[Federal Register: October 20, 2004 (Volume 69, Number 202)]
[Notices]
[Page 61680-61684]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr20oc04-81]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2004N-0454]
Dietary Supplements; Premarket Notification for New Dietary
Ingredient Notifications; Public Meeting
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) is announcing a meeting
and is soliciting comments on FDA's premarket notification program for
new dietary ingredients (NDIs). FDA is soliciting comments from
industry, consumers, and other interested
[[Page 61681]]
members of the public concerning the content and format requirements
for NDI notifications made under the Federal Food, Drug, and Cosmetic
Act (the act). FDA is holding this meeting to give the public an
opportunity to provide information and views on the topics outlined in
this document. The agency intends to consider all comments received
during the meeting and made to the docket in determining whether any
future action is necessary or appropriate.
DATES: The public meeting will be held on November 15, 2004, from 9
a.m. to 5 p.m. Attendees must register to attend.
Submit written or electronic comments by December 3, 2004.
For security and space limitation reasons, you are encouraged to
register early. You may preregister via phone, fax, or e-mail until
close-of-business November 10, 2004, or on site on the day of the
meeting, providing space is available. Those wishing to speak should
contact Kelly Williams-Randolph (see FOR FURTHER INFORMATION CONTACT)
before close-of-business, 3 business days before the meeting.
ADDRESSES: The meeting will be held at the Center for Food Safety and
Applied Nutrition, Harvey W. Wiley Auditorium, 5100 Paint Branch Pkwy.,
College Park, MD 20740.
Submit written comments to the Division of Dockets Management (HFA-
305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments.
FOR FURTHER INFORMATION CONTACT: Kelly Williams-Randolph, Center for
Food Safety and Applied Nutrition (HFS-810), Food and Drug
Administration, 5100 Paint Branch Pkwy., College Park, MD 20740, 301-
436-2506, FAX: 301-436-2639, or e-mail: Kelly.Williams@cfsan.fda.gov.
SUPPLEMENTARY INFORMATION:
I. Background
The Dietary Supplement Health and Education Act of 1994 (DSHEA)
(Public Law 103-417) amended the act by adding, among other things,
provisions that defined the terms ``dietary supplement'' (section
201(ff) of the act (21 U.S.C. 321(ff))) and ``new dietary ingredient''
(section 413(c) of the act (21 U.S.C. 350b(c))). DSHEA also provided
that a dietary supplement containing an NDI is adulterated unless it
meets the requirements set forth in section 413 of the act, which
requires premarket notification for certain NDIs.
Under section 413(a) of the act, a dietary supplement that contains
an NDI is deemed adulterated unless it meets one of two statutory
requirements. One is that the dietary supplement contains only dietary
ingredients that ``have been present in the food supply as an article
used for food in a form in which the food has not been chemically
altered.'' (Section 413(a)(1) of the act). The alternative requirement
is (section 413(a)(2) of the act) that there be:
[A] history of use or other evidence of safety establishing that
the dietary ingredient when used under the conditions recommended or
suggested in the labeling of the dietary supplement will reasonably
be expected to be safe, and, at least 75 days before being
introduced or delivered for introduction into interstate commerce,
the manufacturer or distributor * * * provides [FDA] with
information, including any citation to published articles, which is
the basis on which the manufacturer or distributor has concluded
that a dietary supplement containing such dietary ingredient will
reasonably be expected to be safe.
FDA has issued a regulation Sec. 190.6 (21 CFR 190.6) establishing
the procedure by which a manufacturer or distributor of a dietary
supplement that contains an NDI must submit the information required by
section 413(a)(2) of the act.
II. Why Is FDA Holding This Meeting?
The agency is seeking public comment on several issues that need to
be addressed to clarify the requirements of section 413(a)(2) of the
act for NDIs that have not been present in the food supply as an
article used for food in a form in which the food has not been
chemically altered. FDA has identified a number of omissions and other
problems in previous notifications that have been submitted by firms to
comply with the NDI notification requirements of the act. These
omissions include a failure to do the following: (1) Adequately
describe the identity and composition of the NDI, (2) provide
information that states the basis for a conclusion that the substance
is an NDI, (3) provide adequate safety information about the NDI, or
(4) provide other necessary information. The problems with NDI
notifications described previously suggest that it may be helpful for
FDA to consider ways to assist submitters of NDI notifications to
ensure that they contain the information the agency needs to evaluate
the notification. There is also recognition by the regulated industry
that the quality of NDI notifications could benefit from FDA
clarification of the statutory requirements (Ref. 1). Therefore, FDA is
seeking comments from industry, consumers, and other interested members
of the public concerning the type, quantity, and quality of information
that a notifier should provide in notifications under section 413(a)(2)
of the act.
