USP Global Public Policy Position
Regulatory reform is
necessary to help ensure
the quality of dietary
supplements
Policy Position
1
USP Global Public Policy Position: Regulatory reform is necessary to help ensure the quality of dietary supplements
Issue
To protect consumers from unsafe, poor quality dietary
supplement products—such as those that are contaminated,
mislabeled, adulterated—and help ensure the quality and
consistency of dietary supplements sold in the United States,
public health, health care, patient, consumer advocacy
organizations, and the U.S. Food and Drug Administration
(FDA, Agency) have called for reform to the regulation
of dietary supplements.
17
The current lack of a strong
regulatory framework for dietary supplements has created an
environment in which a given product may vary dramatically
in quality across manufacturers.
An estimated 80 percent of U.S. consumers use dietary
supplements, and the dietary supplement market has
grown signiicantly since the passage of the Dietary
Supplement Health and Education Act (DSHEA) in 1994—
from approximately 4,000 products in 1994 to an estimated
80,000 today.
1,8
Because of the growing industry and gaps in
the outdated law which limits the authority of the FDA, it is
diicult for the Agency to eectively or eiciently monitor the
market and protect public health from dietary supplement
products, and products labeled as dietary supplements,
that are compromised by impurities, contaminants, and
misidentiied, substituted, unknown, or unlawful ingredients.
The FDA has stated three strategic priorities for dietary
supplements: 1) consumer safety, 2) product integrity,
and 3) informed decision-making.
9
The advancement of a
safe and transparent marketplace will require a trustworthy
supply chain and increased adherence to public quality
standards. To enable the FDA to prioritize inspections,
enforcement, and other regulatory actions involving
products that have the greatest potential to cause harm
to consumers, additional policy reform should consider
enhancing dietary supplement post-market surveillance,
increasing visibility into the dietary supplement market with
mandatory product listing, additional labeling requirements
for dietary supplement products, and the utilization of a
risk-based approach for adherence to public quality
standards to advance dietary supplement quality.
Position
U.S. Pharmacopeia (USP) supports new initiatives and policies
that modernize and reform the dietary supplement regulatory
framework, including the Dietary Supplement Health and
Education Act (DSHEA), to help ensure the quality and
consistency of dietary supplements.
1. Improving post-market surveillance
USP supports enhancing existing eorts to improve the
collection of post-market dietary supplement quality and
safety signals in the FDA Safety Reporting Portal (SRP)
including 1) greater enforcement of already required
serious adverse event reporting by manufacturers and
2) encouraging increased voluntary reporting of
suspected adverse events associated with dietary
supplement products by health care professionals,
researchers, public health oicials, and consumers.
2. Adherence to public quality standards
USP supports the development and utilization of a
risk-based approach for adherence to public quality
standards for dietary ingredients and dietary
supplement products by:
a. Requiring adherence to the relevant public quality
standards published in the USPNF or the USP
Dietary Supplements Compendium (DSC) for those
ingredients and products that are identiied as having
a higher potential for public health risk, such as:
products intended for special populations; ingredients
and products that are associated with potential safety
issues; products identiied through post-market safety
signals; and products consumed by a large number
of consumers that can be a potential risk to public
health; and
b. Providing incentives, such as factors that can be
used for risk-based inspection prioritization by the
FDA, for irms to manufacture dietary ingredients or
supplements that voluntarily adhere to public quality
standards.
3. Increasing visibility into the market
USP supports the establishment of an FDA-administered
mandatory product listing regime for dietary supplement
2
USP Global Public Policy Position: Regulatory reform is necessary to help ensure the quality of dietary supplements
dietary supplement manufacturing facilities and products.
7. Increasing FDA resources
USP encourages, in the interests of public health and
consumer safety, increasing FDA resources for the
oversight of dietary supplements to adequately oversee
the growing dietary supplement sector; appropriately
administer updated or new regulations; and explore
additional regulatory reforms that correspond to the risk
that speciic dietary ingredients or dietary supplement
products may pose to consumers.
Discussion
Dietary supplement trends
Since the enactment of the Dietary Supplement Health and
Education Act (DSHEA) in 1994, the dietary supplement
industry has grown from $4 billion with roughly 4,000
products in 1994 to an estimated $60 billion in the United
States, and nearly $200 billion worldwide, by 2025
10,11
with somewhere between 50,000 and 80,000 products,
as reported by the FDA.
12
Recent surveys indicate that
the majority of Americans consume dietary supplement
products.
1,8,1319
Surveys also show that there are signiicant
misperceptions about the safety and intended use of dietary
products that at a minimum requires dietary supplement
manufacturers to provide a listing of products being sold,
the ingredients contained in a product, and a copy of
each product label.
4. Providing ingredient transparency
USP supports additional labeling requirements that
enhance transparency of ingredients,including disclosure
of all the ingredients, and their amounts, in a dietary
supplement product and stability study-supported
expiration dates. Providing this transparency can
facilitate informed conversations and decision-making by
healthcare practitioners and consumers.
