The global regulatory framework for the commercialization of nutrient enriched biofortified foods

Abstract Nutrient enriched crops (NECs) were developed through biofortification as a tool to reach the world's most vulnerable. The delivery model developed by HarvestPlus for the scaling of NECs relies on commercial demand from food businesses and consumers, coupled with the ability to promote and market foods that comply with legislation. This review of standards, regulations, and laws across the value chain in 20 countries demonstrates that existing provisions for food labeling are sufficient to carry out sales and marketing of foods made from conventionally bred NECs. The term biofortification is not necessary to create demand and, potentially, is counterproductive. Promoting the natural source of vitamins and minerals and relevant nutrition claims is the most effective and simple way to signpost healthier products to consumers. Until 2021, it was not possible to distinguish NECs at the grain level from the market standard. The development of a globally relevant Publicly Available Specification allows traders to demand grains that offer a substantial increase in zinc, iron, or vitamin A. Addressing this gap at the grain level ensures that standards and regulations are available end‐to‐end in the food supply chain providing the enabling environment for the rapid scale of NECs.


Overview of biofortification
Biofortification is defined by WHO as: the process by which the nutritional quality of food crops is improved through agronomic practices, conventional plant breeding, or modern biotechnology.
Biofortification differs from conventional fortification in that biofortification aims to increase nutrient levels in crops during plant growth rather than through manual means during processing of the crops. 1 In broad terms, biofortification can cover anything from increasing nutrients in animal feeds that transfers to eggs, milk, and meat, genetic engineering of rice to introduce a gene for vitamin A, 2 or increasing the vitamin D content of mushrooms through UV-light or sunlight exposure. 3 Biofortification is a process that can cover any category of food at many points in the food supply chain before harvest to increase the naturally occurring nutrient content of foods so that further addi- The HarvestPlus program aims to improve the content of the nutrients of global concern in the foods that people rely on. It is staggering to note that while the planet has ∼300,000 edible plant species, humans consume only ∼200; 4 and 60% of the calories consumed by humans are from wheat, maize, and rice. 5 This lack of dietary diversity is a major cause that one quarter of the world population suffers from hidden hunger (micronutrient malnutrition). In the past, plant breeding in both the public and private sectors focused on yield and pest resistance. The green revolution of the 1950s and 1960s concentrated on calories in avoiding a Malthusian catastrophe; little attention was paid to micronutrients, which by then were not recognized as value-added traits. Until very recently, breeders unintentionally compromised micronutrients by developing crops with lower protein/starch ratios. The HarvestPlus program began with the intention to reach the world's most vulnerable consumers, who generally grow their own crops for household consumption; but it was soon realized that to scale biofortified seeds, grains, and foods, wider demand would be required in the full food system. Gaining access to urban markets and higher-value processed food markets is critical for sustained and accelerated adoption of biofortified products, even if some of the consumers targeted do not have the greatest nutritional need. Diversified use and income potential are important along with improving nutritional status. Some of the crops, for example, beans and vegetative crops, begin with a noncommercial planting material system, and, therefore, standards are not deemed essential in these noncommercial seed systems; however, once the crop is ready, it then becomes a commercial commodity, which relies on standards for trade.
Biofortification spans the entire value chain, from agricultural research to consumption points on farm, to the market shopper ( Figure 1). To embed biofortified seeds, grains, and foods into food systems standards, regulations and laws are critical to enable trade at each value chain point. The ultimate priority is to protect the on-and off-farm consumer and deliver foods to beneficiaries that make a genuine and measurable impact on health.
A previous review of the global regulatory frameworks for biofortified crops 6 concluded that "the production and marketing of these [biofortified] products have been conducted without regulatory framework and under limited government control or regulatory guidance" and that "regulatory considerations are rare or nonexistent." However, our review here finds that biofortification, through conventional or genetic modification (GM), has adequate regulatory frameworks to label and promote foods made from nutrient enriched crops (NECs).
Previous efforts to define biofortification were leading researchers in the wrong direction. Mejia et al. 6 also concluded that as all biofortified products derived from conventional breeding are no more than selected crop varieties naturally rich in certain micronutrients, the use of specific standards and regulations may be unnecessary beyond compliance with food quality and general safety requirements on existing food legislation, including proper labeling. However, when the current scenario expands and becomes diversified including other biofortification techniques, such as agronomic fertilization and GM, including the NBTs, an appropriate regulatory framework for biofortified foods will become necessary, covering all stages of implementation.
The generic term for regulatory framework is used in this paper, but what was found is a combination of private standards, public standards, public or government policies, regulations, and laws exist simultaneously and are collectively referred to as regulatory frameworks.

