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Plants > Biotechnology / PNTs > Molecular Farming CFIA
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TABLE OF CONTENTSPART ONE: INTRODUCTION AND OVERVIEW PRESENTATIONS Introduction and Background Opening Remarks Industry Perspective Introduction to Canadian Plants with Novel Traits Regulation Status of U.S. Plant Molecular Farming Regulations PART TWO: WORKSHOP DISCUSSION THEMES Theme 1: Human Health Issues Theme 2: Animal Health and Feed Issues Theme 1 and 2: Discussion Highlights and Key Findings Theme 3: Environmental Issues PART THREE: PROPOSED CFIA INITIATIVES AND NEXT STEPS Overview of Consultation Results Proposed CFIA Initiatives on Regulating Plant Molecular Farming Stakeholder Perspectives - Open Forum in Reaction to the Recommendations Commitment and Next Steps APPENDICES
PART ONE: INTRODUCTION AND OVERVIEW PRESENTATIONS Introduction The Canadian Food Inspection Agency (CFIA), which is responsible for regulating environmental releases of plants with novel traits, is providing opportunities for the public and stakeholders to learn about molecular farming and to express their views and concerns regarding the regulation of plants used in plant molecular farming in Canada. The CFIA intends to take into account all stakeholder input when drafting new regulatory directives that are anticipated to be in place by spring 2002. This document provides an overview of proceedings and recommendations developed at the Plant Molecular Farming Multi-stakeholder Consultation Workshop hosted by the CFIA in Ottawa, Ontario, on October 31 to November 2, 2001. Fifty-five participants attended (see Appendix 1), out of 75 invitees representing academia, consumers groups, producer and trade associations, industry representatives and public interest groups. Background Plant molecular farming uses plants with novel traits (PNTs) to produce substances for scientific, medical or industrial use. Plant molecular farming is still at the experimental stage and currently there are no plants for molecular farming approved for commercial release in Canada. The CFIA is conferring with a wide range of people now, while products of molecular farming are still years away from the marketplace. Public and stakeholder consultation is very important to the assessment and revision of CFIA regulatory directives as they relate to plant molecular farming. We are defining "plant molecular farming" as "the cultivation of plants for industrially, medically or scientifically useful biomolecules, rather than for traditional uses of food, feed or fibre". Plants for molecular farming could be producing vaccines, antibodies or other pharmaceuticals, or industrial enzymes or bioplastics. These products could provide many benefits to society, including drugs and vaccines to respond to diseases such as cancer, diabetes, rabies, foot and mouth disease and the common cold. Through plant molecular farming, existing drugs could potentially be produced more safely and at lower cost, while other drugs that could not otherwise be produced could be made available to the public. Since plants used for molecular farming may be producing biomolecules known to be physiologically active in humans or livestock, a regulatory framework is required to safeguard human and livestock health. The CFIA already provides a strong regulatory system governing the field testing and commercial production of PNTs through the CFIA's Plant Biosafety Office's rigorous science-based environmental safety assessments of PNTs. Development of regulatory partnerships with Health Canada, along with the Feed Section, CFIA, will facilitate the assessment of human and livestock health impacts of plant molecular farming. The regulatory issues associated with plant molecular farming are complex, and involve many sectors of Canadian society, including the biotechnology industry, agriculture, medicine, agricultural trade, academia, environmental interest and other civil society groups. The views of these stakeholders as well as the general public will be considered in the development of the regulatory pathway for plant molecular farming. The following are synopses of presentations made on the first morning of the consultation (Wednesday October 31), including opening remarks by the Executive Vice President of the CFIA, an overview of the plant biotechnology industry perspective by the Chair of BIOTECanada's Task Force on Molecular Farming, and introductions to Canadian and U.S. regulation of plants with novel traits, or bioengineered plants, by representatives of CFIA, Health Canada and USDA-APHIS. (Biographies of the speakers are given in Appendix 2.) Synopses of the question and answer sessions that followed each presentation are also provided. These presentations laid the groundwork for the three themes that formed the focus of breakout discussions over the following day and a half: human health issues, livestock health issues and environmental issues. Opening Remarks Welcome to the CFIA's Multistakeholder Consultation on Plant Molecular Farming. We appreciate that you've taken your valuable time to participate. It's very important that you're here to contribute to the assessment and revision of our regulatory directives as they relate to plant molecular farming. We are defining plant molecular farming as the cultivation of plants for industrially, medically or scientifically useful biomolecules, rather than for traditional uses of food, feed or fibre. Plants for molecular farming could be producing vaccines, antibodies or other pharmaceuticals, or industrial enzymes or bioplastics. The point here is that these plants with novel traits could be producing biomolecules that we know ahead of time may be harmful to humans, animals or wildlife under certain conditions. It is a challenging new field for the CFIA, of which, like all new technologies, the risks to the environment and to animal and human health must be carefully assessed. We expect that in many cases these plants will have environmental or human health impacts over and above other agricultural plants with novel traits. We are also mindful of the perceptions of biotechnology among Canadians and the concerns often raised about the associated risks. Five or six years ago, biotechnology was low-profile - things have changed since then. The public perception on biotechnology is sometimes good, and many times bad, and very seldom neutral. The CFIA provides a strong regulatory system governing the field testing and commercial production of plants with novel traits. The CFIA's Plant Biosafety Office undertakes rigorous science-based environmental safety assessments of novel plants. We are not here today to revisit our entire assessment and regulatory process for plants with novel traits. This consultation is, however, designed to solicit your input on current and future CFIA regulatory policies, procedures and regulatory directives overseeing the field-testing and commercial production of plants with novel traits for molecular farming. What we feel is missing in this area is a partnership with Health Canada for the assessment of human health impacts of this technology, in addition to fully taking into account potential risks to livestock animals and the environment. This process is in keeping with the CFIA's commitment to the recommendations of both the Canadian Biotechnology Advisory Committee (CBAC) and the Royal Society of Canada's Expert Panel on the Future of Food Biotechnology for greater openness and transparency in our policy-making. The regulatory issues are complex, and involve many sectors of Canadian society, including the biotechnology industry, agriculture, medicine, agricultural trade, academia, environmental interest and other public interest groups. We have brought representatives of all these sectors from across the country to discuss these issues. As many of you know, last night the CFIA hosted a public forum in Ottawa on plant molecular farming, to provide others an opportunity to voice their opinions. A report from that meeting will be made at this consultation and will be taken into consideration in the development of our regulatory pathway for plant molecular farming. In addition, the Plant Biosafety Office of the CFIA is posting a questionnaire on its website, open to anyone who wishes to submit their opinions on the regulation of plant molecular farming in Canada. That questionnaire is based on the questions we will be addressing at this consultation. Our website address is included in your consultation package. In these ways we are encouraging Canadians to participate in the development of regulatory directives for plant molecular