Inspections, Compliance, Enforcement, and Criminal Investigations
Cosmed Labs, Inc. 8/3/10
Department of Health and Human Services
|Public Health Service
Food and Drug Administration
Cincinnati District Office
6751 Steger Drive
Telephone: (513) 679-2700FAX: (513) 679-2761
August 3, 2010
VIA United Parcel Service
David R. Self, President
Cosmed Labs, Inc.
1416 Lytle Street
Louisville, KY 40203-1325
Dear Mr. Self:
This letter is in reference to the following products manufactured by your firm: "AIM Renewed Balance Body Cream," "Products of Nature Natural Woman Progesterone Cream," "Products of Nature Relevamine GS," and "Dr. Janet's Glucosamine Cream."
After a review of each of the products' websites and labeling that are affixed to the products prior to shipping them into interstate commerce, your products are drugs as defined in section 201 (g) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 321(g)] because they are intended for the use in the cure, mitigation, treatment, or prevention of disease, and/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 of man.
The products' objectionable claims and statements of ingredients, include, but are not limited to, the following:
AIM Renewed Balance Body Cream
Statements found on the label:
• "Ingredients: Purified water, stearic acid, d-alpha tocopherol (vitamin E), natural glycerin, fatty acid ester, avocado oil, USP-certified natural progesterone (derived from Mexican wild yam), aloe vera oil, rosemary extract, vitamin A palmitate, carrot oil, lemon grass oil ...."
• "Suggested Use: Apply a rounded 1/8 teaspoon to a scant 1/4 teaspoon (1 g to 1.2 g of cream) which supplies 2 to 24 mg of progesterone, per day for 2 to 3 weeks per month ...."
• "CONTAINS NATURAL PROGESTERONE ...."
Statements found on website (www.theaimcompanies.com) that is referenced on the product label:
• "AIM Renewed Balance, in a handy pump container, provides the body with natural progesterone from a wild yam extract and has other natural ingredients including aloe vera oil, rosemary extract, carrot oil, and lemon grass oil to help relieve some of the symptoms commonly associated with menopause ...."
• "Menopause, as uncomfortable as it can become when it is accompanied by hot flashes, vaginal dryness, loss of libido, weight gain, and mood swings, is a reality for women ages 45 to 60 ...."
• "Transdermal progesterone is absorbed through the skin into the underlying fat area, from which it diffuses into the capillaries permeating the fat ...."
Products of Nature Natural Woman Essential Body Cream
Statements found on the label:
• "Ingredients: Purified Water, Natural Glycerin, Stearal Konium Chloride, Vitamin E, Avocado Oil, Natural Progesterone (derived from the Mexican wild yam root), Aloe Vera Oil, Rosemary Extract, Vitamin A Palmitate, Dong Quai, Saw Palmetto, Cramp Bark, Sarsaparilla, Carrot Oil, Lemon Grass Oil ...."
Statements found in the labeling: (fold-out label applied to the top of container)
• "MENSTRUATING WOMEN: ... Use 1/4 tsp. twice daily starting on day 12 (day 1 is first day of period) until day 26 ...."
• "The following is from the research of John R Lee, M.D. For additional applications, refer to his books, What Your Doctor May Not Tell You About Menopause and What Your Doctor May Not Tell You About Premenopause ...."
• "Progesterone Cream"
Products of Nature Relevamine GS (Glucosamine Sulfate Cream with MSM)
Statements found on the label:
• "INGREDIENTS: Water, Stearalkonium Chloride, Glycerine, Soybean Oil, Glucosamine Sulfate, Tocopherol (Vitamin E), Pregnenolone Acetate, Dimethyl Sulfone (MSM), Ginger Extract, Emu Oil, Rosemary Extract ...."
• "DIRECTIONS: Apply 3 times daily to hands, wrists, elbows, knees, ankles or wherever needed ...."
Statements found on (b)(4) website, www.pronature.com
• "Glucosamine sulfate - the preferred form of Glucosamine - works at both relieving pain and stimulating healing. It provides the raw materials used by the body to make cartilage and connective tissue that, in turn, help to provide cushioning and lubrication for each of the body's joints. It reduces pain more effectively than ibuprofen ....."
• "Pregnenolone Acetate: used topically as an anti-inflammatory and anti-itch agent ...."
