Source: https://www.fda.gov/iceci/enforcementactions/warningletters/2014/ucm434928.htm
Timestamp: 2019-04-23 02:50:28+00:00

Document:
On July 12 – August 1, 2013, the U. S. Food and Drug Administration (FDA) conducted an inspection of your dietary supplement repacking and distribution facility located at 2650 Holcomb Bridge Road, Suite 520, in Alpharetta, GA. As part of the inspection, FDA collected product labels and samples of several of your products. FDA has determined that your “HAM™” male enhancement product, and your “CE6™” and “SARMZ™” androgenic modulator products are unapproved new drugs sold in violation of sections 505(a) and 301(d) of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. §§ 355(a) and 331(d)] and are misbranded drugs sold in violation of sections 502 and 301(a) [21 U.S.C. §§ 352 and 331(a)] of the FDCA.
“HAM™,” “CE6™,” and “SARMZ™” are not dietary supplements. According to section 201(ff)(3)(B)(i) of the FDCA [21 U.S.C. § 321 (ff)(3)(B)(i)], a dietary supplement may not include an article that is approved as a new drug under section 505 of the FDCA [21 U.S.C. § 355(a)] unless that article was marketed as a dietary supplement or food prior to FDA approval of such drug. FDA approved Cialis as a new drug on November 21, 2003, and approved Levitra as a new drug on August 19, 2003. Tadalafil and vardenafil were not marketed as dietary supplements or as foods before these dates. As such, “HAM™” is excluded from the definition of a dietary supplement under section 201(ff)(3)(B)(i) of the FDCA [21 U.S.C. § 321 (ff)(3)(B)(i)].
According to section 201(ff)(3)(B)(ii) of the FDCA [21 U.S.C. § 321 (ff)(3)(B)(ii)], a dietary supplement also may not include an article authorized for investigation as a new drug for which substantial clinical investigations have been instituted and made public, unless the article was marketed as a dietary supplement or food before its authorization as a new drug. (2S)-3-(4-cyanophenoxy)-N-[4-cyano-3-(trifluoromethyl)phenyl]-2-hydroxy-2-methylpropanamide) is the subject of substantial clinical investigations, which have been made public (see note 1, infra). Based on the information available to FDA, ostarine was not marketed as a dietary supplement or as a food until after it was under substantial clinical investigation. Therefore, “CE6™” and “SARMZ™,” which contain ostarine, are also excluded from the definition of a dietary supplement under section 201(ff)(3)(B)(ii) of the FDCA [21 U.S.C. § 321 (ff)(3)(B)(ii)].
The intended use of a product may be determined by, among other things, its labeling, advertising, and the circumstances surrounding its distribution, 21 C.F.R. § 201.128. “HAM™,”“CE6™,” and “SARMZ™” are drugs as defined by section 201(g)(1)(B) & (C) of the FDCA [21 U.S.C.§§ 321(g)(1)(B) & (C)] because they are intended for use in the diagnosis, cure, mitigation, ,treatment or prevention of disease, or an article (other than food) intended to affect the structure or function of the body. The claims on your product labeling, indicate that “HAM™,” “CE6™,” and “SARMZ™” products are intended to affect the structure or function of the body or are for use in the treatment of erectile dysfunction or muscle wasting.
“HAM™,” “CE6™,” and “SARMZ™” are also “new drugs” as defined by section 201(p) of the FDCA [21 U.S.C. § 321(p)], because these products are not generally recognized among experts as safe and effective for use under the conditions prescribed, recommended, or suggested in their labeling.
Furthermore, “HAM™,” “CE6™,” and “SARMZ™” are prescription drugs as defined in section 503(b)(1)(A) of the Act [21 U.S.C. § 353(b)(1)(A)], because due to their toxicity or potentiality for harmful effect, the method of their use, or the collateral measures necessary for their use, they are not safe for use except under the supervision of a practitioner licensed by law to administer them. “HAM™” is a prescription drug because it contains several phosphodiesterase type-5 (PDE-5) inhibitors, which are limited by an approved new drug application for use under the supervision of a practitioner licensed by law to administer them. “CE6™” and “SARMZ™” are prescription drugs because they contain a selective androgen receptor modulator, ostarine, and present significant potential safety risks to consumers who take them without the supervision of a practitioner licensed by law to administer such drugs.
