Canadian legal oversight of pharmacogenomics and nutrigenomics.

Equipped with the knowledge that the Human Genome Project yielded, (1) biomedical researchers and clinicians are looking to enhance human health. Research to understand both the interaction between genes and pharmaceutical drugs and the interaction between genes and nutrients is quickly helping to develop new genomic applications. Is Canadian law well prepared to handle these advances? An examination of how federal law addresses pharmacogenomics (2) and nutrigenomics (3) may help provide an answer. This comparison is particularly compelling in light of growing anticipation that a new era of personalized medicine has dawned. (4)

Indeed, both pharmacogenomics and nutrigenomics aim to personalize (5) medicine and nutrition, and ultimately health, by tailoring drugs or foods to individual genotypes. (6) Specifically, through pharmacogenomics, it will become possible to individualize therapies, (7) adapting a patient's treatment by selecting optimal drugs, adjusting dosage, or managing potential adverse effects. (8) Similarly, personalized nutrition will entail decisions about nutrition and overall health based on an individual's knowledge of nutrition and of their genetic make-up, informed either by means of genetic testing or indirectly through family history or personal experience. (9)

Moreover, as both pharmacogenomics and nutrigenomics explore "how chemicals, whether naturally occurring or manufactured, alter and regulate biological processes and how individual genetic variation influences the responses to those chemicals," (10) some researchers have suggested that "nutrigenomics and pharmacogenomics may best be viewed not only as a continuum but also as inseparable in clinical applications. Indeed, the emerging knowledge of nutrient-gene interactions shows that certain chemicals in food directly alter the same molecular pathways targeted by drugs, or alter interacting pathways that may influence drug efficacy." (11)

In 2000, the pharmaceutical company Novartis and the food manufacturer Quaker Oats formed Altus Food to develop functional foods and beverages offering scientifically proven health benefits beyond basic nutrition. (12) Although the joint venture did not survive a subsequent merger between Pepsi-Co and Quaker, (13) it remains an indication of potential genomic-based corporate convergences.

This article does not pretend to assess fully whether Canadian law is compatible with or supportive of genomic advances. Rather, it points to many legal considerations that would need careful examination to derive a definitive answer. This overview begins with a brief discussion of the research and development challenges that confront both the pharmaceutical and food sectors, and the leverage genomic technologies may bring. It also reviews the regulation of clinical trials with a focus on relevant genomic aspects. Finally, it points to potential liability risks that manufacturers or health care professionals may encounter once genomic products and services become more widely available.

Food and Drug Research & Development

During the research and development phases, new drugs and new food products face significant challenges, even though they go through markedly different channels: one commentator noted that the pharmaceutical industry operates in the world of rational drug design and clinical trials where physicians ultimately intervene in decisions regarding patients and medication, whereas the food industry operates in the world of taste and convenience where trials are limited and products are promoted directly to consumers. (14) However, using genomics, it is possible the two worlds will move closer together, a trend already started with the scientifically based health claims made in relation to certain foods.

The challenges of pharmaceutical companies are well known: in the US, the number of new drug applications for major drug products or of biological license applications for new molecular entities submitted to the Food and Drug Administration (FDA) has steadily decreased over the past 15-20 years. (15) Partly in response to this situation, the FDA released a white paper in 2004 offering various strategies to optimize R & D. (16) Key among them is the identification of DNA-based biomarkers or RNA-expression profiles, recognized as a means to improve predictions regarding clinical outcomes and to overcome variability in drug response. Thus, pharmacogenomics offers great hope in circumventing a major barrier to successful drug development. (17)

Similarly, genomics may offer a new window of hope to the food industry, which is relatively saturated in terms of volume, and where market shares can only be increased through more innovative products. (18) However, their development entails a lengthy, costly, and risky pipeline that can span an average of 7 to 10 years, requiring large financial investment with low success rates. For every product that reaches the test market, thirteen do not; and then, only fifty percent of products brought to the test market succeed. Moreover, if new drugs receive 15 years of patent protection before they can be challenged by generics, the competition among new food products is fierce: after five years, less than twenty percent are still on the market. (19)

Food product development initially focused on better preservation methods to ensure food would not spoil easily. Subsequent focus turned to enhancing nutritional value, taste, and convenience. Today, consumers also look for foods that help them maintain or improve their health. (20) Such food product innovation is partly driven by demographic factors, including education, as educated consumers are better equipped to understand and integrate commercial as well as scientific information regarding their food choices. (21) Therefore, nutrigenomics and its potential for personalized nutrition holds much promise for the food industry. (22)

It is worth noting that these potential genomics advances come at a time when Western society already privileges individual autonomy in health care and consumer choice in the market place, which in turns furthers the demand and willingness to pay for private genetic testing.

Regulating the Production of Food and Pharmaceuticals

The overarching regulation of food and drugs shares common roots in consumer protection. Therefore, it should not be too surprising that new food products as well as pharmaceutical drugs and devices are principally governed by a single statute, the Food and Drugs Act, (23) and fall largely within the jurisdiction of the same agency within Health Canada, the Health Products and Food Branch (HPFB).

