As we enter the fourth decade of genetically modified (GM) plants being approved and used internationally, regulatory experience with environmental risk assessments for cultivation approvals, and food safety risk assessments for food and feed approvals should be applied to remove unnecessary pre-market regulatory requirements and broaden market access for safe and beneficial products of biotechnology. Global harmonization of risk assessments for GM plants is an achievable goal that would accelerate regulatory approvals and expand access and deployment of safe and beneficial agricultural products with the potential to secure the food needs of an increasing world population (Koch et al., 2024). Streamlining the regulatory process for GM plants will improve equitable access to the technology for small developers, the public sector, farmers, and consumers. The Organization for Economic Cooperation and Development member countries have been working on global harmonization of environment, food and feed safety reviews for many years and have published a range of consensus reports to guide countries as they set up review standards for GM plants (OECD, 2006; 2015). In addition, others have proposed a core set of studies to support food and feed safety assessments globally (Waters et al., 2021) and encouraged the streamlining of data requirements for environmental risk assessments (Anderson et al., 2021). We expand on these ideas with a model for implementing shared risk assessments and proactive approvals.

Countries with regulatory frameworks that are actively reviewing and making timely decisions on the food and feed safety of GM organisms generally follow the CODEX CAC/GL 45-2003 guidelines (FAO/WHO, 2009). As part of the review process, regulators consider safety data collected on new GM plants and identify potential hazards associated with consumption of food and feed products made from these plants. GM plants are compared to conventional plants that already have a history of safe use. Food and feed biosafety reviews take into consideration how the composition of a new event (event = a unique plant-trait combination) may impact the nutrition of products derived from it, the potential for changes in toxicity or allergenicity, changes to levels of endogenous antinutrients, and whether the modification changes how the plant will be used for food and feed. For any identified potential hazard, reviewers assess the likelihood of harm, the consequences should harm occur, mechanisms to manage risk, and whether the overall risk is acceptable in terms of a country’s national protection goals.

Environmental safety reviews focus on how a new trait could potentially impact a GM plant’s biology compared to conventional plants, and evaluate changes to invasiveness, weediness, persistence, gene flow to sexually compatible plants, and impacts on non-target organisms (OGTR, 2013). For identified, potential environmental hazards, a similar risk assessment as for food and feed considers the likelihood of harm, the consequences should harm occur, mechanisms to manage risk, and whether the overall risk is acceptable in terms of national protection goals.

Experience with safety assessments of GM plants has confirmed that potential risks to the environment or to human or animal health are identifiable and manageable in approved plants (Radin, 2003; Sanchez, 2015). At least 645 GM events have been reviewed for cultivation, food and feed safety in 46 countries (ISAAA, 2024). In most instances, the initial environmental, food and feed safety reviews were completed in the country where the plant was developed, first introduced to farmers, and placed on the market. In an unnecessary abundance of caution, the same food and feed safety reviews for GM plants are repeated in many countries where food and feed from the GM plant will be imported. Re-review is unnecessary to establish that an already approved GM plant is safe for human and animal consumption. Experience tells us that a single, well-constructed review is able to identify potential risks in a newly developed GM plant.

Once the safety has been determined for an approved plant-trait combination, repeated reviews are not needed and are costly for developers and regulators, delay deployment of previously approved GM plants, restrict developers, and limit farmers’ access to improved planting material. An industry study determined that the cost of developing and commercializing a new GM plant was US$ 115 million and 38% of this cost, US$ 43 million, was for regulatory approvals (AgbioInvestor, 2022). For agencies that charge for regulatory reviews, the fees can be from US$ 5,000 to US$ 450,000, but costs agencies accrue to conduct GM risk assessments are likely higher.

We discuss ways to reduce this unnecessary regulatory burden and provide a model for moving ahead with a more streamlined, equally safe and efficient one global risk review of GM plants. In addition, examples are provided of low-risk GM plants where one environmental and one food and feed assessment are also sufficient for cultivation approval in many release environments and for human and animal consumption.

