Finding Balance: Dietary Supplement Regulations Versus Consumer Access

Those tracking dietary supplement regulations have had a busy summer. At the time I began writing this article, it had only been a few days since FDA had released its long-awaited new dietary ingredient (NDI) draft guidance. Moreover, just over a week had passed since Senator Richard Durbin (D-IL) announced a new bill targeting supplements versus conventional food.

Besides these latest developments, this year industry members also watched-and participated in-FDA’s continually increasing Good Manufacturing Practices (GMP) inspections, and kept their eyes on enhanced FDA-FTC joint efforts to catch those breaking the laws.

If you look beyond the scrutiny, it boils down to one simple fact: dietary supplements usage is growing. And, while it’s inevitable that such growth will attract watchful eyes, the goal of both industry members and regulators alike should be to strike a balance to ensure that consumers wishing to maintain their health through supplements use have reasonable access to safe and effective products.

Which Way Are the Scales Tipping?

Let’s start with the most obvious and recent development: NDI guidance. The gauntlet, if you will, has been thrown, and as industry busily digests the contents of the guidance, it will also be preparing its responses to agency. (The comment period is open until October 3, although leading associations have requested a 45-day extension.)

On a positive note, FDA has received support for finally providing guidance on the matter of NDIs, period. Nutritional Outlook editorial advisory board member Cara Welch, PhD, vice president of scientific and regulatory affairs for the Natural Products Association (NPA), stated, “NPA welcomes this guidance by FDA and is closely reviewing it, as it could have major repercussions. The guidance should offer clarity to supplement manufacturers on FDA’s expectations for the safety notification process required for new dietary ingredients. It’s important for the industry to know FDA’s thinking to ensure that our members can continue to provide products utilizing both new and old dietary ingredients, encouraging growth of the marketplace.”

If you haven’t done so already, now is the time to familiarize yourself with the guidance. Although the guidance isn’t law, it sheds light on what FDA believes constitutes a new dietary ingredient and what information may be required for a NDI notification. (Thus far, the agency says, more than 700 notifications have been submitted.)

“I think all of us have to get a better handle on this NDI change,” says Shaheen Majeed, marketing director for ingredient supplier Sabinsa Corp. (East Windsor, NJ). “While many welcome it, others are confused and scrambling for documentation on what they had prior to DSHEA [the Dietary Supplement Health and Education Act].” (Marketers are required to submit a NDI premarket notification to FDA if they cannot provide evidence that their ingredient was marketed as a dietary ingredient in the United States prior to DSHEA’s implementation on October 15, 1994.)

Expect industry members to maintain caution. “Even though the guidance is not binding, we should all be concerned about any attempt by FDA to use this forum to change the rules and practices that have been accepted and in place for 17 years,” warned Michael McGuffin, president of the American Herbal Products Association.

Caution is wise, as the guidance contains more than a few sticking points-some anticipated, some not-that industry will be focusing in on.

Some, including NPA, have openly expressed concern that the new NDI guidance may overstep the bounds Congress approved through DSHEA. As the association stated in July:

The Natural Products Association thanks the FDA for meeting the deadline set by Congress for the release of the NDI guidance. The draft guidance answers a lot of questions for the industry, but it also raises concerns about its overall impact. It could profoundly affect the ability of Americans to get the supplements they want and need.

We believe the draft guidance does not match Congress’s clear intent that products made from ingredients on the market prior to DSHEA should remain on the market. The FDA is asking for far more from the industry to prove that an ingredient was on the market before 1994 than most makers can probably produce. That was not the intent of DSHEA. These requirements will reduce ingredients meeting the established grandfathered status to a regrettably small number.

The draft guidance also addresses a number of situations when a premarket safety notification is required. NDI notifications are required for: components of food marketed before 1994; a change in solvent when processing an ingredient; a change in manufacturing that produces nanoscale particles; and each manufacturer of each supplement containing an NDI. The agency further clarified that synthetic versions of dietary ingredients require an NDI notification, with the exception of synthetic botanical constituents that FDA has declared are not considered dietary ingredients. These situations have the potential to impact dietary supplement manufacturers far and wide.