5. Continued education about dietary supplement quality
USP supports continued eorts to educate consumers,
patients, and healthcare professionals about the use of
dietary supplement products and supports eorts to
increase consumer, patient, healthcare professional, and
retailer awareness of resources to help patients select
quality supplements.
6. Exploring opportunities to increase audits
USP encourages exploring mechanisms, including third-
party audits —where audit standards are based on Current
Good Manufacturing Practices, USP Quality Standards,
and FDA-established criteria—and leveraging existing FDA
programs in new ways to enable increased vigilance of
3
USP Global Public Policy Position: Regulatory reform is necessary to help ensure the quality of dietary supplements
supplements and FDA’s authorities in regulating them.
Research indicates that many consumers incorrectly believe
that dietary supplements are approved by the government,
that dietary supplements have been tested for safety and
eectiveness, that the content of all dietary supplements is
analyzed, and that manufacturers are required to disclose
known adverse eects.
20
Since 1994, the dietary supplement industry has been
reshaped by a complex global supply chain, the Internet,
and newly discovered ingredients of unconirmed safety.
Industry growth, increased consumer use of products
marketed as dietary supplements, and newly identiied
health threats all underscore the importance of
understanding potential concerns about these products
and warrant the need to modernize dietary supplement
regulations to help ensure the quality and consistency
of dietary supplements.
Current dietary supplement regulatory
landscape
United States framework
The FDA regulates the processing, manufacturing, labeling,
and packaging of dietary supplements in the United States
primarily through DSHEA, enacted as an amendment to
the Federal Food, Drug, and Cosmetic Act (FD&C Act)
in 1994.
21
According to DSHEA, dietary supplements are
regulated as a category of food and must include at least
one “dietary ingredient.” Dietary ingredients include
vitamins, minerals, herbs or other botanicals, amino acids,
and dietary substances used to supplement the diet.
22
Dietary supplements come in many forms, including tablets,
capsules, powders, gummies, and liquids, and are available
for purchase over-the-counter in stores throughout the
United States and via the Internet.
Dietary supplement companies are responsible for ensuring
that their products are safe and lawful. Dietary supplements
are not subject to preapproval requirements for safety and
eicacy, nor are they required to meet oicial public quality
standards. Unlike the framework for drugs, conformance
to a United States Pharmacopeia–National Formulary
(USPNF)
23
public quality standard is voluntary for all dietary
supplements. DSHEA states that a dietary supplement
shall be deemed violative if it is represented (e.g., on the
product’s labeling) as conforming to a standard in the
USPNF but fails to so conform.
24
Under DSHEA, dietary supplement manufacturers must
follow current good manufacturing practice (CGMP)
requirements that are intended to ensure the quality of
dietary supplements. The CGMP requirements
25
state that
manufacturers must establish speciications for identity,
purity, strength, composition, and limits on contamination
for each component and for each inished dietary
supplement product to ensure quality.
26
Additionally,
manufacturers are required to set limits for speciications,
including contaminants that may adulterate their products—
such as microbes, microbial toxins, elemental contaminants
(e.g., lead, arsenic, mercury, and cadmium), and residual
solvents—based on toxicological considerations. The
regulations also require that appropriate tests be conducted
to ensure that speciications are met and that the tests and
methods used are appropriate and scientiically valid.
27
However, the CGMP regulations do not include language
specifying the tests and methods to be used or how to
determine whether those tests and methods are appropriate
and scientiically valid. Manufacturers have the lexibility
to determine what tests and methods they use, including
analytical methods and acceptance criteria, unless the
FDA learns of a problem and deems them inappropriate
or scientiically invalid. Dietary supplement products
manufactured from the same ingredients by dierent
manufacturers could vary in quality since the manufacturers
use dierent speciications and dierent tests and methods
to determine whether those speciications are met. Dietary
supplements that do not meet speciications as required by
CGMP regulations are considered violative
28
; however, the
FDA can generally only make such a determination after the
products are on the market. Dietary supplement products on
the market are not routinely tested by the FDA to determine
whether product speciications are met, are appropriate for
the product, or use scientiically valid methods.
The FDA has stated that its three strategic priorities for
dietary supplements include consumer safety, product
integrity, and informed decision-making. In a statement, the
4
USP Global Public Policy Position: Regulatory reform is necessary to help ensure the quality of dietary supplements
Agency has noted that it has a duty to protect consumers
from harmful products; a responsibility to ensure that
dietary supplements contain the ingredients listed on
the label and nothing else, and that those products are
consistently manufactured according to quality standards;
and a desire to foster an environment where consumers
and health care professionals can make informed
decisions before recommending, purchasing, or using
dietary supplements.
