Transcript Document

U.S. FDA Perspective on Food
Supplements/TM
IKHLAS A. KHAN
National Center for Natural Products Research,
Department of Pharmacognosy and Research Institute of
Pharmaceutical Sciences, School of Pharmacy,
The University of Mississippi
What is a dietary supplement in the US?
As defined by the United States Congress in the Dietary
Supplement Health and Education Act (http://www.fda.gov/
opacom/laws/dshea.html#sec3), which became law in 1994, a
dietary supplement is a product (other than tobacco) that
• is intended to supplement the diet;
• contains one or more dietary ingredients (including
vitamins, minerals, herbs or other botanicals, amino
acids, and “other substances”) or their constituents;
• is intended to be taken by mouth as a pill, capsule,
tablet, or liquid;
• and is labeled on the front panel as being a dietary
supplement.
http://ods.od.nih.gov/factsheets/DietarySupplements.asp
What does DSHEA mean?
 Dietary supplements are regulated as
“foods” within the meaning of the act.
 Does not require pre-market notification or
registration of products, except for new
dietary ingredients (NDI).
Dietary Supplement
Food
Drug
Where do you want to go today?
What is the
“Intended” Use Makes a Difference
Not ingested,
applied to the body
Diagnose, cure,
or treat a disease
Intended
use is food
COSMETIC
DRUG
FOOD
Ingested to affect
structure or
function of body
Ingested to
supplement
the diet
DIETARY
SUPPLEMENT
Under US Regulations Botanicals can be
regulated as:
 Foods - conventional foods, functional
foods, spices, dietary supplements
 Drugs - OTC, prescription
 Biologics - allergenic vaccines
 Cosmetics - shampoos
 Devices - dental alginates, poultices,
adhesives
Safety categorization plays a major
role!
Food <<<<<<<<<<<<>>>>>>>>>>>>>Drugs
National Center for
Natural Products Research
Safety Assumptions
 Drugs - Health
benefit vs. risk
evaluation.
 Generally regarded
as unsafe!
 Dietary supplements Components are
Generally Recognized
as Safe (GRAS).
 GRAS Notification
(www.cfsan.fda.gov/~
rdb/opa-gras.htm)
Quality Standard Differences
 Drug
 Utilize Pharm Good
Manufacturing
practices (GMP)
 Main focus on
consistency, potency
and purity.
 DS/Foods
 Utilize Food (GMP)
 Main focus on the
reduction of
contaminants
adulterants and filth.
Drugs vs. Dietary Supplement Claims
 Drug manufacturers
may claim that their
product will
diagnose, cure,
mitigate, treat or
prevent a disease.
 Dietary supplement
manufacturers can
not legally make
these claims!
What can dietary supplement
manufacturers claim?
 A dietary supplement or food product may contain
one of three types of claims:
 A health claim - “diets high in calcium may reduce the
risk of osteoporosis”
 A nutrient content claim - “A good source of …”
 or A structure/function claim - “calcium builds strong
bones.”, “antioxidants maintain cell integrity”
(http://www.cfsan.fda.gov/~dms/hclaims.html)
“Authorized” health claims for DS
 NLEA Authorized Health Claims.
 The Nutrition Labeling and Education Act (NLEA) 1990.
 Must meet a “significant scientific agreement standard.”
 Health Claims Based on Authoritative Statements.
 FDAMA - (FDA Modernization Act of 1997)
 “authoritative statement” from a scientific body of the US
Government or the National Academy of Sciences.
 Qualified Health Claims.
 Claims that contain qualifying language to reflect level of
scientific support and are not misleading to consumers.
 FDA guides http://www.cfsan.fda.gov/~dms/hclmgui3.html
(http://www.cfsan.fda.gov/~dms/hclaims.html)
New Dietary Ingredient (NDI) Notification
 Required for all new ingredients which were not
marketed in the US prior to October 15th 1994
(DSHEA).
 Notifications should be submitted to FDA 75 days
prior to marketing.
 Information must exist which establishes a
reasonable expectation of safety for products
containing the NDI.
 The FDA does not “approve” or “disapprove” the
NDI rather they post objections.
NDI Status 1995-2005
60
50
40
No Obje ction
Objection
30
20
10
0
1995 1997 1999 2001 2003 2005
Items that FDA Currently Enforces




Androstenedione
Ephedra
Steroidal precursor substances
Aristolochic Acid
Guidelines for Botanical Drug Products
 FDA Published on
6/9/2006
 More information at
www.fda.gov/cder/
guidance
Botanical Drugs NDA vs. Monograph
 Botanical drugs can be developed in United
States through:
 New drug applications (NDA)
 Prescription drug
 Over-the-counter drug
 Monographs for Over-the-counter (OTC)
Guidance Principals
 Identification of active constituents not essential
 Purification not required
 Chemistry/Manufacturing and Control (CMC) will
be extended to raw materials
 Non-clinical evaluations may be reduced
 Same level of clinical efficacy/safety requirements
as standard “drugs”
 In general the FDA will utilize the ‘historical’
safety information to expedite early stage testing
and evaluation of botanical products.
Botanical Drug Review
 IND Safety review related to scope of the
proposed clinical studies
 Preliminary studies (Phase I/II)
 Marketed products vs not marketed or
 Marketed with safety concerns
 Expanded studies (Phase III)
 End-of-Phase 2 meeting
 New Drug Application (NDA)
 Safety/efficacy; quality and therapeutic consistency
 Pre-NDA meeting
Botanical IND Considerations
 A botanical or a non-botanical IND?
 Crude extracts, partially purified fractions
 Combination of highly purified compounds from
different plants
 Single herb or multiple-herb product
 Botanical only or botanical with other “active”
components
 E.g., vitamins, minerals, animal parts
BRT Review of Botanical INDs Based on
Prior Human Use
 Comparing the doses and durations of the
botanical product/raw materials in IND with
previous human uses
 Is the product/trial reasonably safe?
 Report known side effects or potential safety issues
 Comment on the relationship between prior human
use and the proposed indications
Common issues of Initial IND Submissions
 Incomplete information on raw materials
 Scientific name or botanical parts not specified
 Multiple plant species used for one botanical material
 Safety information gaps of botanical raw materials
and products
 Yields of extracts from raw materials not provided
 Unreasonably high dose (in weight of raw herb)
 Proposed long trial duration that is not supported
by prior human experience
Botanical Applications to FDA
(as of June 1, 2006)
 Total of 286 Applications
 232 INDs (2/3 active; not necessarily mean currently
enrolling or treating patients);
 54 pre-INDs
 Currently 2-3 new submissions per month
 40% commercial, 60% research
 >2/3 single herb, <1/3 multiple herbs
Increasing #’s of Botanical Applications to FDA
Botanical Applications 1982-2006
120
100
80
Annual Ave
Period Total
60
40
20
0
1982-89
1990-94
01/9507/00
08/0005/04
06/0405/06
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Scientific Issues that Impact the
Regulation of Dietary Supplements
 GMP/GAP-related: Identification/substitutions, purity, quality
issues
 Contaminants: chemical, filth, heavy metals, pesticides,
microbial, sterilization techniques
 Efficacy - identification of "active" components,
standardization issues related to products (markers of quality,
active ingredients, surrogate markers, etc.)
 NDI safety issues - evidence needed to ensure safety
 Interactions with drugs and other dietary ingredients
 Type of safety evidence needed when use expands beyond
traditional user populations/exposures. (children,elderly,
preg/lact women, childbearing age, etc.).