Editing Substantial equivalence

{{Short description|Food safety testing method}}
In [[food safety]], the concept of '''substantial equivalence''' holds that the safety of a new food, particularly one that has been [[Genetic engineering techniques|genetically modified]] (GM), may be assessed by comparing it with a similar traditional food that has proven safe in normal use over time.<ref name="oecd">[http://www.oecd.org/science/biotrack/41036698.pdf Safety Evaluation of Foods Derived by Modern Biotechnology: Concepts and Principles] OECD (1993)</ref> It was first formulated as a food safety policy in 1993, by the [[Organisation for Economic Co-operation and Development]] (OECD).<ref name="agbiotechnet">{{cite journal | url=http://www.bfr.bund.de/cm/349/schauzu.pdf | title=The concept of substantial equivalence in safety assessment of foods derived from genetically modified organisms | author=Schauzu, Marianna | journal=[[AgBiotechNet]]  | date=Apr 2000 | volume=2}}</ref>

As part of a food safety testing process, substantial equivalence is the initial step, establishing [[Toxicology|toxicological]] and [[nutrition]]al differences in the new food compared to a conventional counterpart—differences are analyzed and evaluated, and further testing may be conducted, leading to a final safety assessment.<ref name="kok"/>

Substantial equivalence is the underlying principle in GM food safety assessment for a number of national and international agencies, including the [[Canadian Food Inspection Agency]] (CFIA), Japan's [[Ministry of Health, Labour and Welfare]] (MHLW), the US [[Food and Drug Administration]] (FDA), and the [[United Nations]]' [[Food and Agriculture Organization]] (FAO) and  [[World Health Organization]].<ref name="councilforbiotechinfo">{{cite web | url=http://thebeuselaer.weebly.com/uploads/6/3/8/4/6384873/substantial_equivalence.pdf | title=Substantial Equivalence in Food Safety Assessment | publisher=Council for Biotechnology Information | date=March 2001 | access-date=6 February 2016 | url-status=live | archive-url=https://web.archive.org/web/20160207101449/http://thebeuselaer.weebly.com/uploads/6/3/8/4/6384873/substantial_equivalence.pdf | archive-date=7 February 2016 }} () ([https://web.archive.org/web/20131227220643/http://www.bfr.bund.de/cm/349/schauzu.pdf Page archive])</ref>

==Origin==
The concept of comparing genetically modified foods to traditional foods as a basis for safety assessment was first introduced as a recommendation during the 1990 Joint FAO/WHO Expert Consultation on biotechnology and food safety (a scientific conference of officials and industry), although the term ''substantial equivalence'' was not used.<ref name="faowho1996">{{cite web |url=ftp://ftp.fao.org/es/esn/food/biotechnology.pdf |title=Joint FAO/WHO Expert Consultation on Biotechnology and Food Safety |publisher=FAO/WHO |date=October 1990 |archive-url=https://web.archive.org/web/20170518130948/ftp://ftp.fao.org/es/esn/food/biotechnology.pdf |archive-date=2017-05-18 |url-status=dead |access-date=16 February 2016}} "Joint FAO/WHO Consultation on the Assessment of Biotechnology in Food Production and Processing as Related to Food Safety" (1990)<br />"When molecular, microbial, genetic and chemical data establish that the food or food ingredient is sufficiently similar to its conventional counterpart, only minimal toxicological testing will generally be required." - Section 6.3.1, "Strategies for Assessing the Safety of Foods Produced by Biotechnology", report of a Joint FAO/WHO Consultation, World Health Organization, Geneva, 1991</ref><ref name="millstone">{{cite journal |title=Beyond 'substantial equivalence' |last1=Millstone |first1=Erik |last2=Brunner |first2=Eric |last3=Mayer |first3=Sue |journal=Nature |volume=401 |date=October 1999 |issue=6753 |pages=525–526|doi=10.1038/44006 |pmid = 10524614|bibcode=1999Natur.401..525M |s2cid=4307069 }}</ref> Adopting the term, ''substantial equivalence'' was formulated as a food safety policy by the OECD, first described in their 1993 report, "Safety Evaluation of Foods Derived by Modern Biotechnology: Concepts and Principles.<ref name="agbiotechnet"/> 