The data requirements for food and feed risk assessments are clearly defined and universal (Waters et al., 2021), therefore, once food safety has been determined, a global risk assessment summary could be used to eliminate additional food and feed reviews and inform food and feed approvals in all other countries.

Section 3 in Annex 3 of the CODEX guidelines (FAO/WHO, 2009) encourages member states to share risk assessment and safety information to facilitate food import approvals in other countries (FAO/WHO, 2009). Vietnam took an early step towards a global food and feed safety approval when they introduced a 2014 policy to accept the food safety of a GM plant that had food safety approval from five developed countries (Ministry of Agriculture and Rural Development, 2014). In 2013, Health Canada (HC) and Food Standards Australia and New Zealand (FSANZ) began collaborating on food safety risk assessments to streamline the review process for new GM plants in acknowledgement that food safety in one country is applicable in other countries (FSANZ, 2024). Bangladesh, Bhutan, India and Sri Lanka have been in discussion since 2020 about harmonization of food and feed safety assessments across these four countries (AFSI, 2025).

A review of approvals listed in the International Service for the Acquisition of Agri-biotech Applications (ISAAA) GMO Approval Database indicates that many events have had multiple reviews in multiple countries and by many agencies (ISAAA, 2024). After food safety reviews of 645 GM events in 46 countries, the learnings from these reviews need to be applied to simplify and modernize global reviews for food safety. For example, the maize event, MON810, was approved early in the development of GM crops and has 25 food approvals, 20 feed approvals, and 14 cultivation approvals listed in the ISAAA database (ISAAA, 2025), in addition to many more approvals as a stacked event that was bred together with other approved maize events. We cannot say whether the subsequent approvals identified unique country-specific safety concerns, but ultimately the many reviews did not change the first findings that the GM maize was safe for cultivation, food and feed use.

There may be instances where additional potential hazards are identified when the initial food and feed risk assessment is reviewed in another country. In this case the agency can focus their risk assessment on this concern, considering the pathway to harm, likelihood, consequences and risk management options for the new hazard without the need to reassess the previously reviewed hazards. For example, food consumption patterns or novelty of a food may require additional review in some countries. This happened in the 1990s in South Africa with review of the MON810 maize event for general release approval. United States consumption data do not accurately reflect consumption in South Africa where maize is the staple food and consumed at much higher levels. United States maize consumption is estimated at 2.85 g/person/day (EPA, 2014), nearly eight times lower than the South African per capita consumption of 222 g/person/day (Ranum et al., 2014). The scientific review committee asked the applicant to provide exposure data for the South African population. Importantly, in this example the review committee identified the potential higher exposure that was not addressed in the application and asked for specific data to address that gap. This expedited the food review by focusing only on new potential hazards.

In our experience, following the approval of nine potato events in the United States, subsequent food and feed safety reviews in other countries have not identified any additional potential hazards (Table 1). The pSIM1278 construct is present in eight potato events. Collectively, the safety of the traits in pSIM1278 has been independently assessed and approved in 54 regulatory reviews by 10 agencies in nine countries (United States: Food and Drug Administration (FDA); Canada: HC and Canadian Food Inspection Agency (CFIA); Mexico: Federal Commission for the Protection against Sanitary Risk; Japan: Ministry of Health Labor and Welfare, Ministry of Agriculture, Forestry, and Fisheries; Philippines: Bureau of Plant Industry; Australia/New Zealand: FSANZ; Malaysia: Department of Biosafety; Singapore: Singapore Food Agency). Since the initial food and feed safety assessment by the FDA in 2013, none of the subsequent 53 reviews identified any new potential hazards or raised additional safety concerns regarding these traits in potatoes. These cumulative evaluations have consistently affirmed the safety of the traits and have not added or subtracted from the safety of the events. These events included five potato varieties, six different traits, and one selection strategy. Even with the diversity in genomic backgrounds and traits, no new safety concerns were identified in any of the subsequent reviews undertaken by food importing countries.

This is evidence that the repeated food safety reviews by importing countries do not increase the safety of the products. Instead, these redundant reviews confirmed the functionality of the initial review that was based on the CODEX guidelines. For potatoes, as these same traits are transformed into additional potato varieties, the current country-by-country review process will generate even more redundant risk assessments until a more science based approach to risk assessment is adopted globally.