farming and to explore how we can best apply sound risk management to the regulation of this technology. Both myself, as Executive Vice President, and the President of CFIA, Mr. Ronald Doering, are very interested in the biotechnology file for a number of reasons. It is a very high profile file, and we want to ensure that the Agency is addressing the issues with the right approach. We know that the biotechnology industry is very important for Canada's economy, and that the industry is fighting a battle with some organizations such as Greenpeace and other environmental groups. In this context, and in light of what CBAC and the Royal Society recommended, we know that it is important that we change the way plant molecular farming is handled. In the past, there was a key element absent in our assessment process - and that element was input from Health Canada on the potential health impact that these plants may pose. In some cases the plants that may be used for molecular farming are plants that may also be used for animal feed. And this is certainly a concern of ours. We want to lay the foundations for the regulatory system in the appropriate manner. The public consultation that was held last night went well. If it had taken place in Vancouver, B.C., I think that there would have been more excitement. I also found it amusing that this discussion on the most modern of technologies took place at the Museum of Nature - which is full of dinosaurs! I suppose this helps us keep things in perspective in terms of evolution. Certainly, we are here today to listen to what you have to say. We have our regulatory function and responsibilities that must be considered, and we will do our best to accommodate your needs. The CFIA is constantly under scrutiny. In a media search for CFIA quotes from January 2001 to June 2001, the Agency was quoted in the media 2,600 times. The days when the CFIA and the process of food inspection were low profile are gone. Foot and mouth disease, mad cow disease, and bioterrorism have all brought more focus onto the CFIA, and we want to make sure that what we do is open and transparent and that the public is reassured with our performance. We are facing a major challenge in that the majority of Canadians are not necessarily science-literate. We once thought that by providing more information to the public, they would be less worried. This is not the case. More information, in many cases, results in more questions and concerns, and less reassurance. It is a challenge that industry and government will have to face in terms of making sure that the correct information is relayed to the public and that it is correctly interpreted. There are organizations that have declared open war against biotechnology. However, 90% of the population still have an open mind, and these are the people we have to educate about the Agency and Health Canada, and about how well the regulatory process operates in Canada. We look forward to many lively discussions on these very interesting issues over the coming days. And appreciate and welcome your input. Industry Perspective Today we are talking about the production of pharmaceutical proteins from genetically engineered crop plants. Industry prefers the term "plant-made pharmaceuticals" over "molecular farming". Plants and medicine have been closely associated throughout the ages. Plant-made pharmaceuticals offer a number of benefits: greater and faster access to new drugs; commercialization of drugs that would not otherwise be available; potential to create new types of life-saving drugs; reconvergence of plants as sources of pharmaceuticals for human and animal health; and products to meet acute and chronic medical needs. By using crop plants, plant-made pharmaceuticals can be produced cost-effectively by experienced growers using current agricultural methods, and the infrastructure exists for efficient production and precise handling. Crop plants also are well characterized with respect to pollination, seed dormancy, tendency to weediness and other factors necessary to develop confinement procedures. In addition, they usually do not produce toxins or anti-nutritionals and are much less likely to be invasive of unmanaged ecosystems. Industry is committed to working with regulatory authorities to develop science-based, transparent regulatory systems in North America and has formed the Biologics Task Force to develop recommendations and positions. Industry participation includes companies such as Prodigene, Integrated Protein Technology, Applied Photologics, Medicago, CropTech, Meristem Therapeutics, Planet Biotech, SemBioSys Genetics, MPB-Cologne, Dow AgroSciences, Syngenta, and Aventis. Plants and products covered by these companies include corn, soybeans, barley, rice, alfalfa, safflower seed, potatoes, plant antibodies and the use of inducible promoters. Some of the key findings/recommendations of the Task Force include:
The Task Force proposes that: "The level of the expression product in food or feed must be below that which is detectable using a scientifically validated method of analysis for that specific product until such time as a scientifically established threshold is set. Until a threshold level greater than the level of detection can be established, the defacto scientifically established threshold level for the regulated expression product would be the detection level". The key to controlling the risks associated with the production of plant-made pharmaceuticals are confinement systems that ensure:
The proposal for this system and methodology is rigorous identity preservation. IP (Identity Preservation) systems would be implemented at all levels from initial field trials to commercial production. IP systems will ensure that pharmaceutical crops will be completely segregated from similar and other crops. These systems are developed considering the specific crop, the platform, the expression product (the unique characteristics of the protein) and the expression profile (such as tissue specificity, nature of expression, etc.) IP systems should be approved as part of the permitting process of regulatory agencies and they should be based on best practices methodologies, such as Good Agricultural/Agronomic Practices and Standard Operating Procedures. These best practices are to be applied to every aspect of production, including training, crop production, site selection, crop identification, crop containers, use of protective clothing by workers, post-harvest crop handling and transportation, compliance assessment and verification. Industry is committed to doing everything possible to protect human health and the environment in the production of plant-made pharmaceuticals. Industry will ensure that there is rigorous compliance with confinement procedures, that information is shared with appropriate regulatory authorities (such as methods of analysis used for confirmation of confinement), and that there is full cooperation with agencies in audits of confinement procedure and on-site inspections. As this small, developing and very enthusiastic industry evolves, there is a keen desire to create and recognize high standards for the production of these types of crops. Some of the key perspectives of industry regarding plant-made pharmaceuticals are:
Question and Answer Session Q: Does the Canadian public have to be prepared to accept
contamination? The industry statement is very cautious and carefully worded about
safety and confinement and containment - but also speaks to contamination, acceptable
risk, and levels of tolerance. Is this not sending a mixed message to the public? Q: Are similar guidelines being looked at for bio-industrials
(such as bioplastics)? Q: You have gone strictly with recombinant DNA. What happens if
the product is created using a different method, for example through selective
breeding? Through your methodology, would this not be exempt from oversight? Q: What happens in terms of waste management? Q: What is the difference between the terms "confinement"
and "containment ". Q: Is it acceptable to produce pharmaceuticals in a food crop?
Should we be looking at other platforms rather than food crops for producing these
products? Q: You are talking about proteins exclusively. But when you
talk about plants with novel traits, what if there were a gene technology transfer for the
purpose of producing not a protein but a gene product - not in fact novel but novel to the
species to which it is being produced. An example would be the production of taxol,
which is used in breast cancer therapy and is in very short supply, very expensive, and
which cannot be produced synthetically. What if it were produced in corn?
