The U.S. Food and Drug Administration conducted an inspection of your facility located at 6860 Dallas Pkwy Ste 550, Plano, TX, from April 29, 2019 through May 7, 2019. Based on the inspectional findings and a review of your product labels, we have identified serious violations of the of the Federal Food, Drug, and Cosmetic Act (the Act) and applicable regulations. You can find the Act and FDA regulations through links on the FDA’s home page at
http://www.fda.gov
.
Adulterated Dietary Supplements
The inspection of your facility revealed serious violations of FDA’s regulations for Current Good Manufacturing Practice (CGMP) in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements, under Title 21, Code of Federal Regulations (CFR), Part 111 (21 CFR Part 111). These violations cause your dietary supplement products to be adulterated within the meaning of section 402(g)(1) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 342(g)(1)] in that they have been prepared, packed, or held under conditions that do not meet CGMP requirements for dietary supplements.
Your dietary supplement products manufactured under the brand name Smart Caps are adulterated within the meaning of section 402(g)(1) of the Act [21 U.S.C. § 342(g)(1)] in that they have been prepared, packed, or held under conditions that do not meet the Current Good Manufacturing (CGMP) regulations for dietary supplements, Title 21, Code of Federal Regulations, Part 111 (21 CFR Part 111). We have received your written response dated May 29, 2019, concerning our investigator’s observations noted on the Form FDA 483, Inspectional Observations, which was issued to you on May 7, 2019. However, your response lacked supporting documentation and timely development of corrective and preventive actions and implementation for the reasons further explained below.
Specifically, the significant violations documented during the inspection include, but are not limited to, the following:
- You failed to establish specifications for each dietary supplement for the identity, purity, strength, and composition of the finished batch of the dietary supplement, and for limits on those types of contamination that may adulterate, or that may lead to adulteration 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, you have not established product specifications for the identity, purity, strength, and composition of your finished dietary supplement, Smart Caps. Nor have you established contamination limits for this product.
Once you establish finished product specifications, you must verify that specifications are met, as required by 21 CFR 111.75(c).
We have reviewed your response dated May 29, 2019 in which you stated that a written SOP will be established for product specifications and that such an SOP will also include contamination limits, but you did not actually create any SOPs or submit them with your May 29 response. We reviewed your response dated August 29, 2019, in which you state that product specifications are defined in an attached document titled SOP 001 “Release for Sale.” However, this document does not contain product specifications for all the dietary supplements that you distribute, nor does it contain specifications for all the components declared on the Supplement Facts panel. Additionally, no specifications are established for the purity, strength, and composition of the finished batch of any dietary supplement products. Therefore, we still do not have enough information to assess the adequacy of your corrective actions.
Furthermore, the Supplement Facts panel on your dietary supplement Smart Caps product declares Octodrine as a dietary ingredient. This ingredient is also called, among other names, 1,5-DMHA, 2-amino-6-methylheptane, 2-amino-5methylheptane, 1,5-Dimethylhexylamine, 2-Isooctyl amine, 6-Amino-2-methylheptane, Amidrine, and 2-Metil-6-amino-eptano, and will be referred to hereinafter as DMHA.
The term “dietary supplement” is defined in section 201(ff) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 321(ff)]. Given that you have declared DMHA as a dietary ingredient in the labeling of your product, we assume you have a basis to conclude that DMHA is a “dietary ingredient” under section 201(ff)(1) of the Act [21 U.S.C. § 321(ff)(1)]. If you have a basis to conclude that DMHA is a “dietary ingredient,” it would also be a “new dietary ingredient” (i.e., a dietary ingredient not marketed in the United States before October 15, 1994) under section 413(d) of the Act [21 U.S.C. § 350b(d)].
Under section 413 of the Act [21 U.S.C. § 350b], a dietary supplement that contains a new dietary ingredient shall be deemed adulterated under section 402(f) of the Act [21 U.S.C. § 342(f)] unless it meets one of two requirements:
- The dietary supplement contains only dietary ingredients that have been present in the food supply as an article used for food in a form in which the food has not been chemically altered; or
- There is a history of use or other evidence of safety establishing that the dietary ingredient when used under the conditions recommended or suggested in the labeling of the dietary supplement will reasonably be expected to be safe and, at least 75 days before being introduced or delivered for introduction into interstate commerce, the manufacturer or distributor of the dietary ingredient or dietary supplement provides FDA with information, including any citation to published articles, which is the basis on which the manufacturer or distributor has concluded that a dietary supplement containing such dietary ingredient will reasonably be expected to be safe.
To the best of FDA’s knowledge, there is no information demonstrating that DMHA was lawfully marketed as a dietary ingredient in the United States before October 15, 1994, nor is there information demonstrating that this ingredient has been present in the food supply as an article used for human food in a form in which the food has not been chemically altered. Assuming DMHA is a dietary ingredient, in the absence of such information, DMHA would be subject to the notification requirement in section 413(a)(2) of the Act [21 U.S.C. § 350b(a)(2)] and 21 CFR 190.6. Products for which the manufacturer or distributor is required to submit a new dietary ingredients notification under section 413(a)(2) and 21 CFR 190.6, but for which the required notification has not been submitted, are adulterated under sections 402(f) and 413(a) of the Act [21 U.S.C. §§ 342(f) and 350b(a)].
