Meeting the Demand for Quality Dietary Supplements
Meeting the Demand for Quality Dietary Supplements
Meeting the Demand for Quality Dietary Supplements The promise of improved physical and mental health has helped drive interest in dietary supplement products here in the U.S. as well as in other established and emerging
economies around the world. From food additives to vitamins and minerals, dietary
supplements are becoming an essential component in the daily diet of many healthconscious consumers, providing important nutritional balance and helping them
to better deal with age-related physical and mental conditions. As healthcare costs
continue to escalate, some consumers are even relying on dietary supplements as an alternative to traditional medical treatments.1
In the U.S., most dietary supplements are classified as food by the U.S. Food and Drug Administration (FDA), and are beyond the same rigorous oversight as prescription
drugs and over the counter medications. Unfortunately, the FDA has received more than 10,000 reports of adverse reactions to dietary supplements during the period
between 2008 and 2013.2 In addition, the FDA estimates that about 70% of nutritional supplement manufacturers have failed to follow FDA-mandated good manufacturing practices during that same period.3 These and other concerns have raised the level of scrutiny of dietary supplements by regulators and consumers alike.
This UL white paper discusses how manufacturers can meet consumer demand for quality dietary supplements while reducing the risks associated with unexpected
adverse reactions and product recalls. The paper begins with a brief overview of the dietary supplement marketplace and a summary of the regulations applicable to
dietary supplements in the U.S. The paper then discusses the primary health and safety concerns about dietary supplements among consumers, and the potential risks to
manufacturers and retailers whose products fail to meet regulatory requirements or consumer expectations. The white paper proposes a multi-step preventative action
plan for dietary supplement manufacturers and retailers, and identifies the potential benefits of such an approach.
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Meeting the Demand for Quality Dietary Supplements
What Are Dietary Supplements? The term dietary supplement is generally used to describe any product taken by mouth that contains an ingredient or ingredients specifically intended to
supplement a diet. Dietary supplement
products come in a variety of forms, such as vitamin and mineral products, herbal
nearly $23 billion (USD) in the U.S. in 2012,
supplements often deviates
approximately 4%.5 More than 85,000
a product’s label. For example,
currently available in the U.S, and more
44 different herbal products
takes one or more dietary supplements,
and Canada found that 32% of
multimineral products.
contained none of the herbal
with future annual growth projected at dietary supplement products are 6
ingredients in supplement products can include vitamins and minerals, herbs and other botanical ingredients, and
substances such as amino acids, enzymes and metabolites in concentrated or extract form.
Research by McKinsey & Company places
the global value of the market for dietary
supplements, including vitamins, minerals and nutritional supplements, at $82
billion (USD) annually. Equally important, the future growth in the market for
dietary supplements is expected remain strong, growing between 5-6% per year through 2017. These growth prospects
reportedly reflect the increase in healthconscious consumers as well as aging populations in the U.S., the European Union and Japan. 4
By most accounts, the U.S. market for dietary supplements is the largest in
total size and in the number of dietary
supplement product offerings. According to a separate report by Euromonitor International, the sale of vitamins,
minerals and supplements reached
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Canadian researchers evaluating
than half of the U.S. population regularly
commercially available in the U.S.
primarily in the form of multivitamin and
samples subject to DNA evaluation
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supplements, and specialized nutritional products like protein powders. Dietary
from the composition stated on
ingredient listed on the label,
while 59% of samples contained
Health and Safety-Related Concerns about Dietary Supplements
plant species that were completely omitted from the label.8
• Quantity of ingredients—In
Despite consumers’ general acceptance
addition, quantities of listed
benefits, dietary supplement products
the amounts stated on a product’s
of their potential health and nutritional sold in the U.S. are not required to be independently tested for safety or
efficacy prior to being placed on the
market. Instead, manufacturers are solely responsible for evaluating the safety
and proper labeling of their products for compliance with FDA regulations.
