Transcript FDA Regulation of Product Claims

FDA Regulation of Product Claims
January 25, 2011
Barbara A. Binzak, Ph.D., J.D., M.A.
Attorney
Buchanan Ingersoll & Rooney PC
Washington, D.C.
202-452-7906
[email protected]
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Outline
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Definition of probiotics
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FDA regulation of claims – key principles
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FDA vs. Federal Trade Commission (FTC)
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Summary of claims regulation by product category
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Drug (21 U.S.C. § 321(g))
Dietary Supplement (21 U.S.C. § 321(ff))
“Conventional” Food (21 U.S.C. § 321(f))
Medical Food (21 U.S.C. § 360ee(b)(3))
Device (21 U.S.C. § 321(h))
Cosmetic (21 U.S.C. § 321(i))
“Others”
Combination Products (21 C.F.R. § 3.2(e))
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What are Probiotics?
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“Live microorganisms, which, when administered in adequate
amounts, confer a health benefit on the host.” - United Nations Food and
Agricultural Organization (FAO)/World Health Organization (WHO)
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Panel’s task is to determine how probiotics should be regulated
– Is the current FDA regulatory scheme adequate?
– Should Congress/FDA create a new regulatory paradigm?
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How do claims influence product regulation, and how does
product regulation affect the product claims available?
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How - or should - product claims affect probiotic regulation?
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Key Principles (1)
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You are what you claim!
FDA looks at the available objective evidence to
determine how a manufacturer intends its product
to be regulated
To determine intent, FDA will look at the product’s
– Label (affixed to immediate container (21 U.S.C. § 321(k)); and
– Labeling (labels plus other written, printed, or graphic matter
affixed to or accompanying the article (21 U.S.C. § 321(m)); and
– Other promotional materials and activities (e.g., sales
personnel; trade shows); and
– Advertising
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Key Principles (2)
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Type of product (regulatory category) largely guides
type/scope of claims and FDA’s oversight
– FDA often thinks “in the box”
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Products with FDA pre-approval requirements may have more
defined requirements
– E.g., Rx drug claims are approved by FDA and are product-specific
– E.g., Dietary supplements are not pre-approved by FDA and claims are
not product-specific
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May not introduce any food, drug, device, or cosmetic into
interstate commerce that is adulterated or misbranded (21
U.S.C. § 331(a))
In general, labels and labeling may not be false or misleading
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FDA vs. FTC
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FDA
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– Truth/falsity of
advertising
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Rx drugs
Restricted devices
– Misbranding
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Foods
Drugs
Devices
Cosmetics
– Labeling
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Rx drugs
OTC drugs
FTC
– Truth/falsity of
advertising
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OTC drugs
Food
Devices
Cosmetics
* This presentation covers
FDA’s regulation of
labeling, not advertising
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Drug Claims (1)
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What is a “drug”? (21 U.S.C. § 321(g))
– Articles recognized in USP, HPUS, or NF; and
– Articles intended for use in diagnosis, cure,
mitigation, treatment, or prevention of disease;
and
– Articles (other than food) intended to affect the
structure or function of the body; and
– Articles intended for use as components in any
of the above
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Drug Claims (2)
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OTC drugs
– Developed through public monograph process
(i.e., notice and comment rulemaking;
publication of notices in the Federal Register)
– Claims for particular classes of drugs are set
forth in FDA’s regulations
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However, some OTC drugs are approved with new
drug applications (NDAs), and some begin as Rx drugs
and later become OTC (“OTC switch”)
– Claims for these products are established in NDA
– E.g., OTC monograph for antacid drugs: “For
the relief of heartburn, sour stomach, and/or
acid indigestion” (and permitted variations)
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Drug Claims (3)
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Rx drugs
– Claims must be consistent with FDA’s drug approval
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Scope of claims approval depends upon evidence supplied
– Claims must be truthful and supported by “substantial
evidence”
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Adequate and well-controlled investigations, including clinical
investigations, that can form the basis on which experts can
fairly and responsibly conclude that the drug has the effect it
purports or is represented to have under the conditions set
forth in the product labeling (21 U.S.C. § 355(d))
FDA may determine, based on relevant science, that data
from 1 adequate and well-controlled clinical investigation +
confirmatory evidence are sufficient to establish substantial
evidence (21 U.S.C. § 355(d))
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Dietary Supplement Claims (1)
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What is a “dietary supplement”? (21 U.S.C. § 321(ff))
– Product intended to supplement the diet bearing or containing
one or more