In addition, the safety testing requirements for NDIs are raised to a level well above what was contemplated in DSHEA. These requirements will be harder for manufacturers to meet, inevitably leading to fewer new products in the marketplace.”

The association concluded: “We said this could be a game-changer for the industry, and it is. NPA will monitor and report on how this guidance affects the industry, and develop comments representing these concerns to be submitted to FDA. Today, half of all Americans trust dietary supplements and use them as part of a healthy lifestyle. For them and for our industry, it’s vital that we make sure consumers continue to have access to popular, safe dietary supplements.”

Nutritional Outlook editorial advisory board member Harry Rice, PhD, vice president of regulatory and scientific affairs for both the United Natural Products Alliance and the Global Organization for EPA and DHA Omega-3s, points out another piece of the puzzle that will determine how NDI guidance will ultimately affect industry: “The publication of the NDI guidance [is] a game-changing event. To what extent is unknown. It may be determined, in part, by the extent to which FDA is able to follow through with enforcement. The question that everyone is asking is whether there will be sufficient money left in the budget for enforcement activities.”

This question is especially pertinent if, as FDA indicated in the guidance, the agency is considering requiring NDI notifications not just for individual ingredients but for individual finished products. This would greatly increase the number of notifications industry would need to submit-and that FDA would need to evaluate.

“We have repeatedly urged Congress and the administration to provide government agencies with the resources they need to enforce existing regulations,” says John Gay, executive director and CEO of NPA. “One concern is that budget cuts may lead to delays in processing new dietary ingredient applications, fewer GMP inspections, and reduced enforcement activities aimed at those who violate the law.”

For instance, budgets for the still-shiny Food Safety Modernization Act (FSMA), passed this year, are already facing threats. Among other FSMA mandates are FDA registration every two years, beginning next year; FDA food-facility inspections; and new FDA mandatory recall authority.

“A big piece of what FSMA will mean for industry depends on whether FDA will get the money it needs to enforce the law,” says Steve Mister, president and CEO of the Council for Responsible Nutrition (CRN). “That being said, FSMA should help consumers to feel greater confidence that their food supply-including dietary supplements-is safe and subject to appropriate oversight.”

“The FSMA, while primarily directed at domestic and imported food suppliers, will have an impact on imported nutritional supplement materials because they are ‘foods’ in the eyes of the FDA. The new law introduces sweeping changes in the FDA’s authority and ability to react to real or perceived problems,” adds George Tilton, director of technical affairs for ingredient supplier Charles Bowman & Co. (Holland, MI).

The ability to preserve budgets will also determine whether FDA can continue to increase dietary supplement facility GMP inspections. FDA representatives have expressed their desire to increase the number of inspections performed, and industry has largely supported this.

Ensuring that inspections can continue is crucial for the health of both industry and consumers. FDA has already noted a large number of companies found not to be in compliance. Rice breaks it down: “With respect to 21 CFR 111, the greatest number (30%) of cited violations is associated with Subpart E, Requirement to Establish a Production and Process Control System. Within Subpart E, the most cited violations are associated with, 1) specifications, and 2) finished-product testing. It would behoove the industry to learn from others and make certain that their ‘Is’ are dotted and ‘Ts’ crossed.”

“[GMP inspections are] an area that should be of key importance to the industry,” adds NPA’s Welch. “Compliance with the GMPs is required by law, and the results of noncompliance carry serious consequences. The FDA, along with trade associations like NPA, are working with industry to educate all members on what problem areas are showing up in industry inspections. It’s up to industry to listen and work on changing these perceptions.”

Putting the shoe on the other foot, additionally, she notes, “We are also hearing reports from companies of some unevenness in audits, with differences among FDA district offices and even among inspectors. This is unsurprising, given that FDA is still training their inspectors, but it’s in the interest of both industry and FDA that inspections be consistent.”

Mister concludes: “GMPs will continue to be a big deal in 2011. We are seeing a lot of companies that are working hard to comply; and there are a few companies that still seem to have their heads in the sand. FDA is likely to go after those companies that are not in compliance-especially ones who don’t appear to be taking these requirements seriously. I think the warning letters we’ve seen recently are just a shot over the bow; there are a lot more to come.”

Ideally, regulators and industry members will strike a balance between appropriate oversight and allowing room for innovation.