A key feature of pharmacogenomics is that it often involves both drugs and diagnostics devices, which are differently regulated in Canada. (24) The regulation of pharmaceutical drugs is accomplished through the Therapeutic Products Directorate, which must assess that the benefits and risks of using an approved drug are balanced. (25) This is determined on the basis of the scientific evidence that a manufacturer presents regarding a product's safety, efficacy and quality, (26) data obtained pursuant to clinical trials.

In vitro diagnostic devices (IVDDs) used for pharmacogenomic or nutrigenomic testing, were long governed merely under laboratory accreditation provisions. (27) However, it is instructive to examine relevant provisions of the Medical Devices Regulations. (28) The regulations, which are administered by the Medical Devices Bureau (MDB), establish a risk based classification system. Devices presenting the highest risks are classified as Class IV, those presenting the lowest risks as Class I.

Classification for IVDDs is done according to criteria such as: whether the test is used for screening, diagnostics or monitoring; the technical or medical expertise of the intended user; the importance of the information to the diagnosis (sole determinant or one of several); the natural history of the disease; and the impact of the result (true and false) to the individual and/or to the public health. Instances where an erroneous result would have a major negative impact because it is a critical determinant of a diagnosis, such as cancer screening, represent a high risk. Stress and anxiety linked to the result of a test and potential follow-up measures (e.g. genetic screening) also represent a high risk. In Canada, devices used for genetic testing generally are classified as Class III and require a pre-market scientific assessment of their safety and effectiveness by the MDB. (29)

Turning to food, regulatory oversight was originally framed as a public health regime and was aimed at reducing food-borne diseases caused by bacteria, parasites, viruses or toxins. (30) Today, Health Canada through the Food Directorate and the Canadian Food Inspection Agency establishes standards to govern the safety of foods as well as the nutritional quality, and develops labelling policies related to health and nutrition. (31)

In the past two years, regulatory and administrative reforms have been underway that could impact how these different products are brought to market. (32) In its 2006 Blueprint for Renewal, Health Canada announced that it would develop a regulatory approach that recognizes the life-cycle of health products that encompasses all stages of product development and use, rather than focusing on discrete interventions at rigidly defined points. It also described a modernization strategy affecting the regulatory and policy frameworks for food safety and nutrition that focused on two main points: a new regulatory framework that would permit truthful, substantiated health claims to support informed consumer choice, and improvements to pre-market regulatory processes for food additives and novel foods. (33)

In the 2007 Blueprint for Renewal II, which was prepared subsequent to receiving input from stakeholders, the modernization efforts were somewhat recast. In part, they would focus on: improving predictability, effectiveness, efficiency, and transparency in the food regulatory system, including pre-market clearances and notifications; promoting regulatory responsiveness to food innovation and promoting consumer access to foods with assessed health benefits, including the management of food with health claims and a policy on the discretionary fortification of foods; and modernizing the regulatory toolkit to address "food contributors" to chronic disease such as the development of strategies to reduce the presence of trans fatty acids. (34)

Also in 2007, Health Canada released a discussion document titled, Towards a Regulatory Modernization Strategy for Food and Nutrition. This document re-asserts that a risk-based approach to the regulation of food safety and nutritional quality is good practice, and that it is appropriate for food products to be subject to varying degrees of mandatory regulatory oversight, with strict controls at the pre-market level necessary for some foods or components, while others can be covered under general legislative provisions that do not include pre-market regulatory requirements. It also refers to Health Canada's understanding of risk management principles as essential to determine what microbiological, chemical or nutritional risk to the food supply necessitates intervention to protect the integrity, safety and security of food. (35) From a nutrigenomic standpoint, it is worth noting that the document acknowledges that, although Health Canada has experience in ensuring certain essential nutrients and minerals are present in the food supply to support healthy development, it generally has not addressed food components that are associated with increased risk of chronic disease, nor the role that food and diet can play in chronic disease. (36) The proposal calls for a regulatory system that better addresses "food contributors" to chronic disease.

Pharmacogenomic Trials

Unless their benefits are evaluated through clinical trials, advances in human genomics are unlikely to trigger changes in clinical practice or nutritional habits. In Canada, clinical trials on drugs and devices are regulated by the HPFB. (37) Additionally, Canadian agencies that fund human research have entered into memoranda with recipient institutions to assure that funded research complies with the 1998 Tri-Council Policy Statement that sets out ethical standards. (38)

However, it has been noted that particular aspects of genomic research, such as the use of tissue specimens stored in databanks, may cause new stress-points for biomedical researchers, even in an area of law and ethics believed to be as well settled as informed consent, because authorization to bank and to use specimens for research was not adequately anticipated at the time when most regulatory or policy provisions were developed. (39) For this reason, supplementary guidance is critical. (40)

In the US, the FDA started paying particular attention to pharmacogenomics in 2001. (41) This resulted in guidance being issued in 2005 to help industry sponsors determine when to submit genomic data. (42) Canada similarly issued guidance in February 2007. (43) It requires sponsors, as part of a clinical trial application, to submit pharmacogenomics data that pertain to the pharmacodynamic aspects, pharmacokinetics, and toxicological effects of the investigational product or data that support its safety and/or efficacy, as well as data being used by the sponsor to support the design of the proposed clinical trial or to justify the proposed indication(s)/labelling. Moreover, the guidance distinguishes between pharmacogenomic testing using either a test already licenced for sale in Canada or already authorized for investigational testing, or using a test that is not presently licenced or authorized. In the latter case, the sponsor must obtain an authorization for investigational testing. This entails submission of all available data that supports the analytical validity of the test, to be reviewed by the MDB. (44)

