Import Alert 54-13

(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 # 54-13
Published Date: 08/13/2021
Type: DWPE

Import Alert Name:

"Detention Without Physical Examination of Dietary Supplements And Bulk Dietary Ingredients Containing Ephedrine Alkaloids From All Countries"

Reason for Alert:

NOTE: Revision to this Import Alert dated 8/13/2021 updates the language of the "Guidance" section, agency contacts and PAF section. Changes are noted and bracketed by three asterisks (***).

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:

*** Divisions *** 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.

*** 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 oraoismdssimpcomplsysbr@fda.hhs.gov.

Questions related to testing methodology for ephedrine alkaloids may be directed to the Office of Regulatory Science at oraorsprivatelabimportalerts@fda.hhs.gov.

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
efedra [Spanish]
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
sea-grape
Synonym: shuang sui ma huang
Ephedra helvetica C. A. Mey. uva marina [Italian]
Xinjiang ephedra
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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]

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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

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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]
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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.

Product Description:

Dietary Supplements Containing Ephedrine Alkaloids; Bulk Dietary Ingredients Containing Ephedrine Alkaloids

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

Countries

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 Botanical
    Notes: 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