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Vitamin
Mineral
Herb/botanical
Amino acid
Dietary substance to supplement the diet by increasing total dietary
intake
Concentrate, metabolite, etc. of any of the above; and
– Intended for ingestion; and
– Not represented as a conventional food or as sole item of
meal/diet; and
– Labeled as a dietary supplement
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Dietary Supplement Claims (2)
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Types of claims
– Health claims
– Nutrient content claims
– Structure/function (S/F) claims
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Manufacturers must ensure validity of
product claims, but requirements for
each type vary
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Dietary Supplement Claims (3)
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Health Claims - Describe relationship (explicit or
implied) between food/food component/dietary
supplement ingredient (“substance”) and reduced
risk of a disease or health-related condition
Types
– Authorized – Requires “significant scientific agreement”
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Characterize relationship between substance and disease risk
Based upon totality of public scientific evidence
Pre-reviewed; FDA issues regulations
E.g., Calcium, vitamin D, and osteoporosis: “Adequate calcium
throughout life, as part of a well-balanced diet, may reduce the
risk of osteoporosis” (21 C.F.R. § 101.72)
E.g., Sodium and hypertension: “Diets low in sodium may
reduce the risk of high blood pressure, a disease associated
with many factors” (21 C.F.R. § 101.74)
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Dietary Supplement Claims (4)
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Types of health claims (cont’d.)
– Qualified – Requires less evidence than “significant scientific
agreement”
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Use emerging evidence of a relationship between substance and
reduced risk of disease or health-related condition
FDA does not issue regulations; file petition and FDA issues letter of
enforcement discretion
Require disclaimer explaining level of scientific evidence support
E.g., cardiovascular disease risk - nuts and heart disease (“Scientific
evidence suggests but does not prove that eating 1.5 ounces per day
of most nuts [optional: such as name of specific nut] as part of a
diet low in saturated fat and cholesterol may reduce the risk of heart
disease”)
E.g., diabetes risk - chromium picolinate and diabetes (“One small
study suggests that chromium picolinate may reduce the risk of
insulin resistance, and therefore possibly may reduce the risk of type
2 diabetes. FDA concludes, however, that the existence of such a
relationship between chromium picolinate and either insulin resistance
or type 2 diabetes is highly uncertain”)
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Dietary Supplement Claims (5)
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Nutrient Content Claims – Characterize nutrient levels
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Most claim regulations apply only to nutrients/dietary substances that
have an established daily value
– FDA issues regulations
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Types
– Describe level of a nutrient or dietary substance in the product (e.g., free;
high; low) (21 C.F.R. Part 101, Subpart D)
– Compare level of a nutrient in a food to that of another food (e.g., more;
reduced; lite) (21 C.F.R. Part 101, Subpart D)
– “Healthy” defined by regulation as implied nutrient content claim
characterizing food with respect to total fat, saturated fat, cholesterol, and
sodium (21 C.F.R. § 101.65(d)(2))
– Simple or comparative percentage claims for dietary supplements describe
a % level of a dietary ingredient for which there is no established DV
(e.g., “40% omega-3 fatty acids, 10 mg per capsule”) (21 C.F.R. §
101.13(q)(3)(ii))
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Dietary Supplement Claims (6)
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Structure/Function (S/F) Claims – Address role of a nutrient with respect to S/F
of body
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Historically appeared on conventional food, dietary supplement, and drug labels
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DSHEA established special rules for dietary supplements
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Requires “disclaimer” language (i.e., FDA has not evaluated the claim)
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Must have substantiation that claim is not truthful or misleading; notify FDA of
claim no later than 30d after first marketing of product
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Types
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Describe role of nutrient/dietary ingredient that is intended to affect normal S/F (e.g.,
“calcium builds strong bones”)
Characterize means by which nutrient/dietary ingredient acts to maintain S/F (e.g.,
“fiber maintains bowel regularity”)
Describe general well-being from consumption of nutrient/dietary ingredient
Describe benefit related to nutrient deficiency disease as long as statement tells how
widespread the disease is in the U.S. (e.g., vitamin C and scurvy)
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“Conventional” Food Claims (1)
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What is a “food”? (21 U.S.C. § 321(f))
– Articles used for food or drink; and
– Chewing gum; and
– Articles used as components of “any such
article”
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Use “conventional” food to distinguish
between dietary supplements, medical
foods, and other products that are classified
under the umbrella term “food”
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“Conventional” Food Claims (2)
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Similar to dietary supplement claims, but some
differences
– Health claims
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Permits an additional type of health claim: Health claim
based on authoritative statements by scientific body of U.S.
