Claim Substantiation: A Natural Products Dilemma

The natural products industry is in an era characterized by fiscal challenges, growing safety concerns over adulterated raw materials from foreign suppliers, and a myriad of confusing regulatory pronouncements with overlapping domains. Navigating through legislation such as the 1990 Nutrition Labeling and Education Act (NLEA), the 1994 Dietary Supplement Health and Education Act (DSHEA), the 1997 FDA Modernization Act (FDAMA), or the regulation governing new dietary ingredients (NDIs) requires extraordinary effort.

The greater challenge is the lack of clarity in understanding the regulatory framework necessary for substantiating product claims. Central to the understanding of product claims is recognizing that the regulatory pathway depends on the quality and strength of the supporting scientific evidence.

Regulatory Background
To illustrate the complexity of claim substantiation, a basic review of claim categories and the applicable regulations may be instructive. Claims used on food and dietary supplements fall into one of three categories: health, nutrient content, and structure/function claims.

Health claims describe a relationship between a food, food component, or dietary supplement ingredient, and reducing risk of a disease or health-related condition. Nutrient content claims describe the level of a nutrient or dietary substance in the product, or they compare the level of a nutrient in a food to that of another food. Further, structure/function claims address the role of a specific substance in maintaining normal healthy structures or functions of the body but may not explicitly or implicitly link the relationship to a disease or health-related condition. The responsibility for ensuring the validity of these claims is with the manufacturer, FDA, or-in the case of advertising-the Federal Trade Commission.

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Authorization for these claims is covered by different regulations. First, in accordance with FDAMA, FDA may authorize health claims based on authoritative statements of a scientific body of the U.S. government or of the National Academy of Sciences (Washington, DC). Second, manufacturers may petition FDA to authorize the use of a health claim of a product for a disease or health condition.

FDA applies the "significant scientific agreement standard" when evaluating the petition and reviewing the scientific evidence. Depending on the strength and quality of evidence, a health claim can be authorized as petitioned, where strong evidence exists. Alternatively, a dietary guidance claim would be more appropriate for claims with "generally supportive but not strong evidence," in accordance with NLEA. NLEA also provides for claims that characterize the level of a nutrient in a product.

Third, manufacturers intending to make structure/function claims are governed by yet another regulation, namely DSHEA, which was intended as a safe harbor to market dietary supplements without rendering them as drugs. It was clearly a compromise in that although expressed or implied druglike claims concerning a supplement were not permitted, other supplement-related claims were expressly authorized, provided such claims did not imply therapeutic or preventive value. Statements that address the role of a specific substance in maintaining normal healthy structures or functions of the body have historically appeared on labels of conventional foods and dietary supplements as well as drugs.

In consideration of international efforts to address similar issues, the Canadian government, for example, developed new classifications for health claims for those foods and supplements that fall short of meeting drug claim requirements. These criteria include disease-related claims, function or biological role claims, and general health claims.

Likewise, the European Union (EU) has already begun to address these concerns. In December 2006, the EU Council and Parliament adopted regulations on the use of nutrition and health claims for foods. These regulations established harmonized rules for the use of health or nutritional claims. A key statement in the proposal for the regulation was that "Nutrition and health claims shall be based on and substantiated by generally accepted scientific data."

Problems and Challenges
Many in the nutraceutical industry hold the view that the passage of DSHEA mitigates the stringent FDA regulations normally reserved for drugs, so long as supplements are not promoted for therapeutic applications. This position has unfortunately led to confusion in labeling and advertising of products and, in so doing, challenged both consumers and manufacturers alike. As is generally the case with many well-intentioned regulations and guidelines, contradictory interpretations of DSHEA constitute the necessary precepts for revisions of the act and for clarifying the regulatory framework for food and dietary supplement product development.

Unlike health claims, dietary guidance statements and structure/function claims are not subject to FDA review and authorization. Problems arise because:

• Clarifications are needed for better definition of the different claim categories.

• Criteria required to validate health claims specifically are not clear.

