Between October 10th, 2017 and October 27th, 2017, the U.S. Food and Drug Administration (FDA) inspected your dietary supplement facility located at 100-B Tec Street, Hicksville, NY 11801. During the inspection, our investigators found significant violations of the Current Good Manufacturing Practice (CGMP) regulations for Manufacturing, Packaging, Labeling, and Holding Operations for Dietary Supplements, Title 21, Code of Federal Regulations, Part 111 (21 CFR Part 111). These violations cause the dietary supplements manufactured at your facility to be adulterated within the meaning of section 402(g)(1) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) [21 U.S.C. § 342(g)(1)] in that the dietary supplements have been prepared, packed, or held under conditions that do not meet CGMP requirements for dietary supplements. You can find FD&C Act and the FDA’s regulations through links on FDA’s home page at
www.fda.gov
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We received your firm’s FDA-483 response correspondence, dated November 17th, 2017, January 17th, 2018 and April 23rd, 2018. We provide comments to your response immediately following the violations addressed below.
Unapproved New Drug Violations
Your firm’s marketing and distribution of the product “Arimistane” violates the FD&C Act, as described below.
According to your product label, your product contains the ingredient Arimistane (Androsta-3,5-Diene-7,17-Dione). “Arimistane” is represented as a dietary supplement on its label and other labeling; however, the product does not meet the definition of a dietary supplement in section 201(ff) of the FD&C Act [21 U.S.C. § 321(ff)]. To be a dietary supplement, a product must, among other things, “bear or contain one or more dietary ingredients' as defined in section 201(ff)(1) of the FD&C Act [21 U.S.C.§ 321(ff)(1))]. Section 201(ff)(1) defines “dietary ingredient” as a vitamin; mineral; amino acid; herb or other botanical; dietary substance for use by man to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, extract or combination of any dietary ingredient from the preceding categories.
The “Arimistane” ingredient listed on your product label, Androsta-3,5-Diene-7,17-Dione, is an aromatase inhibitor and does not constitute a dietary ingredient under section 201(ff)(1) of the FD&C Act. The product label for your “Arimistane” does not declare any other ingredients. Therefore, because “Arimistane” does not bear or contain any dietary ingredients as defined in section 201(ff)(1) of the FD&C Act, the product is not a dietary supplement under section 201(ff) of the FD&C Act.
Further, your product label includes claims about the effects of your product, such as the following:
- “Arimistane is a revolutionary Aromatase Inhibitor (AI) that effectively manages estrogen, and thus potentially vastly improves muscle energy, strength, mood & libido!”
- “Pure AI Modulator”
- “FIGHTING THE UPHILL BATTLE AGAINST THE AROMATASE ENZYME”
Under section 201(g)(1)(C) of the FD&C Act [21 U.S.C. § 321(g)(1)(C)], products (other than foods) that are intended to affect the structure or function of the body are defined as drugs. The intended use of a product may be determined by, among other things, its labeling, advertising, and the circumstances surrounding its distribution. 21 Code of Federal Regulations (C.F.R.) § 201.128. The label of your product indicates that it is intended to affect the structure or function of the body by, among other things, building muscle and increasing strength. Accordingly, “Arimistane” is a drug.
Moreover, the product is a “new drug,” as defined by 201(p) of the FD&C Act [21 U.S.C. § 321 (p)], because it is not generally recognized as safe and effective for its labeled uses. The introduction or delivery for introduction, or causing the introduction or delivery for introduction, of any new drug lacking an FDA-approved new drug application (NDA) is a violation of sections 301(d) and 505(a) of the FD&C Act [21 U.S.C. §§ 331(d) and 355(a)]. Your sale of the new drug “Arimistane” in interstate commerce without an approved NDA violates these provisions of the FD&C Act.
Furthermore, your product is a “prescription drug” under section 503(b)(1)(A) of the FD&C Act [21 U.S.C. § 353(b)(1)(A)], in that because of its toxicity or other potentiality for harmful effect, or the method of its use, or the collateral measures necessary to its use, it is not safe for use except under the supervision of a practitioner licensed by law to administer it. Adverse events associated with the use of FDA-approved aromatase inhibitors include the following: decreased rate of bone maturation and growth, decreased sperm production, infertility, aggressive behavior, adrenal insufficiency, kidney failure, and liver dysfunction. Indeed, all aromatase inhibitor drugs which have been approved for marketing by the FDA are limited by an approved new drug application to use under the professional supervision of a practitioner licensed by law to administer such drug.
Additionally, we reviewed your website at the internet address website https://www.vmisports.com/ in February 2018, and we have determined that you take orders there for your dietary supplement products, which are promoted for conditions that cause them to be drugs within the meaning of section 201(g)(1)(B) of the Act [21 U.S.C. § 321(g)(1)(B)]. The therapeutic claims on your website establish that the products are drugs because they are intended for use in the cure, mitigation, treatment, or prevention of disease.
