Nutraceutical and Functional Food Regulations in the United States and Around the World

Debasis Bagchi, Debasis Bagchi

• Publisher: Academic Press
• Year: 2014
• ISBN:
  9780124059122
• Edition: 2
• Topic: Law
• Subtopic: Agricultural Law
• Index: Law

This fully revised and updated edition begins with insights into the scope, importance and continuing growth opportunities in the nutraceutical and functional food industries and explores the latest regulatory changes and their impacts. The book demonstrates the global scenario of the acceptance and demand for these products and explores the regulatory hurdles and claim substantiation of these foods and dietary supplements, as well as addressing the intricate aspects of manufacturing procedures.

As the public gains confidence in the quality of these products based on sophisticated quality control, a broad spectrum of safety studies and GRAS, peer-reviewed publications and cutting-edge human clinical studies have emerged. An increasing number of additional populations around-the-world now recognize the efficacy and functions of nutraceuticals and functional foods as established by those scientific research studies. As a result, a number of structurally and functionally active novel nutraceuticals and several new functional beverages have been introduced into the marketplace around the world.

• Features fully revised and updated information with current regulations from around the world, including GRAS status and DSHEA regulators
• Offers 45% new content including three new chapters – NSF: Ensuring the Public Health and Safety Aspects of Nutraceuticals and Functional Foods; Role of the United States Pharmacoepia in the Establishment of Nutraceuticals and Functional Food Safety; An Overview on the New Dietary Ingredient (NDI) and Generally Recognized as Safe (GRAS) Status, and the addition of cGMP regulations for dietary supplements
• Includes insight into working with regulatory agencies, processes and procedures
• Provides a link to the contact information for most regulatory bodies for readers wishing to gain further knowledge

Part I

Introduction

Outline

Chapter 1 Nutraceuticals and Functional Foods: Aligning with the Norm or Pioneering Through a Storm

Chapter 2 Nutritional Supplements and Functional Foods: Functional Significance and Global Regulations

Chapter 3 Global Market Entry Regulations for Nutraceuticals, Functional Foods, Dietary/Food/Health Supplements

Chapter 1

Nutraceuticals and Functional Foods

Aligning with the Norm or Pioneering Through a Storm

Anthony L. Almada, Vitargo Global Sciences, LLC, Dana Point, California

What factors overcome innovation inertia, compelling a nutrition business entity to develop products that promise and deliver consumer-relevant benefits? In the absence of innovation, and amidst the stream of “invention”, can an enduring bioactive ingredient or finished good be created that enjoys an extended life cycle? When such innovations are achieved what recourse does the innovator have to exclude ostensible duplicates and protect their investment? Within a global climate of regulatory under-enforcement and ubiquitous messaging of unsubstantiated claims can a viral spread of science-driven enterprise manifest and infect even 25% of the industry? Will consumer-centric legal actions eclipse the might of governmental agencies and inject a decisive, otherwise lacking swiftness? Will a brand emerge that enjoys an inspiring evidence base on EACH bioactive or finished good? Where does the ripe, high-hanging fruit rest for the pioneering innovator brand and company willing to climb where others avoid?

Keywords

Nutraceutical; functional food; functional beverage; class action lawsuit; clinical trial; innovation; bioactive; gluten; glycemic index; patent; freedom to operate

The nutrition industry thrives with a global footprint, enjoying substantial economic momentum. In this chapter I define “nutraceuticals”—still nutrition industry/scientific community parlance and lacking a regulatory definition—as supplements or complements to the diet that are comprised of bioactives that occur in food or are produced de novo in human metabolism, botanicals, or their constituents, intended to impart a physiological or medicinal effect after ingestion; and vitamins and minerals, delivered in forms that differ from conventional foods or beverages, e.g., solid dosage forms like capsules, tablets, or ethanolic liquid extracts. “Functional foods and beverages”—another nutrition industry/scientific community descriptor lacking a regulatory parent—I define as the above, yet delivered in conventional food and beverage formats, e.g., a single-serving beverage, a fermented dairy product, or a food bar. Collectively I will refer to these two classes as “NFx.” Biologically, NFx are intended to impart a physiological or medicinal effect, without or in addition to a nutritional effect.

1.1 Myths devolve into faith and dogma

The consumer promise of an NFx holds the allure of improved or preserved physiologic or metabolic function. The spectrum of consumer expectation ranges from disease/condition prophylaxis to disease/condition treatment, to even cure. The quest for “natural,” the drive to engage in “self-care,” and the almost free and boundless access to the virtual, omniscient libraries called the Internet and social media messaging are forging a new breed of companies and consumers. Armed and dangerous, with a modicum of evidence or simply a sugar-coated science tale, bioactives are birthed, brands are born, products are launched, and tribes are formed.

In the world of NFx, from a seedling of science often emerges a fad or a trend. In 1981 a Canadian research team developed the glycemic index (GI), a tool conceived to provide a physiological metric related to a carbohydrate-containing food, supplement, or beverage and its influence on blood glucose dynamics [1]. An NFx exhibiting a “high” GI value is widely believed to deliver its glucose to the circulation at a “faster” rate, while an NFx displaying a “low” GI value is believed to deliver its glucose at a slower rate. However, the GI does not reflect the rate of digestion and absorption of glucose entering the blood [2–5]. Rather, it is simply the net result of how much glucose entered the blood (from the gut; hepatic gluconeogenesis) less how much exited the blood (primarily disposal into tissues, especially skeletal muscle and liver) over a certain time or time interval. Despite this, numerous influencers and marketers of NFx state that GI is correlated to the rate of entry of glucose into the blood or that a low GI NFx is equivalent to a “slow burning” carbohydrate [6–8], despite zero or contravening, direct evidence in place [2–5].

