Canadian legal oversight of pharmacogenomics and nutrigenomics.

• Author: Morin, Karine

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...