Even if a new dietary ingredient notification had been submitted under section 413(a)(2) and 21 CFR 190.6, we know of no evidence that would establish that DMHA could be lawfully marketed as a new dietary ingredient in your Smart Caps product. In the absence of a history of use or other evidence of safety establishing that DMHA, when used under the conditions recommended or suggested in the labeling as a dietary ingredient, will reasonably be expected to be safe, dietary supplements containing DMHA as a new dietary ingredient are adulterated under sections 402(f) and 413(a) of the Act because there is inadequate information to provide reasonable assurance that such ingredient does not present a significant or unreasonable risk of illness or injury. Introduction of such products into interstate commerce is prohibited under sections 301(a) and (v) of the Act [21 U.S.C. § 331(a) and (v)]. To the best of FDA’s knowledge, there is no history of use or other evidence of safety establishing that DMHA will reasonably be expected to be safe when used as a dietary ingredient.
We also note that we have questions about whether DMHA is, in fact, a dietary ingredient. If DMHA were not a dietary ingredient under section 201(ff)(1) of the Act, it would be an unsafe food additive. If a substance is not generally recognized as safe (GRAS) by qualified experts for its intended use in food and does not qualify for any of the other exemptions from the food additive definition, it is a food additive. Food additives require premarket approval based on data demonstrating safety. Any food additive that has not been approved for its intended use in food is deemed to be unsafe and causes the food to be adulterated under section 402(a)(2)(C)(i) of the Act [21 U.S.C. § 342(a)(C)(i)]. Adulterated foods cannot be legally imported into or marketed in the United States.
Section 201(s) of the Act [21 U.S.C § 321(s)] exempts dietary ingredients used in dietary supplements from the food additive definition. However, non-dietary ingredients intended for use in dietary supplements are not exempt from the food additive definition and must meet the same requirements as substances added to conventional foods. In other words, a non-dietary ingredient added to a dietary supplement must be used in accordance with a food additive regulation or be GRAS for its intended use, unless it qualifies for another exception to the food additive definition.
DMHA it is not generally recognized as safe under its conditions of use in your dietary supplement products. If DMHA is not a dietary ingredient under section 201(ff)(1) of the Act, dietary supplements containing DMHA would be adulterated under section 402(a)(2)(C)(i) of the Act because they would contain an unsafe food additive.
The violations cited in this letter are not intended to be an all-inclusive list of violations that exist in connection with your products. 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, including FDA regulations.
You should take prompt action to correct the violations cited in this letter, as well as any other violations associated with your Smart Caps product or other dietary supplement products marketed by your firm, including any that contain DMHA. We also remind you that the new dietary ingredient notification requirement applies to all dietary supplements that contain new dietary ingredients that have not been present in the food supply as articles used for food in a form in which the food has not been chemically altered. Failure to immediately cease distribution of your Smart Cap products and any other products you market that contain DMHA could result in enforcement action by FDA without further notice. Sections 302 and 304 of the Act provide for seizure of violative products and injunction against the manufacturers and distributors of violative products [21 U.S.C. §§ 332 and 334]. Failure to correct these violations may result in enforcement action without further notice, including, without limitation, seizure and/or injunction.
We also offer the following comment about your dietary supplement products:
You are required to establish and follow written procedures for the responsibilities of the quality control operations, including written procedures for conducting a material review and making a disposition decision, and for approving or rejecting any reprocessing, as required by 21 CFR 111.103.
During the inspection, you told our investigator that your firm does not have any written procedures detailing the responsibilities of the quality control operations, but that you do have a procedure in place wherein you require the contract warehouse to inspect incoming finished dietary supplements. You provided a copy of this process titled “Revital U - Incoming Product QC” to our investigator. However, this document does not provide a process for verifying that product specifications are met, nor does the document provide a process for documenting material reviews of products and disposition decisions.
We have reviewed your response dated May 29, 2019 in which you stated that a written SOP will be established for quality control operations by August 2019. We have also reviewed your August 29, 2019 response, wherein you repeat that a Quality Control/Release for Sale will be established, but you have not yet done so. You also note that you rely on contract manufacturers to conduct quality control and maintain appropriate documentation, but you nonetheless intend to establish the previously mentioned SOP.
As a dietary supplement distributor that contracts with other manufacturing firms to manufacture dietary supplements that you distribute under your own label, you have an obligation to know what and how manufacturing activities are performed so that your firm can make decisions related to whether your packaged and labeled dietary supplement products conform to established specifications and whether to approve and release the products for distribution [see 72 Fed. Reg. 34752, 34790 (Jun. 25, 2007)]. Your firm introduces or delivers, or causes the introduction or delivery, of dietary supplements into interstate commerce in their final form for distribution to consumers. As such, your firm has an overarching and ultimate responsibility to ensure that all phases of the production of those products are in compliance with dietary supplement CGMP requirements.
Although your firm may contract out certain dietary supplement manufacturing operations, it cannot, by the same token, contract out its ultimate responsibility to ensure that the dietary supplements it places into commerce (or causes to be placed into commerce) are 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 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 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 Act)). The 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)). Thus, a firm that enters a contract with other firms to conduct certain dietary supplement manufacturing, packaging, and/or labeling operations for it is responsible for ensuring that the product is not adulterated for failure to comply with dietary supplement CGMP requirements, regardless of who actually performs the dietary supplement CGMP operations.
You should notify this office in writing within fifteen (15) business days from your receipt of this letter of the specific steps you have taken to correct the violations noted above. Your response should include documentation of your corrective actions, including an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documents. If you believe that your products are not in violation of the Act, include your reasoning and any supporting information for our consideration. If you cannot complete all corrective actions within fifteen business days, please explain the reason for your delay and the date by which you will make the correction.
Section 743 of the Act [21 USC § 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 USC § 379j-31(a)(2)(B)]. For a domestic facility, 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.