“I am sure the next few years, similar to the last few years, will still provide much room for a growing curve,” says Jason Soltis, Esq., legal counsel to ingredient supplier Ecuadorian Rainforest LLC (Belleville, NJ). “The dietary supplement industry can get fairly complex in many areas. So, on that front, the FDA may need to take some more time to learn a bit more about parts of the industry-for instance, the sheer amount of products offered in the industry alone is staggering.”

“On the flip side,” he continues, “companies will have to start learning how to interact with the FDA in order to keep up with FDA and public health concerns. An industry that was once somewhat lightly regulated is becoming more so on a regular basis. This, however, will be good for the industry as a whole because there have been some dietary supplement outlaws in the past, and these new regulations will assist to make it difficult for those outlaws to stay in business.”
 

Supplements Research: Mixed Messages

One thing that could threaten innovation is an increasingly mixed message of late from FDA regarding investigational new drug (IND) applications.

Thus far, FDA’s new dietary ingredient guidance hints that ingredients for which INDs have been filed may find themselves excluded for consideration as dietary ingredients altogether. However, this contradicts an agency position last October, when FDA published draft guidance questioning whether INDs should be required if companies want to perform dietary supplement studies on humans at all. Suffice it to say, this contradiction has left dietary supplement companies increasingly wary of INDs and research.

Mike Bush, vice president of business development for probiotics supplier Ganeden Biotech (Cleveland), agrees that mixed messages about INDs have struck fear in companies. “The question is, if you do a clinical trial to substantiate a claim, does that then turn your ingredient into a drug? If you do a good trial, will it get you in trouble? That’s why you’re starting to see some companies dial back on the amount that they’re spending on clinical trials.”

“The long-term implications of the IND matter are concerning,” says CRN’s Mister. “We’ve commented on this issue because we worry about the interplay between FDA, on the one hand, pushing researchers to file INDs any time they are looking at a clinical endpoint, and on the other hand, DSHEA’s restrictions on dietary ingredients that have already been the subject of substantive clinical investigations.”

“In the long term,” he states, “these two opposing forces could hurt our ability to bring dietary ingredients to market.”

Turning to another growing industry concern involving supplements research is whether FDA has now come to place undue emphasis on the “gold-standard” randomized controlled trial (RCT) for health-claim supplement studies.

“Our members want to be able to use solid scientific evidence to support their products, and NPA is concerned that agencies may want to go beyond the sufficient level of substantiation required under DSHEA,” says NPA’s Welch.

“We are troubled that FDA seems to be so narrowly focused on RCTs as the basis for any health claims or as substantiation for structure-function claims,” adds CRN’s Mister. “They should focus on the totality of available evidence, and RCTs aren’t necessarily the most appropriate way to assess the health benefits of nutrients. If FDA continues to be overly restrictive, this could hinder industry from gaining approvals for new claims.”

As evidence of what too-narrow an approach can do, one of course has to look no further than criticisms of the European Food Safety Authority (EFSA) and its health-claims process. Many argue that EFSA’s large number of negative health-claim opinions has been the result of putting too much emphasis on RCTs.

“The EFSA process for review of health claims for dietary supplements has become too rigid, dismissing too much legitimate scientific evidence in favor of a drug-like review of only RCTs,” says Mister. “That alone demonstrates that the process has become a technical barrier to trade with the EU. Under the EFSA paradigm, the process of proving benefit is too restrictive and essentially closes the market to a lot of goods if they can’t make legitimate claims for these products.”

“The greatest threat to growth is excessive government regulation,” adds Sam Wright IV, CEO of custom and premix blends supplier The Wright Group (Crowley, LA). “We are seeing this mainly in Europe at the moment where there seems to be no such thing as common sense at EFSA. Health claims for ingredients with decades of safe experience and hundreds of positive clinical trials in many cases have been rejected. We hope the U.S. FDA takes a more-balanced approach.”

“In the face of an aging population, sharply escalating healthcare costs, and declining financial resources, it is hard to believe that governments around the world can afford to be so biased against an industry that very well may be the only solution to the healthcare cost dilemma,” he concludes.
 

High Profile

Speaking of bias, is the media biased against the supplements industry? Sometimes, it seems so, although it’s also likely a measure of increasingly sensationalized reporting.