The intent of these provisions is to minimize the risk of exposing research subjects to harm. Because pharmacogenomics research will depend on determining who is genetically susceptible to an adverse reaction or who may not be responsive to a drug, it may require looking anew at the question of risks, and whether it is ever acceptable to conduct clinical trials with subjects who are more likely to be harmed or to experience no effect from a drug. (45)

Accordingly, it can be anticipated that pharmacogenomics will have a profound effect on every stage of drug development, from Phase I to Phase IV. (46) It will serve to reduce risk in Phase I by analyzing inter-individual and population differences in drug metabolism, to adjust dosages and correlate efficacy with genotype in Phase II, and to predict safety and efficacy in Phase III. (47) Overall, these results will determine whether pharmaceutical companies are able to make genetically-related claims promoting use in a genetically defined subpopulation. (48)

Nutrigenomics in Practice

If the Canadian review processes both for IVDDs used in pharmacogenomic research and for therapeutic products based on pharmacogenomic data appear clear and relatively rigorous, current practices regarding nutrigenetic testing present a different story. Although the testing kits fall under the same medical devices regulations, nutrigenetic tests do not yet appear to have been given a risk classification.

As to nutrigenomic claims being attached to products, a critical distinction in current law presents a significant hurdle. Indeed, the Food and Drugs Act strictly separates food and drugs. Only the latter can relate to "the diagnosis, treatment, mitigation or prevention of a disease, disorder, abnormal physical state, or its symptoms ..." or to "restoring, correcting or modifying organic functions...." (49) Therefore, for a product to be regulated as a food, it cannot carry a claim suggesting that it may have an effect on the body. (50) Only limited exceptions have been introduced. (51) It will be important, therefore, to watch the outcome of proposed regulatory reforms, which indicate that the Canadian government intends to address "food contributors" to chronic disease, a development that could overlap with nutrigenomic advances. (52)

Finally, health care professionals other than physicians may be prevented from engaging in nutrigenomic testing and counselling. For example, in the province of Ontario, regulated health care professionals including dieticians who have completed specific training (unlike nutritionists) cannot communicate a diagnosis identifying a disease or disorder as the cause of symptoms if it is "reasonably foreseeable that the individual ... will rely on the diagnosis." (53)

It is under somewhat comparable legal circumstances that the US Government Accountability Office (GAO) undertook to review nutrigenomic practices. In a report presented in 2006, the GAO explained having investigated a small number of genetic tests sold directly to consumers via the Internet, retail stores, or pharmacies. (54) It found that the results it received from purchased tests made "... health-related predictions that are medically unproven and so ambiguous that they do not provide meaningful information to consumers." (55) The GAO concluded that in the absence of appropriate legal oversight, consumers face a confusing situation: "[a]lthough companies that market nutrigenetic tests typically stress that the results and information they provide are not intended to diagnose or treat any disease or disorder, they do claim that their tests will provide consumers with the information needed to tailor their diet and exercise programs to address their genetically determined health risks." (56)

Currently, Canadian consumers have access to the same products and services as those investigated by the GAO, and no more legal protection than their US neighbors.

Labelling and Delivery

For food products and drugs, strictly regulated labels serve to convey important information to users. It is possible to envision that, as drug labels have begun to carry genetic information, (57) so could food labels. Indeed, if Canada's Food and Drugs Act long contained a prohibition against health claims for food, recent changes now permit narrow health claims, (58) which could be genetically based in the future.

The Canadian guidance on the submission of pharmacogenomic information specifically addresses labelling. (59) It recommends the inclusion of pharmacogenomic information when identified subgroups of patients are likely to experience higher or lower clinical efficacy in order to properly define those subgroups, as well as when there is sufficient evidence to support special dosage considerations for specific subgroups. It also calls for specific instructions when the optimal use of a drug can be determined through pharmacogenomics testing. In contrast, some additional changes to the law governing food and related health claims will likely be necessary before genetic information related to nutrients is found on food labels, but such a possibility is foreseeable.

While labels should assist health care professionals deliver genomic-based products, the prospect of personalized medicine nevertheless presents a major challenge to health care providers. If drug prescriptions are increasingly based on the genotype of patients, clinicians will need to acquire basic genetic knowledge that many currently do not hold. At the very least, physicians will need to learn when to order a pharmacogenomics test and how to use the results in clinical decision-making. (60) These changes will need to occur in a context where clinicians' knowledge and skills in relation to prescriptions vary widely, where many do not use clinical and diagnostic tests when appropriate, and where it is nearly impossible to enforce compliance with labels. (61) The challenge will likely be greatest for primary care physicians. Accordingly, it is argued that pharmacogenomics may be useful only if combined with computerised 'expert' systems that assist clinicians in the safe and effective use of pharmacogenetic tests and drugs. (62) Alternatively, or jointly with the implementation of such systems, it is possible that pharmacists' prescribing authority would be extended.