9
Global frameworks
The World Health Organization’s Traditional Medicine
Strategy 20142023 includes dietary supplements in a
category called Traditional and Complementary Medicines
(T&CM) and recognizes that deinitions for this category vary
signiicantly globally.
29
As an example, certain melatonin
products are regulated in the United States as a dietary
supplement, in Canada as a natural health product (NHP),
and in Australia as a prescription medicine.
30
Additionally,
some countries have dosage requirements for products
to be deined as dietary supplements and/or drugs. For
example, vitamin D3 5000 International Units (IU) is deined
as a drug in the European Union (EU) and the United States
regulates certain vitamin D3 products containing below
50,000 IUs as a dietary supplement and certain vitamin
D3 products containing 50,000 IUs as drug.
30,31
In many
jurisdictions, including the United States, Canada, and
Australia, T&CM products are considered suitable for
self-selection without the involvement of a healthcare
practitioner or a prescription. In other jurisdictions, dietary
supplements or T&CM are prescribed by a professional.
3235
Additionally, the context of usage of a dietary supplement
varies widely from country-to-country; in some countries
supplement use is just limited to general health and well-
being while others permit use for medicinal purposes. To
date, little consensus exists from country to country on the
scope, requirements, deinition, or even the terminology in
which dietary supplement and herbal medicines categories
could be classiied. Transparent science-based quality
standards for the ingredients across these regulatory
frameworks and deinitions has increased importance given
the international supply chain of the ingredients that could
be used in T&CMs.
36
Similar to the variety of product deinitions, no consistent
global approach to product regulations exists. While global
regulatory frameworks often relect national and regional
priorities, most countries regulate T&CMs as a subset of
existing legislation.
30,31
In Canada, NHPs are regulated as a
subset of drugs under the Food and Drugs Act and deined
under the Natural Health Product regulations. While NHPs
are not drugs, the Canadian regulations place requirements
on manufacturers, distributors, importers, packagers,
and labelers and require that NHP manufacturers obtain
a product license through pre-market approval by the
Minister of Health.
37,38
In Australia, the majority of T&CM
products are available over-the-counter and are regulated
by the Australian Therapeutic Goods Administration (TGA)
using a two-tiered, risk-based approach as a subset of
drugs or therapeutic goods.
33,39
The EU regulates some
T&CM products as a subset of drugs under the Traditional
Herbal Medicinal Products Directive (THMPD) and others
as food supplements, which are separately regulated
by the European Food Supplements Directive.
30,31,4042
In
China, dietary supplements are regulated as “health foods”
together with functional foods, and manufacturers are
required to secure product approval from the China Food
and Drugs Administration (CFDA).
31,43
The importance of dietary supplement
product quality
Quality of dietary supplement products can be compromised
by impurities and contaminants which can occur in
amounts beyond levels considered safe for human use;
44
ingredient misidentiication or substitution, often with
an inferior ingredient
4549
; and products purporting to be
dietary supplements but containing unknown or unlawful
ingredients. Documented adherence to public quality
standards can help address these quality concerns and help
ensure dietary supplements’ consistency and quality.
50,51
The most common unlawful products marketed as dietary
supplements are those promoted for weight loss, sexual
function, or athletic performance.
45,5257
Many times, active
pharmaceutical ingredients or their analogues are identiied
in these categories of products marketed as dietary
supplements even after FDA warnings to the manufacturer.
58,59
The consequences of quality assurance failures can range
5
USP Global Public Policy Position: Regulatory reform is necessary to help ensure the quality of dietary supplements
from no noticeable or measurable eects to signiicant
harms, such as internal organ damage, increased risk of
cancer, or death.
60
The drug ingredients in these products
marketed as dietary supplements have the potential to cause
serious adverse events related to accidental misuse, overuse,
interaction with other medications or with other ingredients
within the supplement, and underlying health conditions in
the user.
61
Many of the examples of the inclusion of unlawful
ingredients and adulteration, including the identiication of
undeclared substances in products, can be detected using
appropriate analytical methods, such as those included in
public standards.
23,62
As noted, although quality is built into the regulatory
framework for dietary supplements, it is limited in terms of
speciic quality requirements.
63
The FD&C Act names the
USPNF as oicial compendia for dietary supplements,
23
but
meeting the requirements in any public quality standard of
the USPNF is voluntary for manufacturers and distributors.
Beyond oversight by the FDA and related agencies, the
dietary supplement industry can, and should, play an active
and inluential role in addressing dietary supplement quality.
The supply chain for the manufacture and distribution of
dietary supplements can involve multiple parties in many
countries before a inished product is obtained. Quality issues
with dietary supplement products can arise at various points
and it can be diicult to track the lineage of ingredients and
the identities of parties involved in the production of a single
product. All stakeholders along the supply chain have the
duty to self-regulate through qualifying and validating their
suppliers, ensuring supply chain security, testing ingredients
and inished products, identifying and removing high-risk
products from product assortments, and implementing
other mechanisms to assure quality. Makers of poor-quality
products ignore legal obligations and the FDA lacks the
resources for more frequent inspections, substantive
surveillance, and enforcement of the law.