“While there have been some positive media articles about particular supplements in the past year, like vitamin D, there have been far too many negative pieces, too,” says Mister. “Fortunately, I think consumers are starting to get numb to these reports on the ‘study du jour’-today it’s good for you, tomorrow it’s bad for you, and the day after that, who knows? As consumers start to filter out this daily noise, I think what you will see is a more-educated consumer looking to authoritative sources for good advice about wellness and nutrition. That should lessen the impact these negative stories in the consumer press have on product sales.”

Nevertheless, industry can brace itself for a new wave of public scrutiny on functional foods-a growing category that many industry companies have high hopes for-thanks to Senator Durbin’s recently proposed Dietary Supplement Labeling Act. Spurred by media attention on food and beverages containing melatonin, Durbin says his bill will ask FDA to establish a definition for “conventional foods, which would clarify which products are foods and should be regulated as such, and which products are meant to be health aids and should be regulated as dietary supplements.”

Although there are clear regulations already in place to define food and supplements, Rice says, “I suspect that with the publication of the NDI guidance, the introduction of Senator Durbin’s Dietary Supplement Labeling Act of 2011, not to mention the controversy caused by the Original Lazy Cakes Relaxation Brownie, not to mention energy ‘drinks,’ there will be more focus on how products are marketed-conventional food (which contains GRAS ingredients or approved food additives) versus dietary supplements.”

“Whether or not this means FDA enforcement is anyone’s guess,” he adds. “Many times, products with ingredients that have not been determined to be GRAS for intended users are marketed as dietary supplements, with the intent of escaping FDA’s radar. This was not the intent of DSHEA, and it has to stop.”

“We believe that food products containing melatonin are conventional foods falsely labeled as supplements,” agrees NPA’s Gay. “There are specific rules for what qualifies as a supplement. We continue to publicly urge FDA to take quick action on these or any products masquerading as a dietary supplement. In fact, the FDA has taken such action before, and we urge them to do so again.”
 

Still, A Bright Tomorrow

If you’re in the supplements industry and still reading this article, you might be feeling a bit tense. But take heart. There is one piece of very positive and definitive news-that is, that more consumers than ever before are using supplements.

In April, the latest statistics of the National Health and Nutrition Examination Survey (NHANES) indicated that dietary supplement usage among U.S. adults is up. According to the latest survey, covering 2003 to 2006, more than half of U.S. adults now use supplements. (Specifically, multivitamins are the most used. Other increases in use were seen for calcium and vitamin D supplements.)

Regarding herbal supplements, usage increased 3.3% in 2010, to reach $5.2 billion, according to the American Botanical Council’s latest HerbalGram market report.

Usage isn’t just growing in the United States, but on a global scale. During 2005 to 2010, global vitamin and dietary supplement expenditure per capita rose 22%, according to Euromonitor International.

“We are in the prime season to be optimistic about our industry’s health and well being,” says Mitch Skop, senior director of new product development for ingredient supplier Pharmachem Laboratories (Kearny, NJ).

“The staying power of the natural products industry is strong, as it has weathered many regulatory and economic storms,” says Abhijit Bhattacharya, COO for supplier OmniActive Health Technologies (Short Hills, NJ).

He continues, “Despite the economic recession, the industry has fared well, which speaks to its legitimacy, necessity, and popularity. During this time, every sector-from consumers to retailers to manufacturers-continue to look for a combination of quality and value.”

“We are encouraged by surveys that show half of all Americans trust dietary supplements and use them as part of a healthy lifestyle,” says NPA’s Gay. “For example, studies have shown that an increase in omega-3 fatty acids can reduce coronary heart disease among people age 65 or older, saving an estimated $3.1 billion. There are other studies seemingly daily that show the benefits of other supplements and vitamins.”

“We have a great story to tell as an industry, and it’s one that’s increasingly positive among the media,” he says.

Sidebar: Ingredients to Watch

For this article, we turned to our editorial advisory board member, market researcher SPINS, for an update on which ingredients, broken down by health condition, are currently top sellers in supplements. We also asked companies supplying some of these ingredients why they think demand has been up.