Nutrigenomics may present even greater challenges. (63) The first question to ask is who will deliver such services. (64) If nutrigenomic testing and counselling is delivered by health care professionals, problems discussed above in relation to pharmacogenomics will apply. Additionally, the fate of preventive measures generally is worse than the integration of new diagnostic or therapeutic modalities. (65) If, however, tests are offered directly to consumers, problems identified in the US GAO report will need to be rectified.

Another fundamental question in bringing these new genomic applications to the market place will be one of determining whether to provide more information directly to consumers. So far, there has been much controversy regarding the direct-to-consumer marketing of genetic tests. (66) Whether this controversy will only attach to matters related to medical therapies as conventionally defined or whether it could extend to nutrition is difficult to predict given that food and beverage advertising is a common and accepted practice.

Liability Issues

By requiring manufacturers to prove that a technology or a product is safe, the statutory and regulatory provisions discussed above clearly represent important risk management mechanisms. Litigation, although primarily viewed as a means of reparation after harm is already done, nevertheless can "deter wrongful behavior and encourage correct behavior" and, therefore, represents another risk management tool. (67)

Thus, the conduct of those who will provide pharmacogenomic or nutrigenomic products and services will come under increasing scrutiny from patients and consumers. In fact, US courts already have begun to examine certain medical practices involving genomics. In 2000, patients with a particular genotype (HLA-DR4+) who developed an incurable form of arthritis after being vaccinated for Lyme disease sued SmithKline Beechman, the maker of the LY-MErix vaccine, claiming that the product should have been labeled to indicate that those with such a genotype could suffer adverse events, as observed in animal studies. (68)

While such a lawsuit raises the prospect of more product liability cases, where manufacturers are held accountable for defects in product design or in manufacturing, or in defects related to warnings or instructions, (69) health care professionals providing services based on pharmacogenomics or nutrigenomics will need to conform to standards of care that will be evolving, as well as informed consent requirements that may be in flux in terms of the data available for purposes of fulfilling disclosure requirements. (70) Physicians involved in targeted therapy through pharmacogenetics are likely to encounter the greater risks of liability if patients suffer adverse drug reactions due to inaccurate results, or erroneous interpretations, particularly when reactions are fatal. However, plaintiffs may face evidentiary challenges, as complex questions will likely arise as to whether the cause of harm will have been drug-related or test-related; in other words, "[i]f some of these events are attributed to the drug, while others are attributed to problems with a test or in the use of test results, it will not be possible to assemble a true picture of why patients are being injured...." (71)

Another area that could give rise to liability is the violation of privacy rights that may arise from the negligent or otherwise illegal disclosure of test results. (72) It is worth noting that although the provision of nutrigenetic services may be less likely to give rise to physical injury, privacy violations or claims of discrimination may be more frequent in the context of nutrigenomics than pharmacogenomics. Indeed, "[a] person being tested to determine what drug might be most effective in treating a disease already has a disease; the genetic test is not going to newly categorize him as ill, or as someone who will become ill. In contrast, nutrigenomics screening could reveal previously unknown disease predispositions." (73)

Conclusion

Canadian patients and consumers are on the verge of entering the genomic sphere where biomedical researchers, manufacturers and health care professionals have become increasingly active for the past decade or so. Is Canadian law ready? The above analysis suggests that existing statutes and regulations, along with guidance documents that interpret them, cover some aspects of the principal genomic applications being developed toward personalized medicine and personalized nutrition.

Foremost, the regulations that govern the development of medical devices include many provisions related to the types of tests that underlie both pharmacogenomics and nutrigenomics. However, despite many commonalities between pharmacogenetic and nutrigenomic tests, there are potential distinctions: a same technology may be differently regulated based on its intended use, such that therapeutic purposes may raise greater regulatory scrutiny than products intended primarily for preventive purposes. Or, in other words, "patients" may be given greater protection than "healthy" individuals, perpetuating trade-offs in the allocation of resources toward medicine's curative model rather than toward public health's preventative model. Alternatively, this dichotomy may be eliminated if nutrients and drugs have a comparable genetic impact and genomic technologies give rise to a new era of "personalized" health that supersedes the difference between public health and medicine.

Allocation decisions will also be made by corporate stakeholders. If pharmaceutical companies believe that genomic-based R & D efforts will be more successful, and investment costs more easily recouped through the promise of personalized medicine, there may be new hope for patients who are poor responders to existing medication or who traditionally have fallen into unprofitable orphan drug markets. Alternatively, pharmaceutical companies may be hesitant if the success of their products rests on clinicians' pharmacogenomics competencies. The food industry's investments in the development of new products based on nutrigenomics may also depend on whether health care professionals are given an intervening role and whether they are able to fulfill it competently, or whether manufacturers are able to promote products and testing services directly to consumers.

These questions all point to the uncertainties that are created when new scientific or technological advances have the potential to be delivered through separate channels. Indeed, so far, pharmacogenomics is clearly anchored in the highly regulated clinical interactions between health care professionals and patients, whereas nutrigenomics may escape the strict regulatory framework applied to medical products and services.

These are still unchartered waters and only time will tell whether Canadian statutory and regulatory law appropriately addresses the balance of benefits and risks presented by new genomic applications.

