Sampling and Detection Methods and the Biosafety Protocol: Views of the Global Industry Coalition 1

Sampling and Detection Methods and the Biosafety Protocol: Views of the Global Industry Coalition 1 A number of international organizations, such as Codex Alimentarius (Codex), the Organisation of Economic Co-operation and Development (OECD), and the International Standards Organization (ISO), have well-established work plans focused on development and harmonization of systems and standards for living modified organisms (LMOs) in commerce. These organizations incorporate applicable scientific expertise and experience to determine the appropriate integrated systems, standards, and specifications to best enable global trade in LMOs. Therefore, and in order to create synergies and avoid duplication of efforts, the GIC recommends that Parties to the Cartagena Protocol on Biosafety (Biosafety Protocol) focus on information-sharing with these and other relevant international bodies rather than developing criteria for acceptability and harmonization of sampling and detection techniques under the Biosafety Protocol. I. Sampling and Detection Methods for LMOs: Status of Existing Guidance A total of 331 million acres of biotechnology-derived crops were planted globally in 2009 (ISAAA, 2010). Increasingly, biotechnology is being acknowledged as one of the tools that must be employed to increase agricultural productivity to meet pressing food security challenges in an era of global climate change and reduced availability of arable land. As a result, biotechnology-derived crop production is expected to increase significantly and the occurrence of LMOs in the global commodity trade, which is already significant, will only increase. Most grain used for food, feed or processing is shipped by bulk handling systems. Bulk systems can carry the high volumes of grain that are necessary to keep the costs of the grain as low as possible. Commodity exporters and importers must work with government authorities to ensure compliance with national import requirements, which must be consistent with global standards. Any uncertainty or variability in test results that may arise from the absence of standardized tests or variability in sampling protocols have the potential to cause conflicting test results at the point of origin and destination, in which cases they will significantly increase the costs of grain that will eventually be passed on to the importers. Documentation requirements for importing LMOs that are intended for direct use as food or feed, or for processing (LMO-FFPs) may be met using a variety of different approaches. If testing is employed, the sampling and detection techniques should be easy to use, rapid, reliable, and cost-effective. For the past nine years, the key international organizations with decades of experience and success in establishing sampling protocols, detection methods and reference standards have been directly engaged in developing globally harmonized standards and systems for detecting LMOs in commerce. These 1 The Global Industry Coalition (GIC) for the Cartagena Protocol on Biosafety receives input and direction from trade associations representing thousands of companies from all over the world. Participants include associations representing and companies engaged in a variety of industrial sectors such as plant science, seeds, agricultural biotechnology, food production, animal agriculture, human and animal health care, and the environment. 1 of 10

organizations and the participating experts have developed science-based standards and specifications to best enable global trade in LMO-FFPs for the long term. Parties to the Biosafety Protocol can benefit from the experience and expertise of these organizations in considering the Biosafety Protocol s plan of work and Parties capacity building needs as implementation of the Biosafety Protocol progresses. Annex I provides a detailed overview of the work of these and other organizations relevant to products that fall under the scope of the Biosafety Protocol. II. Background on Sampling and Detection Method Applications and Technologies A number of different entities are involved in developing, assessing, and using detection methods for LMOs. As part of the assembly of dossiers for submission to regulatory agencies, biotechnology developers from both the private and public sector design and validate detection methods and create reference materials. Where required by competent authoritieis, biotechnology developers provide methods that are designed in accordance with existing national and international standards as published by the ISO and Codex Alimentarius. Some governments have chosen in the past to develop their own methods in addition to the method provided by the biotechnology developer, though this is less common today. These and other methods may be used to conduct regulatory studies on LMOs, measure the purity of seed, and analyze seed and food and feed matrices as required by governments that implement mandatory or voluntary labeling laws. Due to the wide variety of uses, these analyses may be performed by seed companies, grain handlers, food/feed companies and/or government agencies. The purpose may be to verify the presence or absence of LMOs, presence or identity of particular LMO events, or to quantify the proportion of an LMO event. For further information on types of detection methods, see Annex II. III. Considerations for Harmonized Approaches If Parties wish to demonstrate compliance with measures addressing illegal transboundary movement of LMOs via testing, it is critical that validated detection methods are used. Testing laboratories that test materials prior to export or at import will need to adhere to internationally-accepted testing protocols and proficiency standards. As indicated above, there are multiple international organizations working towards common (recognized) standards for detection methods. Any testing laboratories that are established will need to be able to test for all commercialized biotechnology traits. Currently there are over 100 traits in more than ten different crop species which have been approved by one or more regulatory agencies in the world. Building capacity for testing for all these events would require Parties to test for all LMOs which are not approved (i.e. illegal) in their country. Alternatively, laboratories in exporting countries could serve this need. Beyond the over 100 events currently approved, laboratories will also need to consider new products that will be entering the market. In addition, some countries may consider stacks or combined-event products as needing differentiation; testing can only be carried out separately for the component events of the stack. Testing for stacks is not possible using existing or any other foreseen method. LMOs already discontinued and removed from commerce may 2 of 10

