canada, with respect to their safety for the environment.

5.0 Gene editing technologies and plant breeding

To consider how gene editing technologies compare to other methods used in developing new plant lines, including conventional breeding, CFIA undertook a comprehensive review of the use of editing technologies in plant breeding. Examples of the literature reviewed can be found in the footnotes.^{Footnote 6Footnote 7Footnote 8Footnote 9Footnote 10Footnote 11Footnote 12} Gene editing technologies can be used to make specific changes to the genome of living organisms by adding, removing, or altering genetic sequences at precise locations. Gene editing tools can produce similar or identical outcomes to conventional breeding technologies. Gene editing technologies enable higher precision and comparable or significantly fewer unintentional genetic changes than are seen with other plant breeding techniques.^{Footnote 13Footnote 14Footnote 15Footnote 16}

The ability to edit the genome helps plant breeders combine valuable traits in a single individual, without needing to make a selection from thousands of offspring generated from multiple parent lines. This can reduce the number of generations and individuals needed to bring the right combination of traits together, while at the same time reducing the inclusion of less-desirable traits that would otherwise be included at random. The rigorous process of characterizing and finishing a variety, as described above, still takes place even when gene editing is used.

There are a number of tools described as a 'gene editing technology'. Perhaps the most widely-used tool is Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR-Cas), but gene editing also refers to other methods such as Oligonucleotide Directed Mutagenesis (ODM), Transcription Activator-like Effector Nucleases (TALENs), Zinc-Finger Nucleases (ZFNs) and meganucleases, as well as variations of these technologies.

Whether using conventional breeding methods, recombinant DNA technologies, or gene editing technologies, random genetic change is to be expected. The rates of genetic change can vary by species, and some techniques introduce more changes than others. Random genetic changes can be stimulated deliberately to create genetic diversity, as is the case with mutagenesis techniques. Random genetic changes can be silent (no observable effect), result in a desirable trait or combination that is selected in the breeding program, or can result in unintended effects that would not be desirable.^{Footnote 14Footnote 17Footnote 18}

Unintended effects from gene editing technologies have been reviewed at length by the CFIA. In comparison to the types of unintended effects anticipated through conventional methods such as mutagenesis, gene editing technologies are targeted and there are numerous tools that plant breeders use to mitigate the potential for unintended effects, screen for the presence of off-target genetic changes, and select lines in subsequent generations that didn't inherit unwanted genetic changes.^Footnote 19 In general, gene editing has been found to have lower rates of unintended effects compared to conventional breeding approaches, where multiple genes are affected at once.^{Footnote 14Footnote 18}

It is the scientific opinion of the CFIA that there is no inherent risk associated with gene-edited plants that would justify a pre-market safety assessment for the environmental release of seed of every product developed using gene editing. Gene editing technologies do not present any unique or specifically identifiable environmental or human health concerns relative to other techniques of plant breeding. Gene editing can be used to accomplish genetically identical outcomes to what would be achievable using conventional breeding practices. Therefore, gene-edited plant products should be regulated like all other products of plant breeding. Namely, by the traits they exhibit and how these traits impact the safety of environmental and human health.

6.0 Regulatory alignment

The consultation on draft guidance that the CFIA held in 2021 highlighted the value of international regulatory alignment. Participants also highlighted the need for alignment across Canadian regulatory programming, particularly with Health Canada (novel foods) and with the CFIA's program for novel feeds. Accordingly, the CFIA sought out opportunities to align with these programs where appropriate. It is important to recognize that the programs each have distinct mandates and assess products for different purposes: for example, a plant with novel traits will not necessarily result in a novel food, and vice versa. Plant breeders remain responsible for being aware of all applicable regulatory requirements. To assist plant breeders in navigating these frameworks, there are several elements in common between these distinct regulatory programs, namely:

• recognizing a history of safe outcomes of conventional breeding, the CFIA does not foresee that outcomes of conventional breeding require pre-market assessment, apart from those products that have direct links to the requirements and safety endpoints identified in the regulatory frameworks
• similarly, products developed using gene editing are regulated like any other product of plant breeding – based on the traits they exhibit
• identical terminology and definitions for elements that the regulatory programs have in common
• policies that accommodate a streamlined assessment for familiar products

7.0 Practical approaches to clarifying regulatory triggers

The goal of this updated guidance is to provide plant breeders with clearly-defined regulatory triggers, while upholding CFIA's product-based approach to assessing the safety of plants with novel traits. For this reason, the guidance was updated with clear statements that aim to minimize subjective interpretation of the Seeds Regulations. These statements are based on the considerations outlined above. The following sections outline how and why the key features of the guidance were developed.

7.1 Environmental assessment criteria

Breeders have a fundamental responsibility to develop lines that meet all applicable regulatory requirements for safety and quality. CFIA's guidance update does not alter that underlying responsibility. To assist breeders in understanding when a plant would be novel, CFIA provided statements about our experience and expectations, and also outlined how we assess whether the release of a plant into the Canadian environment would have a significant negative impact on the environment or human health. The CFIA compares the use and safety of the plant to its counterpart(s) already present in the Canadian environment. This comparative assessment is based on 5 criteria outlined in Part V of the Seeds Regulations and detailed in appendix 2 of the updated guidance. Breeders are expected to apply these same criteria and notify CFIA if a plant is novel so that CFIA can undertake an assessment.