Examples of some of the website claims that provide evidence that your products are intended for use as drugs include:
Cycle Guard
- “Combat the proliferation of free radicals and oxidative stress, which can cause inflammation, neurological disorders, and cardiovascular diseases.”
- “Milk Thistle has been used for thousands of years in herbal medicine…Plus, it has even been used as a method for treating alcoholic liver cirrhosis and alcohol poisoning!”
- “Kudzu is a vine used for thousands of years in Ancient Chinese medicine, as an all natural remedy for a number of ailments. Today, kudzu is used to treat alcoholism and to reduce symptoms of alcohol hangover such as headache, dizziness, vomiting. Kudzu is also being investigated as a treatment for assorted cardiovascular and respiratory diseases.”
Vasogen
- “Hawthorn is a plant used throughout history as an herbal medicine. Modern research has shown that extracts of the plant act as a potent vasodilator, increasing blood flow to the heart and improving circulation. Additionally, it also reduces blood pressure…and exhibits beta-blocking properties.”
Your “Cycle Guard” and “Vasogen” products are not generally recognized as safe and effective for the above referenced uses and therefore, these products are “new drugs” under section 201(p) of the Act [21 U.S.C. § 321(p)]. New drugs may not be legally introduced or delivered for introduction into interstate commerce without prior approval from the FDA, as described in section 505(a) of the Act [21 U.S.C. § 355(a)]; see also section 301(d) of the Act [21 U.S.C. § 331(d)]. Your sale of the new drugs, “Cycle Guard” and “Vasogen,” in interstate commerce without an approved NDA violates these provisions of the FD&C Act.
Misbranded Drug Violations
According to section 502(f)(1) of the FD&C Act [21 U.S.C. § 352(f)(1)], a drug is misbranded if, among other things, it fails to bear adequate directions for its intended use(s). “Adequate directions for use” means directions under which a layman can use a drug safely and for the purposes for which it is intended. 21 C.F.R. § 201.5. Prescription drugs can only be used safely at the direction, and under the supervision, of a licensed practitioner. Therefore, it is impossible to write “adequate directions for use” for prescription drugs. FDA-approved prescription drugs which meet certain requirements, including the requirement that they bear their FDA-approved labeling, are exempt from the requirement that they bear adequate directions for use by a layperson. Section 503(b)(2) of the FD&C Act [21 U.S.C. § 353(b)(2)]; 21 CFR 201.100.
As discussed above, your products “Arimistane,” “Cycle Guard,” and “Vasogen” are unapproved new prescription drugs. Furthermore, their labeling fails to bear adequate directions for the products’ intended uses. Therefore, the products are misbranded drugs under section 502(f)(1) of the FD&C Act [21 U.S.C. § 352(f)(1)]. Therefore, the introduction or delivery for introduction, or causing the introduction or delivery for introduction, into interstate commerce of these misbranded products violates section 301(a) of the FD&C Act [21 U.S.C. § 331(a)].
Adulterated Dietary Supplements: CGMP Violations
1. You failed to establish and follow written procedures for the responsibilities of quality control operations, including written procedures for conducting a material review and making a disposition decision, as required by 21 CFR 111.103. Further, you failed to have documentation of the quality control personnel review and approval for release of any packaged and labeled dietary supplement for distribution (21 CFR 111.127(h) and 21 CFR 111.140(b)(2).
Specifically, during the inspection it was observed that you do not have written procedures for the responsibility of the quality control operations related to material review and disposition decisions, and you do not document how you approve and release dietary supplements for distribution [21 CFR 111.103 and 21 CFR 111.140(b)(2)].
We have reviewed your responses. We acknowledge your procedure (b)(4). However, we find your response inadequate because the procedure does not fully describe your quality control operation’s material review and disposition decision process.
Additionally, we acknowledge the revised (b)(4) that you provided in your response dated November 17, 2017. You state identity testing for finished products will be performed by your contract manufacturer and the results will be sent to your firm for record keeping. We find this response inadequate because you have not provided documentation to support your basis for determining your finished dietary supplements meet product specifications and that they are suitable for release and distribution.
To the extent that another firm manufactures, packages, and/or labels dietary supplements on your behalf that your firm releases for distribution under your firm’s name, your firm has an obligation to know what and how manufacturing, packaging, and/or labeling activities are performed so that you can make decisions related to whether your dietary supplement products conform to established specifications and whether to approve and release the products for distribution. [72 Fed. Reg. 34752, 34790 (Jun. 25, 2007)].
Although a firm may contract out certain dietary supplement manufacturing, packaging, and/or labeling operations, it cannot contract out its ultimate responsibility to ensure that the dietary supplement it places into commerce (or causes to be placed into commerce) is not adulterated for failure to comply with dietary supplement CGMP requirements (see United States v. Dotterweich, 320 U.S. 277, 284 (1943) (explaining that an offense can be committed under the FD&C Act by anyone who has “a responsible share in the furtherance of the transaction which the statute outlaws”); United States v. Park, 421 U.S. 658, 672 (1975) (holding that criminal liability under the FD&C Act does not turn on awareness of wrongdoing, and that “agents vested with the responsibility, and power commensurate with that responsibility, to devise whatever measures are necessary to ensure compliance with the Act” can be held accountable for violations of the FD&C Act).