The term was borrowed from the FDA's 1976 substantial equivalence definition for new [[medical devices]]—under [[Federal Food, Drug, and Cosmetic Act#Medical devices|Premarket Notification 510(k)]], a new [[Medical device#United States|Class II]] device that is essentially similar to an existing device can be cleared for release without further testing.<ref name="agbiotechnet" /><ref name="fda510k">{{cite web |url=https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissions/PremarketNotification510k/ |archive-url=https://web.archive.org/web/20151009122013/http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissions/PremarketNotification510k/ |url-status=dead |archive-date=October 9, 2015 |title=Premarket Notification 510(k) |publisher=US Food and Drug Administration (FDA) |date=16 Sep 2015 |access-date=5 February 2016}}<br />"A 510(k) is a premarket submission made to FDA to demonstrate that the device to be marketed is at least as safe and effective, that is, substantially equivalent, to a legally marketed device ... that is not subject to PMS [Premarket Approval]. Submitters must compare their device to one or more similar legally marketed devices and make and support their substantial equivalency claims."</ref> The underlying approach of comparing a new product or technique to an existing one has long been used in various fields of science and technology.<ref name="agbiotechnet" />

In June 1999, [[G7|G8]] leaders requested the OECD to “undertake a study on the implications of biotechnology and other aspects of food safety.” In 2000, the OECD Edinburgh Conference on Scientific and Health Aspects of Genetically Modified Foods was held. Following those discussions, the OECD published an opinion that substantial equivalence is an important tool in analyzing the safety of novel foods, including GM foods. The document noted that substantial equivalence serves as a framework for approaching food safety assessment, rather than functioning as a quantitative standard or measure.<ref name=":0">{{Cite web |title=Pocket K No. 56: Substantial Equivalence of GM and Non-GM Crops |url=https://www.isaaa.org/resources/publications/pocketk/56/default.asp |access-date=Oct 13, 2024 |website=[[International Service for the Acquisition of Agri-biotech Applications]]}}</ref>

==Description==
The OECD bases the substantial equivalence principle on a definition of food safety where we can assume that a food is safe for consumption if it has been eaten over time without evident harm. It recognizes that traditional foods may naturally contain toxic components (usually called [[antinutrients]])—such as the [[glycoalkaloid]]s [[solanine]] in potatoes and [[Tomatine|alpha-tomatine]] in tomatoes—which do not affect their safety when prepared and eaten in traditional ways.<ref name="biotech-info.net">[http://www.biotech-info.net/antinutrients.html Substantial equivalence of antinutrients and inherent plant toxins in genetically modified novel foods, Novak, W. K.; Haslberger, A. G.,Food and Chemical Toxicology Volume 38 (6) p.473-483, 2000]</ref><ref name="OECD2000">Organisation for Economic Co-operation and Development. Report of the Task Force for the Safety of Novel Foods and Feeds C(2000)86/ADD1.  May 17, 2000 [http://www.biosafety.be/ARGMO/Documents/report_taskforce.pdf] {{Webarchive|url=https://web.archive.org/web/20160311114405/http://www.biosafety.be/ARGMO/Documents/report_taskforce.pdf|date=2016-03-11}}</ref><ref name="faotools">{{cite web | url=http://www.fao.org/3/a-i0110e.pdf | title=GM food safety assessment: tools for trainers | publisher=Food and Agriculture Organization (FAO) | date=2009 | access-date=8 February 2016 | url-status=live | archive-url=https://web.archive.org/web/20160224193755/http://www.fao.org/3/a-i0110e.pdf | archive-date=24 February 2016 }} ()</ref>{{refn|group=note|"The safety of food for human consumption is based on the concept that there should be a reasonable certainty that no harm will result from intended uses under the anticipated conditions of consumption. Historically, foods prepared and used in traditional ways have been considered to be safe on the basis of long-term experience, even though they may have contained natural toxicants or anti-nutritional substances. In principle, food has been presumed to be safe unless a significant hazard was identified." (OECD, 1993)<ref name="oecd"/>}}