Karine Morin is a Research Associate at the University of Ottawa. The author is grateful to Juliana Aiken and Sarah Scott for research assistance and to Nola Ries for comments on a draft of this article. Funding support is acknowledged from the Network of Centres of Excellence for Advanced Foods & Materials (www.afmnet.ca).

1. See National Human Genome Research Institute, "An Overview of the Human Genome Project" (9 July 2007), online: National Human Genome Research Institute <http://www.genome.gov/12011238>.

2. Pharmacogenomics entails the study of the whole spectrum of genes that determine drug response. See U.A. Meyer, "Introduction to Pharmacogenomics: Promises, Opportunities, and Limitations" in J. Licinio & M.L. Wong, eds., Pharmacogenomics: The Search for Individualized Therapies (Weinheim, Germany: Wiley-VCH, 2002) 1; W.E. Evans & H.L. McLeod, "Pharmacogenomics: Drug Disposition, Drug Targets, and Side Effects" (2003) 348 New Eng. J. Med. 538; D.B. Goldstein, S.K. Tate & S.M. Sisodiya, "Pharmacogenetics Goes Genomic" (2003) 4 Nature Reviews Genetics 937. In contrast, the term pharmacogenetics refers to individually inherited variations to drugs and can help explain how an individual's genes determine drug efficacy and toxicity. The International Conference on Harmonisation of Technical Requirements For Registration of Pharmaceuticals for Human Use in its Draft Consensus Guideline: Terminology in Pharmacogenomics, (October 2006), online: Food and Drug Administration <http://www.fda.gov/cber/gdlns/iche15term.html>, defines pharmacogenomics as "[t]he investigation of variations of DNA and RNA characteristics as related to drug response" (s. 2.2.1.1) and pharmacogenetics as a subset of pharmacogenomics focused on "[t]he influence of variations in DNA sequence on drug response" (s. 2.2.1.2).

3. The field of nutritional genomics, or nutrigenomics, focuses on the interactions between diet, gene expression, genetic variability, health and disease. See G. Rimbach & S. De Pascual-Teresa, "Application of Nutrigenomics Tools to Analyze the Role of Oxidants and Antioxidants in Gene Expression" in G. Rimbach, J. Fuchs & L. Packers, eds., Nutrigenomics (Oxidative Stress and Disease) (Boca Raton, Florida: Taylor & Francis Group, 2005) 1. The term nutrigenetics refers to the study of the interaction between nutrient sensitivity and disease through individual variation. Results of individual tests can inform dietary advice to prevent or mitigate diseases. See David Castle, "Clinical Challenges Posed by New Biotechnology" (2003) 79 Postgraduate Medical Journal 65.

4. For a critical view of this proposition, see A. Hedgecoe, The Politics of Personalized Medicine: Pharmacogenetics in the Clinic (Cambridge, UK: Cambridge University Press, 2004).

5. It is interesting to note the debate regarding this terminology. Some scholars suggest that two notions of personalization currently co-exist--personalization as individualization and personalization as categorization--but argue that the trend may lead away from individuality and towards genetic categories, at least in the context of nutrigenomics. See B. Penders et al., "From Individuals to Groups: A Review of the Meaning of 'Personalized' in Nutrigenomics" (2007) 18 Trends in Food Science & Technology 333 at 336.

6. D. Ghosh, D. Skinner & W. Laing, "Pharmacogenomics and Nutrigenomics: Synergies and Differences" (2007) 61 European Journal of Clinical Nutrition 567 at 568.

7. Lawrence J. Lesko & Janet Woodcock, "Translation of Pharmacogenomics and Pharmacogenetics: A Regulatory Perspective" (2004) 3 Nature Reviews Drugs Discovery 763 at 763.

8. B. Evans, "Distinguishing Products and Practice Regulation in Personalized Medicine" (2007) 81 Clinical Pharmacology & Therapeutics 288 at 288.

9. M. Cain & G. Schmid, From Nutrigenomic Science to Personalized Nutrition: The Market in 2010 (2003), online: Institute for the Future <http://www.iftf.org/docs/NCNG_nutrig_to_pers_intro.pdf>. See also Ann L. Yaktine & Robert Pool, Nutrigenomics and Beyond: Informing the Future--Workshop Summary (Washington, D.C.: National Academy Press for the Food and Nutrition Board, Institute of Medicine, 2007) at 13.

10. J. Kaput et al., "Nutrigenomics: Concepts and Application to Pharmacogenomics and Clinical Medicine" (2007) 8 Pharmacogenomics 369.

11. Ibid.

12. M. Massoud et al., The Future of Nutrition: Consumers Engage with Science (2001), online: Institute for the Future <http://www.iftf.org/docs/SR-731_The_Future_of_Nutrition.pdf> at 26.

13. See "Quakers and Novartis Call Halt to Food Venture" Food Productions Daily (25 February 2002), online: Food Production Daily <http://www.foodproductiondaily.com/news/ng.asp?id=27311-quaker-and-novartis>.

14. Yaktine & Pool, supra note 9 at 51. See also G.W. Fuller, New Food Product Development: From Concept to Marketplace, 2d ed. (Boca Raton, Florida: CRC Press, 2005).

