Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
|Kansas City District|
11630 West 80 Street
Lenexa, Kansas 66214-3340
Telephone: (913) 752-2100
July 30, 2012
RETURN RECEIPT REQUESTED
Ref. KAN 2012-11
Jesse E. Rettig, Chief Executive Officer
312 Lowery Drive
Woodbine, lA 51579
Dear Mr. Rettig:
Investigators from the U.S. Food and Drug Administration (FDA or Agency) inspected various Grato, Inc. subsidiaries. Specifically, FDA investigators inspected the pharmaceutical manufacturing facility, Apotheca, Inc., located at 312 Lowery Drive, Woodbine, Iowa on March 14, 2011 to March 25, 2011. The inspection also included Liddell Laboratories, Inc., Energique, Inc., and Peaceful Mountain, Inc., and facilities at the following addresses: 114 Enterprise Drive, 201 Apple Boulevard, 110 Enterprise Drive, 311 Lowery Drive, and 313 Lowery Drive, all located in Woodbine, Iowa.
This inspection, as well as our review of one of your websites at the Internet address www.liddell.net, revealed that your firm is manufacturing and/or marketing unapproved new drugs in violation of sections 301 and 505 of the Federal Food, Drug, and Cosmetic Act (Act) [21 U.S.C. §§ 331 and 355] and misbranded drugs in violation of sections 301,502, and 503 of the Act [21 U.S.C. §§ 331,352 and 353].
Further, the investigator from the FDA identified significant violations of the Current Good Manufacturing Practice (CGMP) regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations (C.F.R.), Parts 210 and 211.
FDA has reviewed the labeling for several of your firm's products including: "Vital Male Sexual Energy,""Vital HGH Skin Hair Nails," "Vital HGH Immune Booster," "Vital HGH," "TinnitusDX," "Fibro Relief," and "AR Arthritis."
Statements on product labeling document the intended uses of your products, including but not limited to the following:
Vital Male Sexual Energy
• "An advanced formula to relieve some symptoms of low male sexual energy, such as: decrease in sexual desire, feelings of fatigue, decrease in performance and enjoyment"
• "treats weak erections, impotency, and orgasm"
• "eases bladder, urethra, and prostate discomfort"
Vital HGH Skin Hair Nails
• "reduces edema; prevents abnormal cell growth"
• "stimulates pituitary gland to produce HGH"
Vital HGH Immune Booster
• "treats minor infections"
• "reduces lymphatic inflammation"
• "relieves edema; prevents abnormal cell growth"
• "Temporarily relieves these symptoms due to aging and/or a run-down condition: ... poor muscle/fat balance"
• "normalizes lipid metabolism"
• "Relief from: Ringing or buzzing in ears; Ear noise; Sensitivity to sound"
• "For relief of fibromyalgia symptoms"
• "treats arthritic joint inflammation"
• "eases rheumatism, gout, and joint swelling"
Based on the above labeling claims, these 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, or 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 any function of the body.
Unapproved New Drugs[§§ 301(d) and 505(a)]
"Vital Male Sexual Energy," "Vital HGH Skin Hair Nails," "Vital HGH Immune Booster," "Vital HGH," and "AR Arthritis" are "new drugs" within the meaning of section 201(p) of 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 § 33l(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. There are no FDA-approved applications on file for the above listed products. Therefore, the marketing of "Vital Male Sexual Energy," "Vital HGH Skin Hair Nails," "Vital HGH Immune Booster," "Vital HGH," and "AR Arthritis" without approved applications constitutes a violation of these provisions of the Act.
We recognize that "Vital Male Sexual Energy," "Vital HGH Skin Hair Nails," "Vital HGH Immune Booster," "Vital HGH," and "AR Arthritis" 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 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 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 also states that "[d]rug products containing homeopathic ingredients in combination with non-homeopathic active ingredients are not homeopathic drug products."
FDA reviewed the labeling and active ingredients for the following products:
"Vital Male Sexual Energy" includes "Testosterone 30X" and "Thymus suis 6X" as active ingredients.
"Vital HGH Skin Hair Nails" includes "Amino Acids 10X," "Biotin 10X," "Epidermis 9C," "Human growth hormone 30C," and "Pantothenic acid 6X" as active ingredients.
"Vital HGH Immune Booster" includes "Human growth hormone 30X," and "Thymus suis 6X" as active ingredients.
"Vital HGH" includes "Human growth hormone 30X" as an active ingredient.
"AR Arthritis" includes "Shark Cartilage 6X" as an active ingredient.
The above listed ingredients are not established homeopathic active ingredients included in the HPUS or any of the addenda or supplements. Furthermore, to our knowledge, these ingredients are not listed in any recognized materia medica containing information on the preparation of homeopathic medicines. Therefore, these ingredients are not considered homeopathic drug ingredients and "Vital Male Sexual Energy," "Vital HGH Skin Hair Nails," "Vital HGH Immune Booster," "Vital HGH," and "AR Arthritis" are not considered homeopathic drug products under the CPG. Accordingly, the policies set forth in the CPG for the marketing of homeopathic drug products do not apply to "Vital Male Sexual Energy," "Vital HGH Skin Hair Nails," "Vital HGH Immune Booster," "Vital HGH," and "AR Arthritis." Please note that these products are only examples of products your firm is marketing as homeopathic that contain active ingredients that are not included in the HPUS or any of its addenda or supplements.