Data requirements for environmental risk assessments are defined clearly and are transportable across countries (Anderson et al., 2021; M. Bachman et al., 2021). While countries differ in their geographical locations and environments, it is not necessarily the case that one global environmental risk assessment would have little value due to environmental differences. Findings of invasiveness, weediness, gene flow, persistence, and impact on non-target organisms in the first country can be used to inform risk assessment in subsequent countries. The risk assessment findings from the initial review will need to be reviewed in subsequent countries, and this can be done with the help of local crop, trait and biodiversity experts without the need for in-country studies or additional data from developers/applicants. Using problem formulation methodology, these experts can identify whether novel pathways to harm are likely and focus any additional assessments on clearly defined, country-specific risk hypotheses that were not addressed in the initial review (Wolt et al., 2010). Importantly, while plant performance is environment-specific, the performance of a plant is not a safety consideration in a regulatory approval.

In cases where regulatory agencies determine traits introduced into GM plants are low risk, one global risk assessment for environmental release should also be feasible. Three decades of environmental safety review of GM plants confirm that some categories of GM events are low risk across many environments.

Three categories of introduced traits have developed a history of safe use in edible crops, have been applied widely in commercial GM plants, and are recognized as safe by regulatory authorities. Examples of low-risk traits include those conferred using RNA interference (RNAi), retransformation of additional varieties of approved vegetatively propagated GM plants, and the use of cisgenic traits that are inserted into sexually compatible plants. These three groups of GM plants are discussed in more detail.

The proposed model for global risk assessments (Figure 1) is designed to minimize regulatory duplication while maintaining a high level of safety. This model maintains country sovereignty for decision making and encourages sharing of risk assessment summaries so that reviews in subsequent countries can focus on country specific potential hazards that were not previously assessed. In this model, after the first review and decision, other countries may review a GM plant reactively in response to a request from an applicant, or proactively by reviewing events for food products that are frequently imported or that local farmers wish to cultivate.

Countries may need to review their local regulatory policy to enable use of risk assessment summaries from other countries for national decisions. In some cases, country policy already lends itself to this process, for example, when regulation focuses on the safety of the product and not on the process used to develop it. In countries where there is a requirement for a formal applications to trigger a review, policies would need to be revised, and specific data requirements may need to be broadened to enable use of risk assessment summaries from other countries. The model does not stipulate what data are required, instead it relies on the outcome of a sound risk assessment using established risk assessment methodology.

Food and feed risks are universal, as are most environmental risks, however, some traits may raise concern unique to some countries. In this case, the national regulatory authority would identify the specific concern and outline a potential pathway to harm (Wolt et al., 2010). When using a global risk assessment summary, regulators use the biology of the conventional plant as the baseline for assessing risk. Once the biology of a plant is understood for the local environment, the impact of the added traits can be assessed to identify any new potential risk. This concern would be provided to the developer to address prior to decision making in that country.

Importantly, outside of regulations for pre-market review of GM plants, the safety of all food and all planting material is already regulated in countries. Implementing global GM plant regulatory processes does not impact the ability to review the safety of a product, nor detract from national public health regulations for food safety and plant pest regulations for environmental impact of conventional plants.

This paper considers the experience regulators have developed with safety reviews for GM plants in the last four decades and proposes a progressive change in how these plants are regulated internationally. The proposal is for one food and feed and one environmental risk assessment summary that will be available to all countries for national decision making. These two risk assessment summaries would be the product of the first country approval. While not all countries issue risk assessment summaries, enough countries make these available to enable the one review model to work.

The model proposed here expands on an earlier proposal for the identification of a core set of studies to support food and feed safety assessments globally (Waters et al., 2021). Using data from one country, these studies could be applied across all countries for risk assessment. These authors concur that problem formulation could be used to identify unique hazards on a country-by-country basis. Our experience, obtaining regulatory approvals for potatoes, suggests that not only are the data requirements between regulatory agencies already harmonized, but the first risk assessment with the harmonized data would be sufficient for all countries to reach national food and feed safety decisions.

