Memorandum

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DEPARTMENT OF HEALTH & FHJMAN SERVICES
Public Health Service
Food and Drug Administration
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DOCKETS
Date:
Memorandum
TRANSMITTAL
MEMO
Ga 2
From:
Division of Dietary Supplement Programs, Of&e of Nutritional Products,
Labeling and Dietary Supplements,HFS-8 10
Subject:
75Day Premarket Notification of New Dietary Ingredients
To:
Dockets Management Branch, HFA-305
Subject of the Notification:
Trifolium pretenseL.
Firm: Hounghwa Global, Inc.
Date Received by FDA:
12/2/02; Amended l/21/03
90-Day Date: 412l/O3
In accordancewith the requirements of section 413(a) of the Federal Food, Drug, and
Cosmetic Act, the attached 75day premarket notification and related correspondencefor the
aforementioned substanceshould be placed on public display in docket number 95S-0316 as
soon possible since it is past the go-day date. Thank you for your assistance.
DEPARTMENT
OF HEALTH AND HUMAN SERVICES
Public Health Service
Food and Drug Administration
College Park, MD 20740
APfl
-
2 2003
Mr. Zhijian Zhang
President
Hounghwa Global, Inc.
705 Canterbury Road
San Marina, California 91108
Dear Mr. Zhang:
This is in responseto your letter to the Food and Drug Administration (FDA) dated
November 20,2002, making a submission for a new dietary ingredient pursuant to
21 U.S.C. 35Ob(a)(2) (section 413 of the Federal Food, Drug, and Cosmetic Act (the
Act)) and 21 CFR 190.6). On January 21,2003, you submitted additional information to
FDA. Your notification notified FDA of your intent to market Golden Phoenix,’a
product containing an extract fi-om Trz$Xum prutense L., a substancethat you assertis a
new dietary ingredient.
The notification contains conflicting information concerning the conditions of use.
On August 20,2002, you indicated that Trzjbliumpratense L. extract in a capsule would
“be suggestedto be taken three times day, 2 capsulesin the morning, 2 capsulesin the
afternoon, and 4 capsules at bedtime.” On November 20,2002, this information was not
amended. On January 21,2003, a statementwas provided which indicated that the “new
dietary ingredient Trzjblium pratense L.” contains 1 ug/capsule of ethyl-phenol, and
recommended “one capsule each for morning and noontime and two capsulesbefore
sleep” or “two capsuleseach morning and noontime before meals and 4 capsulesbefore
sleep.”
Under 21 U.S.C. 35Ob(a)(2),the manufacturer or distributor of a dietary supplement that
contains a new dietary ingredient that has 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 must
submit to FDA, at least 75 days before the dietary ingredient is introduced or delivered
for introduction into interstate commerce, information that is the basis on which the
manufacturer or distributor has concluded that a dietary supplement containing such new
dietary ingredient will reasonably be expected to be safe. FDA reviews this information
to determine whether it provides an adequatebasis for such a conclusion. Under section
35Ob(a)(2),there must be a history of use or other evidence of safety establishing that
the new dietary ingredient, when used under the conditions recommended or suggested
in the labeling of the dietary supplement, will reasonably be expected to be safe. If this
requirement is not met, the dietary supplement is deemed to be adulterated under 21
U.S.C. 342(f)(l)(B) because there is inadequate information to provide reasonable
assurancethat the new dietary ingredient does not present a significant or unreasonable
risk of illness or injury.
Page 2 - Mr. Zhijian Zhang
FDA has carefully consideredthe information in your submission. In the human study
and the other information submitted, it was unclear as to whether the test substances
used in the studies are the same as that of the ingredient in your notification. Moreover,
your submission provides no information that the test substancesused in the referenced
studies are qualitatively or quantitatively similar to your ingredient or how these studies
are relevant to evaluating the safe use of your ingredient under the recommended
conditions of use.