It is not currently expressed in corn. Would that be a novel trait? Introduction to Canadian "Plants With Novel Traits" Regulation CFIA operates under the Canadian Federal Regulatory Framework for Biotechnology, and the use of existing legislation and regulatory institutions. There is no "gene" act or biotechnology agency. The primary trigger for assessment is the novelty of the product rather than the specific means by which it was produced. What that means is that a plant with novel traits (PNT) is not necessarily a recombinant DNA product. For example, whether herbicide tolerance is created through recombinant techniques or traditional breeding doesn't matter, it is still regulated as a novel plant. A novel trait is a characteristic intentionally selected, created or introduced into a distinct population of the same species through a specific genetic change and is not substantially equivalent to existing characteristics in existing populations of the same species with regard to weediness potential, gene flow, plant pest potential, impact non-target organisms, and impact on biodiversity. Livestock feed is considered to be any substance or mixture of substances containing amino acids, anti-oxidants, carbohydrates, condiments, colouring, foaming or flavouring agents and other components for consumption by livestock, for providing the nutritional requirements for livestock, or for the purpose of preventing or correcting nutritional disorders in livestock. A novel feed is a feed comprising an organism or organisms or parts of products thereof that is not listed in Schedules IV or V to the Feeds Regulations or has a novel trait. How does a plant with a novel trait move through the regulatory process? For product-type novel plants, there are set stages from confinement in a laboratory setting to confined research field trials and commercial production. For novel plants in confined research field trials, including those producing pharmaceuticals, there are measures for reproductive isolation, site monitoring, disposition of plant material, post harvest land use restrictions and monitoring. Unconfined release consists of use without requirements for reproductive isolation, site monitoring, and post-harvest land use restrictions. Exceptions include Bt insecticidal protein expressing plants, for which resistance management plans are imposed, and herbicide tolerant Brassica rapa, for which cultivation is restricted to Western Canada. Criteria for unconfined release assessment includes the molecular characterization of the PNT and its biology and interactions. For example, does it have the potential to become a weed? for gene flow? to become a plant pest? to have an impact on non-target species or on biodiversity? For livestock feed assessment, the same criteria and information submitted for review of a plant for environmental release is looked at as well as information on the host and donor organism directly related to use as livestock feed, including the history of the use of the plant as feed, its potential to produce toxic compounds, and available toxicology data. The key issue is the nutrient composition and how it has changed (whether deliberately or not, i.e. crude protein, crude fat, fibre, etc.). To date, 38 PNTs have been authorized for release. These commodity crops include canola, corn, flax, soybeans, potatoes and wheat, and a number of traits including herbicide tolerance; insect pest and virus resistance and oil compositional changes. The actual release is a commercial decision. William Yan, Health Canada, Office of Food Biotechnology The regulation of products of biotechnology falls under three federal areas: Health Canada is responsible for food, drugs, cosmetics, medical devices and pest control products; the Canadian Food Inspection Agency (CFIA) is responsible for plants, livestock feeds, fertilizers and veterinary biologics; and Environment Canada handles microorganisms used in bioremediation, waste disposal, mineral leaching or enhanced oil recovery, etc. Novel foods, like all foods, are regulated under the Food and Drugs Act, which contains the Novel Foods Regulations. The Regulations define a novel food as any food that has no history of safe use as a food; or a food that is manufactured using a process not previously applied to that food; or any food that has been genetically modified. For molecular farming, the third category is most applicable. Safety assessments are based on Guidelines that were developed in 1994 (Guidelines for the Safety Assessment of Novel Foods). These guidelines are currently under revision, and the goal is to have the revisions complete by Summer 2002. It is important that these guidelines be brought up to date, because they were written prior to the development of the Novel Foods Regulations. The guidelines were developed through exhaustive international consultations with the WHO, FAO and OECD. The assessment process is undertaken by a team of scientific evaluators with expertise in molecular biology, toxicology, chemistry, nutritional sciences and microbiology. It is a comparative approach - in other words, we are comparing the modified food to another non-modified or conventional food and looking for any differences. We are looking for both intended and unintended effects as a result of the modification. The assessment focuses on any difference, for example the introduction of a toxin or an alteration in the nutritional content. There are five key areas that a proponent has to address to obtain approval for a novel food product: how the crop was developed; the composition of the novel food in comparison to conventional counterpart; the nutritional composition; toxicity; and allergenicity. How the food crop was developed is assessed, including the molecular biological data which characterizes the genetic change, such as information about the host and the donor, how the modification was done, how stable was the introduced trait. The composition of the novel food product is then compared to its non-modified counterpart food to identify any changes that may have occurred, and to determine if these changes fall outside the acceptable range for that particular food crop. Similarly, the nutritional information for the novel food is compared to its non-modified counterpart. Whenever a new gene, and therefore a new protein, is introduced, there is a potential for the introduction of a new toxin that was not in that food previously, toxicity is a key consideration. Similarly, the potential for allergenicity is another key area that must be evaluated to ensure that an allergen that was not previously present has not been introduced. Since 1994, 50 novel food products have been approved by Health Canada. These have been crop plants (corn, canola, soybean and potato), with altered agronomic traits such as insect and virus resistance, herbicide tolerance, crop yield, delayed ripening, etc. Health Canada's website (http://www.hc-sc.gc.ca/food-aliment) provides information on decisions on new products, Novel Food Regulations, Guidelines for the Safety Assessment of Novel Foods, and summaries of Novel Food Decisions. Question and Answer Session Q: People are going to be using field trials to generate material for
pre-clinical and early phase clinical studies and there is a blanket restriction on the
use of those materials for human or animal consumption. This is a Health Canada
problem, but how do you get around this problem? Q: Do the novel food regulations apply to things that are not food,
things that are never intended to enter into the food supply? Q: Please clarify what is the "product" in the statement:
the primary trigger for assessment is the novelty of the product rather than the
specific means my which it was produced. Q: Would a product, such as St. John's Wort, grown in complete
containment escape regulations? Q: Is it intended that crops grown for industrial purposes (for
example, canola grown for use as an industrial lubricant), fall under these regulations?
If so, this is a huge disincentive to research of this type. Q: What constitutes a food allergy? What is the threshold for
considering something a food allergen? From Health Canada's perspective, on the therapeutic rather than the food side, one of the challenges concerns whether we can ever achieve 100% safety assurance for products from molecular farming. In the traditional biologics sense, there is an acceptance that there are going to be within a population some adverse effects, some of which will be allergic reactions. The question is, what level of allergic reactions could we tolerate in terms of a risk assessment for molecular farming products. The answer probably is, the same level as is acceptable for currently approved products. Health Canada assessments will ask for specific data that addresses allergic reactions or allergic side effects. If we are seeing a large number of allergic reactions to a molecular farming product, we would have concern and that safety issue would need to be addressed. The safety assessment of a novel food takes a comparative approach. That means that we compare a modified version to an unmodified or traditional version. So if you consider soybeans, there is a portion of the population that is allergic to soybeans. We are not asking that a modified soybean be completely non-allergenic. We are asking that it not be more allergenic than unmodified soybean. Status of U.S. Plant Molecular Farming Regulations In the United States, traditional pharmaceutical products are managed by two agencies: USDA-APHIS, Centre for Veterinary Biologics (CVB), which handles veterinary biologics, and the Food and Drug Administration (FDA), which is involved in human biologics and drugs and animal drugs. Pharmaceuticals from plant molecular farming are regulated by those two agencies as well as the USDA-APHIS, Plant Protection and Quarantine (PPQ) section. The PPQ issues permits for the importation, interstate movement and field testing of "pharm plants". Permits for importation require the plant to be quarantined upon arrival in the U.S., and the location is inspected to ensure containment. Generally, PPQ is the first agency which applicants developing "pharm plants" must work with before initiating an FDA or CVB review. The three agencies work together cooperatively. PPQ provides the other agencies with copies of all permits, and the agencies are permitted to share confidential business information. The agencies have jointly inspected field tests. The agencies are also working together to develop expertise and knowledge as plant molecular farming evolves. To this end, they co-sponsored a meeting called "Plant-derived Biologics Seminar and Public Hearing on Plant-derived Biologics" (for transcript see http://www.fda.gov/cber/minutes/workshop-min.htm#plant), and are jointly preparing a document entitled Guidance on Drugs and Biologics Derived from Bioengineered Plants for Use in Humans and Animals, which is expected to be published by the end of the year in the Federal Register for public comment. These are not regulations - it is a "points to consider" document. The three key issues in the field testing of "pharm plants" are:
The PPQ has identified a number of factors that are needed for the commercial production of products from "pharm plants". There will need to be procedures to ensure that the plants/seeds do not enter the food/feed supply unless approved by FDA. The FDA has not yet made a decision regarding tolerance levels, and an adventitious presence policy is in development. This may impact on the acceptability of low-level contamination. An identity preservation system is required to track seeds from shipping to planting and from harvest to product extraction. The federal government will need to be involved in auditing the system. Decisions will be made on a case-by-case basis, because each product is unique and will be produced in different plants or using engineered plant viruses. All pharmaceuticals derived from plants will meet the same safety and efficacy standards that are in place for traditional products. These plants will not be de-regulated by the United States Government, like Bt corn or Roundup ReadyJ Soya. Field production will remain a Federal oversight. None of the products that we have been field testing have completed their evaluations by FDA or the CVB. They are all still in clinical trials, or have yet to start their clinical trial. Although the details of the genes and what is being tested in generally confidential, it is safe to report that most of the products that we have been seeing are biologics (including monoclonal antibodies (vaccines)) or enzymes/proteins. Many of the enzymes that we see are based on products that are already available to reduce the cost of production. An example of this is the enzyme alpha-galactosidase, which is used to treat Fabry's Disease. Although we have not had any field testing on canola or alfalfa for pharmaceuticals in the U.S., corn has raised concerns in the country. The companies that are involved in corn production are going to locate production in areas outside the "corn belt". In 1991, we had our first field test of plant derived biologics, an engineered plant virus, which was conducted by Biosource (which is now called Large Scale Biology). In 1992, the Noble Foundation had its first field test of a plant (alfalfa). Plant derived biologics field tests in 2000 included tobacco mosaic virus (Large Scale Biology), Prodigene corn, Applied Phytologics rice, and Meristem Therapeutics corn. A number of federal agencies are responsible for the management of these plants, and the agencies involved vary depending on the intended use of the product and on the intended use and/or disposal of by-products and waste. Question and Answer Session Q: What is the focus of the document, Guidance on Drugs and Biologics
Derived from Bioengineered Plants or Use in Humans and Animal? Q: In regards to field trials currently underway, what kind of
confinement or containment conditions are being imposed? Q: What about destruction? Q: While there is no commercial production taking place, there is
significant acreage under cultivation for trials. Q: If we took a natural herbal medicine, such as St. John's Wort, and
bred it up to 10 times the seratonin levels and then extracted that out to sell a
commercial drug. Are you telling me that there is no regulatory oversight on that in
the field release areas and if we fed it to an animal in the waste stream? PART TWO: DISCUSSION THEMES After the first morning of presentations, the next day and a half of the consultation were devoted to three themes: human health issues, livestock health issues and environmental issues of plant molecular farming. Following are synopses of presentations and plenary question and answer sessions on each theme, as well as summaries of the results of breakout group discussions. Theme 1: Human Health Issues Introduction and Overview Health Canada's "safety umbrella" is responsible for oversight on therapeutic products, foods, environment, consumer products, diseases (surveillance), pest management, natural health products and medical devices. In April of 2000, Health Canada was reorganized and the Health Protection Branch was divided into three Branches: Population and Public Health Branch, Health Products and Food Branch, and the Healthy Environments and Consumer Safety Branch. The mandate of the Health Products and Food Branch focusses on promotion and safety:
Health Canada takes its regulatory authority from the Food and Drugs Act. The Department is responsible for administering and enforcing the Act, which is aimed at protecting the health and safety of Canadians, and may make regulations for carrying out the purposes and provisions of the Act. The Biologics and Radiopharmaceuticals Evaluation Centre (BREC) operates within the Health Products and Food Branch. "Biologics" are defined as drugs, including vaccines, sera, blood and blood derivatives, certain hormones and enzymes, allergenic extracts, monoclonal antibodies and recombinant DNA derived products (which could be from a transgenic animal or a transgenic plant), and products listed in Schedule D of the Food and Drugs Act. A large number of products from plant molecular farming would fall under the category of biologics and the operational umbrella of BREC. Plant molecular farming presents challenges for each stakeholder group, including regulators. One of the major challenges faced by regulators is what is known as the "safe biologics paradox" - biologics have never been safer, but safe is never safe enough. What are the benefits, versus the risks - how do you balance the two? Another challenge is the precautionary principle. Authorities must act even if there is only a theoretical risk of harm; if risk is possible, then we must err on the side of caution. With any kind of new technology there is risk, and there is an expectation by the public that measures will be put in place to address that risk. Additional regulatory challenges include:
The regulatory framework for molecular farming and other therapies is based on risk management principles. There is a categorization of risk to an appropriate level of control (i.e., if there is high risk, there will be a high level of control). Other requirements of the regulatory framework include:
There are a variety of management strategies that can be applied to address risk, each resulting in specific actions ranging from providing information to the public to formal statutory/regulatory action. The choice and combination of strategies are made by Health Canada based on the risk of the product and manufacturing steps, taking into account the desired level of safety and compliance. The risk assessment process has three main elements:
When regulating and developing guidelines, Health Canada must ensure that government intervention is justified and that regulation is the best alternative, that Canadians have been consulted, that the benefits outweigh the costs to Canadians, their governments and their businesses, and that when managing risks, resources are allocated where they will do the most good. Plant molecular farming is defined as "the use of whole plants, plant cells, tissues or organs or plant cell cultures, as bio-reactors for the production of commercially valuable products". There are a number of key issue areas associated with the plant molecular farming, including human health, animal health, environment, growth of the industry and international trade, and public trust. The two main issues related to human health are the potential risk to patients of products or processes and the potential risk to their parties of products or processes. The goal within Health Canada is to ensure the safety of these products and processes, and to ensure that the benefits outweigh any real or perceived risks. The current regulatory scheme is the same for animal-derived biologics and plant-derived biologics, and fall under the Food and Drugs Act. This includes regulations for labelling, advertising, establishment licensing, good manufacturing practices, clinical trials and other areas. Biopharming products that would be regulated under the Food and Drugs Act include therapeutic biologics, such as blood products, hormones, antibodies, novel proteins and peptides and vaccines (antigens), and therapeutic drugs, including pharmaceutical substances derived from plants used in the treatment of disease. Information that is reviewed for biological products derived from transgenic plants/plants with novel traits include data related to the drug substance itself (toxicology, stability, quality and purity data; efficacy data such as pharmacokinetics and potency) and data related to the manufacturing process (facilities, including confinement and security, GMP evaluation). What kinds of reviews could be considered to assess potential health affects of