August 24, 2018

WARNING LETTER

VIA UNITED PARCEL SERVICE

SIGNATURE REQUIRED

CMS Case # 541391

Mr. Mark C. Faulkner, President

Vireo Systems, Inc.

305 Williams Ave.

Madison, TN 37115

Dear Mr. Faulkner:

On October 24, 2017 through October 26, 2017, an investigator from the U.S. Food and Drug Administration (FDA) conducted an inspection of your dietary supplement manufacturing facility, Vireo Resources, LLC, located at 461 Wiles Rd., Plattsmouth, NE 68048. In addition, FDA reviewed your websites at the Internet addresses https://www.vireosystems.com and http://ph-defense.com in January, 2018 and has determined that you take orders there for the products Amino Activ Pain Relief Capsules, Amino Activ Topical Cream, pH-D Boric Acid Vaginal Suppositories, Con-Cret Creatine HCl Micro-Dosing Natural Capsule (75 capsules), Con-Cret PUMP Blue Raspberry Flavored Powder (4.97 oz), Con-Cret PUMP Lemon Lime Flavored Powder (4.97 oz), Kaged Muscle Patented C-HCl Lemon- Lime Powder (2.70 oz), Kaged Patented C-HCl Capsules (75 Vegetable Capsules), and Kaged Muscle Patented C-HCl Unflavored Powder (1.98 oz), CanineActiv Safe Pain Relief and CanineActiv HP. This inspection and review of your websites revealed serious violations of the Federal Food, Drug, and Cosmetic Act (“the Act”) and applicable regulations. You can find the Act and FDA regulations through links on FDA’s website www.fda.gov. 

Misbranded Homeopathic Drugs

During the inspection, FDA collected product labels and confirmed that you manufacture AminoActiv Pain Relief Capsules and AminoActiv Topical Cream. The claims on your products’ labels and your website establish that these products are drugs under section 201(g)(1) of the Act [21 U.S.C. § 321(g)(1)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or intended to affect the structure or any function of the body.

Examples of claims that provide evidence that your products are intended for use as drugs include, but may not be limited to the following:

AminoActiv Pain Relief Capsules

On the product label:

• “Safe, Non-Toxic Pain Relief …”
• “Homeopathic Analgesic …”
• “Anti-inflammatory …” 

Your webpage www.aminoactiv.com/testimonials/ also contains evidence of intended use in the form of personal testimonials recommending or describing the use of your products for the cure, mitigation, treatment or prevention of disease, and/or to affect the structure or function of the body. Examples of such testimonials include:

• “FIBROMYALGIA / LUPUS PAIN… My wife has tried numerous drugs with no relief for her fibromyalgia. She is using AA now and getting great relief! …Also, I have spinal stenosis (L-3-4- 5 are herniated), spurring, arthritis, and constant pain. I tried 4 of the AminoActiv capsules (2 am- 2pm) and applied the cream that night.
• “Irritable Bowel Syndrome …Patient began taking AminoActiv® (Vireo Systems, Inc.) for chronic lower back pain. The back pain abated with treatment, but patient reported that within 3 days of beginning the anti-inflammatory regimen (2 capsules, 2-3 times per day) the bowel condition was markedly and unexpectedly improved…” 

AminoActiv Topical Cream

On the product label:

• “Safe, Non-Toxic Pain Relief …”
• “Homeopathic Analgesic …”
• “Anti-inflammatory …”

Your webpage www.aminoactiv.com/testimonials/ also contains evidence of intended use in the form of personal testimonials recommending or describing the use of your products for the cure, mitigation, treatment or prevention of disease, and/or to affect the structure or function of the body. Examples of such testimonials include:

• “My husband has a bad back and I just used the AA cream on his back the other night and he was amazed at how well it worked…”
• “PERIPHERAL NEUROPATHY…I suffer with Peripheral Neuropathy and I’m not a Diabetic. I have been using the AminoActiv cream and taking the capsules religiously for 3 months with great success I use the cream on my feet at least 2 to 3 times during a 24 hour period. Along with each application of the cream, I take 2-3 capsules depending on how painful it is during the night. Nothing has controlled my symptoms better…”

We recognize that “AminoActiv Pain Relief Capsules” and “AminoActiv Topical Cream” are labeled as homeopathic drugs with active ingredients measured in homeopathic strengths. 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 400.400)” (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 product must meet the conditions set forth in the CPG. One of those conditions is compliance with section 503(b) of the Act [21 U.S.C. § 353(b)]. The CPG states that homeopathic products intended solely for self-limiting disease conditions amenable to self-diagnosis (of symptoms) and treatment may be marketed OTC. Homeopathic products offered for conditions not amenable to OTC use must be marketed as prescription products.

These products “AminoActiv Pain Relief Capsules” and “Amin Activ Topical Cream” are “prescription drugs” within the meaning of section 503(b)(1)(A) of the Act [21 U.S.C. § 353(b)(1)(A)] because, due to their toxicity or other potentiality for harmful effect, or the method of their use, or the collateral measures necessary to their use, they are not safe for use except under the supervision of a practitioner licensed by law to administer them. Therefore, these products are misbranded under section 503(b)(4) of the Act [21 U.S.C. § 353(b)(4)], in that their labels fail to bear the symbol, “Rx only.”1  It is a prohibited act to introduce or deliver for introduction into interstate commerce a misbranded drug under section 301(a) of the Act [21 U.S.C. § 331(a)].

Unapproved New Drug and Misbranded Drug

Statements on your website http://ph-defense.com establish that pH-D Feminine Health Support Boric Acid Vaginal Suppositories is a drug as defined by section 201(g)(1)(B) of the Act [21 U.S.C. § 321(g)(1)(B)], because it is intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease and/or to affect the structure or function of the body. As explained further below, introducing or delivering this product for introduction into interstate commerce violates the Act.

Examples of claims on your website http://ph-defense.com that establish the intended use of your product include, but may not be limited to:

• “Users report improved vaginal health and reduction in . . . Vaginal irritation, discomfort, and itch…”
• “An unbalanced vaginal pH can leave you more susceptible to serious issues like fertility problems, infections, STDs and PID (Pelvic Inflammatory Disease). When things get out of whack, it’s important to restore balance as quickly as possible. pH-D Feminine Health Support is a natural defense against unbalanced vaginal pH and can help get things back to normal quickly.”
• “This stuff is a lifesaver…for chronic BV and yeast.”
• “This is just so helpful if you suffer from yeast infections and BV.”
• “Clinical studies report that boric acid may assist in treating the symptoms of bacterial vaginosis (BV), recurrent bacterial vaginosis (RBV) and yeast infections.” 

Your product is not generally recognized as safe and effective for the above referenced uses and, therefore, this product is a new drug 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)]. No approved application pursuant to section 505 of the Act [21 U.S.C. § 355] is in effect for this product. Accordingly, the introduction or delivery for introduction into interstate commerce of this product violates sections 301(d) and 505(a) of the Act [21 U.S.C. §§ 331(d) and 355(a)].

A drug is misbranded under section 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)] if the drug fails to bear adequate directions for its intended use(s). “Adequate directions for use” means directions under which a layperson can use a drug safely and for the purposes for which it is intended (21 CFR 201.5). Prescription drugs, as defined in section 503(b)(1)(A) of the Act [21 U.S.C. § 353(b)(1)(A)], are drugs that, because of their toxicity or other potentiality for harmful effect, or the method of their use, or the collateral measures necessary to their use, are not safe for use except under the supervision of a practitioner licensed by law to administer them.