Although the vast majority of dietary
supplements on the market are safe, the FDA receives thousands of consumer
complaints and adverse reaction reports every year in connection with dietary supplements. In addition, there have
been multiple independent reports and
studies pointing to potentially significant
health and safety issues related to dietary
supplements on the market. Most of these issues can be categorized as follows:
• Product composition—The actual ingredient composition of dietary
ingredients can vary widely from label, exposing consumers to
unsafe levels of certain ingredients. In one study, researchers linked
cases acute selenium toxicity in
over 200 patients to a liquid dietary supplement that contained 200
times the selenium concentration listed on the supplement’s label.9 • Safety of ingredients—In some
cases, dietary supplements contain toxic metals and other potentially harmful ingredients. In a widely publicized study, researchers
determined that more than 20% of
ayurvedic medicines sold in the U.S.
via the Internet included detectable levels of lead, mercury or arsenic in excess of daily intake standards.10 In a separate instance, an FDA
laboratory analysis determined that a product marketed as a
vitamin B dietary supplement
Meeting the Demand for Quality Dietary Supplements
actually contained two potentially
ingredients found in dietary supplements.
Registered food facilities are subject to
omitted from the label. One of the
are outside of the strict oversight
and registration can be suspended in
harmful anabolic steroids that were two steroids, methasterone, is a
Schedule III controlled substance in the U.S.11
• Product-related health claims— Finally, some manufacturers
promote dietary supplements
by making false or exaggerated claims regarding health-related
benefits associated with the use
of their products. For example, an
Arizona-based company marketed liquid homeopathic drops as a
weight-loss dietary supplement
that the company falsely claimed would help consumers achieve
rapid and significant weight loss.12 These and other quality and safety issues
related to dietary supplements have raised legitimate concerns among consumers, and have prompted many retailers to
establish quality and safety requirements within their existing procurement
practices. This practice can be especially important when a retailer is sourcing
dietary supplement products to be labeled and sold under the retailer’s proprietary
brand, since the retailer would be directly implicated in cases of quality and safety issues related to their products.
As previously noted, dietary supplements accorded drugs and pharmaceutical
products. Instead, they are categorized as a type of food product, and must comply with regulations promulgated under the federal Dietary Supplement Health and
Education Act (DSHEA) of 1994 and other more recent legislation.
a given facility is responsible for a food product with a reasonable probability of causing serious adverse health
consequences or death to humans or
animals. Food facility registration must be renewed every other year.13 Adoption of Good
directly responsible for evaluating the
As of June 2010, all companies that
prior to marketing them for sale, and
finished dietary supplement products
that are adulterated or misbranded. The
regarding good manufacturing
responsibility for proving that a dietary
supplements. In brief, compliance with
unreasonable risk of illness or injury, or
requirements and/or activities:
manufacturers and distributors are
Manufacturing Practices
safety and labeling of their products
manufacturer, package, hold or distribute
are prohibited from marketing products
must comply with the FDA’s requirements
regulations also place with the FDA the
practices (GMPs) specifically for dietary
supplement presents a significant or
GMP provisions involves the following
contains an ingredient or other substance that could be injurious to human health.
• Establishing and following
written procedures for physical
Although dietary supplement
plant sanitation, manufacturing
relatively limited regulatory oversight,
functions, laboratory testing,
products themselves are subject to manufacturers, importers and
distributors of dietary supplements are
still responsible for meeting a number of FDA requirements. These requirements
are described in the sections that follow.
Regardless of where they are located,
Regulatory Oversight of Dietary Supplements, Dietary Supplement Manufacturers
manufacturers of dietary supplement
In the U.S., the FDA regulates both
processes, packs or holds food for human
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cases where the FDA determines that
Under current FDA regulations,
Registration of Food Facilities
finished dietary supplement products and
periodic inspection by FDA personnel,
products must register their production
facilities with the FDA. This requirement
applies to any facility that manufacturers, or animal consumption in the U.S.
operations, quality control
packaging and labeling, and product complaints
• Establishing and maintaining
written master manufacturing records and batch production records
• Establishing production
and process control system specifications
• Establishing and maintaining quality control systems and procedures
Meeting the Demand for Quality Dietary Supplements
• Conducting identity testing of
dietary ingredients as well as a sample of finished products to
assess whether they meet product specifications
In meeting the above minimum
Notification Process for
and distributors must make sure that
“New dietary ingredients” are ingredients
information requirements, manufacturers any and all information and/or product
claims that appear on the product label are truthful and not misleading. It is 15
The GMP requirement for dietary
supplement products applies to all
domestic and foreign countries that
manufacture, package, label or hold dietary supplements, and is also
applicable to those entities involved
in testing, quality control, packaging, labeling and distribution activities.14 Labeling Requirements
The FDA also regulates dietary
supplement labels, package inserts
and other product literature that may accompany a dietary supplement.