7.2 Plants with a new commercially-viable herbicide tolerance trait (but no inclusion of foreign DNA) always require authorization

Part V of the Seeds Regulations specifically identifies gene flow, weediness, and impacts on biodiversity as novelty criteria. Plants with new commercially-viable herbicide tolerance traits can have a significant negative impact on 1 or more of those 3 criteria if not appropriately managed. Therefore, when a herbicide tolerant plant is authorized for environmental release, it is authorized on the condition that a suitable herbicide tolerance management plan is put in place. Herbicide tolerance management plans outline best practices such as monitoring and crop/herbicide rotation that are designed to:

• delay the development of herbicide tolerant weeds through selection pressure
• delay the development of herbicide tolerance in related species through out-crossing
• address the occurrence of unwanted herbicide tolerant plants through corrective actions
• monitor the effectiveness of these plans and to report on their implementation

The CFIA recognizes that there are many parties throughout the production chain and in government who play a role in the responsible use of herbicide tolerant crops and associated herbicides, including:

• growers – who make on-farm decisions that impact the evolution of herbicide tolerant weeds
• agronomists, crop advisors, sales people – who provide advice to growers based on their unique situation (such as, specific weeds, crop history, field conditions, crops, traits)
• product developers – who develop and implement a herbicide tolerance management plan as described above
• academic researchers – who survey resistant weed populations, confirm cases of weed resistance, investigate mechanisms of resistance development, conduct research to evaluate and recommend best management practices
• • federal government – the Pest Management Regulatory Agency is responsible for reviewing herbicide safety.
  • Best management practices are usually included on herbicide labels.
• • provincial extension – who are responsible for sharing information about best management practices and weed resistance issues with growers.
  • Extension experts communicate with growers and the agricultural sector through field days, media including social media, workshops, and publications.

In many cases, these stakeholders work together towards the common goal of preserving the usefulness of herbicide tolerant crops and associated herbicides. Manage Resistance Now is an initiative by CropLife Canada, industry, academia and government experts to help growers and industry farm in a sustainable and responsible way. Numerous facts sheets and videos are available on Manage Resistance Now website to educate growers on best management practices.

CFIA also recognizes that Canada's regulatory framework is structured differently than many jurisdictions, and this has placed the CFIA in the unique position of having a mandated responsibility to oversee the release of crops that could have impacts on the environment, even when developed through conventional breeding.

The CFIA has assessed over 90 herbicide-tolerant plants, of which over 25 were developed using conventional breeding methods. Taking into account:

• CFIA's familiarity with many crop kinds and herbicide tolerance traits
• the global experience with these types of breeding outcomes
• the roles that industry, farmers, and Health Canada's Pest Management Regulatory Agency play in the responsible use of herbicides in agriculture

CFIA has determined that herbicide-tolerant plants that do not contain foreign DNA are eligible for a streamlined assessment that is focused on stewardship of the herbicide tolerance trait. Details about how the streamlined assessment operates will be available in CFIA's Directive 94-08: Assessment Criteria for Determining Environmental Safety of Plants With Novel Traits.

7.3 Plants containing foreign DNA always require authorization

The CFIA has over 25 years of experience assessing plants that contain foreign DNA. Given this regulatory experience, the CFIA considers that plants that contain foreign DNA are not equivalent to their conventional counterparts. Plants with foreign DNA therefore require a pre-market safety assessment and authorization prior to the seed being released into the environment.

7.4 New crop species (including trees) and new uses are outside the scope of this guidance

The majority of the CFIA's regulatory experience is focused on the environmental release of crop plants commonly used in agricultural systems (for example, field crops and horticultural crops). Given that other uses and species are less familiar within the regulatory context, CFIA has limited the scope of this guidance to cultivated species. Plant breeders planning to work with plants that fall outside of the scope of this guidance are advised to contact the CFIA. Examples include:

• new crop species
• plants intended for release into natural environments
• species that may have unique management considerations (for example, forest trees or aquatic plants)

8.0 Ongoing monitoring and guidance updates

This guidance update is based on the CFIA's knowledge of current breeding practices, technologies, and the types of traits that are novel. The weight of evidence supports that gene editing technologies are suitable for use in plant breeding programs. Together with the established history of breeding outcomes and the breeders' obligation not to release any plants that would have a significant negative environmental impact, CFIA believes that this guidance update achieves an appropriate balance between regulatory oversight and breeder responsibilities.

The CFIA has always conducted horizon-scanning of plant breeding activities, which includes:

• engaging with plant breeders proactively at national and international conferences
• holding technical discussions with international regulatory counterparts
• participating in international working groups on the regulation of biotechnology products
• reviewing peer-reviewed literature and other documents relevant to the regulation of plant biotechnology

The CFIA will continue such activities and will also continue to accept any new information about the safety of plant lines in the Canadian environment. Furthermore, to enhance our monitoring of the rapidly-evolving advances brought through gene editing techniques, CFIA has established routine scans of publicly-available and subscription information sources. CFIA is monitoring these sources on an ongoing basis to remain up to date on the latest information about biotechnology and plant breeding.

The CFIA will update this guidance in the future, should new information arise about breeding goals, technologies, or other practices that relate to safety for environmental release and plants with novel traits.