PNTs/transgenic plants? The scope of the proposal for health assessments of industrial PNTs used for molecular farming includes PNTs developed for molecular farming using traditional food or feed crops whether grown in field or cultivation or under physical containment. Health Canada would carry out the health assessment (risk of exposure) for ingestion, inhalation, topical exposure (accidental or otherwise) and more specifically, issues concerning immunogenicity/allergenicity, toxicological and other risks. There would be sponsor responsibility to provide the safety data respecting risk and risk mitigation strategies to address mild, moderate and severe possible risks. On the regulatory side, Health Canada and CFIA would review safety data, establish defined performance review targets and develop guidance respecting necessary confinement or containment measures. In summary, the current regulatory framework for biologics applies to products to be derived from transgenic plants. Product reviews will be handled on a case-by-case basis, as risks will be specific to the kind of product being produced. The unique aspects of plant molecular farming, such as derivation of transgene constructs, establishment of transgenic crops, extraction of product, processing, purification and process validation, require special consideration and potentially new review standards. In addition, third party risks need to be addressed by sponsors (data submitted to regulator). Question and Answer Session Q: What is meant by recombinant DNA derived product? Q: Would the permit/license be issued to the place where the plant is
fabricated or where it is grown? Q: For plant derived pharmaceuticals, what is meant by
"derivation of transgene"? Q: Would anything grown outdoors, not just products intended for food
or feed, potentially present a third party risk? Q: Do proteins for diagnostic purposes and not therapeutic purposes
fall under the same regulations? Q: Has Health Canada ever licensed a farm - and do you expect to do
so? Q: How will regulations deal with the other proteins that may be
expressed in addition to the desired protein? Theme 2: Animal Health and Feed Issues Introduction and Overview The Feeds Act and Regulations regulate the manufacture, sale and importation of feeds and ingredients in Canada. Only feed ingredients that have been evaluated and approved by the Feed Section may be used in livestock feeds. By-products must also be assessed. Reviews include evaluation of safety and nutrition components. The Act and Regulations are designed to protect livestock, farmer, workers and bystanders, entry into the food chain, the environment and the marketplace (fraudulent labelling, for example). There are a variety of ingredients found in feed that are examined, including chemical, microbial products, plants, by-products, waste products, and processing aids. A "feed" is defined as "Any substance or mixture of substances containing amino acids, anti-oxidants, carbohydrates, condiments, enzymes, fats, minerals, non-protein nitrogen products, proteins or vitamins, or pelletizing, colouring, foaming or flavouring agents and any other substance manufactured, sold or represented for use for consumption by livestock, for providing the nutritional requirements of livestock, or for the purpose of preventing or correcting nutritional disorders of livestock, or any such substance for use in any such substance or mixture of substances (taken from the Feeds Act)". In practical terms, anything that contains carbohydrates, proteins, minerals or vitamins, or that could be used as forage is a potential feed ingredient. Therefore, it is likely that components of molecular farming plants would be a potential feed ingredient. Crops that are currently used in feed include corn, canola, alfalfa, apples, barley, sugar beets, rice, coconut, cotton, sunflower, wheat, peanut, potato, rye, safflower, sugarcane, vegetables, flax, and soybean. The most common feed source is corn, with 60% of production going to livestock feed. Items from corn that are approved for livestock feed include corn and cob meal, corn bran, dehydrated corn cob, corn distillers grains, ground corn ears, corn endosperm oil, fermented, condensed corn extractive, corn feed meal, corn flour, corn germ meal, corn gluten feed, corn gluten meal, corn grains, corn grits, corn oil, corn zein. Cotton, though not often thought of as a feed, is used in livestock feed in the form of cotton hulls, cotton seeds, mechanically extracted cotton seed meal, solvent extracted cotton seed meal, cotton seed hulls, and cotton seed meal. There are two paths of entry into the food chain for molecular farmed plants:
The possibility of consumption by livestock will have to be taken into account for both of these pathways. The following are currently considered when assessing safety of plants with novel traits:
When considering risk in a safety assessment, risk equals toxicity times exposure. Therefore, the higher the potential toxicity the lower the exposure will have to be so that the risk is acceptable. And conversely, a lower the risk of exposure can support a higher toxicity level. Toxicity means the inherent toxicity of molecular farming product to livestock. Exposure is considered in terms of where the product is expressed in the plant (e.g., seed, pollen, leaf, etc.) and residues in feed including extraction efficiency. There are a number of risk management options to be considered:
The key points to consider in terms of safety assessment molecular farming plants in relation to livestock feed include:
Question and Answer Session Q: Currently, is pharmaceutical waste fed to livestock animals? Q: Why then is it inevitable that waste from
molecular farming crops would be used? Q: Is allergenicity a concern for livestock feed? Q: Are there tolerance levels associated with livestock feed
ingredients? Q: What are the current regulatory standards associated with waste
products coming out of bacterial and yeast biofermentors in case they go to feed? Q: What about the left-over, waste material at the bottom?
Themes 1 and 2, Human and Livestock Health Issues: Discussion Highlights and Key Findings Following Dr. Ganz's and Ms. Webster's presentations and subsequent plenary discussions, breakout groups were charged to consider the following questions regarding human and livestock health issues:
The following is a summary of the groups' discussions and conclusions on these questions. Risks A number of risks were identified, including:
Mitigation Many stakeholders agreed that physical and genetic mitigation strategies for containment and confinement should be assessed on a case by case basis, depending on the risk level; that there is a need for good stewardship through long-term monitoring and "Good Agricultural Practices" (GAP); that education and awareness building with the public is important; and that waste must be incinerated. Fences can prevent accidental grazing by livestock. Appropriate Plant Species Some stakeholders felt that traditional food or feed crops could be acceptable for molecular farming provided they are kept out of food and feed supplies, while others felt they should be avoided if possible; however, it was suggested that plants with unknown biology should not be used. Stakeholders identified "promiscuous" (e.g., canola) or weedy plants as inappropriate as well; parameters such as seed dormancy and probability of outcrossing should be considered. Plants with known toxicity/allergenicity were considered inappropriate. It was suggested that containment and/or confinement be required when food or feed species are used, depending on the risk level. There might be a need to look into US/Canada harmonization with regard to acceptability of plant species. Segregation Systems Many stakeholders felt that systems for isolating PNTs for molecular farming from other agricultural products should be more rigorous than existing segregation systems. Current Identity Preservation (IP) systems could be replaced with tighter "Safety Preservation" systems. Stakeholders felt that this may involve better definitions and standards of GAP, increased awareness among producers, and possibly a licensing requirement, industry incentives and/or third party validation for compliance with segregation requirements. It was suggested that CFIA should develop guidelines on segregation practices. Human and Livestock Health Risk Assessments Stakeholders were asked whether they felt that either toxicity and allergenicity assessments or full food or feed safety assessments should be made for products of plant molecular farming, as a requisite either for confined research field trials, for confined or unconfined commercial field production, or contained production. While products of plant molecular farming are not intended for use as food or feed, some stakeholders felt that full food or feed safety assessments should be required when the plant species used is a traditional food or feed crop, particularly for unconfined production. Other stakeholders felt that human and livestock health risk assessments may not be necessary for confined research field trials or commercial field production, depending on a case by case evaluation of confinement practices and of the risk of the product. Some stakeholders felt that a toxicity and allergenicity assessment would be adequate where such an assessment is required. Many stakeholders agreed that a human or livestock health risk assessment would not be required where production is in strict containment, provided there is confidence in the containment. THEME 3: ENVIRONMENTAL ISSUES Molecular Pharming: Impact Considerations on Non-Target Organisms There is not a lot of data on this issue - and understanding of the technology and issues is constantly changing (for example, as a result of forums such as this one). Most biopharmaceuticals will not pose a significant threat to non-target organisms and therefore they will