In addition, the one page of clinical information provided does not contain adequate
information on the test article, any information describing elementsof the clinical study
design, or any specific clinical data. Therefore, no safety conclusions can be drawn
from the information presented. You also provided a one paragraph statement
describing a Golden Phoenix product sold overseas,and a marketing statement of
satisfaction. This does not provide an adequatebasis for the history of use or other
evidence of safety. Therefore, your product may be adulterated under 21 U.S.C.
342(f)(l)(B) as a dietary supplementthat contains a new dietary ingredient for which
there is inadequate information to provide reasonableassurancethat such ingredient
does not present a significant or unreasonablerisk of illness or injury. Introduction of
such a product into interstate commerce is prohibited under 21 U.S.C. 331(a) and (v).
We have enclosed a copy of section 21 CFR 190.6 for your future reference. You also
may wish to review FDA’s Web site at httn://www.cfsan.fda.gov/-dmslds-ingrd.html for
additional details on new dietary ingredient notification requirements.
Your submission will be kept confidential for 90 days from the date of receipt, and after
April 2 1,2003, your submission will be placed on public display at Dockets
Management Branch (Docket No. 953-03 16). Commercial and confidential information
in the notification will not be made available to the public.
Pleasecontact Victoria Lutwak at (301) 436-1775 if you have questions concerning this
matter.
Sincerely yours,
-L--L
Suss Walker, M.D.
Acting Director
Division of Dietary Supplement Programs
Office of Nutritional Products, Labeling
and Dietary Supplements
Center for Food Safety
and Applied Nutrition
Enclosure
WAIS Document Retrieval
Page 1 of 2
[Code of Federal Regulations]
[Title
21, Volume 31
[Revised as of April
1, 20011
From the U.S. Government Printing
[CITE: ZlcE'R190.61
Office
via
GPO Access
[Page 569-5701
TITLE 21--FOOD AND DRUGS
CHAPTER I--FOOD
PART 190--DIETARY
AND DRUG ADMINISTRATION, DEPARTMENTOF HEALTH AND HUMAN
SERVICES (CONTINUED)
SUPPLEMENTS--Table
Subpart
Sec.
190.6
B--New
Requirement
for
Dietary
premarket
of Contents
Ingredient
Notification
notification.
(a) At least
75 days before introducing
or delivering
for
introduction
into interstate
commerce a dietary
supplement that contains
a new dietary
ingredient
that has 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,
the manufacturer
or distributor
of that supplement,
or of the new dietary
ingredient,
shall
submit to the Office
of
Nutritional
Products,
Labeling
and Dietary
Supplements
(HFS-820),
Center
for Food Safety and Applied
Nutrition,
Food and Drug Administration,
5100
Paint Branch Parkway, College
Park, MD 20740, information
including
any
citation
to published
articles
that 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. An original
and two copies of this notification
shall
be submitted.
(b) The notification
required
by paragraph
(a) of this section
shall
include:
(1) The name and complete address of the manufacturer
or distributor
of the dietary
supplement
that contains
a new dietary
ingredient,
or of
the new dietary
ingredient;
(2) The name of the new dietary
ingredient
that is the subject
of
including
the Latin binomial
name (including
the premarket
notification,
the author)
of any herb or other botanical;
(3) A description
of the dietary
supplement
or dietary
supplements
that contain
the new dietary
ingredient
including:
(i) The level
of the new dietary
ingredient
in the dietary
supplement;
and
(ii)
The conditions
of use recommended or suggested in the labeling
or if no conditions
of use are recommended or
of the dietary
supplement,
suggested in the labeling
of the dietary
supplement,
the ordinary
conditions
of use of the supplement;
(4) The history
of use or other evidence
of safety
establishing
that
when used under the conditions
recommended or
the dietary
ingredient,
suggested in the labeling
of the dietary
supplement,
will
reasonably
be
any citation
to published
articles
or
expected to be safe, including
other evidence that is the basis on which the distributor
or
manufacturer
of the dietary
supplement
that contains
the new dietary
ingredient
has concluded
that the new dietary
supplement will
reasonably
be expected to be safe. Any reference
to published
information
offered
in support of the notification
shall be
[[Page
57011
L
W A IS Document Retrieval
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accompanied by reprints
or photostatic
copies of such references.