Misbranding [§§ 301(a) and 503(b)(4)]
Section 503(b)(1) of the Act [21 U.S.C. § 353(b)(1)] identifies criteria for determining the prescription status of a product. "Vital Male Sexual Energy," "Vital HGH Skin Hair Nails," "Vital HGH Immune Booster," "TinnitusDX," "Fibro Relief," and "AR Arthritis" are prescription drugs within the meaning of section 503(b)(1) of the Act because they are intended to treat diseases that require diagnosis and treatment by a physician or are intended to provide treatment for symptoms usually caused by an underlying disease process that requires diagnosis and treatment by a physician. Because they may be dispensed only by prescription of a licensed practitioner, 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 The marketing of these misbranded products violates section 301(a) of the Act [21 U.S.C. § 331(a)].
Misbranding [§§ 301(a) and 502(a)]
Under section 502(a) of the Act [21 U.S.C. § 352(a)], a drug is misbranded if its labeling is false or misleading in any particular. "TinnitusDX" lists "Vitamin A (Palmitate), Vitamin B1 (Thiamine Mononitrate), Niacin (Vitamin B3 & Inositol Hexaniacinate), Folic Acid, Vitamin B12 (methylcobalamin), PABA, Selenium Aspartate, Gingko Biloba, Ipriflavone, Vinpocetine, L-Arginine HCL, Lipoic Acid, Inositol Hexanlacinate, Black Cohosh, Chromium Polynicotinate, Magnesium Oxide, Magnesium Stearate, Magnesium Citrate, Zinc Gluconate, ZincOxide, Manganese Aminomin, N-Acetyl L-Cysteine, Copper Gluconate, CoQ1O, Ginger, Grape Seed Extract 4:1, Odorless Garlic, Bioperine (Black Pepper Extract)" as "other ingredients." In addition, "Fibro Relief' lists "Fibro Relief herbal blend, 540mg/cap (Condurango bark, Couch Grass root, European Elder fruit, Fragrant Waterlilly root, Lobelia herb, Sheep Sorrel herb)" as "other ingredients." However, under 21 C.F.R. § 210.3(b ), drug components are either active ingredients or inactive ingredients; the term "other ingredients" is neither applicable nor allowable with respect to components of a drug product. The use of the term "other ingredients" is false or misleading because it does not identify the ingredient as either an active or inactive ingredient. Therefore, "TinnitusDX" and "Fibro Relief' are misbranded under section 502(a) of the Act [21 U.S.C. § 352(a)] because their labeling is false or misleading. The marketing of these misbranded products violates section 301(a) of the Act [21 U.S.C. § 331(a)].
Your firm was issued a Form 483 on March 25, 2011. Your firm failed to respond to the Form 483 observations. During the inspection, FDA identified significant violations of the Current Good Manufacturing Practice (CGMP) regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations (C.F.R.), Parts 210 and 211.
1. Your firm has failed to extend an investigation to other batches of the same drug product or other drug products that may have been associated with the specific failure or discrepancy [21 C.F.R. § 211.192].
For example, your firm failed to extend your existing investigations (i.e., QC Observations Reports RON-2, RON-3, RON-4, QCOR-RON-07, and QCOR-RMH-05) to other batches of drug products when your firm identified possible metal shaving contamination generated during the Capsule Filler production. Your investigations failed to include a scientific rationale to justify the release of drug products that may have been contaminated with metal shavings.
2. Your firm's quality control unit failed to conduct complaint investigations or include a written record of the reasons that an investigation was found not to be necessary [21 C.F.R. § 211.198(b)(3)].
For example, your firm failed to conduct an investigation into 19 complaints associated with broken, leaking, or damaged bottles for various drug products. In addition, your firm failed to include any documentation stating why an investigation was deemed not necessary.
3. Your firm failed to conduct at least a visual identification of containers and closures for conformity with all appropriate written specifications [21 C.F.R. § 211.84(d)(3].
For example, your firm relies solely on the supplier's certificate of testing and does not perform a visual identification of incoming containers and closures used for drug packaging. We note that your firm conducted an investigation into leaking containers for Mercury Plus Detox and determined that the spray toppers had a different neck size than the bottles. Although the closures were replaced with the correct closures, you did not implement a corrective action to require identification of containers and closures.
4. Your firm has not conducted at least one specific identity test and has not established the reliability of the supplier's analyses through appropriate validation of the supplier's test results at appropriate intervals [21 C.F.R. § 211.84(d)(2)].
For example, your firm has failed to conduct identity tests on incoming shipments of components. Your firm must conduct testing of incoming components using a specific identification test. For other attributes, it may be appropriate to accept components based on the supplier's Certificate of Analysis (CoA) if you have established the reliability of the supplier's Certificate of Analysis. Subsequent evaluations of the supplier CoA must also occur at appropriate intervals to determine if test results continue to be reliable. It is your firm's responsibility to establish an adequate qualification program that ensures that suppliers of appropriate capability are selected and remain reliable. Your firm's practice of solely using supplier questionnaires to perform supplier qualification is inadequate to ensure that your suppliers can consistently provide material that meets all specifications and quality standards.
The violations cited in this letter are not intended to be an all-inclusive statement of violations that exist at your facility. 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 compliance 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. Other federal agencies may take this Warning Letter into account when considering the award of contracts. Additionally, FDA may withhold approval of requests for export certificates, or approval of pending drug applications listing your facility, until the above violations are corrected. FDA may re-inspect to verify corrective actions have been completed.
Within fifteen working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct violations. Include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the time within which you will complete the correction.
Your response should be sent to Patrick L. Wisor, Compliance Officer, U.S. Food and Drug Administration, Kansas City District, 11630 West 80th Street, Lenexa, Kansas 66214-3340.
John W. Thorsky
Kansas City District Office
1We note that the CPG states that, in accordance with section 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."
This page was posted on August 11, 2017.