Your pH-D Feminine Health Support Boric Acid Vaginal Suppositories is intended for treatment of one or more diseases that are not amenable to self-diagnosis or treatment without the supervision of a licensed practitioner. Therefore, adequate directions for use cannot be written so that a layperson can use your product safely for its intended purposes. Accordingly, pH-D Feminine Health Support Boric Acid Vaginal Suppositories fails to bear adequate directions for its intended uses and, therefore, the product is misbranded under section 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)]. The introduction or delivery for introduction into interstate commerce of this misbranded drug violates section 301(a) of the Act [21 U.S.C. § 331(a)].

Unapproved New Animal Drugs

In addition, claims on your product labels and the website (www.canineactiv.com) establish that your CanineActiv Safe Pain Relief and CanineActiv HP 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 cure, mitigation, treatment, or prevention of diseases in animals. Further, as discussed below, these products are unapproved new animal drugs and introducing or delivering these products for introduction into interstate commerce for such uses violates the Act.

An example of a claim on the label for your product, Canine Activ Medium 25-65 lbs, that provides evidence that this product is intended for use as a drug includes:

On the product label: 

• “Anti-Inflammatory …”

Examples of some of the website claims (www.canineactiv.com) that provide evidence that these products are intended for use as animal drugs include:

On the http://canineactiv.com/ webpage regarding your firm’s CanineActiv products:

• “The dogs’ owners administered CanineActiv and after one month, the owners reported that CanineActiv was (1) better than joint supplements and (2) basically as effective as prescription based medications (but without drug toxicity concerns) …” 

The http://canineactiv.com/ webpage links to a webpage on which for your CanineActiv High Performance Breed product can be purchased. This page includes the following statement:

• “CanineActiv … Use to treat pain and inflammation”

Your products are not generally recognized among experts qualified by scientific training and experience to evaluate the safety and effectiveness of animal drugs, as safe and effective for the above referenced uses. These products are not the subject of an approved new animal drug application, conditionally approved new animal drug application, or index listing under sections 512, 571, and 572 of the Act [21 U.S.C. §§ 360b, 360ccc, and 360ccc-1]. Therefore, these products are unsafe within the meaning of section 512(a) of the Act, [21 U.S.C. § 360b(a)], and adulterated under section 501(a)(5) of the Act [21 U.S.C. § 351(a)(5)]. The introduction or delivery for introduction into interstate commerce of these adulterated new animal drugs violates section 301(a) of the Act [21 U.S.C. § 331(a)].

Dietary Supplement CGMP Violations

 Your dietary supplement products are adulterated dietary supplements within the meaning of section 402(g)(1) of the Act [21 U.S.C § 342(g)(1)] because the products have been manufactured under conditions that do not meet the Current Good Manufacturing Practice (CGMP) regulations for Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements, Title 21, Code of Federal Regulations, Part 111 (21 CFR 111).

During the inspection of your facility, the following significant violations of these CGMP requirements were observed:

1.    You failed to establish product specifications for each dietary supplement that you manufacture for the identity, purity, strength, and composition of the finished batch of the dietary supplement to ensure the quality of the dietary supplement, as required by 21 CFR 111.70(e). Specifically, your firm has not established finished product specifications for the identity, purity, strength, and composition of the dietary supplement products you manufacture. Once you have established these finished product specifications, you must verify, as described in 21 CFR 111.75(c), that your finished batch of the dietary supplement meets product specifications.

We have reviewed your undated response, received November 6, 2017. Your response stated you would be establishing finished product specifications and that all products will be tested by a third-party laboratory. We are unable to evaluate your response because of lack of supporting documentation. We will evaluate the adequacy of these proposed changes at our next inspection.