64
A regulatory paradigm to create
trust in the quality of dietary
supplements
Improving dietary supplement post-market surveillance
could improve quality and safety signal detection
To identify products that are unsafe and/or contain unlawful
ingredients, the FDA relies on post-market surveillance eorts
including inspection of dietary supplement manufacturing
sites, review of adverse event reports and consumer
complaints, and screening of imported products.
Quality concerns with dietary supplement products are
widespread, as demonstrated by the number of FDA
Warning Letters for dietary supplements that have not
met certain CGMP and other requirements.
65
Within the
past decade, top observations stated in FDA 483 Forms—
forms issued to irms at the conclusion of an inspection
when an investigator(s) has observed any conditions
that may constitute violations of the FD&C Act—for
dietary supplement products include failure to establish
6
USP Global Public Policy Position: Regulatory reform is necessary to help ensure the quality of dietary supplements
speciications and inadequate testing or testing methods to
determine if those speciications have been met.
66,67
Additionally, in the United States, clinical and other research
studies are not required for dietary supplements, making
post-market surveillance a key part of identifying quality
or safety problems associated with dietary supplement
products. The FD&C Act deines a dietary supplement
adverse event as “any health-related event associated with
the use of a dietary supplement that is adverse”
24
(e.g.,
headache, abdominal pain, allergic reaction, rash, and
dizziness or lightheadedness). A serious adverse event is
deined as an adverse event that “results in death, a life-
threatening experience, inpatient hospitalization, a persistent
or signiicant disability or incapacity, or a congenital anomaly
or birth defect; or requires, based on a reasonable medical
judgement, a medical or surgical intervention to prevent
an outcome described above.”
68
The Dietary Supplement
and Nonprescription Drug Consumer Protection Act
(DSNDCPA)
38
created a mandatory reporting system for
serious adverse events for nonprescription drugs and
dietary supplements, and the number of serious adverse
events reported by dietary supplement manufacturers has
increased since its implementation.
The U.S. Government Accountability Oice (GAO) estimates
that, of the estimated 50,000 adverse reactions each year
from dietary supplements, a small fraction is reported to the
FDA. However, literature documents that concomitant use of
dietary supplements and prescribed medications is common,
problematic, and can result in life-threatening adverse
events, hospitalizations, and fatalities.
69
Many products and
7
USP Global Public Policy Position: Regulatory reform is necessary to help ensure the quality of dietary supplements
ingredients have been implicated in interactions and adverse
events, yet investigators note underreporting, lack of case
reports, and incomplete reports.
6974
The lack of reporting of
adverse events from all stakeholders, along with the poor
quality of the information received in some of the reports,
make it diicult for the FDA to ind and remove dangerous
supplements.
75,76
The GAO has called on the FDA to improve
tracking of adverse events related to dietary supplements,
including utilizing data from poison centers in addition to its
present sources, which mainly includes industry reports.
77
The FDA also underscores the importance of reporting
adverse reactions to dietary supplements in resources for
healthcare professionals and consumers.
78
USP supports enhancing existing eorts to improve the
collection of post-market dietary supplement quality and
safety signals
79
in the FDA Safety Reporting Portal (SRP)
80,81
including 1) greater enforcement of already required
serious adverse event reporting by manufacturers and 2)
encouraging increased voluntary reporting of suspected
adverse events associated with dietary supplement
products by health care professionals, researchers, public
health oicials, and consumers.
Dietary supplement quality can be enhanced
using a risk-based approach
Reform of the current regulatory framework for dietary
supplements is needed to help ensure the quality and
consistency of dietary supplements sold in the United
States. Adherence to public quality standards, which are
developed by volunteer experts in a framework based on
science and strict rules against conlict of interest, can help
ensure that dietary supplements are produced according
to robust scientiic expectations for quality and can help
reduce the potential for public health risk. Public standards
can help address quality concerns, such as the presence of
impurities and contaminants, and ingredient misidentiication
or substitution. For example, adulteration can be detected
using appropriate analytical methods, and public standards
can help to set appropriate speciications for identity to catch
the misidentiication or substitution. Public standards can be
used universally and consistently by dietary ingredient and
supplement manufacturers, rather than using speciications
set by individual manufacturers for the same ingredients
and products. Use of a common set of quality standards
throughout the industry provides transparency on the
quality expectations for the ingredients and/or products for
manufacturers and regulators.
A risk-based approach for adherence to public quality
standards for dietary ingredients and dietary supplement
products would allow the FDA to prioritize inspections,
enforcement, and other regulatory actions involving
products that have the greatest potential to cause harm
to consumers. Risk-based regulation is used by the FDA in
various product areas, including recordkeeping requirements
for foods designated as high-risk
82
and a risk-ranking model
decision support tool to assist in adding foods to the Food
Traceability List;
83
and approaches to monitoring the conduct
of clinical investigations of human drug and biological
products, medical devices, and combination products.