The FD&C Act prohibits a person from introducing or delivering for introduction, or causing the delivery or introduction, into interstate commerce a dietary supplement that is adulterated under section 402(g) for failure to comply with dietary supplement CGMP requirements (see 21 U.S.C. §§ 342(g) and 331(a)).
A firm that contracts out some or all of its operations must establish a system of production and process controls to ensure the quality of its dietary supplements and that the dietary supplements are packaged and labeled as specified in the master manufacturing record (21 CFR 111.55). The quality control personnel must ensure that the manufacturing, packaging, labeling, and holding operations ensure the quality of the dietary supplement and that the dietary supplement is packaged and labeled as specified in the master manufacturing record (21 CFR 111.105). Further, your firm must have documentation of the quality control personnel review and approval for release of any packaged and labeled dietary supplement (21 CFR 111.127(h) and 21 CFR 111.140(b)(2).
2. You failed to establish and follow written procedures for holding and distributing operations, including written procedures for holding dietary supplements under appropriate conditions of temperature, humidity, or light so that the identity, purity, strength, and composition of the dietary supplements are not affected, as required by 21 CFR 111.455(a). Specifically, you receive packaged and labeled dietary supplements from (b)(4), your contract manufacturers, for distribution to customers. The (b)(4) Contract Manufacturing Agreement has specific storage requirements which state “(b)(4) (b)(4).” During the inspection, our investigator noted that your firm has no written procedures for ensuring that the dietary supplements were held under appropriate temperature and humidity conditions.
We have reviewed your responses. We acknowledge your procedures (b)(4). Upon review of these procedures we find them to be inadequate in that they do not include the conditions of temperature and humidity in which your dietary supplements are stored.
Misbranded Dietary Supplements
Your A-XR PCT product is misbranded within the meaning of section 403(a)(1) of the Act [21 U.S.C. 343(a)(1)] in that the labeling is false and misleading. Specifically, the label of your product declares Androst-3, 5-dien-7, 17-one as a dietary ingredient. Under section 201(ff)(1) of the Act [21 U.S.C. § 321 (ff)(1)], a dietary ingredient is a vitamin; mineral; herb or other botanical; amino acid; dietary substance for use by man to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of the preceding substances. Androst-3, 5-dien-7, 17-one is not a vitamin, mineral, herb or other botanical, or amino acid. In addition, Androst-3, 5-dien-7, 17-one is not a dietary substance for use by man to supplement the diet by increasing the total dietary intake. Finally, Androst-3, 5-dien-7, 17-one is not a concentrate, metabolite, constituent, extract, or combination of vitamins; minerals; herbs or other botanicals; amino acids; or dietary substances for use by man to supplement the diet by increasing the total dietary intake. Accordingly, Androst-3, 5-dien-7, 17-one is not a dietary ingredient within the definition set forth in section 201(ff)(1) of the Act. Declaring this ingredient on your product label as dietary ingredient causes your product marketed as dietary supplement to be misbranded under section 403(a)(1) of the Act [21 U.S.C. § 343(a)(1)] in that the labeling is false or misleading in any particular.
This information was communicated to you during your inspection by the FDA. We acknowledge that you promised to no longer make the product. However, this will be verified during your next establishment inspection.
This letter is not an all-inclusive list of violations that exist at your facility or in connection with your products or their labeling. 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 ensure 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, seizure or injunction.
Section 743 of FD&C Act (21 U.S.C. § 379j-31) authorizes FDA to assess and collect fees to cover FDA’s costs for certain activities, including re-inspection-related costs. A re-inspection is one or more inspections conducted subsequent to an inspection that identified noncompliance materially related to a food safety requirement of FD&C Act, specifically to determine whether compliance has been achieved. Re-inspection-related costs means all expenses, including administrative expenses, incurred in connection with FDA’s arranging, conducting, and evaluating the results of the re-inspection and assessing and collecting the re-inspection fees (21 U.S.C. § 379j-31(a)(2)(B)).
For a domestic facility, FDA will assess and collect fees for re-inspection-related costs from the responsible party for the domestic facility. The inspection noted in this letter identified noncompliance materially related to a food safety requirement of FD&C Act. Accordingly, FDA may assess fees to cover any re-inspection-related costs.
Please respond in writing within fifteen (15) working days from receipt of this letter. Your response should outline the specific things you are doing to correct the violations described in this letter and to prevent similar violations from occurring in the future. Include any documentation necessary to show that correction has been achieved. If you cannot complete all corrections before you respond, explain the reason for the delay and state when you will correct any remaining violations.