Global and local definitions of biofortification and nutrient enriched crops
The term biofortification was introduced by Steve Beebe, a bean researcher at the International Centre for Tropical Agriculture (CIAT), at a meeting convened in early 2001 by CIAT. The meeting aimed to inform representatives of the Bill and Melinda Gates Foundation (BMGF) and the Micronutrient Initiative (now Nutrition International) about the CGIAR Micronutrients Project and the "biofortification" strategy. 7 The terminology caught on in the field of research and has been used ever since. As the HarvestPlus program escalated, more crops developed and more governments embraced the practice, the WHO then developed working terminology. 8 There are several Alimentarius commission was engaged to discuss the definition and led by Zimbabwe and South Africa, an Electronic Working Group (EWG) was formed. 10,11 Following several years of EWG discussion and member consultation at the CCNFSU41 meeting on November 26, 2019, the committee agreed to discontinue the work. The concluding remarks of the meeting refer to Nutrition and Health claims (CAC/GL  and that the nutrient reference values (NRVs) for nutrition labeling should be used for biofortified foods where appropriate. During the process, member states had raised concerns about the suffix "bio," meaning organic in several countries and possibly creating confusion with genetic engineering standards and regulations that were already in place. In the years that were spent in the codex negotiations, the delivery of seeds, grains, and foods kept growing; 12 thus, the scaling of biofortified foods was not held back by lack of a definition.

Stakeholder research in 2018
Stakeholder research has revealed other barriers to scale. 13 Following interviews with almost 100 seed, grain, and food businesses as well as 250 stakeholders, it was clear that supply chain actors were unaware of standards, regulations, or laws that governed trade and marketing of biofortified commodities. While academic publications set breeding targets for the levels of nutrients required, 14 this was of academic nature, and standards for trade were not available. Several publications at the time, including Mejia et al., 6 concluded that "the production and marketing of these [biofortified] products have been conducted without regulatory framework and under limited government control or regulatory guidance." This assumption was based on the lack of definition, and at the time of publication, the codex affirmation stated that existing food labeling provisions, Codex texts, standards, and regulations already covered biofortified grains and foods and products thereof.
Not so much the lack of an agreed definition of the term biofortification but the actual use of the word caused issues for stakeholders.
Opinions from leading global regulatory experts 15 concluded that given that the term biofortification had no regulatory status and was not a regular term used by consumers, it would be misleading and confusing for food product labeling and, therefore, should be avoided in packaging and promotion. 16 The word biofortification is still used in academic and policy documents, but outside of these subject areas, a better description was required. The Food Fortification Advisory Services (2FAS) is an advisory service funded by the European Union (EU) and implemented through a partnership between Landell Mills and the Global Alliance for Improved Nutrition. 17 In 2019, 2FAS developed a new term nutrient enriched crop, which are crops grown to have an enhanced nutritional value. Unlike other forms of fortification, in which vitamins and minerals are added to foods manually and postharvest, NECs are cultivated to have a higher nutrient content. This is achieved through agricultural practices or plant breeding. 18 GM (or genetic engineering or biotechnology) is a tightly regulated area of food production covered by detailed Codex guidelines, 19 European Union Regulations, 20 and the USFDA. 21 We shall discuss only NECs developed through conventional breeding technologies.
NECs derived from any other technologies are subject to different and specific food labeling codes and international laws.
It has been recommended not to use the term biofortification in any consumer facing materials 16 and to describe NECs specifically by the nutrients they provide when they meet the specific recommended daily amounts (RDAs) for the nutrient according to Codex or national provisions. For example, biofortified beans with an elevated level of iron, which contain 15% of the NRV of iron per 100 g, should be called "iron beans." When the term biofortification is removed from the discussion, a regulatory review takes on a new form. Foods made from conventionally bred biofortified crops/grains are no different to standard crops except for the increased amount of a specific micronutrient, notably, iron, zinc, or vitamin A. Therefore, the foods fall under the jurisdiction or codes for all other foods.

METHODOLOGY OF REVIEW OF THE REGULATORY FRAMEWORKS FOR SEEDS, GRAINS, AND FOODS
The biofortification value chain is long (Figure 1 Table 1 shows the existing standards and regulations for fortification and biofortification available in various regions across the world.