If any
part of the material
submitted
is in a foreign
language, it shall be
accompanied by an accurate and complete English translation;
and
(5) The signature
of the person designated
by the manufacturer
or
distributor
of the dietary
supplement that contains
a new dietary
ingredient.
(c) FDA will
acknowledge its receipt
of a notification
m a d e under
section
413 of the Federal Food, Drug, and Cosmetic Act (the act) and
will
notify
the submitter
of the date of receipt
of such a notification.
The date that the agency receives
the notification
submitted
under
paragraph
(a) of this section
is the filing
date for the notification.
For 75 days after
the filing
date, the manufacturer
or distributor
of a
dietary
supplement that contains
a new dietary
ingredient
shall not
or deliver
for introduction,
into interstate
commerce the
introduce,
dietary
supplement that contains
the new dietary
ingredient.
(d) If the manufacturer
or distributor
of a dietary
supplement that
or of the new dietary
ingredient,
contains
a new dietary
ingredient,
provides
additional
information
in support of the new dietary
ingredient
the agency will
review all submissions
pertaining
to that
notification,
including
responses m a d e to inquiries
from the agency, to
notification,
determine
whether they are substantive
and whether they require
that the
If the agency determines
that the new submission
75-day period be reset.
assign a new filing
date. FDA will
is a substantive
amendment, FDA will
acknowledge receipt
of the additional
information
and, when applicable,
notify
the manufacturer
of the new filing
date, which is the date of
receipt
by FDA of the information
that constitutes
the substantive
amendment.
(e) FDA will
not disclose
the existence
of, or the information
ingredient
notification
for 90 days after
contained
in, the new dietary
the filing
date of the notification.
After
the 90th day, all information
in the notification
will
be placed on public
display,
except for any
information
that is trade secret or otherwise
confidential
commercial
information.
(f) Failure
of the agency to respond to a notification
does not
constitute
a finding
by the agency that the new dietary
ingredient
or
the dietary
supplement that contains
the new dietary
ingredient
is safe
or is not adulterated
under section
402 of the act.
162 FR 49891,
Sept.
23,
1997,
as amended at
66 FR 17359,
Mar.
30,
20011
Hounghwa Global, Inc.
705 Canterbury Road
San Marino, CA 91108
November 20,2002
Felicia Satchel1
Director
Division of Standards
and Labeling Regulations
Office ofNutritional Products, Labeling
and Dietary Supplements
Center for Food Safety
and Applied Nutrition
Docket No. 95S-03 16
RF2
Dear MS Satchel&
This is in responseto your letter dated Nov 6,2002. We would like to clarify the
following item:
1.
2.
Trifolium pretense L. has been used in the world for the last few hundred
years. Pleasesee the attached for the scientific reference. All of these
referencescan prove that the product is safe.
Attached is a copy of “Traditional Chinese Medicine Dictionary” edited by
Jiangsu Academy of New Medical Sciencesand published by Shanghai
Science and Technology Press in 1975. This shows that TrifoEiumpretense L
is collected as poisonless.
My contact information is as follows:
Tel: 6267962988
Fax:626 395 93 19
e-mail: [email protected]
Thank you for your attention. If you have any questions or concerns,please feel ffee to
contact me.
Sincerely,
Zhijian Zhang
Attachments
1. He Xiao-guo, Lin Lang-ze, Analysis of flavonoids from red clover by liquid
chromatography-electrospraymass spectrometry, Journal of Chromatogr A,
1996,755 127-132
2. David R. Biggs and Geofiey A. Lane, Identification of Isoflavones Caiycosin and
Pseudobaptigenin in Trifolium Pratense,Phytochemktry, 1978.17: 1683 - 1684
3. Ingram D. Sander IS. Kolybaba, M. and Lopez, D. Case control study of phytooestogensand breast cancer. Lancet, 1997,350: 990-994.
