(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).
Import Alert Name:
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.
*** Divisions *** 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. *** Divisions *** may DWPE any products labeled as dietary supplements if the labeling declares a plant listed in this Guidance or an extract of such a plant. *** Divisions *** may DWPE dietary ingredients intended for dietary supplement use if the labeling declares a plant listed in this Guidance 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.
*** Questions or issues involving import operations should be addressed to ORA/DIO at 301 796-0356 or FDAImportsInquiry@fda.hhs.gov.
Questions or issues involving OASIS or PREDICT screening should be addressed to ORA/DSS/Import Systems Branch at email@example.com.
Questions related to testing methodology for ephedrine alkaloids may be directed to the Office of Regulatory Science at firstname.lastname@example.org.
Questions related to dietary supplements referenced in this Alert may be directed to CFSAN, Office of Compliance/Division Of Enforcement/Dietary Supplement And Labeling Assessment Branch at CFSANEnforcement@fda.hhs.gov
Questions or issues involving compliance of imported drug products should be addressed to the CDER Imports Compliance Branch at CDERImports@fda.hhs.gov. ***
This Guidance is a list of plants compiled by CFSAN that have been shown to contain ephedrine alkaloids.
Scientific names and synonyms Common names
Ephedra distachya L. Chinese ephedra
Subordinate taxa ephedra
Ephedra distachya subsp. distachya jointfir
Ephedra distachya L. subsp. helvetica ma huang (stem)
(C.A.Mey.) Asch. & Graebn. Meertrubchen [German]
Ephedra distachya L. subsp. raisin de mer [French]
monostachya (L.) Riedl
Synonym: shuang sui ma huang
Ephedra helvetica C. A. Mey. uva marina [Italian]
Ephedra equisetina Bunge Chinese ephedra
Synonym: Chinese jointfir
Ephedra shennungiana Tang. ephedra
Ephedra nebrodensis Boiss. Ephedrae Herba
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
ma huang gen (root & rhizome)
There are orthographic variants of some of the common names by the addition ofa 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.
OASIS charge code - EPHEDALK
MULTIPLE COUNTRIES (PODS ONLY)
(54 F - - --) Herbal & Botanicals(other than teas)Notes: Dietary Supplements Containing Ephedrine Alkaloids; Bulk Dietary Ingredients Containing Ephedrine Alkaloids
(54 E - - --) Herbal and BotanicalNotes: Dietary Supplements Containing Ephedrine Alkaloids; Bulk Dietary Ingredients Containing Ephedrine Alkaloids
(54 Y - - --) Vit/Min/Prot/Unconv Diet Spec N.E.C.Notes: Dietary Supplements Containing Ephedrine Alkaloids; Bulk Dietary Ingredients Containing Ephedrine Alkaloids