• "Dimethyl Sulfone (MSM): a stable form of sulfur, which can be derived from plants grown either on land or sea. MSM acts as both an anti-inflammatory agent and as an analgesic ...."
Dr. Janet's Dual Action Transdermal Glucosamine Cream
Statements found on the label:
• "Ingredients: .. Purified Water ... Natural Glycerin ... Stearalkonium Chloride ... Vitamin E ... Emu Oil ... Glucosamine Sulfate MSM ... Cetyl Alcohol Pregnenolone ... Rosemary Extract ... Green Tea Extract Boswellia ... Bromelain Citric Acid and ... Silver Citrate ...."
• "The ingredients in this formula work to soothe joints while helping the rebuilding process .."
• "Transdermal Delivery ...."
Statements found on website (www.drnewtons.com) that is referenced on product label:
• "If you suffer from headaches, sore knees, carpal tunnel, or more serious conditions such as arthritis and fibromyalgia, you know how quickly pain disrupts your day ...."
• "Dual-Purpose All-Natural Pain Relief
Unlike any other Glucosamine product, Dr. Janet's cutting edge formula has dual capabilities to bring you fast-acting and long-term relief. Emu Oil (anti-inflammatory) and Pregnenolone (a natural pain relieving hormone) combine with Glucosamine to build the body's natural pain fighting mechanisms. It also helps stimulate the reformation of cartilage to reverse the painful effects of aging and sports-related injuries. Dr. Janet's Glucosamine Cream bypasses digestion to give you one of the fastest, most effective pain relievers on the market.
As a result, we've partnered with Dr. Janet Maccaro - a holistic expert at the National Health Federation to bring you a potent Glucosamine Cream formula that helps stop your muscle and joint pain in less than 15 minutes ...."
Unapproved Drug Charges
Over-the-Counter (OTC) topical hormone-containing products labeled or promoted for use as drugs are subject to the final rule under 21 Code of Federal Regulations (CFR) § 310.530. This rule states that any OTC drug product, other than hydrocortisone, that is labeled, represented, or promoted as a topically applied hormone-containing product for drug use is regarded as a new drug. All of the products listed above-AIM Renewed Balance, Products of Nature Natural Woman Essential Body Cream, and Dr. Janet's Dual Action Transdermal Glucosamine Cream-fall within this rule because their labeling describes them as containing a hormone ingredient and promotes them as topical hormone-containing products for drug use. Moreover, OTC topical hormone creams are new drugs as defined in section 201(p) of the Act [21 U.S.C. § 321(p)] because there is no evidence that they are generally recognized by qualified scientific experts as safe and effective for their labeled uses. (See 21 CFR § 310.530.) Since AIM renewed Balance, Products of Nature Natural Woman Essential Body Cream, and Dr. Janet's Dual Action Transdermal Glucosamine Cream are not the subjects of approved new drug applications, their marketing in the United States violates sections 301(d) and 505(a) of the Act [21 U.S.C. §§ 331(d) and 355(a)].
FDA's regulations state that a drug may be considered a new drug because of the newness of its dosage form or the method or duration of administration or application suggested in its labeling [21 CFR § 310.3(h)(5)]. A transdermal delivery system for a drug is a novel dosage form and is not generally recognized by experts to be safe and effective for its intended uses as found in its labeling. Accordingly, FDA considers all transdermal drug delivery products to be new drugs under § 201(p) of the Act [21 U.S.C. § 321(p)] and under 21 CFR § 310.3. AIM Renewed Balance and Dr. Janet's Dual Action Transdermal Glucosamine Cream are labeled as having a transdermal delivery system; accordingly, they are new drugs under the Act and its implementing regulations. As stated above, since they are not the subjects of approved new drug applications, their marketing in the United States violates sections 301(d) and 505(a) of the Act [21 U.S.C. §§ 331(d) and 355(a)].
Drug products intended for topical administration for indications related to pain are being evaluated under the OTC Drug Review. The Tentative Final Monograph (TFM) issued on February 8, 1983 for OTC External Analgesics (48 Fed. Reg. 5852) is part of this evaluation.