84
The FDA also conducts surveillance inspections for human
drug manufacturing sites using a risk-based site selection
model; risk factors include compliance history and inherent
product risk, among others.
85
The Agency has also proposed
the use of risk-based approaches for building oversight of
laboratory developed tests
86
and assessing and verifying the
security and quality of software used in the medical device
manufacturing and quality control process.
87
The FDA has
indicated that they are seeking to promote best practices to
help manufacturers raise their product quality and comply
with existing regulations and that industry should focus on
producing quality and safe products for patients at every step
of the manufacturing process.
88
The FDA’s Compliance Program Guidance Manual for dietary
supplement inspections, sampling, and imports (dietary
supplement CPGM) indicates that the FDA conducts risk-
based surveillance inspections for dietary supplements,
focusing on compliance with CGMP, products containing
ingredients at risk for contamination with higher levels
of toxic elements, and supplements spiked with drug
ingredients or other unlawful ingredients.
89
The FDA already
prioritizes inspections for high-risk dietary supplements,
which include, but are not limited to:
• Botanical ingredients which may contain toxic elements
or microbial pathogens and may present challenges with
identity and strength testing;
8
USP Global Public Policy Position: Regulatory reform is necessary to help ensure the quality of dietary supplements
and quality control,
87
risk-based required adherence to public
quality standards can help manufacturers raise product
quality, comply with existing regulations, and focus on
producing quality products for consumers at every step of
the manufacturing process; which are in alignment with
stated FDA priorities to improve consumer safety, product
integrity, and informed decision-making.
9
To help ensure the quality of those ingredients and
products identiied as potentially higher-risk, the FDA
should be given the authority to require adherence to
public quality standards. A list of higher-risk products and
ingredients should be developed for required adherence
and should consider factors such as products intended
for special populations; ingredients and products that
are associated with potential safety issues; products
identiied through post-market safety signals; and products
consumed by a large number of consumers that can be a
potential risk to public health.
The USPNF includes more than 800 dietary-supplement-
related documentary standards and approximately 200
physical reference standards to verify that a product and its
ingredients can pass tests indicating adherence to quality
standards. USP prioritizes the development of additional
dietary supplement standards based on considerations that
include the extent of use, interest from a governmental
body, and potential safety risk associated with use. The
majority of dietary supplement standards in the USPNF
are for commonly used botanicals, vitamins, and minerals,
accounting for approximately 70 percent of prominently
marketed ingredients. The standards for botanical ingredients
help ensure quality related to ingredient misidentiication
and substitution.
91
The vitamin and mineral standards are
important due to the high consumer use of these products.
Requiring adherence to USP standards will help ensure the
quality of these ingredients and products.
92
Additionally, dietary supplement products containing
impurities and/or contaminants can present potential quality
and safety concerns. Some contaminants of concern include
heavy metals, bacteria and fungi, toxins, and pesticides.
93
Adherence to public quality standards can help ensure that
valid testing is conducted for the presence of impurities and
contaminants in dietary supplements. Further, as noted in
• Bovine ingredients;
• Supplements that may contain new dietary ingredients
without safety assessments; and
• Supplements with multiple dosage forms such as powder,
liquid, gummy, or softgel dosage forms.
In addition to the high-risk factors for dietary supplements
indicated in the FDA’s dietary supplement CPGM, such as
ingredients that may contain contaminants, and to promote
best practices to produce quality and safe products for
consumers, the FDA should consider additional factors for
dietary ingredients and supplements that have a higher
potential for public health risk than others, including:
• Products intended for special populations, for example,
prenatal vitamins and vitamin D drops for infants;
• Ingredients and products that are associated with
potential safety issues, such as products that commonly
include impurities or contaminants or products that are
more susceptible to economic adulteration, such as
substitution of ingredients;
• Products identiied through post-market safety signals
such as FDA 483 Forms or post-market surveillance
reporting; and
• Consumer usage or number of products on the market.
A large majority of Americans report taking dietary
supplements, and almost all of these supplement users
(98 percent) reported taking vitamins and minerals.
18
Another survey reported the top ten most popular
supplements as vitamin D, magnesium, ish oil/omega-3,
Coenzyme Q10, multivitamins, probiotics, curcumin/
turmeric, vitamin C, vitamin B, and calcium.
90
With the
large number of consumers regularly exposed to these
products and the limitations associated with current
post-market surveillance, there follows a substantial
increase in the potential risk to public health with the
most utilized products.