Regarding labeling, the FDA requires
that dietary supplement product labels include, at a minimum, the following information:
• A “statement of identity,” that is, the name of the dietary supplement
• The “net quantity of contents,” that is, the amount of the supplement contained in the package
• Nutrition labeling, also referred to as “Supplement Facts”
• A list of all ingredients contained in the supplement
• A U.S. phone number or complete U.S. mailing address that allows
consumers to notify the company
in case of a serious adverse event.
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also important to note that, in addition
to FDA labeling requirements for dietary supplements, the U.S. Federal Trade
Commission (FTC) has oversight over
the advertising of dietary supplements.
FTC regulations address the truthfulness of claims made in advertising and
New Dietary Ingredients
that were used in any dietary supplement marketed in the U.S. in 1994 or later.
Manufacturers and distributors who wish to market dietary supplement
products with any such ingredient must first provide the FDA with a premarket notification at least 75 days before the product is introduced into interstate commerce in the U.S.
other promotional materials for dietary
The premarket notification for a product
regulations.
must contain information about the
Recording and Reporting
other information demonstrating that
supplements, and are in addition to FDA
of Adverse Events
Under FDA regulations, manufacturers, distributors and retailers of dietary
supplements are required to maintain
records and reports of all adverse events related to their products. These records
are subject to inspection by FDA officials upon request. In addition, companies
distributing or offering for sale dietary supplements are required to report to the FDA any information they receive
regarding all serious adverse events. To
facilitate this required reporting process,
containing a new dietary ingredient ingredient, along with evidence or
the supplement containing the new
ingredient will generally be safe when used in a manner consistent with the
information accompanying the dietary supplement. Although the FDA does not currently prescribe the specific
information required, it recommends
that manufacturers conduct a thorough
search of available scientific literature for evidence of safety and for any adverse effects associated with the use of the ingredient.16
the FDA has recently initiated a new
Internet-based reporting mechanism
that allows companies to file adverse
event reports online. Finally, as previously noted, FDA regulations require that labels on dietary supplement products include
information that can facilitate the prompt and efficient reporting of serious adverse events associated with a specific dietary supplement.
The Cost of Noncompliance Given the dramatic increase in adverse events reported to the agency,
the FDA has recently stepped up
inspection activities in connection with dietary supplement manufacturers and distributors. According to one
independent analysis of FDA records, 444 of 626 inspections of GMPs at
Meeting the Demand for Quality Dietary Supplements
dietary supplement manufacturing or
unsubstantiated, false or misleading. The
of their source. Such a program
2010 through 2012 produced a finding of
injunction that will prevent it from
batch checks to assure product
distribution facilities conducted from
possible violations of FDA regulations. The same analysis indicated that, during 2012, 116 dietary supplement firms received a
warning letter, citing anywhere from two
company is now bound by a permanent
marketing or selling dietary supplements in the future.20
As the above cases illustrate, the cost
to 58 separate violations.
of noncompliance can lead to dire
In recent years, the FDA has also initiated
manufacturers of dietary supplements.
17
legal action against several dietary
supplement makers for violations of GMP regulations and for the misbranding of products. In one case, the FDA issued a permanent injunction against a
Pennsylvania-based dietary supplement manufacturer for its failure to comply with GMP requirements, and for
failing to report serious adverse events
regulatory and legal consequences for
Of course, even for those manufacturers who eventually prevail in such cases,
unwanted publicity can adversely impact the public image of a company and
its products with consumers. This can
result in reduced demand for otherwise legitimate and helpful products, and place a company at risk.
to cease production and distribution of more than 400 dietary supplements.
18
In a separate case, U.S. marshals seized dietary supplements produced by a
Wisconsin manufacturer that made
false claims regarding the safety and
effectiveness of its dietary supplements in treating a number of diseases. The
action followed multiple inspections of
the company’s facilities by FDA inspectors that uncovered numerous violations of the FDA regulations.19
Aside from the consequences for
noncompliance with FDA requirements, manufacturers may also be subject
to private legal action and more. For example, in a civil enforcement case
settled in early 2014, an Ohio company
agreed to pay nearly $1.8 million (USD) for promoting its line of dietary supplements based on health claims that were page 6
quality and periodic independent testing of ingredients.