2.    You failed to conduct at least one appropriate test or examination to verify the identity of components that are dietary ingredients, prior to their use, as required by 21 CFR 111.75(a)(1)(i). Specifically, you failed to conduct identity testing on Caffeine Anhydrous, Lot # (b)(4), Bioperine, Lot # (b)(4), and Niacinamide, Lot # (b)(4) These three batches of dietary ingredients were used in the manufacture of Con-Cret PUMP Lemon Lime Flavored Powder (4.97 oz), Lot #3PL17071, and Con-Cret PUMP Blue Raspberry Flavored Powder (4.97 oz), Lot #3PR17071. Before using a component that is a dietary ingredient, you must conduct at least one appropriate test or examination to verify the identity of the dietary ingredient, unless you have petitioned FDA for an exemption from such testing, consistent with the requirements of 21 CFR 111.75(a)(1)(ii), and FDA exempts you from such testing. Your firm has not petitioned the FDA for such an exemption.  A Certificate of Analysis from the supplier may not be used in lieu of an identity test. You must also ensure that the tests and examinations that you use to verify the identity of components that are dietary ingredients are appropriate, scientifically valid methods, as required by 21 CFR 111.75(h)(1), and you must make and keep records of the specifications established related to the identity of components that are dietary ingredients, as required by 21 CFR 111.95(b)(1).

We have reviewed your undated response, received November 6, 2017. Your response stated testing was performed on the referenced batches of ingredients, all dietary ingredients were checked to ensure testing was performed on the dietary ingredients, and all dietary ingredients will be tested every three years. We are unable to evaluate your response because of lack of supporting documentation. We will evaluate the adequacy of these proposed changes at our next inspection.

The violations cited in this letter are not intended to be an all-inclusive statement of violations that exist in connection with your product. 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, seizure and injunction.

We offer the following comments:

1.  In accordance with 21 CFR 111.260(k)(2), each batch production record must contain an actual or representative label, or a cross-reference to the physical location of the actual or representative label specified in the master manufacturing record. The representative labels within the batch production records for Con-Cret PUMP Lemon Lime Flavored Powder (4.97 oz), Lot #3PL1707, and Con-Cret PUMP Blue Raspberry Flavored Powder (4.97 oz), Lot #3PR17071, do not contain complete labels. For example, the nutrition information (e.g. Supplement Facts panel) is missing from the labels associated with these batch records.  As such, the batch production records for these products do not have an actual or representative label or a cross-reference to the physical location of the actual or representative label.

Within fifteen (15) working days of the receipt of this letter, please notify this office in writing of the specific steps you have taken to correct the violations noted above and to ensure that similar violations do not occur. Your response should include any documentation necessary to show that corrective  action has been achieved. If you believe that your products are not in violation of the FD&C Act,  include your reasoning and any supporting information for our consideration.  If you cannot complete all corrections within fifteen (15) working days, you should explain the reason for your delay and the time within which the remaining corrections will be completed.

Address your reply to the U.S. Food and Drug Administration; Attn: Victoria A. Wagoner, Compliance Officer, 8050 Marshall Dr., Suite 205, Lenexa, KS 66214. If you have any questions regarding any issue in this letter, please contact Victoria Wagoner, Compliance Officer at (913) 495-5150 or  [email protected].

Sincerely,

/S/ 

Cheryl A. Bigham

Program Division Director

Office of Human and Animal Foods – Division II West

Cc:

Ms. Sarah C. Byrne, Quality Assurance Manager

Vireo Resources, LLC

461 Wiles Rd.

Plattsmouth, NE 68048 

_______________________

1 We note that the Agency’s Compliance Policy Guide entitled, “Conditions Under Which Homeopathic Drugs May be Marketed (CPG 400.400)” (the CPG) states that, in accordance with § 503(b)(1) of the Act, homeopathic drug products offered for conditions that require diagnosis or treatment by a licensed practitioner must bear the prescription legend, “Caution: Federal law prohibits dispensing without prescription.” The CPG was issued by the agency in 1988. In 1997, Congress enacted the Food and Drug Administration Modernization Act (FDAMA)  (Public Law 105-115); section 126 of FDAMA amended section 503(b)(4) of the Act to require that the label of a prescription drug product must bear, at a minimum, the symbol “Rx only.”