Curcumin
Shaheen Majeed, Marketing Director, Sabinsa Corp.
We certainly see an increased demand for turmeric-specifically, curcumin 95% extract. Since this is an ingredient Sabinsa supplies, we can talk confidently about this demand, as we have evidence from our facility scale-up to meet the world demand and scarce supply situation. Currently, we are extracting curcumin through our continuous production facilities rather than just our vessel plants.

One of the major attributes has to be the studies that curcumin has been in involved in. Sabinsa’s patented and branded Curcumin C3 Complex has been involved in over 50 clinical studies worldwide and continues to receive further study protocols every month. These clinicals, a majority of them, boil down to targeting inflammation, and people are seeing results.

Unfortunately, the supply situation also created a buzz in the marketplace. People always talk about what they cannot get, and this was one product that experienced shifts in supply and demand. While supply was tight for the past two years, we’re seeing more material enter the marketplace-from Sabinsa, at least. Our cultivation, harvesting, and continuous extraction are providing more and more curcumin every day to meet our customers’ needs.

One last note on curcumin: for the past two years, even when our customers couldn’t get material, Sabinsa still managed to supply curcumin to research centers and universities that requested it from us. “Keep the research alive” became our motto. While some customers may have been upset they didn’t receive enough material, Sabinsa helped ensure that research on curcumin will continue for companies to use and commercialize over the coming years.

Also, we are seeing good growth, not just from curcumin but other herbal extracts that support cardiovascular health and/or blood sugar management. We also see growth in other aspects of our business, like the probiotics sector.

Probiotics
Mike Bush, Vice President of Business Development, Ganeden Biotech
I think the key is that people have decided that there are certain things that are important to them-one being digestive health and another being immune health. They’re starting to understand that there’s science behind probiotics and that it’s a product that you can take, whether it’s in a food or a supplement, and you can actually feel a difference in a relatively short period of time. Unlike vitamin C, which you take and think, “Well, I hope it’s working,” probiotics in general typically will elicit-as long as it’s a quality product-a result that you can feel in a relatively short period of time. So I think consumers like that.

Also, one of the things that we’re hearing from consumers is that they like the fact that there’s clinical work being done in more than just a single area around probiotics.

As an ingredient supplier, we are excited to see that our clients or potential clients are really excited about quality, and that they’re starting to understand the difference between commodity and branded ingredients-especially if those branded ingredients have a good science base to them. So, personally, we think that branded ingredients with good scientific backing and good intellectual property behind them will outpace the rest of the market.

Botanicals
David Romeo, Managing Director, Nutraceuticals InternationalFenugreek (for Diabetes): Long used as an herbal remedy, fenugreek seed and leaf show promise as a natural approach to managing diabetes and sustaining cholesterol. Fenugreek seeds are rich in protein and contain the unique amino acid called 4-hydroxyisoleucine, which has been characterized as an active ingredient for blood glucose control. According to a study conducted in 2009, this amino acid has been reported to help stimulate the secretion of insulin, reduce insulin resistance, and decrease blood sugar levels in diabetes patients.

Licorice (for Insomnia): Holistic treatment for insomnia is versatile and incorporates many techniques, one of which is most popular-herbal medicine. Consumers have become so desperate for sleep that they have taken over-the-counter sleep aids and even sometimes allergy medicine to catch that badly needed sleep, but only to wake up feeling groggy and more exhausted. Fortunately, herbs can serve as the best medicine, gaining the maximum benefit for sleep time, without the troubling side effects. The Korea Food Research Institute conducted a study that showed that drinking a cup of licorice tea before bedtime may help insomnia. The research study’s results showed that licorice helped the test subjects fall asleep faster and stay asleep longer. These results were published in the August 2010 issue of the Journal of Ethnopharmacology.Rose Hips (for Joint Health): An increase of interest in rose hips has been seen tremedously by our company as well as a branch of our company, PetIngredients.com. Not only has rose hips sparked new hope in human joint health but for animals as well. Rose hips contain an antioxidant that has been reported to have an anti-inflammatory effect. It has been shown that reduced inflammation in human joints can be confirmed by a decreased level of C-reactive protein in the patient’s blood. This protein is a marker for the amount of inflammation that a person, horse, or, incidentally, a dog, is suffering. It has been marketed as a new hope for sufferers of joint pain and osteoarthritis.