Dr. Janet's Dual Action Transdermal Glucosamine Cream is a product that is marketed for use as an external analgesic. The External Analgesics TFM did not include any of the labeled ingredients contained in Dr. Janet's Dual Action Transdermal Glucosamine Cream: purified water, natural glycerin, stearalkonium chloride, vitamin E, emu oil, glucosamine sulfate, MSM, cetyl alcohol, pregnenolone, rosemary extract, green tea extract, boswellia, bromelain, citric acid, and silver citrate. These ingredients were not evaluated as part of the OTC Drug Review for any external use, including any of the indications found in the labeling for Dr. Janet's Dual Action Transdermal Glucosamine Cream. Since there is no differentiation on the labeling between active and inactive ingredients, all ingredients are regarded as active. Furthermore, indications for fibromyalgia and carpal tunnel are not included in any part of the OTC Drug Review. Additionally, we are not aware of a product with these ingredients for topical application to treat any of the conditions found in the labeling of Dr. Janet's Dual Action Transdermal Glucosamine Cream having been available in the U.S. market as an OTC drug at the inception of the OTC Drug Review. Therefore, this product is not eligible for the OTC Drug Review. Thus, the current marketing of Dr. Janet's Dual Action Transdermal Glucosamine Cream violates section 301(d) and 505(a) of the Act [21 U.S.C. §§ 331(d) and 355(a)] because it is a new drug and it is not the subject of an approved new drug application.
Since the adequacy of the indications for the labeled uses have not been established for AIM Renewed Balance, Products of Nature Natural Woman Essential Body Cream, and Dr. Janet's Dual Action Transdermal Glucosamine Cream, these products are misbranded under section 502(f)(1) of the Act [21 U.S.C § 352(f)(1)].
In addition, each of these products is sold over-the-counter (OTC) as a drug, and as required by 21 U.S.C. § 352(e)(1)(A)(ii) and (iii), OTC drug products must list the active and inactive ingredients separately. The labeling provided for AIM Renewed Balance, Products of Nature Natural Woman Essential Body Cream, and Dr. Janet's Dual Action Transdermal Glucosamine Cream does not differentiate between active and inactive ingredients as required. Therefore, these products are misbranded under section 502(e)(1)(A) of the Act [21 U.S.C. § 352(e)(1)(A)].
AIM Renewed Balance, Products of Nature Natural Woman Essential Body Cream, and Dr. Janet's Dual Action Transdermal Glucosamine Cream are further misbranded under section 502(c) of the Act [21 U.S.C. 352(c)] because they do not follow the drug labeling format requirements under 21 CFR 201.66.
AIM Renewed Balance, Products of Nature Natural Woman Essential Body Cream and Dr. Janet's Dual Action Transdermal Glucosamine Cream are misbranded under section 502(o) of the Act [21 U.S.C. § 352(o)], because they were not manufactured, prepared, propagated, compounded or processed in an establishment duly registered under section 510 of the Act [21 U.S.C. § 360], nor were they included in a list required by section 510(j) of the Act [21 U.S.C. § 360(j)].
In addition, Products of Nature Relevamine GS is misbranded under section 502(a) of the Act [21 U.S.C. § 352(a)] because it is false or misleading in that the product lacks adequate labeling for its intended uses that are found on the (b)(4) website www.pronature.com. Under regulation 21 CFR § 201.128, intended uses for a product manufactured by you include those uses for which you are aware. The objective intent
may be shown by the circumstances that the article is, with the knowledge of such persons or their representatives, offered and used for a purpose for which it is neither labeled nor advertised ... if a manufacturer knows, or has knowledge of facts that would give him notice that a drug introduced into interstate commerce by him is to be used for conditions, purposes, or uses other than the ones for which he offers it, he is required to provide adequate labeling for such a drug which accords with such other uses to which the article is to be put.
In this case, your firm manufactures the product for the (b)(4) includes the name of the (b)(4) on the product label, and would have access to the (b)(4) website, making the drug claims listed above. The label of your product is misleading because it "fails to reveal facts material in the light of such representations or material with respect to consequences which may result from the use of the article to which the labeling or advertising relates under the conditions of use prescribed in the labeling or advertising thereof or under such conditions of use as are customary or usual." Section 201(n) of the Act [21 U.S.C. § 321(n)]. Specifically, you do not include information on the anti-inflammatory or analgesic uses of the product as promoted by the (b)(4). Therefore, your product is misbranded under § 502(a) of the Act [21 U.S.C. § 352(a)] and also under section § 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)] because the product label fails to provide adequate directions for use.