The report proposes that, while biotechnology broadens the scope of food modification, it does not inherently introduce additional risk, and therefore, GM products may be assessed in the same way as conventionally bred products.<ref name="oecd"/> Further, the relative precision of biotech methods should allow assessment to be focused on the most likely problem areas.<ref name="oecd"/> The concept of substantial equivalence is then described as a comparison between a GM food and a similar conventional food, taking into account food processing, and how the food is normally consumed, including quantity, dietary patterns, and the characteristics of the consuming population.{{refn|group=note|"For foods and food components from organisms developed by the application of modern biotechnology, the most practical approach to the determination of safety is to consider whether they are ''substantially equivalent'' to analogous conventional food products, if such exist. Account should be taken of the processing that the food may undergo, as well as the intended use and the exposure. ''Exposure'' includes such parameters as the amount of food or food component(s) in the diet, the pattern of dietary consumption, and the characteristics of the consuming population(s). The approach provides a basis for an evaluation of food safety and nutritional quality." (OECD, 1993)<ref name="oecd"/>}}
<!--A quote from FAO, one of the agencies that developed the concept, is useful for defining it: "Substantial equivalence embodies the concept that if a new food or food component is found to be substantially equivalent to an existing food or food component, it can be treated in the same manner with respect to safety (i.e., the food or food component can be concluded to be as safe as the conventional food or food component)".<ref>Joint FAO/WHO Expert Consultation on Biotechnology and Food Safety.  Rome, Italy, 30 September to 4 October 1996 [https://web.archive.org/web/20170518130948/ftp://ftp.fao.org/es/esn/food/biotechnology.pdf] p.&nbsp;4</ref>-->

==Assessment process==
Substantial equivalence is the starting point for GM food safety assessment: significant differences between a new food item and its conventional counterpart would indicate the need for further testing. A "targeted approach" is taken, by selecting specific relevant molecules for comparison. For plants, selection of a suitable comparator may involve growing the new plant side by side with genetically closely-related varieties, or using publicly available composition data for closely-related varieties.<ref name=":0" />

Evaluation for substantial equivalence can be applied at different points in the food chain, from unprocessed harvested crop to final ingredient or product, depending on the nature of the food item and its intended use.<ref name="faotools" /> 

For a GM plant, the overall evaluation process may be viewed in four phases:<ref name="kok">{{cite journal |author=Kok EJ, Kuiper HA |title=Comparative safety assessment for biotech crops |journal=Trends Biotechnol. |volume=21 |url=http://www.ask-force.org/web/Food/Kok-Comparative-Safety-2003.pdf |issue=10 |pages=439–44 |date=October 2003 |pmid=14512230 |doi=10.1016/j.tibtech.2003.08.003 |url-status=live |archive-url=https://web.archive.org/web/20160214044505/http://www.ask-force.org/web/Food/Kok-Comparative-Safety-2003.pdf |archive-date=2016-02-14 }} ()</ref>

# '''Substantial equivalence analysis'''<br />Considering introduced genes, newly expressed proteins, and new secondary metabolites
# '''Toxicological and nutritional analysis''' of detected differences<br />Gene transfer, allergenicity, degradation characteristics, bioavailability, toxicity, and estimated intake levels
# '''Toxicological and nutritional evaluation'''<br />If necessary, additional toxicity testing, possibly including whole foods (return to Phase 2).
# '''Final safety assessment of GM plant'''
<!--A 2003 review in ''[[Trends (journals)|Trends in Biotechnology]]'' identifies seven main components of a standard safety test:<ref name="kok">
# Study of the introduced DNA and the new proteins or [[metabolite]]s that it produces;
# Analysis of the chemical composition of the relevant plant parts, measuring nutrients, antinutrients, and any natural toxins or known allergens;
# Assess the risk of gene transfer from the food to microorganisms in the [[Gut (anatomy)|human gut]];
# Study the possibility that any new components in the food might be allergens;
# Estimate how much of a normal diet the food will make up;
# Estimate any toxicological or nutritional problems revealed by data comparison with equivalent foods;
# Additional animal toxicity tests if there is the possibility that the food might pose a risk.-->