• The myth persists that such requirements are identical for those of drugs with similar costs.

• Under the current DSHEA guidelines, it can be, in many instances, more difficult to properly substantiate a structure/function claim than a disease or therapeutic claim. Delineation of structure/function claims is especially difficult because it requires the identification of healthy populations, as well as selection of appropriate study outcomes or variables for analysis.

 Furthermore, for dietary ingredients introduced to market since October 15, 1994, additional regulations apply and must be met to comply with two stated conditions: evidence to support a reasonable expectation of safety for the marketed use, and FDA must be provided with safety data 75 days prior to marketing or a premarketing notification. Hence, in order for claims to be developed for a new ingredient, an NDI notification must be made; complete with criteria for efficacy of the finished product in meeting either structure/function or specific health claims.

Often companies do not perform adequate clinical research to meet these regulatory requirements and substantiate claims due to misconceptions of anticipated costs and the perception that FDA does not have adequate resources to manage and enforce compliance. The problem may also persist since most food and dietary supplement companies do not have the expertise or operational knowledge of regulatory and clinical research processes. Unlike in the pharmaceutical industry, many food and dietary supplement companies lack research capacity, which only exacerbates the gap between the industry and the research and regulatory communities.

Undoubtedly, the regulatory agencies and the well-informed and concerned consumers both perceive the importance and the necessity of evidence-based promotional guidelines to substantiate claims. While many in the industry are truly dedicated to producing safe, efficacious, and health-promoting natural products, some questionable promotional practices raise valid concerns from the healthcare and scientific communities, as well as regulatory agencies.

Potential Solutions and Opportunities
Forward-thinking food and dietary supplement stakeholders have turned their attention to the development of continuing education programs for the industry, encouraging and promoting the use of published scientific data that are grounded in basic research and well-controlled clinical trials documented in peer-reviewed journals. This also includes education for new good manufacturing practices (GMPs) legislation that ensures that anyone engaged in activities related to manufacturing, packaging, or holding dietary ingredients or supplements does so in a manner that will not adulterate or misbrand such products.

To further advance the healthcare agenda from the natural products industry viewpoint, what is clearly needed is the cultivation of an information resource and a forum for various stakeholders to come together in dialogue with the intent to share knowledge about the needs, expectations, and impediments to achieving common goals. This forum would include manufacturers, regulators, academicians, healthcare insurance providers, and other industry professionals. The intent is to better understand and clearly define success factors, opportunities, and challenges-both short and long term-especially in this climate of healthcare reform. Obstacles to funding research should also be delineated and circumvented, and protection for proprietary processes and considerations for product reimbursement must be improved.

Strategies to improving the industry's image in the scientific and academic communities should be developed and adopted to gain respectability, especially in the eyes of the educated consumer. Finally, an opportunity to better understand the practical interpretations of the regulatory requirements governing food and dietary supplement product claims must be cultivated by shedding light on valuable preclinical research and the necessary clinical trials as a means to generate credible data essential for claim substantiation.

It is clear that regulatory agencies as well as concerned industry participants and informed consumers perceive the importance and the necessity of evidence-based guidelines for substantiation of product claims. Exercising sound scientific principles in product development can best be viewed not only as an investment with potential marketing and intellectual property benefits, but also as insurance against future litigations or regulatory challenges.

Zuhair Latif, PhD, currently serves as the chief scientific officer at CRP. Latif's industry experience includes management of clinical research, marketing, quality control, and manufacturing of investigational new drugs and diagnostic products. Jay Yourist, PhD, serves as president and CEO of Clinical Research Partners (CRP) LLC (Coral Gables, FL), a clinical research firm dedicated to performing clinical research and consulting for the natural products, biotechnology, and medical device industries. He is also executive director of the International Institute for Healthcare and Human Development. For more information, call 800/979-3458, visit www.ClinicalResearchPartners.net. Yourist can also be reached by sending e-mail to jyourist@clinical-researchpartners.net.