III. Registration, Written Questions, and Requests for Oral
Presentations
Persons interested in attending the November 15, 2004, meeting may
send their registration information (including name, title, business
affiliation, address, telephone, and fax number) to the contact person
(see FOR FURTHER INFORMATION CONTACT) by close-of-business November 10,
2004, or you may register onsite on the day of the meeting, providing
space is available. To expedite processing, this registration
information also may be sent to the contact person (see FOR FURTHER
INFORMATION CONTACT) by fax or by e-mail. If, in addition to attending,
you wish to make an oral presentation during the meeting, you must
inform the contact person 3 days before the meeting when you register
and submit the following: (1) A brief written statement of the general
nature of the views you wish to present, (2) the names and addresses of
all persons who will participate in the presentation, and (3) an
indication of the approximate time that you request to make your
presentation. Depending upon the number of people who register to make
presentations, we may have to limit the time allotted for each
presentation. Interested persons are encouraged to submit their
presentations and any additional comments to the docket. Any person who
wishes to distribute written material at the meeting is responsible for
the copy and distribution of such material. If you need special
accommodations due to disability, please notify the contact person at
least 7 days in advance. There is no registration fee for this public
meeting, but early registration is encouraged because space is limited
and it will expedite entry into the building and parking area. Because
the meeting will be held in a Federal building, you should also bring
photo identification and plan for adequate time to pass through
security systems.
IV. Scope of the Meeting
We are holding the public meeting on November 15, 2004, in part, to
identify and receive comment on the information a firm should provide
in an NDI notification under section 413(a)(2) of the act. As follows,
we provide a list of questions intended to focus public comment on
specific NDI issues.
[[Page 61682]]
A. Status of a Substance as a ``New Dietary Ingredient''
1. What should FDA consider to determine whether a substance falls
within a particular category of the statutory definition of ``dietary
ingredients'' under sections 201(ff)(1)(A) through (F) of the act?
2. What changes in chemical composition to a dietary ingredient
would cause it to become a substance that is not a dietary ingredient?
3. What should FDA consider to determine whether a dietary
ingredient was not marketed in the United States before October 15,
1994, and is therefore an NDI?
4. What changes in chemical composition to a dietary ingredient
that was marketed in the United States before October 15, 1994, would
lead to the dietary ingredient becoming an NDI subject to the
notification requirement in section 413(a)(2) of the act?
5. What changes to the conditions of use (e.g., serving size,
duration, frequency of use) recommended or suggested in the labeling
for a dietary supplement that contains an NDI would trigger the need
for a separate NDI notification?
6. Is there an authoritative list of dietary ingredients that were
marketed prior to October 15, 1994, and therefore are not NDIs? If not,
should there be? Who should compile such a list and what criteria
should be considered for placement of the dietary ingredient on such a
list?
B. Chemical Identification of the NDI
1. What types of chemistry information should be included to
describe an NDI for purposes of the NDI notification? Please consider
the following types of information:
a. Chemical name.
b. Chemical Abstract Service (CAS) registry number (if available).
c. Empirical formula.
d. Structural formula.
e. Quantitative composition.
f. Chemical characterization.
g. Chemical specifications.
2. Are there additional types of chemistry information that should
be included in the description of an NDI?
3. What types of information should be included to describe a
botanical NDI for purposes of the NDI notification? Please consider the
following types of information:
a. Botanical family name.
b. Part(s) of plant used.
c. Conditions of propagation.
i. Sexual reproduction (propagated from seeds).
ii. Seeds produced through selective breeding--variety and
cultivar.
iii. Seeds are bioengineered.
1. Variety, cultivar and seed producer.
2. Asexual reproduction by cloning.
3. Vegetative propagules.
4. tissue culture.
d. Geographical location of cultivated or wild harvested plant.
e. Conditions of cultivation.
i. Time of cultivation--month and year.
ii. Field cultivation--soil pH, fertilizers, pesticides and
herbicides.
f. Greenhouse cultivation.
i. Soil pH, fertilizers, pesticides and herbicides.
ii. Hydroponic growth media--nutrients, growth hormones and
minerals.
g. Method of drying--air or heat.
h. Processing information--hand or machine sorted, chopped or
milled.