Similarly, this model expands on an earlier proposal to simplify and modernize the data requirements for environmental risk assessment of GM plants (Anderson et al., 2021). There is already alignment on environmental protection goals across many countries, making the alignment of data requirements and data transportability across countries an easy step in harmonization of environmental risk assessments (Garcia-Alonso et al., 2014; Nakai et al., 2024). The model presented here suggests that the first environmental risk assessment is applicable to most countries for local decision making. Some countries may identify country-specific potential environmental hazards that need additional data and risk assessment, but no additional safety is achieved by repeating the review of the hazards already addressed in the initial assessment.

While regulatory cooperation and harmonization preserve national sovereignty, their implementation demands sustained political resolve. The AFSI, 2025, whitepaper for advancing regional cooperation on agricultural biotechnology regulation states “Regulatory cooperation and harmonization do not compromise domestic autonomy but do require political will to implement.” Several examples of harmonization across countries have emerged. Through the Health Canada-FSANZ Shared Assessment Process, applicants seeking food use of their biotech product for use in Canada, Australia, and New Zealand can submit an application to Health Canada and FSANZ. The food assessment is prepared by one of the agencies and then shared with the other. This risk assessment sharing is functioning and results in time and resource saving benefits for the agencies, improved efficiency in the authorization process, faster authorization times, and cost saving for the applicant. The Memorandum of Understanding, between Argentina, Brazil, Paraguay, and Uruguay, is another example of how countries can cooperate in regulatory assessments, while also maintaining domestic autonomy (Ministerio de Economia, 2025). As these examples evolve, they will serve as models for other countries and regions. Importantly, countries do not need MOUs to implement the model proposed here. Countries can make unilateral decisions to accept existing regulatory risk assessment summaries for GM plants they deem to have no additional risk for local conditions.

Reasons for a country to conduct further review would include country-specific information that raises a new potential hazard or an identified hazard in a new release environment, however these types of cases should be rare and based solely on traits that would pose identifiable and clearly documented risks. In particular, approved products that have been on the market for years, and which are cultivated safely in the environment, and consumed safely by humans and animals, likely would not require re-review.

The regulatory improvements suggested in this model also incorporate regulatory trends to extend approvals from one event to subsequent events with the same traits in the same crop, and to widen approvals for low risk traits. Evidence shows that approved RNAi-based crops and cisgenic crops pose no change to risk that is different from conventional, already-used food crops. Many regulatory agencies have recognized the safety of RNAi and cisgenes, especially when the traits could arise through traditional breeding. This alignment and a shift toward product-based, risk-proportionate oversight rather than process-based regulation, reflects current science and supports innovation. Similarly, reassessing vegetatively propagated crop varieties with the same trait or traits that have already been approved for food and environmental safety, has not identified new risks. The repeated reviews slow innovation, and result in unnecessary time and cost spent by both developers and governments.

Actionable recommendations arising from this regulatory risk assessment proposal are listed in Table 4.

Decades of experience with risk assessments and approvals of GM plants have identified areas where regulatory efficiencies are possible without reducing the safety of GM products. Global access to environmental, food and feed risk assessment summaries from the first approval of a GM plant would remove the redundancy of numerous duplicated risk assessments in countries that subsequently review the plant for local cultivation or food import. With access to risk assessment summaries, countries can review these food, feed and environmental risk assessments and focus their risk assessment on unique potential hazards not previously reviewed. Maintaining national decision making, ensures that the final approval of GM plants remains the responsibility of each country. In addition, expanding approvals for GM plants with RNAi or cisgenic traits and to subsequent events of vegetatively propagated plants with the same traits, is supported by the low risk associated with these modifications. We encourage national regulatory agencies to implement this model which will reduce their reviewing time without compromising safety. This will provide benefits to developers by reducing regulatory redundancy, to farmers by facilitating increased access to improved planting material allowing more sustainable food production, and to consumers by providing access to high quality, affordable food.