Government policy
Our paper is not a systematic review of country policy for support for biofortification, nutrition-sensitive agriculture, or NECs in agriculture, public health, institutional feeding, or public health policy. Policy documents were found for established local use of definitions of biofortification. There is large-scale policy support from governments from agricultural practice and guidelines to institutional feeding procurement standards. Increasingly, governments are viewing the range of available interventions to tackle micronutrient deficiencies with a more holistic and complementary approach. The best examples of countries having an integration of interventions are, as mentioned above, India, [52][53][54][55] Nigeria, 27-29 and Zimbabwe. [45][46][47] Once a government endorses the practice of biofortification, the seed, grain, and food industries are more likely to adopt it. The BMGF is a major sponsor of work on both expanding policy coverage and implementation guidelines. Scaling NECs is also achieved by catalyzing governments to integrate biofortification in agriculture and health policies, programs, regulations, and standards and varietal release protocols. As a result of the work to demonstrate impact evidence to governments (advocacy), biofortification has been included in 24 countries' national health and agriculture strategies and policies, with many more to be published in 2022.

TA B L E 1 Overview of standards and regulations for fortification and biofortification
Local definition of biofortification

Breeding standards
Crop breeding is the basic and most critical part of implementing biofortification programs. Biofortification was originally intended to be a public health tool, with basic but fundamental calculations on typical daily intake of a given staple, then the amount of nutrient required to achieve adequate micronutrient intake, "  With the demand in the private sector and the public health needs in the public sector, nutritional targets for micronutrients will increasingly be part of the norm, from crop breeding targets to mainstream food systems for production of foods. Mainstreaming in the context of biofortification has been reviewed by experts in the CGIAR, and breeders will have an integrated push for mainstreaming nutrition through simultaneous selection for micronutrients as core traits of interest in future breeding. 70 To ensure adoption by agricultural researchers in the public and private sector, micronutrient content should be a mandatory consideration and allocated equal importance as yield. Governments play a critical role at this first step of the value chain by including these breeding standards in agricultural policy, the best example found for this is India, 71 where mandatory minimum threshold levels for pearl millet variety have been established. It remains unsettled whether these breeding standards should become legal requirements or adopted by the public and private sector. As nutritional breeding standards are adopted more freely, it will be easier to translate breeding targets into the food products and nutrition claims. If breeding standards are followed, the grain and resulting food produced will contain the required amounts of micronutrients to signpost to consumers.

Seed standards and protocols
Seed standards are critical for identity preservation and aggregation in developing the supply chain for biofortified crops. Certified seed is defined by the USDA as "progeny of breeder, foundation or registered seed, handled under procedures acceptable to maintain satisfactory genetic purity and identity"; 72 this definition has been adopted in all countries covered in our review. This is the critical stage in the value chain to ensure that the original seed comes from breeders and varieties that adhere to breeding targets; if the seeds are not genuinely biofortified varieties or have been mixed, then the entire value chain for the nutrient collapses and the value for value chain actors is lost: Certification is the process by which a state seed certifying agency gives official recognition to seeds produced of a cultivar or named variety under a limited generation system which ensures genetic purity, identity, and a given minimum level of quality. 72 There are different types of seed developed in the breeding process: breeders seed, foundation seed, registered seed, and certified seed.
The latter class is commercial seed, and it produces grain that enters the food system, frequently through the private sector, initiating the food supply chain for NECs. All countries reviewed herein were found to have country-specific seed standards or certified seed schemes. In addition, there are regional and global schemes, such as the Organization for Economic Co-operation and Development (OECD) schemes for the Varietal Certification of Seed and Seed Codex 73 in Nigeria that aims to increase crop productivity by tackling counterfeit seeds. The OECD is a good example of a process or set of standards to ensure the use of certified agriculture seed that is of consistently high quality. 74 For certified seed, the genetic potential of the variety seed to express the micronutrient levels, as measured during the official registration and testing process, is guaranteed. The micronutrient content of the seed is not determined given the cost involved. When setting standards in the value chain, it is more important to set breeding standards and ensure that certified seed protocols are followed in identity preservation, and then test for nutrient content at grain level.

Grain standards
Regulations and standards play an important role in supporting commercialization. Across the various countries whose policies have been At the level of agroprocessors and retailers, prior to food reaching the consumers, there is moderate to significant regulatory oversight.
Most countries have a local regulatory system of labeling standards for nutritional claims relating to processed agricultural products (e.g., source of a particular nutrient claim). In several countries (e.g.,  and their agencies wishing to improve nutrition in staple crops and resulting foods for their population's health and wellbeing will be able to follow the good practice set out in the standards, and organizations producing food products using these crops can be assured of their provenance.