4. Is there other information that should be included in a
botanical NDI notification due to unusual production conditions of the
botanical? Please consider the following possible situations:
a. Saccharomyces cerevisiae is cultured in medium with unusually
large amounts of selenium. Should the notification describe the degree
of selenium uptake as well as the levels of selenium compounds in the
final dietary supplement product?
b. Traditional or bioengineering methods are used to produce a
plant variety with novel properties. What chemistry information is
needed to describe the plant variety in sufficient detail to identify
the botanical product?
5. Is there processing information that should be included in the
description of a botanical extract in order to adequately describe the
NDI? Please consider the following types of information:
a. Description of the method of preparation (e.g., extraction) in
sufficient detail so as to make clear:
i. The identity of the source material (dietary ingredient).
ii. How the extract (NDI) is obtained from that source material.
iii. How the extract is standardized from batch to batch.
iv. How potential adulterants such as nonfood solvents, pesticides,
heavy metals and filth are excluded.
b. Documentation of the absence of toxins or other by-products that
may affect the safety of the ingredient produced by fermentation or
bioengineering.
c. Documentation that the extracts of cultured isolates are neither
infectious nor toxic.
6. Are there additional types of information that should be
included in the description of a botanical NDI?
C. Information About the Dietary Supplement
1. What types of information about the dietary supplement product
should be included in an NDI notification?
2. Please consider the following types of information:
a. Composition/formulation of the dietary supplement product,
including any contaminants.
b. A copy of the proposed product label and of any other labeling
that recommends or suggests conditions of use in addition to or
different from those recommended or suggested in the product label.
D. Establishing a Reasonable Expectation of Safety
1. What types of information should be included in an NDI
notification in order to establish a reasonable expectation of safety
based upon history of use? Please consider the following types of
information:
a. A description of the population that consumed the food or
dietary supplement containing the NDI.
b. The consumption levels (per serving and total exposure).
c. How often and how long the population consumed the food or
dietary supplement containing the dietary ingredient.
d. The number of independent references documenting history of safe
use.
e. The number of consecutive years of exposure.
f. Documentation of the health monitoring system(s) and database(s)
associated with the consumption of the NDI during the historical period
of safe use.
g. Reliability of historical safety information if no health
monitoring system is in place to detect adverse effects that may be
associated with the human consumption of the dietary ingredient.
2. Are there additional items that should be included to establish
a reasonable expectation of safety based upon history of use?
3. What quality and quantity of data and information are needed to
establish a reasonable expectation of safety based upon evidence other
than history of use?
4. In considering the data and information necessary to establish
reasonable expectation of safety, how would the following differences
in the use of the NDI in the dietary supplement from historical use
affect safety determinations?
a. Significantly higher serving level (e.g., twice the serving
level historically used).
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b. Longer duration of consumption than historically used (e.g.,
instead of recommending that a consumer drink an herbal tea for a few
days or occasionally, the label of the dietary supplement containing
the NDI label suggests or recommends continuous daily use for improved
digestive function).
c. Different route of administration (e.g., the dietary ingredient
was historically administered by poultice or injection, whereas the
dietary supplement containing the dietary ingredient is ingested).
d. Change from historical use that might increase potential toxic
effects (e.g., an NDI that will be consumed as ground root in capsules
when the historical use was a tea made from the roots).
e. Change in consumer target group (e.g., from general population
to young children, pregnant women, lactating women).
5. What criteria should FDA use to evaluate whether preclinical and
clinical studies are of sufficient duration to establish a reasonable
expectation of safety?
6. When notifications do not provide any information concerning
recommendations for length of product usage, should FDA assume chronic
use (i.e., daily) and evaluate safety on that basis?
7. What types of studies, if any, should be included in order to
establish a reasonable expectation of safety when the proposed daily
serving amount is comparable to or less than the safe historical daily
serving amount? What if the proposed daily serving amount is greater
than the safe historical daily serving amount? Please consider the
following types of studies:
a. Genetic toxicity 2-3 study battery (e.g., a bacterial gene
mutation assay, mammalian cell gene mutation assay, or deoxyribonucleic
acid (DNA) repair assay).
b. Short-term feeding studies (< 30-day) (rodent).
c. Subchronic feeding studies (90-day) (rodent, nonrodent).
d. Single dose human tolerance studies.
e. Repeat dose human safety studies (30- to 90-day duration).
f. Teratology studies (rodent, nonrodent).
g. Multigeneration reproduction studies (rodent, nonrodent).
h. Special studies (e.g., carcinogenicity, absorption, metabolism
and distribution and excretion).
i. Other studies.