4. Trifolium PratenseL. Traditional Chinese Medicine Dictionary Volume 1:
page 1012 - 1013
Hounghwa Global, Inc.
705 Canterbury Road
San Marino, CA 91108
January 2 1,2003
Catalina Hockersmith
Food & Drug Administration
Center For Food Safety & Applied Nutrition
Office of Nutritional Products, Labeling
& Dietary Supplements
5100 Paint Branch Parkway
College Park, MD 20740
Re:
Docket No. 958-03 16
Dear Ms Hockersmith
This is in responseto your fax dated January 8,2003. Attached please find the document
you needed.
Pleasefeel free to contact me at 626 796 2988 if you have any questions. Thank you for
your concern,
Sincerely,
Zhijian Zhang
President
GuANG,ZMRJ
#iAl
LIAIWOMPANY
UNiT C,D, 12/F., TAI FU CENTRE,
TAI HONG PLAZA, 111 TAI KANG
ROAD, GUANGZHOU, CHINA
TEL: 83367?52,83367229
FAX: 83334626
POSTCODE: 510115
Nutritional
Products,
labeling
and Dietary
sup,plements
(HFS-8201,
Center for Food Saf.ety Andy applied
Nutrition,
Food and Drug
Administration
5100 Paint branch Parkway,
College
Park, MD20740.
Premarket
Notification
Dear Sir,
Please kind,ly
refer
to the following
information
regarding
your
requirement
for premarket
notification:
The name and comp'lete address of the distributor
of the
1.
dietary
supplement
that contains
a Ned .dietary
ingredient,
or of th‘e new dietary
ingredient
is'GU=G
THOU I&I LIAN
COMPANY.
2.
3.
a.
b.
4.
_
The name of the new dietary
ingredient
is Trifolium
pretense
L, which is Leguminssae
belonging
to Trifolim
L.
A description
of the dietary
supplement
or dietary
supplements
that contain
the new dietary
ingredient
including:
The level
of ethyl-phenol
in the dietary
supplement
is
1 ug/capsule.
The ordinary
conditions
of use of the supplement
recommended:
one' capsules
each for 'morning and noontime
before
meals and 2 capsules
before
sleep.
People has
symthoms of menopause are recommended:
2 capsules
each
for morning and noontime
before
meals and 4 capsules
before
sleep.
Please kindly
refer
to the attachment
for the history
of
use and the evidence
of safety
establishing
that the
dietary
ingredient,
when used under the conditions
recommended or suggested
in the labeling
of the dietary
will
reasonably
be expected
to be safe.
supplement,
QlE!J'N%L@E 111 38
Z$WJ%FBBS~IU 12IC.W
g;z : 83367252,83367229
*wa
GUANG ZHOU HAI LIAN COMPANY
: 83334526
ROAD, GUANGZHOU. CHINA
TEL: 83367252, 63367229
FAX: 83334526
POSTCODE: 510115
labeling
and Dietary
supplements
Nutritional
Products,
Center for Food Safety and applied
Nutrition,
Food and
Administration
5100 Paint branch Parkway, College
Park, MD20740.
(HFS-820),
Drug
Premarket
Notification
Dear Sir,
Please kindly
refer
to the following
information
regarding
your
requirement
for premarket
notification:
1.
The name and complete
address of the distributor
of the
dietary
supplement
that contains
a new dietary
ingredient,
or of the new dietary
ingredient
is GUANG ZHOU HA1 LIAN
COMPANY.
2.
3.
a.
b.
4.
The name of the new dietary
ingredient
is Trifolium
belonging
to Trifolim
L.
pretense
L, which is Leguminosae
A description
of the dietary
supplement
or dietary
supplements
that contain
the new dietary
ingredient
including:
The level
of ethyl-phenol
in the dietary
supplement
is
1 ug/capsule.
The ordinary
conditions
of use of the supplement
one capsules
each for morning and noontime
recommended:
People has
before
meals and 2 capsules
before
sleep.