government or Nat’l. Academy of Sciences
E.g., "Diets rich in whole grain foods and other plant foods
and low in total fat, saturated fat, and cholesterol may
reduce the risk of heart disease and some cancers”
– S/F claims
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Focus on effects derived from nutritive value
– For dietary supplements, S/F claims may focus on both nutritive
and non-nutritive effects
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No notification to FDA
No disclaimers required
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Medical Food Claims (1)
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What is a “medical food”? (21 U.S.C. §
360ee(b)(3))
– Food which is formulated to be consumed or
administered enterally (through GI tract,
whether orally or by tube) under a physician’s
supervision and which is intended for specific
dietary management of a disease or condition
for which distinctive nutritional requirements
(based on recognized scientific principles) are
established by medical evaluation
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Medical Food Claims (2)
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Medical foods are exempt from normal food labeling
regulations (21 C.F.R. § 101.9(j)(8)); exemption applies only if
product is
– Specially formulated and processed for partial or exclusive
feeding of patient orally or by enteral tube; and
– Intended for dietary management of a patient when cannot be
achieved by modifying the normal diet (e.g., chronic medical
needs; limited/impaired capacity to ingest, digest, etc.; other
special medically-determined nutrient needs); and
– Provides nutritional support to manage unique nutrient needs
resulting from a specific disease/condition (per medical
evaluation); and
– Intended for use only under medical supervision; and
– Intended only for patient receiving active/ongoing medical
supervision
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Medical Food Claims (3)
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FDA proposed to evaluate its medical foods oversight
– No medical food regulations (61 Fed. Reg. 60661 (November 29,
1996))
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FDA: “…point to the need for a strong standard of scientific evidence
for the composition and effectiveness of medical foods.”
FDA: “The agency’s preliminary view is that the scientific standard
contained in the statutory medical food definition may require some
of the same types of data for medical foods as are needed to support
drug claims (e.g., data from clinical investigations).”
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Examples of purported medical food claims
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– Restrict phenylalanine/PKU – “A phenylalanine-free food to aid in the
nutritional management of hyperphenylalaninemia including PKU.”
– Hypermetabolic states, such as severe burns, trauma, or infection – “A
nutritionally complete formula that provides a concentrated source of
calories for patients with restricted fluid allowance or increased energy
needs…useful in the dietary management of volume-restricted patients,
oncology patients, hypermetabolic conditions, trauma, sepsis, and post
major surgery.”