also be present in the commodity chain for some time (further details can be found in Annex II). Significant resources are required to implement a single analytical method in an existing laboratory. In developing countries, this would not only require building the capacity to independently test for each event but will also include the need to build and equip facilities, train personnel, develop validation and quality-control procedures that are aligned with international standards, and staff the facility to a level sufficient for routine sampling and analysis, potentially at multiple ports of entry, and at a sample throughput level that does not hinder trade. Beyond the technical development, validation and analysis capacity, enforcement personnel, information systems, and a management/decision-making structure will be required. Such activities will and are already competing for resources with other activities that are necessary to ensure food security. The Parties should recognize that, should they take on the task of testing all, or a portion of imports, the magnitude of testing will be ever expanding and more complex and become more costly as the globalization of the technology continues. For this reason, it is the view of the GIC that Parties would be better served by developing policies that do not require perpetual testing of food and feed for possible illegal transboundary movement of LMOs. These policies should recognize that the zero-tolerance approach is not feasible given the realities of what is practical within the global grain trade. To ensure access to global grain supplies, they should aim to address issues caused by asynchronous authorization of LMOs, be science-based and consistent with international trade rules, and should permit the establishment of administrative tolerances for products that are approved in at least one country. While testing may be helpful in determining the integrity of certified systems of identity-preserved production, the optimum approach to identity-preserved production requires the establishment of commercially reasonable, widely-trusted systems comparable to those already in use for controlling the quality and identity of grain in global markets. IV. GIC Conclusions Due to the large number of LMOs that are currently commercialized, and LMOs that are in research and development to be commercialized in the future, and the intention of certain Parties to employ sampling and detection methods, it is the view of the GIC that: The Secretariat of the Convention on Biological Diversity should focus its efforts on information-sharing with relevant international bodies working on sampling and detection methods to ensure that information on sampling and detection methods for LMOs are available to the Parties. One mechanism that can be used to reach this goal is the database of information that will be made available by the private sector. In 2011, CropLife International launched a new website that will make its members detection methods for products on the market and information about associated reference materials available in a centralized, online, user-friendly, resource. This website is available at www.detection-methods.com. Interested Parties should take advantage of the work of these relevant international bodies related to criteria for acceptability and harmonization of sampling and 3 of 10

detection techniques for LMOs to ensure awareness of existing work and to create synergies and avoid duplication of efforts, rather than expending resources under the Biosafety Protocol. 4 of 10

Annex I: Organizations with Technical Expertise and Global Mandates Relevant to the Harmonization of Detection Methods and Reference Standards for LMOs 1. Codex Alimentarius Description: Codex Alimentarius, a body under the Joint FAO/WHO Food Standards Programme, is the global reference point and standards-setting body for consumers, food producers and processors, national food control agencies and international food trade. The purpose of Codex Alimentarius is to protect the health of the consumers and ensure fair practices in the food trade; and to promote coordination of all food standards work undertaken by international governmental and non-governmental organizations. Current Relevant Initiatives: The Codex Committee on Methods of Analysis and Sampling (CCMAS) defines procedures, protocols, guidelines for the assessment for food laboratory proficiency and quality assurance systems. Over the last 8 years, CCMAS developed Guidelines on Performance Criteria and Validation of Methods for Detection, Identification and Quantification of Specific DNA Sequences and Specific Proteins in Foods", which was adopted by the Codex Alimentarius Commission in July 2010. The guideline covers the detection of specific DNA and specific proteins in foods, including those foods containing materials derived from modern biotechnology. ISO supported the development and the text of this document. This document is now available to countries as the guidance document for those wishing to test for the presence of GMOs. 2. Organization for Economic Cooperation and Development (OECD) Description: The OECD brings together the governments of countries committed to democracy and the market economy from around the world to enable sustainable economic growth, including world trade in new technologies. The Organisation provides a setting where governments compare policy experiences, seek answers to common problems, identify good practice and coordinate domestic and international policies. Current Relevant Initiatives: The majority of OECD Member countries have a system of regulatory oversight for the products of modern biotechnology (including genetically engineered organisms) which are intended for release to the environment. The OECD has formed the Task Force on the Safety of Novel Foods and Feeds and the Working Group on Harmonization of Regulatory Oversight in Biotechnology with the goal of promoting international harmonisation in biotechnology. Both groups develop science-based consensus documents, which are mutually acceptable among member countries. These consensus documents contain information for use during the regulatory assessment of a particular food/feed product. In the area of food and feed safety, consensus documents are being published on the nutrients, anti-nutrients or 5 of 10