• Good manufacturing practices— FDA regulations requires all
manufacturers, distributors,
packagers or holders of dietary
supplements to implement and
maintain GMPs. But more than a regulatory requirement, a good
GMP program can help a producer to achieve production efficiencies that can improve overall product quality and even reduce production costs. • Product testing—Production
processes should incorporate raw
connected with the company’s products. The injunction required the producer
can include random factory audits,
Action Plan for Dietary Supplement Manufacturers The most successful programs for
compliance with FDA’s regulations for dietary supplements usually involve a multi-step approach involving every
aspect of a producer’s operation, from raw material sourcing to final product validation. Here are some of the key
aspects of an effective compliance plan for dietary supplement manufacturers and distributors:
• Sourcing of quality materials— Quality dietary supplement products start with quality ingredients and materials.
Manufacturers should establish a
responsible sourcing program that assures the quality and purity of
the raw materials used, regardless
material and finished product
testing to assess whether product specifications are being achieved and to quickly identify potential production challenges. Such
testing can assess microbiological, analytical or physical qualities of raw materials and finished products as well as possible contamination.
• Information management—A
robust information management system is a critical tool to assure the retention of important data
and other records and to facilitate the creation of meaningful reports. It also provides
evidence of compliance with
FDA GMP requirements related
to documentation. Detailed and well-organized data may also
address retailer requirements for
Meeting the Demand for Quality Dietary Supplements
evidence of quality and safety in product production.
• Independent validation testing—
consumers alike with assurances
regarding the quality, purity and safety of their dietary products.
The best compliance programs rely on the use of independent third
Conclusion
product content and to verify the
The U.S. market for dietary supplement
In addition, product packaging
more than 85,000 different products
of a qualified third party can
Unfortunately, quality and safety issues
regarding the quality and integrity
number of adverse events and product
parties to periodically confirm
absence of any harmful substances.
products is highly competitive with
that displays the validation mark
currently available to consumers.
provide consumers with assurances
are a significant concern, with a growing
of a dietary supplement.
recalls resulting in increased negative
• Employee training—Finally, an
publicity for the industry and greater
scrutiny by the FDA and other regulators.
effective regulatory compliance
Manufacturers can reduce their risk and
commitment to employee
retailers and consumers by taking specific
commitment to training means
their dietary supplement products.
understand the reasons for specific
With over 50 years of in-depth dietary
greater appreciation for their role in
helps manufacturers and retailers meet
program requires an ongoing
strengthen their market position with
education and training. A
steps to assure the quality and safety of
that employees are more likely to
policies and activities and to have a
supplement knowledge and expertise, UL
producing safe, quality products.
the demand for high-quality, safe and
Manufacturers of dietary supplements
test methods to determine the quality
other initiatives are not only better
addition, UL can help clients implement
with FDA requirements. They are also
programs, including independent audits
effective products. UL uses recognized
who proactively implement these and
and integrity of dietary supplements. In
positioned to achieve compliance
and maintain effective quality assurance
more likely to reduce the incidence
to maintain supply chain integrity.
associated with their products. In doing
For additional information about
their position in a highly competitive
services for dietary supplements, contact
of adverse events and product recalls so, manufacturers can strengthen
UL’s testing, verification and auditing
marketplace, providing retailers and
[email protected] or visit www.ul.com/ consumer-products.
©2014 UL LLC All rights reserved. This white paper may not be copied without permission. It is provided for general information purposes only and is not intended to convey legal or other professional advice.
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Meeting the Demand for Quality Dietary Supplements
Works Cited 1
”Complementary and Integrative Medicine: Emerging Therapies for Diabetes, Part 1: Preface,” Diabetes Spectrum, Volume 14, Number 3, 2001, the American Diabetes Association. Web 7 August 2014. http://spectrum. diabetesjournals.org/content/14/3/129.full.pdf+html.
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“Dietary Supplement Adverse Event Reports Increase,” Natural Products Insider, April 2, 2014. Web. 21 May 2014. http://www. naturalproductsinsider.com/news/2014/04/dietary-supplement-adverseevent-reports-increase.aspx.
13
Further details about the FDA’s food facility registration requirements can be found in “Guidance for Industry: Questions and Answers Regarding Food Facility Registration (Fifth Edition),” December, 2012, U.S. Food and Drug Administration. Web. 21 May 2014. http://www.fda.gov/Food/ GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/ ucm331959.htm.