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Device Claims (1)
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What is a “device”? (21 U.S.C. § 321(h))
– An instrument, apparatus, implement, machine,
contrivance, implant, in vitro reagent, or other similar or
related article (including any component, part, or
accessory), which is:
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Recognized in the USP or NF; or
Intended for diagnosis of disease or other conditions, or in
the cure, mitigation, treatment, or prevention of disease; or
Intended to affect the structure or any function of the body;
and
– Does not achieve its primary intended purposes through
chemical action within or on the body and which is not
dependent on being metabolized for the achievement of
the primary intended purposes
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Device Claims (2)
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Two regulatory tracks
– Premarket Approval Application (PMA) (21 C.F.R. Part 814)
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Requires FDA pre-approval
Application includes indications for use plus a summary of supportive
studies
Claims formulated during device development process
– Premarket Notification (510(k)) (21 C.F.R. Part 807, Subpart E)
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Demonstrates that the proposed device is substantially equivalent
(not identical) to a predicate device
– Substantial evidence based upon intended use and technological
characteristics
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Must have support to demonstrate substantial equivalence
Claims often similar to those of the predicate device
FDA must declare substantial equivalence before marketing
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Cosmetic Claims (1)
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What is a “cosmetic”? (21 U.S.C. § 321(i))
– Articles intended to be rubbed, poured,
sprinkled, or sprayed on, introduced into, or
otherwise applied to the human body or any part
thereof for cleansing, beautifying, promoting
attractiveness, or altering the appearance; and
– Articles intended for use as a component of any
of the above; and
– Does not include “soap”
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Cosmetic Claims (2)
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FDA does not pre-approve labeling; may not label a cosmetic to
implicate FDA approval
Promoting a product with claims about disease treatment/
prevention or about affecting S/F of body may cause the product to
be a drug
Product that is both an OTC drug and a cosmetic must comply with
both OTC drug and cosmetic labeling requirements
– E.g., antidandruff shampoos; toothpastes with fluoride;
antiperspirant/deodorants; makeup with sun-protection claims
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Suspect claims (although significant lack of enforcement) (FDA
Import Alert 66-38)
– “anti-aging”
– “counteract,” “retard,” or “control” aging
– “rejuvenate,” “repair,” or “restructure” skin
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Others (1)
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Food for Special Dietary Use/Special Dietary Food (21 C.F.R. §
105.3(a)(1))
– Particular uses of food for
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Supplying particular dietary needs existing due to physical, physiological,
pathological, or other condition (e.g., diseases; convalescence; pregnancy;
lactation, allergic hypersensitivity to food; underweight; overweight); and
Supplying particular dietary needs existing by reason of age (e.g., infancy and
childhood); and
Supplementing or fortifying ordinary or usual diet with a vitamin, mineral, or
other dietary property
Biological Product (42 U.S.C. § 262(i))
– A virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood
component or derivative, allergenic product, or analogous product, or
arsphenamine or derivative of arsphenamine (or any other trivalent
organic arsenic compound), applicable to the prevention, treatment, or
cure of a disease or condition
– If have a biologics license application (BLA), do not need an NDA;
however, most of Federal Food, Drug, and Cosmetic Act still applies to
biologicals
– Claims are product-specific
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Others (2)
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A variety of other terms are popularly used
to refer to combination product categories
– Used in different manners
– No legal meaning
– Examples
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“Cosmeceutical” - “Cosmetic” + “pharmaceutical”
“Neutraceutical” - “Nutrition” + “pharmaceutical”
“Farmaceutical” - “Farm” + “pharmaceutical”
“Functional Food” - Food supplying a health/disease
prevention benefit
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Combination Product Claims (1)
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What is a “combination product”? (21 C.F.R. §
3.2(e))
– Product comprised of 2 or more regulated components that are
physically, chemically, or otherwise combined or mixed and
produced as single entity
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E.g.,
E.g.,
E.g.,
E.g.,
drug + device
biologic + device
drug + biologic
drug + device + biologic
– Two or more separate products packaged together in a single
package or as a unit comprised of a biologic, drug, and/or device
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FDA recognizes that there are other combinations
possible, even though not recognized by regulation
– E.g., drug/device/biologic + dietary supplement/cosmetic/food
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Combination Product Claims (2)
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Office of Combination Products (OCP)
– Classifies single-entity products when category unclear
– Determines jurisdiction/lead Center when combination product
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Jurisdiction can be shared
One Center will have primary oversight
– Center jurisdiction assigned based upon product’s primary mode
of action (PMOA)
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Sponsor can submit proposal for which Center should have oversight
– Centers may collaborate with each other
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Combination product claims depend upon
– Nature of individual components
– Assignment of lead Center
– Intercenter agreement on scope of claims
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Conclusions
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You are what you claim!
Do probiotics fit within one or several
of these FDA regulatory schemes?
How is your view of probiotic
regulation influenced by FDA’s
oversight of product claims?
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