15. Lesko & Woodcock, supra note 7 at 763.

16. U.S., Food and Drug Administration, Innovation or Stagnation: Challenges and Opportunity on the Critical Path to New Medical Products (March 2004), online: Food and Drug Administration <http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.html>. See also S. Hogarth et al., "Regulating Pharmacogenomics: An Overview of Developments in Various Countries and Industry Response to Regulatory Initiatives--A Report for Health Canada" (2006), online: University of Cambridge <http://www.phpc.cam.ac.uk/epg/pgx.pdf>.

17. Lesko & Woodcock, supra note 7 at 764.

18. W. Jongen & M. Meulenberg, eds., Innovation of Food Production Systems: Product Quality and Consumer Acceptance (Wageningen, Netherlands: Wageningen Pers, 1998) at 1.

19. Matthijs Dekker & Anita R. Linnemann, "Product Development in the Food Industry" in Jongen & Meulenberg, supra note 18, 67 at 69.

20. Ibid. at 71.

21. M. Meulenberg & J. Viaene, "Changing Food Marketing Systems in Western Countries" in Jongen & Meulenberg, supra note 18, 5 at 10; T. Lang, "Food Control or Food Democracy? Re-engaging Nutrition with Society and the Environment" (2005) 8 Public Health Nutrition 730.

22. Castle, supra note 3 at 65.

23. Food and Drugs Act, R.S.C. 1985, c. F-27.

24. Ibid. ss. 8-15, 19-21. Importantly, this also is the case in the United States, the principal country from which new pharmaceutical products are launched. See B.M. Psaty & R.A. Charo, "FDA Responds to Institute of Medicine Drug Safety Recommendations--In Part" (2007) 297 Journal of the American Medical Association 1917 at 1919. Essentially, the Food and Drug Administration (FDA) is generally responsible for pharmaceutical drugs and devices, including diagnostic devices sold as kits or systems under the Medical Device Amendments of 1976. In this context, the FDA primarily focuses on test accuracy. Additionally, the Center for Medicare and Medicaid Services, the federal agency responsible for health insurance programs that cover the elderly and the indigent, oversees laboratory practices through the Clinical Laboratory Improvements Amendments of 1988, which focuses on laboratory quality. Yet, the FDA jointly approved trastuzumab (Herceptin[R]) and the associated tests for HER2 over expression in breast cancer tumors, which demonstrates the agency's capacity to regulate pharmacogenomics drugs and diagnostics in combination. See K.A. Phillips & S.L. Van Bebber, "Regulatory Perspectives on Pharmacogenomics: A Review of the Literature on Key Issues Faced by the United States Food and Drug Administration" (2006) 63 Medical Care Research & Review 301 at 304-305, 308-309. For a brief description of the regulatory structure for diagnostic testing technologies in the US, see L.J. Lesko & J. Woodcock, "Pharmacogenomic-Guided Drug Development: Regulatory Perspective" (2002) 2 Pharmacogenomics Journal 20.

25. Health Products and Food Branch, Health Canada, Access to Therapeutic Products: The Regulatory Process in Canada (Ottawa: Health Canada, 2006), online: Health Canada <http://www.hc-sc.gc.ca/ahc-asc/alt_formats/hpfb-dgpsa/pdf/pubs/access-therapeutic_acces-therapeutique_e.pdf>.

26. Health Canada, Drug Products (Ottawa: Health Canada), online: Health Canada <http://www.hc-sc.gc.ca/dhp-mps/prodpharma/index_e.html>.

27. See Timothy Caulfield, "Genetic Testing, Liability, and Regulatory Policy: The Canadian Situation" (2000) 41 Jurimetrics 7 at 11, nn. 15-16.

28. Medical Device Regulations, S.O.R./1998-282. See, in particular, Part 2 of Schedule 1. See also Medical Devices Bureau, Health Canada, Guidance for the Risk Based Classification of In Vitro Diagnostic Devices--Draft (Ottawa: Health Canada, 1998), online: Health Canada <http://www.hc-sc.gc.ca/dhp-mps/md-im/applic-demande/guide-ld/ivd-rsk_idiv-rsq_main_principal_e.html>.

29. Medical Device Regulations, ibid. s. 32(3). See also ss. 2.1, 2.2 and 5.1.2 of the Medical Devices Bureau, Health Canada, Preparation of a Premarket Review Document for Class III and Class IV Device Licence Applications (Ottawa: Health Canada, 1998), online: Health Canada <http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/md-im/prmkt2_precomm2_e.pdf>.

30. Ronald L. Doering, "Foodborne Illness and Public Health" in Tracey M. Bailey, Timothy Caulfield & Nola M. Ries, eds., Public Health Law & Policy in Canada (Markham, ON: LexisNexis Canada, 2005) 409 at 409. It is worth noting that there is an ongoing international debate as to whether food safety regulation is essentially a matter of public health (with health departments having the lead responsibility) or one of food production (where placing responsibility with agriculture and fishery departments).

31. Health Products and Food Branch, Health Canada, Guidelines for the Safety Assessment of Novel Foods (Ottawa: Health Canada, 2006), online: Health Canada <http://www.hc-sc.gc.ca/fn-an/alt_formats/hpfb-dgpsa/pdf/gmf-agm/guidelines-lignesdirectrices_e.pdf> at 4.