not require additional regulations beyond the regulations for the crop or platform that they will be expressed in and beyond the regulations that will apply to the biopharmaceutical itself. In specific cases where concerns do exist, technologies and management strategies exist to reduce exposure of those biopharmaceuticals of concern to the environment. "Exposure" is the element of the equation that is the predominant factor in risk assessment and risk management. Why is this technology worth pursuing? It offers cost effective production, safer products (decreased pathogens), requisite synthesis machinery and it has the potential to improve quality of life here and abroad. Examples of products that have been expressed in plant tissues include edible vaccines for Hepatitis -, dental caries, autoimmune diabetes, cholera, rabies, HIV, rhinovirus, foot and mouth, enteritis virus, malaria, influenza, and cancer; antibodies such as immunoglobulins against S. mutans to prevent dental caries and antibodies for treatment of non-Hodgkin's lymphoma and cancer tumour antigens; and a number of pharmaceuticals. Non-target organisms (NTOs) are defined as "organisms in the environment that are unintentionally affected by the product". The groups at greatest risk due to increased exposure are insects, especially those that are of benefit to and who live within the agricultural setting, and soil microorganisms. The problem with NTOs is that they are sometimes difficult to identify in terms of what could be at risk, and they are very difficult and expensive to study. The risks to NTOs from plant molecular farming depends on a number of elements, including the type and category of recombinant protein that is expressed. There is a diversity of products that are not equitable (i.e., no two biopharmaceuticals are the same). While a case-by-case approach for risk assessment is warranted, there are some generalities:
But not all biopharmaceuticals are going to be the same, and there will be areas where there are concerns about environmental exposure to these pharmaceuticals. Some specific examples include:
Precautions must be taken to limit exposure to the environment through management strategies and technologies, such as inducible genes post harvest (glucocerebrosidase is produced with this technology); product activation post purification, terminator technology to prevent pollen development, and chloroplast transformation to limit gene flow, transgene tracking tools, marker proteins to label specific biopharmaceutical plants and fluorescent protein technology (GFP). A three-tiered approach can be used. First, look at the product in a controlled laboratory settings to see what gets affected by the product itself. The second tier takes a more ecological setting, such as a greenhouse or enclosed field, and looks for any indication that something is different about this product. Barring any adverse results, a field trial is undertaken. Isolation/containment strategies include: buffer fields around biopharmaceuticals; secluded or enclosed fields; and greenhouse restrictions. An important consideration is that there must be economic feasibility in terms of the relative risk and benefits. In summary, most biopharmaceuticals will be benign to non-target organisms. Most products that would be in a position for large release are not going to require additional regulations. Product-focussed evaluations will reveal specific cases of concern - not the fact that it is in a plant. Utilizing technology to limit environmental exposure will be key - exposure is the wild card element in risk assessment. The hazards of a specific pharmaceutical are the same whether it is in a plant or in another product - and the hazard can be assessed. It is the risk of exposure once placed in an agricultural setting that is of concern - and exposure can be managed and monitored with the technologies that are available, that bears on risk, and that can be monitored and managed. Questions and Answer Session Q: In order to grapple with these environmental issues, what are the
worst case scenarios? What are valid concerns - is there the potential for disaster? Q: Can we trust environmental assessments? Q: If bio-industrials were to be considered within molecular
farming (in addition to biopharmaceuticals), what differences, if any, would there be in
their treatment? Q: It is important to understand that the proteins of
biopharmaceuticals are not small, indestructible molecules like DDT, but that they are
stable proteins that will degrade and destruct upon exposure to the environment. This
needs to inform the scientific analysis of the risk assessment.
Q: Environmental assessments and reviews for the first generation of
crops looked at a number of species and indicators, including bees, worms, fish, bacteria
in soil, other herbivores that would feed on the crop particularly insects, birds, whether
pollen enters the water and feeding studies on mammals. Would not these types of studies
be mandatory for biologically active products, as for BT corn for example? Q: The dilemma is that a lot of the concern is not product focussed,
but rather process focussed in the food chain. Q: There is evidence that agricultural intensification has resulted
in a decline in global biodiversity. What is the potential for bio-farming to change the
way agriculture is carried out? Theme 3, Environmental Issues: Discussion Highlights and Key Findings Following Mr. Richards's presentation and the subsequent plenary discussion, breakout groups were charged to consider the following questions:
The following is a summary of the groups' discussions and conclusions on these questions. Risks Identified environmental risks include outcrossing and gene flow; possible accumulation in food chain, persistence in soil, and danger to non-target organisms (NTOs) from biologically active proteins. Stakeholders noted that some risks may be unknown or unpredictable. Mitigation Gene flow can be mitigated by confinement measures currently used for research field trials such as guard rows, isolation distances, etc., as well as genetic mechanisms such as male sterility or "Terminator" type technologies. Stakeholders suggested that exposure to NTOs could be mitigated by using tissue-specific or post-harvest inducible promoters. It was proposed that genetic and physical mitigative measures should be re-evaluated regularly to ensure efficacy. Production Outside Containment Many stakeholders felt that plant molecular farming should be permitted outside containment only when risks are mitigable, depending on toxicological and persistence studies and on the proposed confinement measures. It was suggested that CFIA develop regulatory directives for containment. Potential Additional Information to be Required for CFIA Approval Stakeholders suggested that the current indicator species list should be broadened. Some felt that environmental monitoring protocols and procedures should be required. The expected total hectarage of production might also be considered in granting approvals. An assessment of technologies used to restrict gene flow should possibly be required. Post-Harvest Land Use Restrictions Many stakeholders felt that post-harvest land use restrictions specified in the current confined research field trial guidelines (Regulatory Directive 2000-07) should apply for both field testing and commercial production of PNTs for molecular farming. Ongoing research may be required to verify current standards and to evaluate persistence of expressed product. Monitoring for long-term effects may be required. Biological or Genetic Confinement It was proposed that biological or genetic confinement can be acceptable, but it must be justified by data and it must pose no inherent risk. PART THREE - PROPOSED CFIA INITIATIVES AND NEXT STEPS On the final morning of the consultation, the Plant Biosafety Office presented a summary of the discussions of the preceding two days and proposed a number of initiatives to address the concerns raised. A plenary discussion on these proposals and general issues followed, then representatives of CFIA and Health Canada made commitments for the next steps in the development of regulations for plant molecular farming. Below are synopses of these proceedings. Overview of Consultation Results Stephen Yarrow, National Manager, This has been a "technical" consultation, because there are a lot of technical issues that have to be discussed. It is important to think about why we are doing this consultation at this time. For the first time in the history of regulating confined field trials, we have put some field trial applications on hold as the area of plant molecular farming needs to be carefully examined before moving forward. We need to think about how to change existing or create new regulatory directives to help industry have certainty about the future. The delays are more related to biotechnology in general than to molecular farming. Some of the key factors have been GM wheat and the CFIA's handling of trials, Starlink corn issues, and the increasing acknowledgement that "confinement" does not necessarily mean zero plant movement. There are also a number of concerns and issues related to specific stakeholder groups, such as the organic farming community. The nature of plant molecular farming is different than that of other PNTs, because these plants will have the ability to introduce substances that we know may have physiologically harmful effects on humans and animals if consumed or if exposed to in the wrong way. The regulatory directives for plant molecular farming will therefore be over and above those for regular PNTs, and will address the need for confined research field trials, commercial cultivations (probably also under confined conditions), and an enhanced regulatory partnership between Health Canada and the CFIA's Feed Section. At this point, we cannot say there will never be unconfined commercial production. But for now, we will be building on our existing confined field testing regulatory directive, and also building a new set of guidelines to accommodate confined commercial cultivation. These may be combined or separate directives - the intellectual content needs to be created. We also need to build on the relationship and partnerships with Health Canada and CFIA's Feed Section to ensure early and ongoing input at all stages, rather than just providing biomolecule assessment at the commercialization stage. These connections will include food assessments, livestock feed assessments and drug assessments, and the new directives will have to reflect these new relationships. Participants at this consultation hold widely ranging views and concerns about plant molecular farming, its impacts and the associated regulatory environment. Some people have concerns about the research trials, others worry about the feasibility of commercialization under confined conditions. There are issues surrounding pharmaceuticals and bio-industrials, adventitious presence in other food crops, and waste/by-product disposal. Should we be using traditional food/feed crops for plant molecular farming, or some other "exotic" non-food crop species? Is the CFIA looking at Health Canada for full-blown assessments based on new testing information, or are we looking for more of an advisory type oversight role? Among the key perspectives of the stakeholders were the following:
