The OECD would like to respond to a recent letter in Nature entitled Beyond Substantial Equivalence by Erik Millstone, Eric Brunner and Sue Mayer. The main conclusion of their letter is that:

"Substantial equivalence is a pseudo-scientific concept because it is a commercial and political judgement masquerading as if it were scientific. It is, moreover, inherently anti-scientific because it was created primarily to provide an excuse for not requiring biochemical or toxicological tests."

There are quite a number of erroneous assumptions behind the arguments presented in the letter, which inevitably lead to this misguided conclusion. In effect, the authors have set up a target which they have then elaborately tried to knock down.

The OECD would like to address some of the erroneous arguments in their letter by explaining:

• who developed the concept of substantial equivalence;
• why they chose to elaborate this particular concept;
• how the concept can - and cannot - be used; and
• the continuing work to further develop the concept.

Who Developed the Concept of Substantial Equivalence?

The concept of substantial equivalence was first described in an OECD publication Safety Evaluation of Foods Derived by Modern Biotechnology: Concepts and Principles (1993). This publication was the report of a group of about 60 experts from 19 OECD Member counties who spent more than two years discussing the challenge of how to assess the safety of novel foods, including genetically modified foods. The OECD Member countries accepted this report.

The majority of these experts (who were all nominated by governments) were regulatory scientists from those government agencies and ministries in Member countries who have the onerous responsibility for ensuring consumer safety.

In undertaking this responsibility, one of the most powerful tools that regulators have in their armoury is sound science. So it was natural for the OECD to provide a forum for government experts at the beginning of the 1990s, to address the challenge of developing scientific principles for the safety assessment of novel foods.

Why the concept of Substantial Equivalence?

The concept of substantial equivalence was not developed as an excuse for not requiring biochemical or toxicological tests. In fact, there were a number of important observations, arising during the discussions of the experts in the early 1990s, which led to the emergence of the concept. One of the most significant of these was the recognition that, in general, new varieties of whole foods coming to the market do not undergo extensive toxicological testing. A second observation was the knowledge that traditional whole foods often contain natural toxicants and/ or anti-nutritional substances. So it is likely that a battery of traditional toxicological tests on a given traditional variety of whole food (for example, a new variety of potato) might well reveal undesirable effects in animal tests. But despite this, we know that whole foods (such as potatoes) if prepared and used in appropriate ways have been considered safe on the basis of long-term experience.

>From these observations, it became clear that the results of traditional toxicological testing on whole foods could often lead to misleading results. And this conclusion can also be confirmed, for example, through the extensive literature on the lessons learned through the toxicological testing of irradiated foods.

It was also clear, that in assessing the safety of a genetically modified food, it was unreasonable and unscientific to expect an absolute standard of safety, which could be demonstrated through traditional testing. What was required was the notion that a new modified variety should be as safe as traditional varieties. So the important starting point in a safety assessment should be a comparison between the new variety (say a genetically modified potato) and its traditional counterpart (say an unmodified variety) with a view to demonstrating that it is as safe as the traditional counterpart. In other words, that it is substantially equivalent.

How the concept can - and cannot - be used

The OECD would like to emphasise that substantial equivalence is not in itself a substitute for a safety assessment. It is a guiding principle or concept, which is intended to be a useful tool to those engaged in safety assessments. It is the starting point, which allows a regulator - through a comparative process - to analyse the differences between a traditional variety and a novel variety. This analysis - the demonstration of substantial equivalence - may be relative simple process if there is extensive knowledge of the parental variety and of the trait which is the focus of the modification. On the other hand, if that type of information is not readily available, it might require a more sophisticated process involving analytical work or even testing.

The use of substantial equivalence is an important tool which allow regulators in an assessment, to focus on the safety issues which are of most importance.

Continuing work

Since the concept of substantial equivalence was first described, the OECD and others have further developed the concept. It has been recognised, since the beginning, that there may be new foods, which are so novel in certain respects, that they could not be considered substantially equivalent. And in such cases, clearly there will be a need for a sophisticated safety assessment. Similarly, there might be foods which could be substantially equivalent except for the novel trait. In these cases, the safety assessment should focus on the novel trait.

As mentioned earlier, the concept of substantial equivalence was developed in a proactive way in that it was developed before any new genetically modified foods cane to the market. In the meantime, a number of new foods have been assessed in a number of countries and there has been accumulation of knowledge on how to apply the concept. To take account this knowledge, the OECD's Task Force on the Safety of Novel Foods and Feeds is continuing work on safety assessment and continues to focus on the application of the concept. This includes work on assessment methodologies when substantial equivalence can not be applied. There is also work under way to identify the critical nutrients and toxicants which are found in major crop plants which would be an important focus of a demonstration of substantial equivalence. For further information, please contact Nicholas Bray in the OECD's Media Relations Division
(tel. 33 1 45 24 80 90 - e-mail: nicholas.bray@oecd.org).

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