toxicants, information of the product's use as a food/feed and other relevant information. These documents are updated to take into account new knowledge on the topic and can be accessed on the OECD Website at http://www.oecd.org/document/9/0,3343,en_2649_34391_1812041_1_1_1_1,00.html, and at http://www.oecd.org/document/51/0,3343,en_2649_34387_1889395_1_1_1_1,00.html. Through the work of the Task Force and the Working Group, the OECD Member countries want to ensure that environmental health and safety aspects are properly evaluated, while avoiding non-tariff trade barriers to products of the technology. The outcome will be used by governments, industry and other stakeholders. The other important part of the programme is an Outreach activity including the development of BioTrack Online. It includes information related to the regulatory contacts in OECD countries and online databases on the products of modern biotechnology. The OECD Member countries have recently adopted an agreed set of Guidelines for Quality Assurance in Molecular Genetic Testing. The Guidelines address genetic testing for variations in DNA sequences in humans to assess conditions of health. Although the guidelines focus on molecular genetic testing for the diagnosis of a particular disease or condition and predictive genetic testing, guidelines of this kind represent the capability of the OECD to mobilize the experts required to develop standard protocols and references for detection measurements. 3. International Organization for Standardization (ISO) Description: The International Organization for Standardization (ISO; http://www.iso.org/) is a nongovernmental organization established in 1947 with members consisting of the leading and recognized national standards organizations of 159 countries. ISO provides a technological and scientific reference framework that takes into consideration safety, health and environment. ISO has a specific status with many UN agencies, including the WHO and FAO. It is also an observer at the WTO Committee on Trade and Environment (CTE), the Committee on Technical Barriers to Trade (WTO TBT) and the Committee on Sanitary and Phytosanitary Measures (SPS). In the area of technical assistance, ISO regularly cooperates with the WTO and ITC, and has entered into a Memorandum of Understanding with UNIDO. ISO Technical Committee 34: Food and Food Products (ISO TC 34) ISO TC 34 is responsible for standards regarding food and food products, and their propagules. This technical committee has published 756 ISO deliverables (International Standards, Technical Specifications and Technical Reports) of which 65 % are test methods. ISO TC 34 maintains 16 subcommittees that develop standards for food and feed, as well as grains. TC 34 activities on sampling standards: There were a number of sampling standards in use for commodity grain that have been applied widely to sampling of GMOs. In May 2008, an international workshop on sampling was convened in Seattle, USA, that was attended by experts from Asia, S. 6 of 10

America, Europe, North America and Australia. A significant conclusion of this workshop was that GMO should not be dealt with separately from sampling of grain for other purposes. A draft standard covering all sampling of grains was prepared. TC 34 has since convened a working group to develop this standard further and harmonise sampling standards across all grains including for the purpose of determining the presence of GMOs. TC 34/SC 16: The primary ISO TC 34 subcommittee involved in standards for testing methods is Subcommittee 16 on Horizontal Methods for Molecular Biomarker Analysis (TC 34/SC 16). It has released a number of standards related to nucleic acid extraction, nucleic acid and protein based methods of analysis, including: 1. ISO 21572, Foodstuffs Detection of genetically modified organisms and derived products - Protein based methods 2. ISO 21569, Foodstuffs Methods of analysis for the detection of genetically modified organisms and derived products Qualitative nucleic acid based methods; 3. ISO 21570, Foodstuffs Methods of analysis for the detection of genetically modified organisms and derived products Quantitative nucleic acid based methods; 4. ISO 21571, Foodstuffs Methods of analysis for the detection of genetically modified organisms and derived products Nucleic acid extraction. 5. ISO 24276, Foodstuffs Methods of analysis for the detection of genetically modified organisms and derived products - General requirements and definitions. 6. ISO TS21098, Foodstuffs Nucleic acid based methods of analysis of genetically modified organisms and derived products Nature of the information to be supplied and procedure to annex methods to the International Standards ISO 21569, ISO 21570 and ISO 21571 4. BIPM and National Measurement Institutes Description: The BIPM (Bureau International des Poids et Mesures) operates under the terms of the Metre Convention and the exclusive supervision of the International Committee for Weights and Measures (Comité International des Poids et Mesures, CIPM). The CIPM itself comes under the authority of the General Conference on Weights and Measures (Conférence Générale des Poids et Mesures, CGPM). The CGPM elects the members of the CIPM and brings together periodically, at present once every four years, representatives of the governments of Member States. The CIPM has established a number of Consultative Committees that bring together the world's experts in their specified fields as advisers on scientific and technical matters. The CCQM (Comité consultatif pour la quantité de matière) was set up in 1993. Its members are the National Metrology Institutes (NMI s) in those countries that belong to the Metre Convention. Present activities concern primary methods for measuring amount of substance, and international comparisons, establishment of international equivalence between national laboratories, and advice to the CIPM on matters concerned with metrology in chemistry. Current Relevant Initiatives: 7 of 10