Mandatory adherence to public quality standards will
help ensure quality of higher-risk products
Similar to FDA draft guidance for verifying the security and
quality of software used in medical device manufacturing
9
USP Global Public Policy Position: Regulatory reform is necessary to help ensure the quality of dietary supplements
For example, the FDA could consider adherence to public
quality standards, such as USP General Chapters <2740>
Manufacturing Practices for Dietary Ingredients and <2750>
Manufacturing Practices for Dietary Supplements
94,95
or other
ingredient-speciic standards, as a factor in its risk-based
inspection model. In the FDA’s dietary supplement CPGM,
it states, “A primary objective of FDA’s dietary supplement
inspection program is to ensure that dietary supplement
products meet federal standards for quality and accurate
labeling.”
89
Further, when the FDA performs analyses on
ingredient samples, the CPGM says that “[c]ompendial
methods must be considered before non-compendial
methods are considered.”
89
Additionally, “[a]ll methods used
whether compendial or non-compendial, must be validated
through the use of recovery and reproducibility studies, use
of positive and negative controls, use of Standard Reference
Material, when available, or in-house quality assurance/quality
control materials, etc.”
89
Therefore, if dietary ingredients and supplements adhere to
public quality standards, use of such validated methods could
assist and facilitate FDA inspection protocols and ingredient
and product test methods.
FDA’s dietary supplement CPGM, certain dietary ingredients
may contain toxic elements or microbial pathogens and
present challenges with identity and strength testing,
complicated by multiple dosage forms.
89
USP public
standards include multiple dosage forms when applicable,
and limits for microbial pathogens, elemental contaminants,
and other known adulterants. Admission evaluations (safety
evaluations based on available literature) are part of the USP
Dietary Supplement Compendium (DSC).
Incentivizing voluntary adherence with public quality
standards will promote quality
A challenge associated with required adherence to public
quality standards for higher-risk products is a misconception
that products outside the high-risk category are exempt
from quality concerns. To address this perception, an
additional consideration for a risk-based approach to dietary
supplement ingredient and product oversight could include
regulatory incentives to increase voluntary adherence to
quality standards within the dietary supplement industry for
those products not deemed higher-risk.
USP Global Public Policy Position: Regulatory reform is necessary to help ensure the quality of dietary supplements
Under DSHEA, manufacturers and distributors of dietary
supplements and dietary ingredients are prohibited from
marketing products that are adulterated or misbranded and
manufacturers are responsible for labeling their products
to ensure that they meet all the requirements of DSHEA and
FDA’s implementing regulations.
32
The FDA can take action
against any adulterated or misbranded dietary supplement
once a product on the market is found to be in violation.
Post-market surveillance methods such as adverse event
monitoring, inspections, and Internet searches are the
primary means to monitor the safety of marketed products.
The FDA can only restrict the use of a product or mandate
a recall once the product is being marketed.
98,99
Because
dietary supplement manufacturers are not required to
submit certain product information before marketing, the
FDA has insuicient authority and resources for real-time
and useful monitoring to know which dietary supplement
products are on the market or any additional information
about them.
The FDA noted in a 2022 draft guidance that it currently
lacks information about an estimated 4,600 new supplement
ingredients.
100
Because there are an unknown number of
dietary supplement ingredients and products currently on
the market, additional transparency for the FDA and the
public about the type and volume of dietary supplement
Providing incentives, such as factors that can be used for
risk-based inspection prioritization by the FDA, for irms
to manufacture dietary ingredients or supplements that
voluntarily adhere to public quality standards could facilitate
increased quality in the dietary supplement industry.
This approach could be a more eicient use of FDA’s
limited resources and sta for inspections and testing of
dietary ingredients and supplements, allowing the FDA more
resources to focus on prioritizing enforcement and other
regulatory actions on products with a potential for higher
public safety risk.
89,96
Dietary supplement mandatory product listing
will provide more transparency to regulators,
healthcare professionals, and help inform
consumers
Under existing law, the FDA does not have the authority
to require approval of dietary supplement labeling before
dietary supplements are sold. Post-market oversight of
dietary supplement marketing, including labeling and
advertising, are shared authorities between the FDA and
Federal Trade Commission (FTC). The FTC acts as the
primary regulator of dietary supplement advertising and
the FDA possesses primary regulatory responsibility for
dietary supplement labeling.
97
10
11
USP Global Public Policy Position: Regulatory reform is necessary to help ensure the quality of dietary supplements
industry the ability to respond more quickly to emerging
safety concerns, support FDA eorts to prioritize resources
and expertise, promote risk-based regulation, support
consumer access to quality products, and increase the
transparency and awareness of the ingredients in dietary
supplements.
109
Additional labeling requirements could
facilitate dietary supplement quality
Regulatory reform should also provide additional authority
to the FDA to require that irms adhere to additional labeling
requirements related to transparency of ingredients and the
quality of the product. Currently, dietary supplement labeling
must include: 1) the statement of identity (including the
term “dietary supplement” or “supplement” and a modiied
and appropriately descriptive term indicating the type of
dietary ingredient(s) in the product); 2) the net quantity of
contents statement (amount of the dietary supplement); 3)
the Supplement Facts labeling; 4) the ingredient list; and 5)
the name and place of business of the manufacturer, packer,
or distributor.