Standards and regulations for foods-practical applications for food packaging
Once breeding standards have been followed, certified seed protocols adhered to, and certified seed demanded by farmers and the crop has been grown and tested at grain level, the final step in the chain is the production of food. If all previous steps have been followed correctly, the nutrient will be present in the food. Previous reviews had not found food labeling regulations for biofortification. In 2017, Garcia-Casal et al. 75 concluded that "Regulatory considerations are rare or nonexistent for biofortification by conventional plant breeding." In the same year, Mejia et al. 6 found that "the production and marketing of these format of the staple, such as flour, bread, or brown rice, are in most cases able to make claims to consumers; however, once the biofortified grain is "diluted" by other ingredients in composite foods, the nutrient may not be in sufficient quantities to make nutrition and health claims.
The nutrient content of the food can initially be calculated by using nutritional databases, such as McCance and Widdowson, 76 or the USDA Food Data Central. 77 However, when making this calculation, the nutrient values of the biofortified crop will need to be entered manually using data obtained from the nutrient-specific PAS or from HarvestPlus; the values used in standard data sets are not from biofortified varieties. Table 2 provides approximate values of the nutrient per biofortified crop. It is advisable that finished food products are also  It is possible to communicate to the consumer that the food is a natural source of the vitamin. However, it is important not to imply that the product itself is natural or contains natural ingredients, especially if it is a composite food. Natural foods and natural food ingredients are often subject to separate rules and guidelines, such as those found in the UK 78 or the United States. In the absence of any country-specific rules, these can be followed as a comprehensive approach to protect the consumer.
Logo or signpost schemes also exist in several markets, in India provisions to use the F+ logo are available as part of the promotion of fortified foods to consumers; this logo could be used on biofortified wheat and rice products 79 and in Nigeria, it is possible to use the eye logo for vitamin A products (Figure 4). 80 HarvestPlus is also in the process of creating and registering a consumer logo.
It is not always possible to make nutrition and health claims and then subsequently, signpost the nutritional benefits to the consumer.
There are other ways in which populations benefit from the use of NEC Biofortification was designed to prevent and treat malnutrition, but when it comes to the promotion of foods to consumers, it is paramount not to make claims about disease prevention or cure. The benefits of the nutrients should be positive, such as building and maintaining health. Some countries, such as the EU, do permit disease risk reduction claims, but they are generally approved on a case-by-case basis with a lengthy approval process and dossier of population-specific evidence.
Nutrition and health benefits of biofortified foods should not be made on processed foods, which are high in fat, salt, or sugar. While the debate continues as to what makes a food unhealthy, foods of this nature should not be overly promoted. These foods should still be made using biofortified commodities but not promoted by the benefits.
Limiting biofortified foods to only healthy foods would create divides in supply chains and negatively affect consumers with the poorest diets.

Enforcement of standards and regulations
Enforcement is rare and often limited to high-income countries and mass marketed foods. Trading standards, advertising standards, and consumer protection are often unavailable, and breaches of rules are highlighted on high-volume foods that are heavily promoted and, therefore, attract attention. Little attention is paid to the way that SMEs promote their products in LMICs, therefore, it is essential to provide regulatory advice and support to growing businesses aiming to develop healthy affordable foods. Partners in Food Solutions is an independent, nonprofit organization, which supports business in Africa with services, such as labeling. HarvestPlus has also released white papers to support businesses.
All food businesses should be advised on consumer protection and making nutrition and health claims that promote the products but are completely truthful and helpful to the consumer. Sticking to the facts about the food is always safe advice to provide food marketers.

Consumer understanding and best methods to promote to consumers
Foti et al. 81 concluded that consumers of biofortified food products are generally confused and uninformed, even though they show a high willingness to pay. This confusion seems to result, moreover, from the lack of a clear definition of a biofortified product. The same conclusion was found by Timpanaro et al., 82 who concluded that "at present the potential consumer of biofortified food products is generally confused and uninformed." These findings were due to the use of the term bioforti-  87 found that there is significant scope for promoting zinc wheat in the country.
Positioning of biofortified foods is fundamental to consumer acceptance. Promote the benefits of NECs and not the biofortification process, focus on natural nutrition, clean label, and the ethical story.
Consumer research assessing current consumer understanding of biofortification becomes irrelevant when the term biofortification is removed. Manufacturers should be advised not to use the term biofortification: it is misleading to consumers and could also potentially breach local or regional food labeling regulations by using terminology unknown to consumers or lacking any regulatory endorsement; but most importantly, the term will not be used to promote or sell the product to the consumer.

CONCLUSIONS
We have found that in every country evaluated, standards exist at each step of the value chain to enable trade and marketing of nutrient enriched seeds, grains, and foods, especially with the publication of the PAS for grain. Standards, labeling, and marketing for biofortified foods are not complicated as once thought. Even with the long value chain (from agricultural research to processed foods) and the many consumption points from farming family consumption, sale of the basic commodity (flour), minimally processed foods, such as bread, and more highly processed, composite foods. NECs are commonly consumed staples and infiltrate the food system in most processed food categories. Previous thinking on searching for regulations for biofortified foods was hampered using the term biofortification. In all this research, the conclusions of Mejia et al. 6