8. How would the evaluation of such studies (previously listed) to
establish reasonable expectations of safety, differ under varying
duration and frequency of use scenarios such as the following:
a. The labeling of the dietary supplement containing an NDI
recommends or suggests daily chronic use, and the documented historical
duration and frequency of use support safe daily chronic use.
b. The labeling of the dietary supplement containing an NDI
recommends or suggests intermittent use, and the documented historical
duration and frequency of use support safe intermittent use.
c. The labeling of the dietary supplement containing an NDI
recommends or suggests intermittent use, and the documented historical
duration and frequency of use support safe daily chronic use.
d. The labeling of the dietary supplement containing an NDI
recommends or suggests daily chronic use, and the documented safe
historical duration and frequency of use support intermittent use.
e. There is no history of use data to establish safe intermittent
or chronic daily use.
9. What are appropriate and authoritative references for notifiers
to consider when developing protocols for collecting safety data in
support of NDI notifications?
10. What considerations should apply to FDA's evaluation of the
safety of a dietary supplement containing an NDI with respect to the
following special populations?
a. Women of child bearing potential.
b. Pregnant women.
c. Lactating women.
d. Children.
e. Geriatric adults.
f. Other.
E. The Role of Definitions in Evaluating NDIs
1. Are there terms that should be defined so that the NDI
notification program can be more transparent and consistent?
2. FDA seeks comment on how the following terms should be defined:
a. Amino acid.
b. Botanical.
c. Chemically altered.
d. Concentrate.
e. Constituent.
f. Extract.
g. Ingestion.
h. Metabolite.
i. Mineral.
j. Salts of dietary ingredients.
k. Tincture.
l. Vitamin.
F. Is There a Need for Guidance or Amendment of Current Requirements?
The information presented as follows, could assist FDA in
efficiently reviewing NDI notifications. Comment is invited on whether
FDA should consider the issuance of draft guidance or amendments to
current requirements to include the following:
1. Table of contents and ``continuous pagination'' in the
notification;
2. A discussion that clearly indicates why the notifier has
concluded that the ``new dietary ingredient'' is a dietary ingredient
under 21 U.S.C. 321(ff)(1);
3. Detailed requirement for chemical characterization of the NDI;
4. Requirement for composition/formulation of the dietary
supplement containing the NDI;
5. A tabular listing of studies, articles and other scientific
information provided in the notification to support a conclusion that
the NDI, when used under the conditions recommended or suggested in the
labeling of the notifier's dietary supplement, will reasonably be
expected to be safe, with an indication of whether the test material in
these studies is the same substance as is used in the notifier's
dietary supplement;
6. A safety document'' that clearly describes the scientific
reasoning used by the notifier to establish a reasonable expectation of
safety, based upon the data provided in the notification; and
7. Option for electronic submission of notifications.
VI. Transcripts
You may request a transcript of the meeting in writing from the
Freedom of Information Office (HFI-35), Food and Drug Administration,
rm. 12A-16, 5600 Fishers Lane, Rockville, MD 20857, approximately 15
working days after the meeting, at a cost of 10 cents per page. You may
also examine the transcript of the meeting at the Division of Dockets
Management between 9 a.m. and 4 p.m., Monday through Friday, as well as
on the FDA Internet at http://www.fda.gov.
VII. Reference
We have placed the following reference on display in the Division
of Dockets Management (see ADDRESSES). You may see it at that office
between 9 a.m. and 4 p.m., Monday through Friday.
1. M. McGuffin and A. L. Young, Premarket Notifications of New
Dietary Ingredients--A Ten-Year Review, Food and Drug Law Journal,
59(1): 2004.
VIII. Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments regarding this document.
Submit a single copy of electronic comments or two paper copies of any
mailed comments, except that
[[Page 61684]]
individuals may submit one paper copy. Comments are to be identified
with the docket number found in the brackets in the heading of this
document. Received comments may be seen in the Division of Dockets
Management between 9 a.m. and 4 p.m., Monday through Friday.
Dated: October 13, 2004.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 04-23439 Filed 10-15-04; 2:59 pm]
BILLING CODE 4160-01-S