110
Additionally, the FDA requires manufacturers
to list all the ingredients in a dietary supplement on the
Supplement Facts panel of the product, along with the amount
of each by weight, except when the ingredients are part of
“proprietary blend;” proprietary ingredients are disclosed,
but not their amounts.
111
Manufacturers should be required
to disclose all of the ingredients, and their amounts, in a
dietary in a dietary supplement product. Listing out the
amounts of the ingredients in a proprietary blend would
improve the transparency of ingredients included in such
dietary supplements, help the FDA determine if a labeled
ingredient is new and/or lacks adequate safety evidence,
and provide necessary information to consumers and
healthcare providers.
Additionally, there is currently no requirement for
manufacturers to include expiration dates on dietary
supplement products. However, if such information is
placed on the label, the manufacturer must have data to
support the expiration date.
112
To support the quality and
stability of the product, labeling requirements should
include expiration dates supported by stability studies.
products available on the U.S. market could facilitate FDA
regulatory actions.
12,101
USP supports modernization of DSHEA, granting the
FDA the authority to establish an FDA-administered
mandatory product listing regime for dietary supplement
products. This system would require dietary supplement
manufacturers to provide at a minimum a listing of
products being sold, the ingredients contained in the
product, and a copy of each product detail.
With mandatory product listing authority, the FDA could
require dietary supplement manufacturers to provide basic
information about the products being sold, including the
ingredients contained in the product, a copy of the label, and
information about whether the product complies with public
quality standards. Requiring dietary supplement manufacturers
to list all products marketed as dietary supplements with the
FDA would support greater transparency in the supply chain
and would provide the FDA with a comprehensive view of the
products potentially on the market.
6
Public health, health care, patient, and consumer advocacy
organizations have long called for reform of the DSHEA
framework and many have speciically called for mandatory
product listing.
13,5,102,103
The concept of a mandatory
product listing for dietary supplements has had bipartisan
Congressional support and is supported by the FDA and 95
percent of American adults.
6,104107
Some trade organizations
also support the concept of mandatory product listing.
108
Additionally, some advocates for dietary supplement
safety call for additional safeguards to be integrated in the
listing system, such as quick response (QR) codes for easy
identiication and the ability to lag products produced by
manufacturers who have received warning letters from the
FDA to further boost transparency and facilitate the recall of
harmful products more quickly and thoroughly.
63,73
A mandatory product listing would provide additional
transparency to the FDA and the public on the type and
number of dietary supplement products available on the
U.S. market and would help facilitate FDA actions against
non-compliant products and the manufacturers and/or
distributors of such products. It would provide the FDA and
12
USP Global Public Policy Position: Regulatory reform is necessary to help ensure the quality of dietary supplements
Resources are available to educate healthcare professionals
and consumers about how dietary supplements are
regulated in the United States, beneits, and risks of
using dietary supplement products, and choosing dietary
supplements with quality in mind.
78,116
USP supports continued eorts to educate consumers,
patients, and healthcare professionals about the use of
dietary supplement products and supports eorts to
increase consumer, patient, healthcare professional, and
retailer awareness of resources to help patients select
quality supplements.
Opportunities to increase audits
should be explored
Public quality standards provide valuable information to
manufacturers to support building critical quality attributes
into processes beginning in the early development phases
of new and existing products and address common quality
issues. Standards, such as USP General Chapters <2740>
Manufacturing Practices for Dietary Ingredients, <2750>
Manufacturing Practices for Dietary Supplements,
94,95
ingredient-speciic standards when available,
23
as well
as associated analytical methods provide tools to create
eiciency in product development, create consistency
across manufacturers, and increase transparency in quality
expectations for industry and regulators.
Continued education can facilitate
awareness about dietary supplement
quality considerations
Many people purchase and consume dietary supplement
products without advice from a healthcare professional.
Without engagement in risk-based conversations about
dietary supplement product use with a healthcare
professional, important quality factors may not be
considered or understood. These risk-based conversations
should include discussion about the variable quality of
dietary supplements, the presence of unreputable products
in the marketplace, and information on which products
are commonly adulterated. As noted, surveys indicate
that a majority of Americans consume dietary supplement
products and have misperceptions about the safety and
intended use of dietary supplement products.
1,8,1319
Many
people report purchasing dietary supplement products
in pharmacies,
113
however, a minority of consumers
report discussing dietary supplements with a healthcare
professional
114
and 75 percent of people report using at
least one dietary supplement without a recommendation
from a physician.
115
Healthcare professionals, including pharmacists and
physicians, provide guidance and answer patient and
consumer questions regarding medicines and dietary
supplements. Consumers are inundated with options
when they go to purchase dietary supplement products.
