| Public Health Service Food and Drug Administration |
| Los Angeles District 19701 Fairchild Irvine, California 92612 Telephone (949) 608-2900 Fax (949) 608-4415 |
Department of Health and Human Services
June 03, 2011 W/L: 45-11
CERTIFIED MAIL
RETURN RECEIPT REQUESTED
William J. Hemelt, President and CEO
Matrixx Initiatives, Inc.
8515 East Anderson Drive
Scottsdale, AZ 85255
WARNING LETTER
Dear Mr. Hemelt:
This letter is to advise you that the United States Food and Drug Administration (FDA or Agency) has reviewed your firm’s website at www.zicam.com. FDA reviewed your firm’s labeling and marketing information for the products “Zicam Cold Remedy RapidMelts with Vitamin C & Echinacea” and “Zicam Cold Remedy RapidMelts with Vitamin C” (collectively referred to as "RapidMelts Vitamin C products"). Based on labeling for these products and our review of your website at www.zicam.com, RapidMelts Vitamin C products are unapproved new drugs in violation of sections 301(d) and 505(a) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. §§ 331(d) and 355(a)). The RapidMelts Vitamin C products are also misbranded under section 502 of the Act (21 U.S.C. § 352).
“Get over your cold faster”
“Reduces duration and severity of a cold”
“[R]educes severity of cold symptoms:
- sore throat
- stuffy nose
- sneezing
- coughing
- congestion”
Your RapidMelts with Vitamin C product is prominently labeled as containing zincum aceticum, zincum gluconicum, and vitamin C. Your RapidMelts with Vitamin C & Echinacea product is prominently labeled as containing zincum aceticum, zincum gluconicum, vitamin C, and echinacea. The front panel of the carton prominently states “RapidMelts with Vitamin C” and “RapidMelts with Vitamin C & Echinacea,” along with and in close proximity to the product line name (“Cold Remedy”) and the statements “Get over your cold faster” and “Reduces the duration of a cold.”
In addition to the above statements regarding the intended uses of your products, your internet website at www.zicam.com includes similar statements and other statements related to these products’ intended uses, including:
“Extra boost of Vitamin C in every RapidMelt.”
“Extra boost of Vitamin C and Echinacea in every RapidMelt.”
“Reduces the duration of cold symptoms when taken at the first sign of a cold.”
“Now, I always keep Zicam with me and know I’ve dodged another cold or two since. Zicam is a lot easier to take and carry than my individual zinc, Echinacea & vitamin C tablets.”
A. Unapproved New Drugs [§§ 301(d) and 505(a)]
Based on these statements in the labeling and on your website, the RapidMelts Vitamin C products are drugs under section 201(g)(1)(B) of the Act (21 U.S.C. § 321(g)(1)(B)), because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man, and under section 201(g)(1)(C) of the Act (21 U.S.C. § 321(g)(1)(C)), because they are intended to affect the structure or function of the body of man.
The intended use to reduce the severity and duration of the common cold and the duration of cold symptoms, renders these products drugs. Although vitamin C and echinacea could be marketed separately as dietary supplements, in this case they are combined with other drug ingredients. FDA’s position on the regulatory status of over-the-counter (OTC) drug products that combine drug ingredients with dietary ingredients in a single dosage form for drug indications has been described in five previously issued Warning Letters.[1] Where, as here, drug and dietary ingredients are combined in a single dosage form, the combination becomes a “drug” under section 201(g) of the Act (21 U.S.C. § 321(g)). There is no provision in the Act, as amended by the Nutrition Labeling and Education Act of 1990 (NLEA) or by the Dietary Supplement Health and Education Act of 1994 (DSHEA), that exempts any part of the RapidMelts Vitamin C products from the scope of 201(g) of the Act. In addition, under section 201(g)(1)(D) of the Act (21 U.S.C. § 321(g)(1)(D)), the vitamin C and echinacea used in combination with the other active ingredients listed in the “Drug Facts” panels for these products are also drugs because the vitamin C and echinacea are components of these finished drug products.
Notwithstanding the fact that the labeling for these products and the related statements about them on your website identify the vitamin C and echinacea as inactive ingredients, the vitamin C and echinacea in the RapidMelts Vitamin C products are “active ingredients” under 21 C.F.R. § 201.66(b)(2) because, based on representations on your website (e.g., “Zicam Cold Remedy RapidMelts with Vitamin C & Echinacea . . . [r]educes the duration of cold symptoms when taken at the first sign of a cold.”) and product labeling (e.g., the prominent identification of the products as being “RapidMelts with Vitamin C” and “RapidMelts with Vitamin C & Echinacea,” along with the repeated references to “Cold Remedy,” “Get over your cold faster,” and “Reduces the duration of a cold”), the vitamin C and the echinacea are intended to furnish pharmacological activity or other direct effect in reducing the duration and severity of cold symptoms.