Stakeholders recognized the complexity of the subject in the variety of crop species used, the type of biomolecule being produced, and the biological, genetic and physical strategies employed. A recurring recommendation was that applications must be assessed on a "case-by-case basis". Proposed CFIA Initiatives on Regulating Plant Molecular Farming As an outcome of the consultation, the CFIA proposes to undertake the following initiatives:
Stakeholder Perspectives - Open Forum in Reaction to the Recommendations Participant 1
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Commitment and Next Steps Stephen Yarrow, National Manager, The Canadian Food Inspection Agency, along with Health Canada, will seriously and very thoroughly go through all the information that we have gleamed during this workshop. An information sheet or communiqué will be produced - a snapshot of why we were here, who was here, the areas covered and the outcomes and conclusions of the workshop. We will get this out to participants and posted on the website as soon as possible, but at least by Christmas. The proceedings, that will contain summaries of the presentations, a full participants' list and the key highlights of our discussions and recommendations, will be made available early in the new year. As for the next steps, in terms of a regulatory directive, the direction we are going to take is to concentrate on the confined research level and on pharmaceutical production. The other areas will be tackled in due course. They require further consultation, either face to face or through the website, for example, to define the commercial cultivation elements of the directive and to cover other areas of molecular farming beyond pharmaceutical production. We have heard that 60 days is not enough for a comment period, but we are also conscious of the fact that there will be a growing period next summer. The people who are in the business of doing this type of research will want to start planning those trials, and will require some direction from us sooner rather than later. The draft regulatory directive will be completed by the end of the year. There are other existing guidelines, Dir2000-07 (for the confined research trials) and Dir94-08 (release directives for plants with novel traits) and the feed guidelines, that are currently under review and will be undergoing revision. This will be taken into account in creating this new regulatory directive for molecular farming for pharmaceutical production. Whether this is included in the revised existing directives or developed as a stand alone directive, is still to be decided. The Novel Food Guidelines will also be revised in the next 12 months and, similarly, it is unknown how guidelines for molecular farming will interact with them. I would like to thank everyone who worked to bring this workshop together, and especially thank all the participants, some of whom travelled from afar to be here, who shared their expertise and brought information and insight to us all. Karen Dodds, Director General, Food Directorate, Health Canada Canadians look to the government to protect them, to protect their environment, to protect the biodiversity that exists, including the use of genetically modified plants and the use of different products. There are several federal acts that can come into play, and Canadians see these as the systems that safeguard them. Our sound, science-based regulatory system is very well respected around the world. But because science is so rapidly evolving, we are challenged on a weekly basis. And we recognize that how we regulate needs to evolve as well. The field of plant molecular farming has enormous potential benefit for many sectors, from the farmer to health and the environment. There are also many challenges that clearly go beyond the science. I challenge you to think of ways that you can help us ready the Canadian environment for what you have been discussing here at this workshop. We need to work multilaterally to ready the environment, and it's not just the science-based regulation. There are potentially contentious issues that we have to prepare for. CFIA's goal is to have guidelines in place for the next planting season - and so there is a lot of work to be done, not just in the science and the regulatory agencies, but out in the public as well. In Canada, developers have to notify CFIA prior to conducting field trials and notify HC prior to marketing products for human consumption of therapeutic use of biotechnology. Field trials go to CFIA, while many of the consumer products come to Health Canada. This allows us to do the scientific risk assessment associated with the proposed activities. Simply put, approval is not granted until our scientific evaluators have no concerns left about safety. One of our key principles is that we work in as open and transparent a manner as possible, and that we obtain input from as many stakeholders as possible, including different areas of the government, industry, non-governmental organizations, environmental organizations, and other interested parties. Academics are one of the most important sources of information for us, as is the private sector. By consulting with these various stakeholders and advising the public, public confidence is created. The public knows that mechanisms are in place to ensure that we are doing our job and that we are ensuring the safety of products, in terms of environmental, human and animal perspectives. Both Health Canada and CFIA are committed to increasing the transparency with respect to the consultative and regulatory processes and product reviews. The purpose of this consultation was to seek the advice of both technical experts and interested parties to help identify some of the key issues and areas of concern surrounding plant molecular farming. The discussion at this workshop has been rich, and there has been very valuable input and guidance provided to us. The outcomes of this workshop will be helpful in assisting us as we work to develop guidelines to address this field and the safety of its products. Health Canada has agreed to assist the CFIA to develop a draft directive by the end of the year and guidelines in place for the next growing season. It will take all of us, everyone who has a role to play in this area, to help get the public environment ready for what you have heard in terms of a regulatory commitment. APPENDICES Appendix 1 CONSULTATION PARTICIPANTS
Appendix 2 BIOGRAPHIES OF SPEAKERS
Dr. André Gravel, Executive Vice-President, Canadian Food Inspection Agency Dr. Gravel received his Bachelor of Arts degree from the University of Laval, Quebec City. He graduated from the University of Montreal as a Doctor of Veterinary Medicine and from the University of Guelph with a diploma in Veterinary Preventative Medicine. Dr. Gravel started with Agriculture Canada as a veterinarian in charge of meat processing plants. From that position, he progressed through the ranks, always within the meat hygiene program, to National Supervisor, then to Program Chief and on to Associate Director. In 1980, Dr Gravel accepted a position with the provincial government of Quebec as Director, Veterinary Services Branch in which he was responsible for the application of the preventative medicine program for the province, the administration of the contributory animal health insurance program, and the administration of eight regional animal pathology laboratories. In 1981, he rejoined Agriculture Canada, and in 1987 was appointed Director of the Meat and Poultry Products Division in Ottawa. He remained in this position until his appointment in August 1993 as Director General, Food Production and Inspection Branch for the Atlantic Region. In September 1996, Dr. Gravel was appointed as Director General of the Animal and Plant Health Directorate until April 1997. In April 1997 when the new Canadian Food Inspection Agency was formed, he acted as Vice President, Programs until his appointment on August 6, 1998. On April 5, 2000, Prime Minister Jean Chrétien appointed Dr. Gravel as Executive Vice-President to the Canadian Food Inspection Agency. Dr. Larry Holbrook, BIOTECanada Task Force on Molecular Farming Dr. Holbrook received an M.Sc. and Ph.D. from the University of Toronto, Department of Zoology in the areas of developmental and neurobiology. He began in agricultural biotechnology research at Agriculture Canada in Ottawa in 1981. Since 1986 he has been involved in the plant biotechnology industry as a senior research scientist. Dr. Holbrook is currently head of field trial operations and field regulatory affairs for SemBioSys Genetics Inc. as well as associate adjunct professor at the University of Calgary, Department of Biological Sciences. Mr. Phil Macdonald, Chief, Environmental Release Assessments, Plant Biosafety