Investigator(s) from the FDA also identified significant violations of Current Good Manufacturing Practice (cGMP) regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations, Parts 210 and 211. These violations cause your drug product(s) to be adulterated within the meaning of section 501 (a)(2)(B) of the Act [21 U.S.C. § 351(a)(2)(B)] in that the methods used in, or the facilities or controls used for, their manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, cGMP. Specific cGMP violations observed during the inspection include, but are not limited, to the following:
1. Your firm has failed to establish written procedures describing the handling of all written and oral complaints regarding a drug product, including provisions requiring quality control unit review and a determination as to the need of an investigation [21 CFR § 211.198(a)]. Your firm has also failed to maintain a written record of each complaint, including the findings of the investigation [21 CFR § 211.198(b)]. For example,
a. You failed to establish written procedures describing how to investigate complaints or require a review of the complaint investigations.
b. You failed to conduct an investigation after receiving a complaint from AIM International stating that the progesterone levels in your Renewed Balance were sub-potent in the pump containers and superpotent in the jar containers.
c. You failed to conduct an investigation after receiving a complaint from AIM International for Renewed Balance (lot 160805) stating that the separation of the cream in the pump affected the appearance and viscosity of the product.
2. Your firm failed to establish a quality control unit that has the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging material, labeling, and drug products, and the authority to review production records [21 CFR § 211.22(a)].
a. You have not established a Quality Control Unit (QCU) that reviews batch records for accuracy. The responsible official only reviews batch records when personnel note a problem with the finished product. This review only verifies whether the correct amount of raw materials was added to the batch.
b. Changes to your raw material dispensing sheets are not reviewed. Specifically, we observed 37 of 100 preprinted raw material dispensing sheets where you changed the materials or quantities to be used for batch manufacture without QCD review. This occurred between February 2007 and January 2010.
3. Your firm failed to have separate or defined areas to prevent contamination or mix-ups during the course of receipt, identification, storage, and withholding from use of components pending the appropriate sampling, testing, or examination [21 CFR § 211.42 (c)(1)]. For example, you do not have a process to segregate components upon receipt from those components already determined as approved or rejected. We observed components in your warehouse that were not identified as quarantined, approved, or rejected.
4. Your firm failed to withhold each lot of components from use until the lot has been sampled, tested, or examined as appropriate, and released by your quality control unit [21 CFR § 211.84(a)]. For example, you do not test incoming components. During the inspection, you indicated to our inspection team that if you receive a Certificate of Analysis (COA) with the component, you discard the COA without conducting any review.
5. Your firm does not have adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess [21 CFR § 211.100(a)]. For example, you have not validated your manufacturing processes and you do not have procedures that describe manufacturing parameters.
6. Your batch product and control record, for each batch of drug product, fail to include complete information relating to the production and control of each batch [21 CFR § 211.188]. For example, you do not document each significant step in the manufacturing, processing, packing, or holding of the batch. In addition, records do not consistently identify the persons performing or checking each significant step in the operation.
7. Your firm does not have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release [21 CFR § 211.165(a)]. For example, you do not test drug products for the identity or strength of each active ingredient prior to release. In addition, you do not routinely test your products for microbial contamination. Your firm only conducts visual examination of the drug products and limited testing for pH and mold.
The issues and 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. A description of the new drug approval process can be found on FDA's internet website at http://www.fda.gov/cder/regulatory/applications/default.htm. Any questions you may have regarding this process should be directed to the Food and Drug Administration, Division of Drug Information (HFD-240), Center for Drug Evaluation and Research, 10903 New Hampshire Avenue, Silver Spring, Maryland 20993-0002.
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 awarding of contracts.
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. Furthermore, please advise this office what actions you will take to address product that you have already distributed.
Additionally, if another firm manufactures the product identified above, your reply should include the name and address of the manufacturer. If the firm from which you receive the products is not the manufacturer, please include the name of your supplier in addition to the manufacturer. Address your reply to the U.S. Food and Drug Administration, Cincinnati District Office.
Teresa C. Thompson