==Technological developments==
There has been discussion about applying new [[biochemical]] concepts and methods in evaluating substantial equivalence, such as [[Metabolomics|metabolic profiling]] and [[Proteomics|protein profiling]].  These concepts refer, respectively, to the complete measured biochemical spectrum (total fingerprint) of compounds (metabolites) or of proteins present in a food or crop.  The goal would be to compare overall the biochemical profile of a new food to an existing food to see if the new food's profile falls within the range of natural variation already exhibited by the profile of existing foods or crops.  However, these techniques are not considered sufficiently evaluated, and standards have not yet been developed, to apply them.<ref name="fao2000">{{cite web | url=http://www.fao.org/fileadmin/templates/agns/pdf/topics/ec_june2000_en.pdf | title=Safety aspects of genetically modified foods of plant origin | publisher=World Health Organization (WHO) | date=June 2000 |at=4. Approaches to the Nutritional and Food Safety Evaluation of Genetically Modified Foods |access-date=12 February 2016 | author=Joint FAO/WHO Expert Consultation on Foods Derived from Biotechnology | archive-date=16 February 2016 | url-status=live |archive-url=https://web.archive.org/web/20160216073624/http://www.fao.org/fileadmin/templates/agns/pdf/topics/ec_june2000_en.pdf}}</ref>{{better source|reason=Outdated as source for new and emerging technologies|date=February 2016}}

==Adoption==
Approaches to GM food regulation vary by country, while substantial equivalence is generally the underlying principle of GM food safety assessment. This is the case for national and international agencies that include the [[Canadian Food Inspection Agency]] (CFIA), Japan's [[Ministry of Health, Labour and Welfare]] (MHLW), the US [[Food and Drug Administration]] (FDA), and the [[United Nations]]' [[Food and Agriculture Organization]] (FAO) and  [[World Health Organization]].<ref name="faotools"/><ref name="loc">{{cite web | url=https://www.loc.gov/law/help/restrictions-on-gmos/index.php | title=Restrictions on Genetically Modified Organisms | publisher=Library of Congress | date=9 Jun 2015 | access-date=9 February 2016}}</ref><ref name="councilforbiotechinfo"/> In 1997, the [[European Union]] established a [[novel food]] assessment procedure whereby, once the producer has confirmed substantial equivalence with an existing food, government notification, with accompanying scientific evidence, is the only requirement for commercial release, however, foods containing genetically modified organisms (GMOs) are excluded and require mandatory authorization.<ref name="agbiotechnet"/>

To establish substantial equivalence, the modified product is tested by the manufacturer for unexpected changes to a targeted set of components such as [[toxin]]s, [[nutrient]]s, or [[allergen]]s, that are present in a similar unmodified food.  The manufacturer's data is then assessed by a regulatory agency. If regulators determine that there is no significant difference between the modified and unmodified products, then there will generally be no further requirement for food safety testing. However, if the product has no natural equivalent, or shows significant differences from the unmodified food, or for other reasons that regulators may have (for instance, if a [[gene]] produces a protein that has not been a food component before), further safety testing may be required.<ref name="oecd"/>

==Issues==
There have been [[Genetically modified food controversies#Substantial equivalence|criticisms of the effectiveness of substantial equivalence]].

==See also==
* [[GRAS]] - Generally Recognized As Safe, an FDA designation

==Notes==
{{Reflist|group=note|2}}
==References==
{{Reflist|2}}

[[Category:Food safety]]
[[Category:Genetically modified organisms in agriculture]]
[[Category:Biotechnology]]