14
More details about the FDA’s GMP requirements for manufacturers of dietary supplements is provided in “Guidance for Industry: Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements; Small Entity Compliance Guide,” December 2010, U.S. Food and Drug Administration. Web 21 May 2014. http://www.fda.gov/Food/GuidanceRegulation/ GuidanceDocumentsRegulatoryInformation/ucm238182.htm.
15
See the FDA’s “Guidance for Industry; A Dietary Supplement Labeling Guide” for additional information about labeling requirements for dietary supplements. April 2005, U.S. Food and Drug Administration. Web. 21 May 2014. http://www.fda.gov/Food/GuidanceRegulation/ GuidanceDocumentsRegulatoryInformation/DietarySupplements/ ucm2006823.htm.
16
Additional information about the FDA’s requirements regarding new dietary ingredients is available in its draft guidance document, “Draft Guidance for Industry: Dietary Supplements: New Dietary Ingredient Notifications and Related Issues,” July, 2011, U.S. Food and Drug Administration. Web. 21 May 2014. http://www.fda.gov/Food/ GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/ ucm257563.htm.
17
“DNA barcoding detects contamination and substitution in North American herbal products,” Newmaster, Steven, et.al., BMC Medicine, October 11, 2013. Web. May 21, 2014. http://www.biomedcentral.com/17417015/11/222.
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18
“Acute selenium toxicity associated with a dietary supplement,” MacFarquhar, J.K., et.al., Archives of Internal Medicine, February 8, 2010. Web. 21 May 2014. http://archinte.jamanetwork.com/article. aspx?articleid=415585.
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19
“U.S. Marshals seize dietary supplements, drugs manufactured by Syntec, Inc.,” press release, U.S. Food and Drug Administration, December 1, 2011. Web. 12 June 2014. http://www.fda.gov/NewsEvents/Newsroom/ PressAnnouncements/ucm282030.htm.
20
“Seller of Unapproved Dietary Supplements Agrees to Pay $1,796,114.50 in Penalties & Restitution,” press release issued by the Office of the District Attorney, Alameda County (California), January 30, 2014. Web. 12 June 2014. http://www.alcoda.org/news/archives/2014/jan/unapproved_ dietary_supplements_seller_to_pay_17m.
3
“FDA Official: 70% of supplement companies violate agency rules,” Newsday, August 23, 2013. Web. 15 May 2014. http://www.newsday.com/ news/health/fda-official-70-of-supplement-companies-violate-agencyrules-1.5920525.
4
“Cashing in on the booming market for dietary supplements,” Consumer & Shopper Insights, a report by McKinsey & Company, December 2013. Web. 21 May 2014. http://csi.mckinsey.com/knowledge_by_region/ americas/dietary_supplements.
5
“Vitamins and Dietary Supplements in the U.S.,” Report by Euromonitor International, April 2013. Web. 21 May 2014. http://www.euromonitor. com/vitamins-and-dietary-supplements-in-the-us/report.
6
“FDA Uses New Authorities to Get OxyElite Pro Off the Market,” Blog posting by Daniel Fabricant, Director of Division of Dietary Supplement Programs, U.S. Food and Drug Administration. FDA Voice, November 18, 2013. Web. 21 May 2014. http://blogs.fda.gov/fdavoice/?s=dmaa.
7
“Dietary Supplement Use Among U.S. Adults Has Increased Since NHANES III (1988-1984),” NCHS Data Brief, U.S. Centers for Disease Control and Prevention, April 2011. Web. 21 May 2014. http://www.cdc.gov/nchs/data/ databriefs/db61.htm.
8
9
10
“Lead, Mercury, and Arsenic in US- and India-Manufactured Ayurvedic Medicines Sold via the Internet,” Saper, Robert B., MD, MPH, et.al., The Journal of the American Medical Association, August 27, 2008. Web. 21 May 2014. http://jama.jamanetwork.com/article.aspx?articleid=182460 &resultClick=3.
11
“FDA warns consumers about health risks with Healthy Life Chemistry dietary supplement,” FDA News Release, July 26, 2013. Web. 21 May 2014. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ ucm362799.htm.
12
“Sensa and Three Other Marketers of Fad Weight-Loss Products Settle FTC Charges in Crackdown on Deceptive Advertising,” press release from the U.S. Federal Trade Commission, January 7, 2014. Web. 21 May 2014. http:// www.ftc.gov/news-events/press-releases/2014/01/sensa-three-othermarketers-fad-weight-loss-products-settle-ftc.
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