Under sections 301(d) and 505(a) of the FDCA [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 FDA approved application is in effect for it. No approved applications are in effect for your “HAM™,” “CE6™,” and “SARMZ™” products. Consequently, your marketing and sale of these products without such approved applications violates these provisions of the FDCA.
According to section 502(f)(1) of the FDCA [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 CFR Part 201.5]. Prescription drugs can be used safely only at the direction, and under the supervision of a licensed practitioner and therefore, it is impossible to write “adequate directions for use” for prescription drugs. FDA-approved prescription drugs which bear the FDA-approved labeling are exempt from the requirements that they bear adequate directions for use by a layperson [21 CFR Part 201.100(c)(2) and 201.115]. Because there are no FDA-approved applications for your firm’s “HAM™,” “CE6™,” and “SARMZ™” products, their labeling fail to bear adequate directions for their intended use, causing them to be misbranded under section 502(f)(1) of the FDCA [21 U.S.C. § 352(f)(1)].
Under section 502(a) of the FDCA [21 U.S.C. § 352(a)], a drug is misbranded if its labeling is false or misleading in any particular. According to section 201(n) of the FDCA [21 U.S.C. § 321(n)], in determining whether the labeling or advertising is misleading, there shall be taken into account (among other things) not only representations made or suggested . . . but also the extent to which the labeling or advertising fails to reveal facts material in the light of such representations . . ..” The labeling for “HAM™” does not declare that it contains the PDE-5 inhibitors listed in the table above. The use of PDE-5 inhibitors, like tadalafil and vardenafil can be associated with significant safety issues and the risk of serious adverse events. The undeclared PDE-5 inhibitors in this product may pose serious health risks because consumers with underlying medical issues may take the product without knowing that it can cause serious harm or interact in dangerous ways with other drugs they may be taking. For example, PDE-5 inhibitors may interact with nitrates found in some prescription drugs (such as nitroglycerin) and can lower blood pressure to dangerous levels. Consumers with diabetes, high blood pressure, or heart disease often take nitrates. The failure to disclose the presence of the PDE-5 inhibitors contained in your “HAM™” product renders its labeling false or misleading. Accordingly, “HAM™,” is misbranded under section 502(a) of the FDCA [21 U.S.C. § 352(a)].
“HAM™,” is also misbranded under section 502(f)(2) of the FDCA [21 U.S.C. § 352(f)(2)] in that the product’s labeling lacks adequate warnings for the protection of users. There is a potential for adverse events associated with this product, particularly since someone who takes it would be unaware of the presence of the undeclared drug ingredients, tadalafil and vardenafil. Patients with underlying medical issues may take this product without knowing that it can cause serious harm or interact in dangerous ways with other drugs they may be taking. These undeclared ingredients may interact with nitrates found in some prescription drugs, such as nitroglycerin, and may lower blood pressure to dangerous levels. Among consumers who take nitrates are those with diabetes, high blood pressure, high cholesterol, or heart disease.
Your “HAM™,” “CE6™,” and “SARMZ™” are misbranded for all of the before-stated reasons. The introduction or delivery for introduction into interstate commerce of these misbranded drug products violates section 301(a) of the FDCA [21 U.S.C. § 331(a)].
Your firm failed to make and keep written procedures for the responsibility of quality control operations, including written procedures for conducting a material review and making a disposition decision, as required by 21 CFR 111.103 and 21 CFR 111.140(b)(1). Your firm's quality control personnel must approve for release, or reject, any packaged and labeled dietary supplement (including a repackaged or relabeled dietary supplement) for distribution, as required by 21 CFR 111.127(h). You provided no written procedures for the approval and release of your dietary supplements by the quality control personnel.
You must establish a system of production and process controls to 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 111.55). You must establish and follow written procedures for the responsibilities of the quality control operations (21 CFR 111.103). The quality control personnel must ensure that your 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, you 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 111.140(b)(2)). However, you provided no documentation of the quality control review to ensure the quality of the dietary supplements you distribute and that they are packaged and labeled according to the master manufacturing record. You failed to establish specifications for dietary supplement labels and for packaging that may come in contact with dietary supplements, as required by 21 CFR 111.70(d). Your firm has no written procedures to address the labeling and packaging of your dietary supplements.