Yerba Mate (for Energy): We are definitely noticing an increase in the number of requests for yerba mate used as an ingredient in supplements for weight loss and natural energy. It has been one of the hottest drink trends in the natural products industry for the past couple of years. There are many different ways you can attack the large energy product market, such as with energy bars, energy shakes, energy drinks, energy pills, and even dissolving tabs or gum that is supposed to provide you with energy. Consumers don’t want to use a product that contains a large amount of synthetically added caffeine or sugar, simply because it is unnatural and unhealthful to the body. In my research, yerba mate has been said to have the strength of coffee, the health benefits of tea, and the euphoria of chocolate. It contains naturally occurring nutrients, such as 24 vitamins and minerals, 15 amino acids, and 11 polyphenols.

Lutein
Corey Jansen, Product Manager, Kemin Health LC
We continue to see growing demand for products that contain FloraGLO lutein. A recent consumer survey from the American Optometric Association indicated that vision is the number one thing that people fear losing later in life. In addition, a recent scientific consensus panel of eye-health experts estimated that nearly half of Americans have low levels of lutein in their eyes, which could put those people at greater risk for developing an age-related eye condition later in life. FloraGLO is the most clinically researched lutein ingredient worldwide (according to Kemin Health LC internal memorandum based on PubMed search), and studies show that taking an eye vitamin with 10 mg of FloraGLO per day can increase lutein levels in the eye to help reduce the risk of developing age-related eye conditions later in life. As consumers have become more concerned with their vision and more aware of the fact that there are nutrients such as lutein that can keep their eyes healthy, the demand for products should continue to grow.

In addition to protecting one’s vision for the future, newer clinical research has shown that FloraGLO lutein, 10 mg/day, paired with Optisharp zeaxanthin at 2 mg/day, offers benefits for visual performance, including increased tolerance of glare, faster recovery from glare, and better contrast acuity. These visual performance benefits are certainly applicable to anyone who relies on their vision to help them perform at their best, whether that be an athlete or someone who drives at night and has to deal with glare from oncoming headlights. These new visual-performance benefits should also contribute to future growth.

Finally, besides the proven benefits for vision, recent clinical research has also shown FloraGLO to have benefits for healthy skin, specifically in the areas of skin hydration and skin elasticity. These new clinically proven benefits offer manufacturers an opportunity to launch products into the growing beauty-from-within market in the United States and around the world.

Abhijit Bhattacharya, COO, OmniActive Health Technologies
The SPINS numbers [reflecting growing lutein sales] are no surprise to us at OmniActive Health Technologies, as we have experienced continuous growth each year since we opened our doors. In fact, we have seen a consistent rise in demand for lutein, which we have measured through an increase in both sales and market share, even through this challenging economic time. OmniActive’s range of Lutemax free lutein and Lutemax lutein esters products, as well as our Lutemax 2020, which offers a unique combination of lutein along with zeaxanthin in two of its isomeric forms-RR-zeaxanthin and RS-(meso)-zeaxanthin-in a balanced ratio, has become a favorite amongst our customers, and demand has steadily increased through the year…. Lutein has made its way into the mainstream, and this general increase in lutein awareness with consumers has also played a significant role in heightened demand.

Vitamin K2
Kevin Salerno, President, Nutraceuticals Division, The E.T. Horn Co.
Current research on vitamin K2, specifically as natural menaquinone-7 (MK-7), was pioneered by Dr. Cees Vermeer (The University of Maastrict, The Netherlands). Utilizing soy-derived MK-7 from Gnosis S.p.A., first to market in the United States as Nutri-K via The E.T Horn Co., the clinical research revealed a critical link between K2 MK-7, which naturally binds to osteocalcin in the bone-building matrix, and healthy skeletal and cardiovascular systems. The link proved that vitamin K2 is imperative to bone and heart health, and it initiated a steady growth progression, which appears to be burgeoning now. K2 is more beneficial for the bones and heart than K1 because of its osteocalcin and cardiovascular functions. The consumer is taking notice. The more educated the public becomes, the greater demand we see. We view K2 MK-7 as one of the strongest products in our innovative lineup this year.