32. Health Products and Food Branch, Health Canada, Blueprint for Renewal: Transforming Canada's Approach to Regulating Health Products and Food (Ottawa: Health Canada, 2006), online: Health Canada <http://www.hc-sc.gc.ca/ahc-asc/alt_formats/hpfb-dgpsa/pdf/hpfb-dgpsa/blueprint-plan_e.pdf> [Blueprint for Renewal]; Health Products and Food Branch, Health Canada, Blueprint for Renewal II: Modernizing Canada's Regulatory System for Health Products and Food (Ottawa: Health Canada, 2007), online: Health Canada <http://www.hc-sc.gc.ca/ahc-asc/alt_formats/hpfb-dgpsa/pdf/hpfb-dgpsa/blueprint-plan_ll_e.pdf> [Blueprint for Renewal II]; Health Products and Food Branch, Health Canada, Towards a Regulatory Modernization Strategy for Food and Nutrition (Ottawa: Health Canada, 2007), online: Health Canada <http://www.hc-sc.gc.ca/fn-an/alt_formats/hpfb-dgpsa/pdf/consultation/rmsfn-smran_e.pdf> [Regulatory Modernization Strategy].

33. Blueprint for Renewal, supra note 32 at 19-20.

34. Blueprint for Renewal II, supra note 32 at 21.

35. Regulatory Modernization Strategy, supra note 32 at 7.

36. Ibid. at 12.

37. K.C. Glass, "Questions and Challenges in the Governance of Research Involving Humans: A Canadian Perspective" in T. Lemmens & D.R. Waring, eds., Law and Ethics in Biomedical Research (Toronto: Toronto University Press, 2006) 35 at 38.

38. Ibid. at 39. See also Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, & Social Sciences and Humanities Research Council of Canada, Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (Ottawa: Public Works and Government Services Canada, 1998, with 2000, 2002 and 2005 amendments, online: Government of Canada <http://pre.ethics.gc.ca/english/pdf/TCPS%20October%202005_E.pdf>.

39. B.J. Evans & E.M. Meslin, "Encouraging Translational Research through Harmonization of FDA and Common Rule Informed Consent Requirements for Research with Banked Specimens" (2006) 27 J. Legal Med. 119 at 122. See also B.J. Evans, "What Will it Take to Reap the Clinical Benefits of Pharmacogenomics?" (2006) 61 Food & Drug L.J. 753 [Evans, "Clinical Benefits of Pharmacogenomics"].

40. European Nutrigenomics Organisation (NuGO), Bioethics Guidelines on Human Studies (2006), online: NuGO <http://nugo.dife.de/bot/files/NUGO-Bioethics-Guidelines-on-Human-Studies.pdf>.

41. See L.J. Lesko et al., "Pharmacogenetics and Pharmacogenomics in Drug Development and Regulatory Decision Making: Report of the First FDA-PWG-PhRMA-DruSafe Workshop" (2003) 43 Journal of Clinical Pharmacology 342; R.A. Salerno & L.J. Lesko, "Pharmacogenomics in Drug Development and Regulatory Decision-Making: The Genomic Data Submission (GDS) Proposal" (2004) 5 Pharmacogenomics 25; R.A. Salerno & L.J. Lesko, "Pharmacogenomic Data: FDA Voluntary and Required Submission Guidance" (2004) 5 Pharmacogenomics 503.

42. Food and Drug Administration, U.S. Department of Health and Human Services, Guidance for Industry: Pharmacogenomic Data Submissions (March 2005), online: Food and Drug Administration <http://www.fda.gov/cder/guidance/6400fnl.pdf>.

43. Health Products and Food Branch, Health Canada, Guidance Document: Submission of Pharmacogenomic Information (Ottawa: Health Canada, 2007), online: Health Canada <http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/brgtherap/pharmaco_guid_ld_2007-02_e.pdf>.

44. Medical Device Regulations, supra note 28 at Part 3; Medical Devices Bureau, Health Canada, Preparation of an Application for Investigational Testing--In Vitro Diagnostic Devices (IVDD)--Guidance Document (Ottawa: Health Canada, 1998), online: Health Canada <http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/md-im/test_iv3_e.pdf>.

45. T. Mandry, "Legal Implications of Pharmacogenomics Regarding Drug Trials, Drug Labeling, and Genetic Testing for Drug Prescription: An International Approach" (2004) 59 Food & Drug L.J. 519 at 523; B.A. Binzak, "How Pharmacogenomics Will Impact the Federal Regulation of Clinical Trials and the New Drug Approval Process" (2003) 58 Food & Drug L.J. 103 at 106.

46. Hogarth et al., supra note 16 at 8.

47. Ibid. at 20.

48. J. Woodcock, "FDA Policy on Pharmacogenomic Data in Drug Development" (2005) 66 La. L. Rev. 91.

49. Supra note 23 s. 2.

50. Bureau of Food Safety and Consumer Protection, Canadian Food Inspection Agency, 2003 Guide to Food Labelling and Advertising (2003), online: Canadian Food Inspection Agency <http://www.inspection.gc.ca/scripts/priimp/priimppage.php?lang=e&ser=www.inspection.gc.ca&ref=/english/fssa/labeti/guide/toce.shtml> at Chapter 8, "Diet-Related Health Claims".