You failed to establish specifications for the dietary supplement labels (label specifications) and for packaging that may come in contact with the dietary supplements (packaging specifications), as required by 21 CFR 111.70(d). You provided no documentation of specifications for your dietary supplement labels and for the packaging that may come into contact with the dietary supplements.
Your firm failed to establish specifications for the labeling of the finished packaged and labeled dietary supplements, including specifications that ensure that you applied the specified label, as required by 21 CFR 111.70(g). You provided no documentation of specifications for the packaging and labeling of your finished packaged and labeled dietary supplements.
In addition, your firm assigns an expiration date on most of your products. Any expiration date or equivalent term you place on a product label should be supported by data that demonstrates the product’s shelf life [See 72 Fed. Reg. 34752, 34856 (Jun. 25, 2007). Please note that the term “shelf life dating” includes shelf life dating, as well as expiration dating and “best if used by” dating [See 72 Fed. Reg. 34912, 34856 (Jun. 25, 2007).
The above is not intended to be an all-inclusive list of violations in connection with your products or your firm. You should take prompt action to correct all violations. To date, we have not received a response to the FORM FDA 483 issued at the close of the inspection. It is your responsibility to assure your firm complies with all requirements of federal law and FDA regulations. Failure to correct and prevent these violations or similar ones may result in legal action without further notice to you, including, without limitation, seizure and injunction.
Section 743 of the FDCA [21 U.S.C. 379j-31] authorizes FDA to assess and collect fees to cover FDA’s costs for certain activities, including reinspection-related costs. A reinspection is one or more inspections conducted subsequent to an inspection that identified noncompliance materially related to a food safety requirement of the Act, specifically to determine whether compliance has been achieved. Reinspection-related costs means all expenses, including administrative expenses, incurred in connection with FDA’s arranging, conducting, and evaluating the results of the reinspection and assessing and collecting the reinspection fees (21 U.S.C. 379j-31(a)(2)(B)). FDA will assess and collect fees for reinspection-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 the Act. Accordingly, FDA may assess fees to cover any reinspection-related costs.
Please respond to this office in writing within 15 working days from your receipt of this letter. In your response, identify the steps you have taken or will take to correct the above noted violations and prevent similar ones. In your response, please include the timeframe in which the corrections will be completed and provide any documentation that will effectively assist us in evaluating whether the corrective actions have been made and the adequacy of such. If you are unable to complete the corrective actions within 15 working days, identify the reason for the delay and the time within which you will complete the corrections.
Your written response should be sent to the U.S. Food and Drug Administration, Attn: Lakisha N. Morton, Compliance Officer, at the address noted in the letterhead. If you have questions, please contact Mrs. Morton at 404-253-1285 or write her at the noted address.
http://www.sec.gov/Archives/edgar/data/1260990/000095014405009387/g97259exv99w1.txt;,GTx Initiates Phase IIb Ostarine Clinical Trial for Cancer Cachexia, available at http://phx.corporate-ir.net/phoenix.zhtml?c=148196&p=irol-newsArticle&ID=1022240&highlight, (July 3, 2007) (indicating that Phase II trials had been initiated for ostarine in the treatment of cancer cachexia); GTx Announces Investigational Ostarine (TM) (MK-2866) Met the Primary Endpoint in the Phase II Cancer Cachexia Clinical Trial (available at http://www.businesswire.com/news/home/20081013005333/en/GTx-Announces-Investigational-Ostarine-TM-MK-2866-Met#.VFyqGclP1v4 (October 13, 2008) (stating that Phase II trials were completed); GTx Inc., FDA to Begin Trials on Cancer Drug, available at http://www.memphisdailynews.com/news/2011/jun/13/gtx-inc-fda-to-begin-trials-on-cancer-drug//print (June 13, 2011) (explaining that Phase 3 trials were being initiated for ostarine in the treatment of cancer cachexia).

References: § 321
 § 355
 § 321
 § 321
 § 321
 § 201
 § 321
 § 353
 § 352
 § 352
 § 352
 § 321
 § 352
 § 352
 § 331