A more recent entrant into the faith-fueled NFx category is the gluten-free moniker. Despite the identifier, a gluten-free NFx is not free or devoid of gluten but exhibits ≤20 parts per million of gluten in the final consumable form. In the United States, from 2012 forward the Food and Drug Administration issued 17 product withdrawals due to undeclared wheat allergen in foods [9]. Over the same interval Health Canada issued 13 undeclared gluten recalls [10]. This, coupled with the observation that most “gluten-free” certifications do not typically require quantitative, post-manufacturing testing for gluten on each batch of any certified product, imparts a questionable degree of confidence to the gluten-sensitive or celiac individual (who typically pays a premium for “gluten-free”). What if a manufacturing or labeling error or omission was committed, or an intentional act of domestic bioterrorism was perpetrated, within a manufacturing facility, rendering an NFx labeled as gluten-free to be effectively gluten-rich?

In the previous edition of this book I wrote:

From this author’s perspective the NFx products that enjoy (or have enjoyed) robust, sustainable revenues are those defined by one of two phenomena: 1) consumer experience, and 2) high circulation, incremental media editorial messaging.

Reflecting upon this passage I see the lack of emphasis upon the operative phrase “one of two” and word “sustainable” as problematic. Numerous NFx action words/phrases (low glycemic; gluten-free; açai; probiotic, antioxidant; super fruit; anti-inflammatory; coconut water; omega-3) enjoy moderate to broad consumer awareness, linked to salutary or desirable effects. However, few enjoy robust and sustainable (or incremental) revenues, with less being buttressed by an even semi-compelling evidence base.

1.2 Value addition or illusion?

Our own market and scientific research still indicates that less than one out of a thousand finished NFx products—not individual bioactive ingredients but the final form purchased and ingested by a consumer—enjoys at least a single randomized controlled trial (RCT) performed against a placebo or a positive control (e.g., an appropriate drug), and demonstrating a statistically significant outcome superior to that of the placebo, or equivalent or even superior to a positive drug comparator. Add in the additional criterion of such an RCT published in a reviewed journal and the percentage of qualifying NFx falls precipitously. What is more unsettling is our finding that of the ~250–300 RCTs conducted on NFx products in North America annually only a fraction are made public (via presentation or publication). This underscores the prevalence of publication bias and reveals the far more haunting truth that data suppression is not uncommon. Sadly, the “gagging” of investigators related to dissemination of clinical trial data on NFx products reaches into the ranks of publicly traded and multinational NFx marketing entities. The “burial” of this data is achieved by increasing numbers of studies performed with contract research and clinical service organizations, where data ownership (and intellectual property rights) is exclusive to the study sponsor.

The emergence and adoption of clinical trials registries (http://clinicaltrials.gov/; http://www.controlled-trials.com) has augmented the integrity of reporting while reducing publication bias, albeit in biomedical journals that require timely clinical trial registration (before enrolling the first participant within a 60 day grace period). A large proportion of the journals that entertain a large number of NFx publications do not require registration of a clinical trial as an inclusion criterion for publication (and editors of the “elite” journals may assert that the rigor and sample size of many NFx manuscripts do not warrant inclusion in their journals…). Given that a notable number of registered clinical trials on NFx do not publish their results after completion suggests that clinical trial registration alone is insufficient to convey transparency of research outcomes. Nevertheless, the adoption of clinical trial registration requirements [11] by the editors of journals that de facto cater to NFx manuscripts would raise the bar.

The importance and utility of NFx is defined not by revenues, share price, the annualized number of product introductions, nor calculated annual growth rate of the sector. NFx should serve the consumer by making a favorable, measurable impact upon her/his biology, congruent with the claimed benefit of the product and perhaps beyond. A probiotic beverage or solid dose that improved laxation and reduced LDL cholesterol could become a product that enjoys legions of brand zealots. The provision of NFx products, in its purest form, can be viewed as a public health initiative, centered upon offering consumer goods that meet four criteria: (1) excellent tolerability and hedonics, at least equal to the conventional food or beverage category leader (for solid dose forms, excellent tolerability, acceptable dose frequency, and ease of use/swallowing); (2) demonstration of consumer-relevant and scientific community-relevant efficacy through an incremental series of clinical trials; (3) aligning with existing, demographically dense unmet or undermet needs; and (4) remaining within a retail price comfort zone.

Aversion to “good for you” foods and beverages can be a significant deterrent for many consumers. Creating an equal or superior sensory experience with a functional food or beverage can have a dramatic impact upon consumer trial and repeat purchasing. The post-ingestive experience also has significant import, especially in relation to gastrointestinal symptoms. NFx products that are intended to have a gastrointestinal effect (e.g., prebiotics or synbiotics; fiber; anti-Helicobacter pylori agents) have the highest likelihood of causing gastrointestinal distress. Solid dose forms need to be delivered in a manner that does not require multiple dosing throughout the day nor large dose formats (e.g., large tablets or capsules). Liquids need to be easily measured and palatable, with masking/debitterizing agents considered for use. Powders need to be easily mixable and non-hygroscopic under normal storage conditions. The unrelenting growth in the interest in natural and sugar-free also demands NFx compositions to seek natural, non- or low-caloric bulk and/or high-intensity sweetener systems that exhibit high gut tolerability and palatability.

One cannot emphasize the critical need for a series of clinical trials on an NFx. One of the elements lacking among consumers of NFx products is confidence: in the claims, in the taste, and in the brand. A specific consumer product buttressed by even one well-designed RCT—where the number of servings or dose used in the study matches the labeled use directions and is not cost prohibitive—can exalt a brand into a new level of equity with consumers. It is a widely held misperception that sponsoring an RCT requires a budget in excess of $100,000. Harkening back to our finding of less than 0.1% prevalence of a...