IA #54-13, 7/13/04, IMPORT ALERT #54-13, "DETENTION WITHOUT PHYSICAL
EXAMINATION OF DIETARY SUPPLEMENTS AND BULK DIETARY INGREDIENTS CONTAINING
EPHEDRINE ALKALOIDS FROM ALL COUNTRIES" ATTACHMENT A 7/13/04
TYPE OF ALERT: Detention Without Physical Examination (DWPE)
(Note: This import alert represents the Agency's current
guidance to FDA field personnel regarding the
manufacturer(s) and/or products(s) at issue. It does not
create or confer any rights for or on any person, and does
not operate to bind FDA or the public)
PRODUCT: Dietary Supplements Containing Ephedrine Alkaloids; Bulk
Dietary Ingredients Containing Ephedrine Alkaloids
PRODUCT
CODE: 54 F - - -
54 E - - -
54 Y - - -
PROBLEM: Adulteration
PAF: AAP
PAC FOR
COLLECTION: 21008
COUNTRY: All
MANUFACTURER/
SHIPPERS FEI: All
CHARGE: "The product is subject to refusal of admission pursuant to
Section 801(a)(3) in that it is a dietary supplement or a
dietary ingredient that appears to contain ephedrine
alkaloids, which presents an unreasonable risk of illness or
injury under the conditions of use recommended or suggested
in the labeling, or if no conditions of use are suggested in
the labeling, under ordinary conditions of use
[Adulteration, Section 402(f)(1)(A)]."
OASIS CHARGE
CODE: EPHEDALK
RECOMMENDING
OFFICE: CFSAN, Office of Compliance, Imports Branch (HFS-606)
REASON FOR
ALERT: Section 402(f)(1)(A) of the Act provides that a dietary
supplement or dietary ingredient is adulterated if it
presents a significant or unreasonable risk of illness or
injury under conditions of use recommended or suggested in
the labeling of the product, or if no conditions of use are
suggested in the labeling, under ordinary conditions of use.
We issued "Final Rule Declaring Dietary Supplements
Containing Ephedrine Alkaloids Adulterated Because They
Present an Unreasonable Risk" (69 FR 6787, Feb. 11, 2004)
based upon the well-known and scientifically established
pharmacology of ephedrine alkaloids, the peer-reviewed
scientific literature about the effects of ephedrine
alkaloids, published case reports of adverse events, and the
adverse events reported to us that have occurred in
individuals using products containing ephedrine alkaloids,
particularly dietary supplements. As set forth in the rule,
we have concluded that dietary supplements containing
ephedrine alkaloids pose a risk of serious adverse events,
including heart attack, stroke, and death, and that these
risks are unreasonable in light of any benefits that may
result from the use of these products under their labeled
conditions of use, or under ordinary conditions of use if
the labeling is silent. The final rule took effect on April
12, 2004.
GUIDANCE: Districts may detain without physical examination (DWPE) any
products labeled as dietary supplements that claim to
contain ephedrine alkaloids or one or more of the following
individual ephedrine alkaloids, if the labeling indicates
that the ephedrine alkaloid content derives from a botanical
source: ephedrine, pseudoephedrine, norephedrine,
methylephedrine, norpseudoephedrine, and
methylpseudoephedrine. Districts may DWPE dietary
ingredients intended for dietary supplement use that claim
to contain ephedrine alkaloids or one or more of the above
listed individual ephedrine alkaloids if the labeling
indicates that the ephedrine alkaloid content derives from a
botanical source. Districts may DWPE any products labeled
as dietary supplements if the labeling declares a plant
listed in Attachment A or an extract of such a plant.
Districts may DWPE dietary ingredients intended for dietary
supplement use if the labeling declares a plant listed in
Attachment A or an extract of such a plant.
A detained product or bulk ingredient may be released if a
firm is able to provide documentary evidence, such as
laboratory worksheets or certificates of analysis, that
provide assurance that it is free of ephedrine alkaloids.
Attachment A is a list of plants compiled by CFSAN that have
been shown to contain ephedrine alkaloids.
Questions related to dietary supplements may be directed to
CFSAN, Office of Compliance/Imports Branch (HFS-606) at
(301) 436-2413.
Questions related to drug issues may be directed to CDER,
Office of Compliance/Imports Branch (HFD-310), attention Ada
Irizarry at 301-827-8967.
Questions related to testing methodology for ephedrine
alkaloids may be directed to the Division of Field Science
(HFC-141), attention George Salem at 301-827-1031.
PRIORITIZATION
GUIDANCE: I
FOI:
KEYWORDS: ephedrine, dietary supplement, Ephedra spp.