Within the CCQM, the JCTLM (Joint Committee for Traceability in Laboratory Medicine) is a practical example of how DNA metrology best practices could be harmonized. The goal of the JCTLM is to provide a worldwide platform to promote and give guidance on internationally recognized and accepted equivalence of measurements in laboratory medicine and traceability to appropriate measurement standards. A long term effort is in place to eventually work through the BAWG (Bio-analysis Working Group) of the CCQM to establish internationally recognized DNA metrology standards. 8 of 10

Annex II Detection Methods and Challenges The presence of LMOs or their derivatives can be determined by the detection of either DNA sequences present as a result of insertion of a new transgene or the protein produced by the inserted gene. Protein-based detection methods are rapid and relatively inexpensive and offer a high degree of selectivity and sensitivity. Lateral flow strips can be used to show the presence or absence of a particular protein and can be deployed in non-laboratory conditions. Enzyme-linked immunosorbent assays (ELISAs) are more suited to laboratory use, and provide a means of quantifying the amount of a protein present in a sample. However, protein-based detection methods have limitations such as an inability to differentiate between genetic events that produce the same protein or to detect an LMO when no specific protein is present. In addition, the proteins in highly processed food are generally not recognized by the antibodies employed in these tools, and so they are not suitable for assaying such materials. Methods of detection of the transgenic insertion of DNA based on polymerase chain reaction (PCR) amplification of the specific target sequences are widely used for the detection of LMOs. Qualitative PCR methods can be used to show the presence or absence of a particular DNA sequence in a sample. Quantitative PCR detection methods provide a means of estimating the amount of a target DNA sequence in a sample. DNA-based methods can be used to distinguish between LMO events and are amenable to global standardization. However, the methods are time-consuming, costly, and technically complex. In addition, PCR must be performed under specially designed laboratory conditions, as it is susceptible to false positive results due to contamination by aerosols or dust. Beyond the many events currently approved for which detection methods have been developed, Parties will also need to consider a number of other situations. For example, stacks or combined-event products can represent a challenge, should countries choose to regulate them separately from their component events. These varieties are created by combining multiple events in a single LMO. However, the existence of multiple events, and thus multiple detection method target sequences, in a single LMO can influence the determination of the percentage of LMO kernels in a seed or grain sample, depending on the approach used. For example, bulk commodity shipments usually contain a mixture of single-event LMOs, combined-event LMOs, and conventional grain. Testing approaches usually involve grinding samples taken from a bulk commodity shipment into meal which is then analyzed. The PCR approach used is then to compare the amount of target DNA specific to one or more events with the total plant DNA present. The number of detection method target sequences per individual LMO may not be one; it may be several. Once individual LMOs have been reduced into meal, it is not possible to determine whether the DNA detected came from in a single kernel or more than one kernel. This precludes the ability to accurately determine the percentage of LMO kernels in a sample. Unfortunately, the problem of measuring combined events is a practical limitation of measuring DNA or protein and is thus, independent of the type or quality of detection method used. The only approach that can reliably determine the percentage of LMO kernels is to analyse each one 9 of 10

individually; this is impracticable at the low levels that are required by regulatory regimes in many countries, although it is employed by Japan, where the regulatory level is 5%. An additional target for testing are the many LMOs that have been removed from commerce as part of their normal life cycle. These products will gradually diminish in presence within commercial trade channels -- ultimately, to de minimis levels -- this is a stage that all products will pass through as a natural progression of the typical product life cycle. They represent a situation where Parties may commit resources to testing for these products for many years even though the probability of an illegal transboundary movement would be vanishingly small. Any kind of analytical testing has an inherent measurement uncertainty, and this is being considered by CCMAS. Since sampling and testing is a statistical process, repeated sampling and testing conducted on the same material where the presence of an analyte is low can produce different results. This is particularly the case when extremely low levels are set as thresholds. Variability in test results can also arise from lack of test standardization, variability in sampling protocols and the inherent error rate of the test. When these factors cause conflicting test results at origin and destination, they can significantly disrupt trade. 10 of 10