The use of vitamin C for the treatment or prevention of the “common cold” was specifically evaluated under FDA’s OTC Drug Review[2] and was not included in the final monograph for Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug Products for Over-the-Counter Use (final monograph for OTC Cold Cough Drug Products) (see 21 C.F.R. part 341) because the evidence was insufficient to classify vitamin C as safe and effective for such OTC use.[3] In the 1976 Advance Notice of Proposed Rulemaking for OTC Cold-Cough Drug Products, FDA published the recommendations of the Advisory Review Panel on Over-the-Counter Cough, Cold, Allergy, Bronchodilator and Antiasthmatic Drug Products. In those recommendations, the Advisory Review Panel stated the following with respect to the use of vitamin C for treatment or prevention of the "common cold":
The Panel is cognizant of the popular use of vitamin C (ascorbic acid) for the prevention or treatment of the "common cold." The Panel has reviewed the available data for the ingredient as a single entity and finds that the data are insufficient to permit final classification as safe and effective for OTC use in the prevention or treatment of the cold.
41 FR 38312 at 38324 (Sept. 9, 1976)
Because vitamin C is not generally recognized as safe and effective for reducing the duration and severity of the common cold, any drug product intended for such use that includes vitamin C as an active ingredient, alone or in combination with other active ingredients, is also not generally recognized as safe and effective. Accordingly, the RapidMelts Vitamin C products are new drugs under section 201(p) the Act (21 U.S.C. § 321(p)) because they are not generally recognized as safe and effective for their intended uses.
Under sections 301(d) and 505(a) of the Act (21 U.S.C. §§ 331(d) and 355(a)), a new drug may not be introduced or delivered for introduction into interstate commerce unless an application approved by FDA under either section 505(b) or (j) of the Act (21 U.S.C. § 355(b) or (j)), is in effect for the product. Based upon our information, there are no FDA-approved applications on file for either one of the RapidMelts Vitamin C products. The marketing of these products without an approved application constitutes a violation of these provisions of the Act.
We recognize that the labeling for the RapidMelts Vitamin C products identifies them as homeopathic drug products. The definition of “drug” in section 201(g)(1) of the Act (21 U.S.C. § 321(g)(1)) includes articles recognized in the official Homeopathic Pharmacopeia of the United States (HPUS), or any supplement to it. Homeopathic drugs are subject to the same regulatory requirements as other drugs; nothing in the Act exempts homeopathic drugs from any of the requirements related to adulteration, labeling, misbranding, or approval. We acknowledge that many homeopathic drugs are manufactured and distributed without FDA approval under enforcement policies set out in the Agency’s Compliance Policy Guide entitled, “Conditions Under Which Homeopathic Drugs May be Marketed (CPG 7132.15)” (the CPG). As its title suggests, the CPG identifies specific conditions under which homeopathic drugs may ordinarily be marketed; thus, in order to fall under the enforcement policies set forth in the CPG, a homeopathic drug product must meet the conditions set forth in the CPG. The CPG defines a homeopathic drug as: “Any drug labeled as being homeopathic which is listed in the Homeopathic Pharmacopeia of the United States (HPUS), an addendum to it, or its supplements.” The CPG additionally states that “Drug products containing homeopathic ingredients in combination with non-homeopathic active ingredients are not homeopathic drug products.”
Although zincum aceticum, zincum gluconicum, and echinacea are established homeopathic active ingredients included in the HPUS, vitamin C (ascorbic acid) is not a recognized active ingredient in the HPUS or any of the addenda or supplements. Furthermore, to our knowledge, vitamin C (ascorbic acid) is not listed in any recognized Materia Medica containing information on the preparation of homeopathic medicines.
Therefore, vitamin C (ascorbic acid) is not considered a homeopathic ingredient, and the RapidMelts Vitamin C products are not considered homeopathic drug products under the CPG because they contain homeopathic ingredients in combination with non-homeopathic active ingredients. Accordingly, the policies set forth in the CPG for the marketing of homeopathic drug products do not apply to these products.
B. Misbranding – Failure to Identify Active Drug Ingredients [§§ 502(e) and 301(a)]
The RapidMelts Vitamin C products are misbranded under section 502(e)(1)(A)(ii) of the Act (21 U.S.C. § 352(e)(1)(A)(ii)), because their respective labels fail to identify vitamin C (ascorbic acid) as an active drug ingredient, and also because the labels fail to bear a statement of the quantity and amount of vitamin C in the product. See 21 CFR §§ 201.10 and 201.66(c)(2).
“Zicam Cold Remedy RapidMelts with Vitamin C & Echinacea” is also misbranded under section 502(e)(1)(A)(ii) of the Act (21 U.S.C. §352(e)(1)(A)(ii)), because the label fails to identify echinacea as an active drug ingredient and also because the label fails to bear a statement of the quantity and amount of echinacea in the product. See 21 CFR §§ 201.10 and 201.66(c)(2).
Your marketing of these misbranded products violates section 301(a) of the Act (21 U.S.C. § 331(a)).