13
USP Global Public Policy Position: Regulatory reform is necessary to help ensure the quality of dietary supplements
Increasing FDA resources is a necessary
component of dietary supplement reform
Currently, the FDA faces challenges to overseeing the
rapidly growing dietary supplement industry. Although
more products enter the market each year, the FDA can only
dedicate a small percentage of its resources to regulating
the dietary supplement industry.
76
In a typical year, the FDA
conducts about 500 to 600 dietary supplement inspections,
which represents approximately 5 percent of manufacturing
facilities
125
with the caveat that the FDA does not have
comprehensive knowledge of all dietary supplement
manufacturers.
76
With violations documented in over half of
recently inspected dietary supplement manufacturers,
56,126
and known limitations in inspection capacity, additional
resources for FDA inspections are necessary.
Furthermore, reports indicate that the FDA lacks the resources
for more frequent inspections, expansive surveillance,
and more frequent enforcement actions.
64
An important
consideration for any legislative, regulatory, or policy reform
and modernization is providing adequate resources for
enforcement. All consumers will beneit from a regulatory
framework that promotes product quality and provides
appropriate tools and resources for the FDA to maintain
appropriate oversight.
45
In the interests of public health and
patient safety, increasing FDA resources for the oversight of
dietary supplements is necessary to appropriately oversee
the growing dietary supplement sector.
All supplements marketed and sold in the United States
must comply with the CGMP requirements in 21 CFR 111
and portions of 21 CFR 117,
21,117
and the top violations cited
in manufacturer audit reports include failure to set proper
speciications for products that are manufactured and
insuicient quality control operations.
118
As a means to drive
product quality and the production of consistent dietary
supplement products, USP encourages conducting more
risk-based FDA audits as outlined in the CPGM at the dietary
supplement product level, however, also recognizes that the
FDA currently lacks the resources to more frequently audit
all listed manufacturing facilities.
Some policy proposals include: 1) consideration of authorizing
third-party CGMP dietary supplement auditors to better
enforce regulations, more frequently audit, and ease the
burden on the FDA;
2
2) leveraging the existing Voluntary
Qualiied Importer Program (VQIP) along with remote
regulatory assessments;
119,120
or 3) some combination of
these proposals. Questions remain about the goals and
logistics of some proposals since varying quality standards
can exist
23,121123
with current dietary supplement third-party
audits that may dier from—sometimes with requirements
below—FDA CGMP requirements.
25
Some programs evaluate
only a manufacturing facility to ensure the facility has the
CGMP systems in place, and fail to evaluate how CGMP
systems are working for the production of individual dietary
supplement products that are marketed. The FDA already has
a voluntary program to recognize “accreditation bodies” that
have the responsibility of accrediting third-party “certiication
bodies” to conduct safety audits for food products,
124
but
questions remain about how the FDA could or would apply a
similar program to ease their dietary supplement audit burden.
Finally, questions remain about the accountability third-party
auditors would have should a manufacturer or product receive
a violation citation following their inspection. Considering
these questions as well as how authorized third-party
dietary supplement audits could overlap with facets of the
proposed risk-based paradigm, USP encourages exploring
mechanisms, including third-party audits— where audit
standards are based on CGMP, USP Quality Standards, and
FDA-established criteria— and leveraging existing FDA
programs in new ways to enable more audits of dietary
supplement manufacturing facilities and products.
About USP
The U.S. Pharmacopeia (USP) is an independent,
scientiic nonproit organization focused on building
trust in the supply of safe, quality medicines, dietary
supplements, and foods, through setting public
quality standards in its various compendia. The USP
Dietary Supplements Compendium (DSC) includes
over 970 monographs and 190 general chapters for
manufacturers and suppliers.
123
Additionally, USP
provides services through its Dietary Supplements
Veriication Program.
127
14
USP Global Public Policy Position: Regulatory reform is necessary to help ensure the quality of dietary supplements
18. Council for Responsible Nutrition. CRN Reveals Survey Data from 2020
Consumer Survey on Dietary Supplements. 2020.
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21. 21 C.F.R. § 111 - Current Good Manufacturing Practice in Manufacturing,
Packaging, Labeling, or Holding Operations for Dietary Supplements.
22. U.S. Food and Drug Administration. Federal Food, Drug, and Cosmetic
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23. United States Pharmacopeia. United States Pharmacopeia–National
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24. Section 403(s)(D) of the FD&C Act.
25. U.S. Food and Drug Administration. Code of Federal Regulations Title 21:
21 CFR 111.
26. U.S. Food and Drug Administration. Code of Federal Regulations Title 21:
21 CFR 111.70(b) and 21 CFR 111.70(e).
27. U.S. Food and Drug Administration. Code of Federal Regulations Title 21:
21 CFR 111.75.
28. U.S. Food and Drug Administration. Federal Food, Drug, and Cosmetic
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