Office, Mr. Macdonald's graduate work was done at Carleton University in plant physiology and molecular biology, concentrating on herbicide tolerant weeds. He began his scientific career at the National Research Council in Ottawa in the Cell Signaling Group, developing targeted leukemia therapies and later working to produce transgenic animal models for disease states. In 1993 he moved to Research Branch, Agriculture and Agri-Food Canada to work on molecular tools for germplasm improvement for agricultural production. In 1995 he took a secondment to what is now the CFIA to work as an evaluator in the Livestock Feed Section, doing safety assessments of novel plants intended for livestock feed use. In August 1999 Mr. Macdonald began working for the Plant Biosafety Office where he is currently the Chief of the Environmental Assessment Group. Dr. William Yan, Health Canada Dr. William Yan is currently the Head of the Office of Food Biotechnology, Food Directorate, Health Canada. This office is responsible for the safety assessment of novel food products in Canada. Dr. Yan obtained his Ph.D. degree in Medical Microbiology and Infectious Diseases from the University of Alberta in 1990. He completed his post-doctoral training at Tufts University Medical School, Boston MA in 1992. Since then, he has participated in and led research, regulatory and policy development programs in Health Canada. Dr. Yan is also an Adjunct Professor in the Department of Biochemistry, Microbiology and Immunology, University of Ottawa. Dr. Jim White, Senior Operations Officer for the Biotechnology Assessment Branch, USDA-APHIS Dr. White received his Bachelor and Masters degrees in Science from Florida Atlantic University in microbiology. He received his Doctorate of Philosophy degree from the Department of Botany and Plant Pathology from Michigan State University specializing in plant virology. As a research scientist, he was employed at the University of Hawaii, Manoa; University of California, Riverside; University of Nebraska, National Research Council of Canada (Saskatoon); and University of Maryland, College Park. He joined USDA, APHIS in 1987 as a reviewer for field testing of genetically engineered plants and microorganisms and since 1992 has been the Senior Operations Officer for the Biotechnology Assessment branch. He has been involved in authorizing more field tests of engineered plants and microorganisms and reviewing more applications commercialization of engineered plants than anyone at USDA. Dr. Peter Ganz, A/Director, Biologics and Radiopharmaceuticals Evaluation Centre, Health Canada Dr. Ganz is currently A/Director of the Biologics and Radiopharmaceuticals Evaluation Centre (BREC), Biologics and Genetic Therapies Directorate, Health Canada. Dr. Ganz received his bachelors (biochemistry, magna cum laude) and doctoral degrees (protein and nucleic acid biochemistry) from the University of Toronto and York University, respectively. As a Leukemia Society of America Post-Doctoral Fellow, he trained in the area of virology at both the Univerity of Toronto and Harvard Medical School. Before moving to Health Canada, he served as Research Director at the Ottawa Blood Centre, Canadian Red Cross Society (CRCS). Dr. Ganz moved to Health Canada in 1996 and, prior to his current acting appointment, his substantive position is Chief of the Blood, Tissues and Organs Division within the Biologics and Radiopharmaceuticals Evaluation Centre, BGTD, Health Canada. He currently holds an adjunct professorial cross appointment in the Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa. He is well known internationally for his research in the blood area and examining the expression of blood factors in transgenic plant systems. He has published over a 100 research articles in peer reviewed journals, reviews and book chapters with a focus on blood and transfusion science. Ms. Linda Webster, Feed Section, Canadian Food Inspection Agency Ms. Webster has an undergraduate degree from Queen's University in Biology a graduate degree from Concordia University in Ecotoxicology. Ms. Webster has seven years experience as a toxicologist in the regulation of agricultural products. Prior to her current role as Toxicology and Biotechnology Coordinator for the CFIA Feed Section she was a toxicologist in the Fertilizer Section. In 1999-2000 she was appointed as the Society of Environmental Toxicology and Chemistry's Science Fellow. In this capacity Ms. Webster provided expert scientific advice to Members of Parliament and Senators through the Library of Parliament. Mr. Harry Richards, Ph.D. candidate, University of North Carolina, Greensboro Mr. Richards is a Graduate Research Assistant in the Department of Nutrition, University of North Carolina at Greensboro (UNCG). He holds a Masters in Plant Physiology and Genetics from the University of Tennessee, and plans to complete his Ph.D. in Nutrition and Biotechnology in May 2002 from UNCG. He is studying under the supervision of Dr. Neal Stewart of UNCG, a well-known expert in ecological risks of genetically modified plants. Dr. Stephen Yarrow, National Manager, Plant Biosafety Office, Canadian Food Inspection Agency Stephen has over nine years experience in the regulation of biotechnology products with the Canadian Food Inspection Agency (and prior to the creation of the CFIA, with Agriculture and Agri-Food Canada), including policy development work, both with the plant programs and animal biotechnology. In addition, Stephen has represented the CFIA and the Government of Canada during the negotiation of the United Nations Cartagena Protocol on Biosafety. Other international activities have included various activities with the International Plant Protection Convention and its regional North American Plant Protection Organization, and with the OECD. Previous to working for the Federal government, Stephen was a biotechnology consultant with the Ontario Science Centre, Toronto, and from 1983-1991, as Research Scientist and Project Coordinator at Allelix Crop Technologies (and later Pioneer Hi-Bred Canada), also in Toronto. Dr. Karen Dodds, Director General, Food Directorate, Health Canada Dr. Karen Dodds is currently the Director General, Food Directorate in the Health Products and Food Branch of Health Canada. The Food Directorate's function is to protect and improve the health and well-being of the Canadian public by defining, advising on and assessing the risks associated with the food supply. Dr. Dodds began her career with the National Research Council in Ottawa and joined Health Canada in 1987 as a research scientist. Dr. Dodds became Chief of the Evaluation Division of the Bureau of Microbial Hazards in the Food Directorate in 1992. She has also been Director, Food Policy Integration, Food Directorate. She was special advisor to the former Deputy Minister of Health, David Dodge, and had the opportunity to become involved in all issues within Health Canada. Dr. Dodds also served as Director General, Office of Biotechnology and Science, Health Products and Food Branch. Mr. John A.L. Bowman, Office of Biotechnology, Canadian Food Inspection Agency Since joining the CFIA in 2000, Mr. Bowman's work has primarily been related to the development of national and international standards for the labelling of biotechnology-derived foods. These activities include work with a Canadian General Standards Board committee as well as with the Codex Committee on Food Labelling. Mr. Bowman has gained a wide range of biotechnology-related experience from academic, industrial, and regulatory research settings. He completed his graduate work in the Department of Molecular and Medical Genetics at the University of Toronto, receiving an M.Sc. in 2001, and completed his undergraduate degree in biology at the University of Waterloo in 1998. Appendix 3 OVERVIEW OF PUBLIC FORUM, OCTOBER 30, 2001
John Bowman, Office of Biotechnology, Canadian Food Inspection Agency The Canadian Food Inspection Agency (CFIA) held a Public Forum to solicit the public's views on plant molecular farming, on the evening of October 30, 2001. The forum provided an opportunity for members of the public to hear presentations from experts in the field, to express their opinions and concerns, to ask questions and participate in discussions in a facilitated forum. The following provides an overview of the evening's proceedings and the key discussion areas. Moderator Alain Rabeau of Intersol Consulting Associates Ltd., opened the forum by introducing the four panellists and Bart Bilmer, Director of the Office of Biotechnology, who provide some opening remarks. Presentations by the panellists covered a range of issues related to plant molecular farming. Dr. Louis Vézina, from Medicago Inc., gave an introduction to plant molecular farming, and an overview of some potential medical applications of the technology. Mr. Harry Richards, of the University of North Carolina at Greensboro, presented some of the potential environmental impacts of plant molecular farming applications. Dr. Bill Leask, of the Canadian Seed Trade Association, briefly discussed some of the production challenges and considerations applicable to different applications of plant molecular farming. Dr. David Castle, of the University of Guelph, discussed the ethical debate surrounding the introduction of new technologies, such as plant molecular farming. Approximately 100 people attended the forum. Following the presentations, audience members were invited to present their views and concerns, and to ask questions of the panellists. The main issues raised were:
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