51. Food and Drug Regulations, C.R.C., c. 870, B.01.600--B.01.603.

52. Regulatory Modernization Strategy, supra note 32 at 12.

53. Regulated Health Professions Act, S. O. 1991, c. 18, s. 27(2)(1).

54. U.S. Government Accountability Office, Nutrigenetic Testing: Tests Purchased from Four Web Sites Mislead Consumers (GAO-06-977T) (Washington, D.C.: U.S. Government Accountability Office, 2006), online: U.S. Government Accountability Office <http://www.gao.gov/new.items/d06977t.pdf>.

55. Ibid. at 5.

56. Ibid. at 2.

57. In the US, there is genomic guidance on about 60 different drug labels, often in relation to CYP450 genes, which play a critical role in metabolizing drugs. Usefulness and clarity vary; more recent labels are generally more informative, whereas older ones provide genomic information but no guidance on appropriate testing. See Hogarth et al., supra note 16 at 29; B. Evans, "Distinguishing Product and Practice Regulation in Personalized Medicine" (2007) 81 Clinical Pharmacology & Therapeutics 288 at 290-291.

58. Section 3(1) of Canada's Food and Drugs Act, supra note 23, provides: "No person shall advertise any food, drug, cosmetic or device to the general public as a treatment, preventative or cure for any of the diseases, disorders or abnormal physical states referred to in Schedule A."

59. Guidance Document, supra note 43. More generally, see Health Products and Food Branch, Health Canada, Guidance for Industry: Product Monograph (Ottawa: Health Canada, 2004), online: Health Canada <http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/prodpharma/pm_mp_e.pdf>.

60. J.A. Robertson et al., "Pharmacogenetic Challenges for the Health Care System" (2002) 21 Health Affairs 155.

61. T. Ling & A. Raven, "Pharmacogenetics and Uncertainty: Implications for Policy Makers" (2006) 37 History & Philosophy of Biological & Biomedical Sciences 533.

62. See D. Melzer et al., My Very Own Medicine: What Must I Know? Information Policy for Pharmacogenetics (Cambridge: Department of Public Health and Primary Care, University of Cambridge, 2003), online: Department of Public Health and Primary Care, University of Cambridge <http://www.phpc.cam.ac.uk/epg/Report.pdf> at 49-51; L. Noah, "The Coming Pharmacogenomics Revolution: Tailoring Drugs to Fit Patients' Genetic Profiles" (2002) 43 Jurimetrics 1 at 22-24.

63. David Castle & Nola M. Ries, "Ethical, Legal & Social Issues in Nutrigenomics: The Challenges of Regulating Service Delivery and Building Health Professional Capacity" (2007) 622 Mutation Research 138.

64. Castle, supra note 3.

65. Robert F. Kushner, "Barriers to Providing Nutrition Counseling by Physicians: A Survey of Primary Care Practitioners" (1995) 24 Preventative Medicine 546 at 548-549. See also K.M. McTigue et al., "Screening and Interventions for Obesity in Adults: Summary of the Evidence for the U.S. Preventive Services Task Force" (2003) 139 Annals of Internal Medicine 933; U.S. Preventive Services Task Force, "Behavioral Counseling in Primary Care to Promote a Healthy Diet: Recommendations and Rationale" (2003) 24 American Journal of Preventive Medicine 93.

66. Bryn Williams-Jones, "Where There's a Web, There's a Way: Commercial Genetic Testing and the Internet" (2003) 6 Community Genetics 46. See also American College of Medical Genetics, "ACMG Statement on Direct-to-Consumer Genetic Testing" (2004) 6 Genetics in Medicine 60.

67. S.H. Yoshida, "Food Biotechnology and U.S. Products Liability Law: The Search for Balance Between New Technologies and Consumer Protection" in J.R. Neeser & J.B. German, eds., Bioprocesses and Biotechnology for Functional Foods and Nutraceuticals (New York: Marcel Dekker, 2004) 377 at 381.

68. See Susan Warner, "SmithKline Beecham Faces Lawsuit for Lyme Disease Vaccine's Negative Effects" Philadelphia Inquirer (13 June 2000); Holcomb B. Noble "Three Suits Say Lyme Vaccine Caused Severe Arthritis" New York Times (13 June 2000), online: New York Times <http://query.nytimes.com/gst/fullpage.html?sec=health&res=9F01E4DB143EF930A25755C0A9669C8B63>. See also Vroom v. SmithKline Beecham Corp., 58 Pa. D & C 4th 557 (2001); Marra v. SmithKline Beecham Corp., 815 A.2d 1042 (Pa. 2003); Vroom v. SmithKline Beecham Corp., 815 A.2d 1043 (Pa., 2003).

69. P.N. Ossorio, "Product Liability for Predictive Genetic Tests" (2000) 41 Jurimetrics 239; M.A. Rothstein, "Liability Issues in Pharmacogenomics" (2005) 66 La. L. Rev. 117.

70. Noah, supra note 62 at 24-26.

71. Evans, "Clinical Benefits of Pharmacogenomics", supra note 39 at 771.

72. Nola M. Ries & Timothy Caulfield, "First Pharmacogenomics, Next Nutrigenomics: Genohype or Genohealthy?" (2006) 46 Jurimetrics 281 at 295.

73. Ibid.