PREPARED BY: Brian S. Landesberg, CFSAN, (301) 436-1622
Gary L. Coody, OE, 301-827-4142
George C. Ziobro, Ph.D., CFSAN, 301-436-1965
John E. Verbeten, DIOP, 301-594-3853
DATE LOADED
INTO FIARS: July 13, 2004
Attachment A 7/13/04
Plants that have been shown to contain ephedrine alkaloids
Scientific names and synonyms Common names
Ephedra distachya L. Chinese ephedra
efedra [Spanish]
Subordinate taxa ephedra
Ephedra distachya subsp. distachya jointfir
Ephedra distachya L. subsp. helvetica (C. A. ma huang (stem)
Mey.) Asch. & Graebn. Meertr„ubchen [German]
Ephedra distachya L. subsp. raisin de mer [French]
monostachya (L.) Riedl
sea-grape
Synonym: shuang sui ma huang
Ephedra helvetica C. A. Mey. uva marina [Italian]
Xinjiang ephedra
Ephedra equisetina Bunge Chinese ephedra
Synonym: Chinese jointfir
Ephedra shennungiana Tang. ephedra
Ephedra nebrodensis Boiss. Ephedrae Herba
ma huang,
mahwang [Korean]
Mongolian ephedra
mu zei ma huang
[chvojnik
chvoscovyj] [Russian]
Ephedra intermedia Schrenk ex C.A. Mey. Chinese ephedra
Subordinate taxa: ephedra
Ephedra intermedia Schrenk & C. A. Mey. Ephedrae Herba
var. intermedia ma huang (stem)
Ephedra intermedia Schrenk & C. A. Mey. ma huang gen (root & rhizome)
var. tibetica Stapf oman [Kashmir]
Synonyms: zhong ma huang
Ephedra ferganensis V.V. Nikitin
Ephedra glauca Regel
Ephedra intermedia var. glauca Stapf
Ephedra intermedia var. persica Stapf
Ephedra intermedia var. schrenkii Stapf
Ephedra intermedia var. tibetica Stapf
Ephedra microsperma V.V. Nikitin
Ephedra persica (Stapf) V.V. Nikitin
Ephedra tesquorum V.V. Nikitin
Ephedra tibetica (Stapf) V.V. Nikitin
Ephedra valida V.V. Nikitin
Ephedra sinica Stapf cao ma huang
Synonym: Chinese ephedra
Ephedra ma-huang Liu Chinese joint fir
Chinesisches Meertr„ubel
[German]
ephedra
Ephedrae Herba
ma huang
ma huang gen (root & rhizome)
mahwang [Korean]
mao [Japanese]
There are orthographic variants of some of the common names by the addition of
a dash or a space, e.g. jointfir, joint fir, joint-fir, mahuang, ma-huang, ma
huang.
Caveney, S., D.A.Charlet, H. Freitag, M. Maier-Stolte, and A.N. Starratt
(2001) New Observations on the Secondary Chemistry of World Ephedra
(Ephedraceae), American Journal of Botany 88:1199-1208.
He, Y.K., T.G. Lu, and C.S. Sun (1995) Biotechnology in Agriculture and
Forestry 33:361-376
Jian-fang Cui, Tong-hui Zhou, Jian-sheng Zhang, and Zhi-cen Lou (1991)
Analysis of Alkaloids in Chinese Ephedra Species by Gas Chromatographic
Methods, Phytochemical Analysis 2:116-119.
Mamoru Noguchi, Katsuko Hosoda, and Hideyo Suzuki (1987) Normal Phase High-
Performance Liquid Chromatography of Ephedra Alkaloids, Yakugaku Zasshi
107:372-376
Smith, T.A. (1977) Phenethylamine and Related Compounds in Plants,
Phytochemistry 16:9-18.
Ying-Mei Liu, shuenn-Jyi Sheu, Shiow-Hua Chiou, Hsein-Chang Chang, and Yuh-Pan
Chen (1993) A Comparative Study on Commercial Samples of Ephedra Herba, Planta
Medica 59:376-378.
Zeng Quan, Liu Chengji, Zheng Lizhen, and Xiao Lixin (1990) Separation and
Determination of Diastereomers l-Ephedrin and d-Pseudoephedrine in Ephedra
Herba and its Process Products, J of China Pharmaceutical University 21:236-
238.
Zhang Jian (Zhang Jian-sheng), Tian Zhen, and Lou Zhi-cen (1988) Simultaneous
Determination of Six Alkaloids in Ephedra Herba by High Performance Liquid
Chromatography, Plant Medica 54:69-70.
Zhang, J., Tian, Z., and Lou, Z (1989) Quality evaluation of twelve species of
Chinese Ephedra (Ma Huang), Zhongguo Yaoxue Zazhi (Acta Pharmaceutica Sinica)
24:865-871.