April 8, 2004

by Dr. Willy De Greef
Director, International Biotechnology Regulatory Services (IBRS)
AgBioView via Agnet April 9/04

The recent BioVision meeting in Alexandria (http://www.bibalex.org) once again showcase the astonishing range of GM crops in the pipeline. Much emphasis was put on work done by public goods research institutions on crops and traits of interest to resource poor farmers and countries. A fascinating glimpse of the potential future was on offer, with proof of concept demonstrated for a range of disease resistant crops and, even more importantly, for improved abiotic stress tolerance.

Technically, we seem to be for abiotic stress where we were in 1986-1987 for Bt and for herbicide tolerance. We know it works in some species. We see early stage results in the contained environment and even in some early field trials, and Proof of Concept, that vast watershed which divided blue sky research from applied technology and product oriented projects is very close. Technically, we should be able to make a difference in the hands of the farmer with regard to drought tolerance between 2010 and 2015. I said, technically, because in practice, larger hurdles than the still daunting task of translating all that promise into stress tolerant tropical varieties of key staple crops loom, and they have to be addressed soon, if we are not to let those target dates slip. The hurdles come in two forms.

First is the need to agree rapidly on formats and experimental approaches for a rational environmental risk assessment of these crop-trait combinations. For insect resistance and herbicide tolerance, these issues were intensively debated and rapidly agreed upon in a dialogue between the technology developers and key regulators in the late eighties, and the remarkable safety record of GM crops in the field is a tribute to the quality of the work done in that period.

Today, the regulatory environment is far more complex and hostile. It is not certain that technology developers would be able to find the regulators as open and willing to help us analyse the issues an create a high quality and science based approach to risk assessment for the new classes of traits. A quite different issue is that the technology leaders for the current batch of traits are mostly public research institutions, most of which do not have much previous experience with the regulatory and biosafety environment in which their material will soon be evaluated.

The second, and more intractable, issue is the cost of regulatory release and compliance, which is already the most important roadblock for public goods research projects in this field. Almost all regulatory compliance work for ag-biotech at the scale of commercial release and international trade is done in the regulatory affairs departments of the big technology companies. They have seen the costs of regulatory compliance soar over the past decade. The cost of obtaining regulatory clearance for, say, a new Bt maize event, grown in the U.S., Canada and Argentina, and registered in the main export markets of these countries for food and feed use, has been estimated by different companies as between 7 and 15 million $ and rising. On top of the very considerable financial burden this poses for the developers (a rule of thumb is that regulatory clearance of GM crops absorbs about half of the total product development investment), comes the certain knowledge that this is not the full picture.

As more countries set national regulations for GM crops and their products, technology developers have to keep registering their products in ever more markets. The Cartagena Protocol should, in principle, lead to a significant reduction of that burden, because it allows importing countries to accept new GM events without additional requirements. Unfortunately, it is rather the refusal of biosafety assessment data of exporters in favour of massive duplication of data gathering that seems to be the rule today. As a result, regulatory clearance has become a major component of life cycle management of GM crops.

The core biosafty assessment of a GM crop is only a fraction of the total regulatory cost. It has been estimated at between 800000$ and 2 million $ by various teams. The rest is mainly attributable to two factors: duplication and administrative burden.

In many countries, the duplication of biosafety assessments for regulatory submissions has become a sizable industry, which in many cases provides more jobs than actual product development. In many developing countries, in the absence of a biotechnology strategy, and in the absence of sufficient belief in the future of their own biotechnology programmes, authorities redirect donor funding for biotechnology towards me-to biosafety assessments, most of which are only intended to confirm in other hands what was already demonstrated in the core regulatory package.

A widely traded GM crop such as maize will have to be cleared in well over twenty markets now, from Argentina through China and the EU to Russia. Each of these jurisdictions requires applicants to follow their national regulatory pathways. Even though the actual technical questions, the elements of the risk assessment, are usually very similar, authorities have almost systematically attempted to differentiate their approaches by different regulatory file format requirements, distribution of authorising responsibility and approval procedures. A task such as translating regulatory files, which can run up to a thousand pages or more, into dozens of languages, is by itself a major challenge and a significant cost.

If we are to see some of the public goods research breakthroughs making it to resource poor farmers, these non-technical hurdles have to be addressed urgently. It is not likely that donor agencies which are currently paying for the research, will be willing to foot the bill for this massive undertaking. That leaves two options: cut the losses and forget about things like Golden Rice (not really an option…), or working to reform a system of regulatory review that has spiralled out of control. This reform is as much a priority for the biotechnology community as the continued scientific work. There are several avenues for rapid improvement.

The first is to tackle the duplication of data gathering requirements, document it as a source of waste of biosafety assessment money and therefore probably a negative biosafety impact. The default approach of any authority should be Mutual Acceptance of Data. Duplication of experiments (especially the baseless requirement in some countries to duplicate generation of compositional data for imported crops, based on trials in the receiving country) should be the exception, and based on a scientific rationale.

The second immediate need is to promote the use of a uniform set of application formats, and to accept a limited need for translation of technical files. This would increase biosafety. Translation of highly technical filings in widely different languages is a challenging task, and companies achieve it reliably only at massive cost. Public sector institutions are unlikely to have the resources for the necessary quality control, and may therefore be working with files that have different meanings for the applicant and the regulator, a recipe for disaster. A uniform format already exists. It is found in the different guidelines developed by OECD between 1986 and 1995, which are the technical basis for the annexes of almost every regulatory system in the world today.

A third burden which has to be challenged urgently is the “time limited permit”. This system, in which countries approve GM crops only for a limited period of time (e.g. in the EU for ten years), leads to a nightmare of complexity. Applications for product approval extensions have to start several years before the actual end of the approval period. During that time, which in the EU is typically 3-4 years, developers shoulder massive risks in their product development pipeline, since permit renewal cannot be taken for granted and large breeding and seed production programmes may well have to be abandoned at the last moment. The institutionalised inability of many regulatory authorities to respect their own official timelines for reviewing files adds to the uncertainty.

It is hard enough for herbicide tolerant and insect resistant crops to survive in this hostile regulatory environment. Applications such as Golden Rice, CMV resistant cassava or drought tolerant wheat can not possibly reach their potential under these constraints. We urgently need a strategic review of the regulatory maze in the light of the coming generation of public goods GM crops, in a setting where the actual science of the regulatory system can again be a major part of the discussion.

There are not many policy platforms left where this is possible. That observation by itself is a sad reflection for how far we have lost contact with scientific and farming reality in the biotechnology debate. Much of the science based framework for risk assessment which proved itself so well in the field over the past decade was agreed upon in a Group of National Experts of OECD, working between 1983 and the mid-90s. Given the current political environment around biotech, the chances are slim that a similar group of experts could be brought together to do a reasonably politics-free job today. It is impossible to imagine this happening in the Cartagena Protocol, where science is systematically discredited as a source of decision making on safety.

The scientific community urgently has to ask policy makers about where they think they are heading with the current approach for biotechnology regulation. It is vastly inefficient in terms of biosafety assessment. It is also actively undermining the sustainability policies of the international community, and a major cause for the delays in reaching the global objectives for poverty eradication and for improvement of the sustainability of agriculture. Not being able to achieve food security and a reduction of the environmental footprint by lack of technological or other resources is one thing. Not being able to do so because we cannot get the policies set up to translate our proven capacities into decisive change is entirely unacceptable.