C. Misbranding – False or Misleading Labeling [§§ 502(a) and 301(a)]
Section 502(a) of the Act (21 U.S.C. 352(a)) states that a drug is misbranded if its labeling is false or misleading in any particular. The RapidMelts Vitamin C products are labeled as homeopathic, but for the reasons stated above, these products are not homeopathic. Your marketing of these misbranded products violates section 301(a) of the Act (21 U.S.C. §§ 331(a)).
In addition to the violations discussed above, we would like to discuss adverse event reporting requirements for OTC drugs. Section 760(b)(1) of the Act (21 U.S.C. § 379aa(b)(1)) requires that a manufacturer, packer, or distributor whose name appears on the label of a nonprescription (over-the-counter or “OTC”) drug marketed without an approved application in the United States submit to FDA any report received of a serious adverse event associated with such drug when used in the United States. Under sections 760(c) and (d) of the Act (21 U.S.C. §§ 379aa(c) and (d)), serious adverse event reports received through the address or telephone number on the product label, and new medical information that is related to a previously submitted report and that is received within one year of the initial report, must be submitted to FDA within 15 business days of receipt of such reports and information, and must be submitted using the MedWatch form, which for mandatory reporting is Form FDA 3500A.
During the periods of (b)(4) investigators from the FDA conducted inspections of Matrixx postmarketing adverse event reporting activities at its facility located at 8515 East Anderson Drive, Scottsdale, AZ. Agency personnel also inspected Matrixx’s contractor, (b)(4) located at (b)(4). These inspections were conducted to determine Matrixx’s compliance with the postmarketing adverse drug event reporting requirements of section 760 of the Act (21 U.S.C. § 379aa). Based on the inspectional findings and review of other submissions by your firm to the Agency, we conclude that Matrixx did not submit certain serious adverse event reports as required by section 760 of the Act (21 U.S.C. § 379aa). We acknowledge your responses dated May, October and November 2009. In your November 2009 response, Matrixx committed to submit reports of anosmia beginning with reports the firm received as of November 6, 2009, and to retrospectively begin reviewing and preparing reports received since December 22, 2007. We believe that your proposed corrective action plan is adequate and you are submitting reports as promised. However, we believe that a (b)(4) is warranted to further clarify your reporting requirements under section 760 of the Act to ensure that your firm sustains compliance with the reporting requirements going forward. Prior to the (b)(4) regulatory meeting, we expect Matrixx to provide a detailed status update since the last response dated November 2009.
Conclusion
The violations described in this letter are not intended to be an all-inclusive list of violations that exist in connection with your facility, or with your firm’s products. You are responsible for investigating and determining the causes of the violations identified above and for preventing their recurrence or the occurrence of other violations. It is your responsibility to assure that your firm complies with all requirements of federal law and FDA regulations.
You should take prompt action to correct the violations cited in this letter. Failure to promptly correct these violations may result in legal action without further notice, including, without limitation, prosecution or injunction. Other federal agencies may take this Warning Letter into account when considering the award of contracts.
We request that you notify this office in writing within fifteen (15) business days of receipt of this letter. Your response should address the comments listed above and include examples of documentation showing that corrections have been achieved. If corrective action cannot be completed within 15 business days, please state the reason for the delay and the time within which corrections will be completed.
If you no longer manufacture or market the products referenced in this letter, your response should so indicate, including the reasons that, and the date on which, you ceased production. Additionally, if another firm manufactures the products identified above, your reply should include the name and address of the manufacturer. If the firm from which you receive these products is not the manufacturer, please include the name of your supplier in addition to the manufacturer.
Please send your reply to the attention of Dr. Raymond W. Brullo, Compliance Officer at the address below. We also recommend that you contact us within five days of receipt of this letter to schedule a regulatory meeting. If you have questions or concerns regarding this letter, please contact:
Dr. Raymond W. Brullo, DPM, FAPWCA
Compliance Officer
FDA -- Los Angeles District (LOS-DO)
19701 Fairchild
Irvine, CA 92612
Phone: 949.608.2918
Fax: 949.608.4415
Sincerely,
/S/
Alonza E. Cruse
District Director
Los Angeles District
[1] See , http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm188361.htm, http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2008/ucm1048456.htm, http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2008/ucm1048083.htm, http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2001/ucm178287.htm, and http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2001/ucm178286.htm.
[2] We acknowledge that homeopathic drug products were excluded from the OTC Drug Review. 37 F.R. 9464, 9466 (May 11, 1972). However, as discussed below, FDA does not consider the RapidMelts Vitamin C products to be homeopathic drug products. Furthermore, we note that the final monograph for OTC Cold Cough Drug Products does not include any products in any dosage form containing zinc or any salt of zinc as their active ingredient.
[3] See 41 F.R. 38312 at 38324 (Sept. 9, 1976); 67 F.R. 78158 at 78159 (Dec. 23, 2002).
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