2 capsules
each
symthoms of menopause are recommended:
for morning and noontime
before
meals and 4 capsules
before
sleep.
Please kindly
refer
to the attachment
for the history
of
use and the evidence
of safety
establishing
that the
when used under the conditions
dietary
ingredient,
recommended or suggested
in the labeling
of the dietary
will
reasonably
be expected
to be safe.
supplement,
UNJT C. D, 12/F., TAI FU CENTRE,
TAI HONG PLAZA, 111 TAI KANG
ROAD,GUANGZHOU,CHtNA
JANG ZHOU
GUANG
ZHOU HAI
HAI LIAN
LIAN COIWPANY
CCBfWPANY
Nutritional
Products,
Center ~for Food Safety
Administration
5100 Paint
branch
History,of
labeling
and Dietary
supplements
(HFS-820),
and" applied
Nutrition/Food
and Drug
Parkway,
use
TEL: 83367252, 83367229
FAX: 83334526
POSTCODE: 510115
and
College
Park,
evidence
of
MD20740.
safety
and
satisfact.ion
We have sold more than '50,000 cases of Co,lden Ph0en.i.x Brand
dietary
supplements
in the past five years.
Every case of this
product
can provide
the long-term
usages of 10 people.
According
to a market poll
conducted
with 1,300 users,
the satis,faction
level
to its anti-aging
effects
for females has reached 98.5%.
So far no
side effect
has been detected.
We therefore
have full
confidence
to continue
the sales of Golden Phoenix Brand product
to further
develope
the market.
QOWbNW%BB
12KG
DrE:
;ft;8 : 83367252,83367229
s
fibI
%f
f@
G
a
GUANG ZHBU HAI LIAN COMPANY
~i&FG$ : 83334526
fi!mIdE
UNIT C. D. 12/F., TAI FU CENTRE,
TAI HONG PLAZA, 111 TAI KANG
ROAD GUANGZHOU CHINA
TEL: 8’3367252. 6336;229
FAX. 83334526
POSTCODE: 510115
111 %
~@~$iwl%~Ce~B
: 510115
Nutritional
Products,
labeling
and Dietary
Center for Food Safety and applied
Nutrition,
Administration
5100 Paint
branch
History
Parkway,
of
use
and
College
Park,
evidence
of
supplements
(HFS-820),
Food and Drug
MD20740.
safety
and
satisfaction
We have sold more than 50,000 cases of Golden Phoenix Brand
dietary
supplements
in the past five years.
Every case of this
product
can provide
the long-term
usages of 10 people.
According
to a market poll conducted
with 1,300 users,
the satisfaction
level
to its anti-aging
effects
for females has reached 98.5%.
So far no
side effect
has been detected.
We therefore
have full
confidence
to continue
the sales of Golden Phoenix Brand product
to further
develope
the market.
705 Canterbury Road
San Marino, CA 91108
November 20,2002
Felicia Satchel1
Director
Division of Standards
and Labeling Regulations
Office of Nutritional Products, Labeling
and Dietary Supplements
Center for Food Safety
and Applied Nutrition
REl:
Docket No. 95S-0316
Dear MS Satchell,
This is in responseto your letter dated Nov 62002. We would like to clarify the
following item:
1.
2.
Trifolium pretenseL. has been used in the world for the last few hundred
years. Pleaseseethe attached for the scientific reference. All of these
referencescan prove that the product is safe.
Attached is a copy of “Traditional Chinese Medicine Dictionary” edited by
Jiangsu Academy of New Medical Sciencesand published by Shanghai
Scienceand Technology Pressin 1975. This shows that Trifoliumpretense L
is collected as poisonless.
My contact information is as follows:
Tel: 626 796 2988
Fax:626 395 93 19
e-mail: [email protected]
Thank you for your attention. If you have any questions or concerns,please feel free to
contact me.
Sincerely,
Zhijian Zhang
This document contains copyrighted material. The documents may be
viewed to:
Dockets Management Branch
Food and Drug Administration
5630 Fishers Lane, Room 1061
Rockville, MD 20852