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This is to advise you that the United States Food and Drug Administration (FDA) conducted an inspection of your facility located at 2215 E Germann Rd, Chandler, Arizona, from April 11 through April 27, 2022. Based on the inspectional findings we have identified 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 in FDA's home page at www.fda.gov.
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 Act [21 United States Code (U.S.C.) § 342(g)(1)] because they have been prepared, packed, or held under conditions that do not meet CGMP requirements for dietary supplements. In addition, the (b)(4) brand (b)(4) and (b)(4) brand (b)(4) (in (b)(4) and (b)(4) sizes) dietary supplement products that you manufacture are misbranded within the meaning of section 403 of the Act [21 U.S.C. § 343].
FDA acknowledges the receipt of your e-mail correspondence dated May 20, 2022 and June 23, 2022, written in response to the Form FDA 483, Inspectional Observations, issued to you at the close of the inspection. Not all of the items on the issued Form FDA 483 were addressed in your response. We address your response below, in relation to the applicable violations to which you responded.
Dietary Supplement CGMP Violations
Your significant violations of CGMP requirements are as follows:
1. You failed to establish an identity specification for your (b)(4) used in the manufacture of the (b)(4) brand (b)(4) product. Your raw material data sheet for (b)(4) states “(b)(4) Potency” as the specification for identity, but this does not establish standards to confirm the identity of the component used in the manufacture of your (b)(4) brand (b)(4) product, as required in 21 CFR 111.70(b)(1). Additionally, your raw material data sheet for (b)(4) used in the manufacture of the (b)(4) brand (b)(4) product has five minerals in the blend but your purported ICP-MS specification for identity lists “mineral detected” as the specification and fails to establish standards which can be used to confirm the identity of the (b)(4) component, as required in 21 CFR 111.70(b)(1).
2. You failed to establish component specifications that are necessary to ensure that specifications for the purity and composition of the dietary supplement manufactured using the components are met, as required in 21 CFR 111.70(b)(2). For example, you have not established specifications for the (b)(4) Premix used in the manufacture of the (b)(4) brand (b)(4) product and specifications for several of the components used in the manufacture of the (b)(4) brand (b)(4) product to ensure that specifications for purity and composition of these products are met.
We have reviewed your June 23, 2022 response to the form FDA 483. We are unable to evaluate the adequacy of your response because you did not provide documentation demonstrating you have established specifications in accordance with 21 CFR 111.70(b)(1) and 21 CFR 111.70(b)(2). You provide documents you describe as revised finished product specifications for the (b)(4) brand (b)(4) product and (b)(4) brand (b)(4) product. We note that these documents do not demonstrate that you have established specifications that provide standards to confirm the identity, purity, strength, and composition of the finished batch of your dietary supplements. For example, the finished product specification for (b)(4) brand (b)(4) product lists an “identification” specification of “Conforms to Standard” with a test method of “Eurofins or eq.” and a frequency of “Rotational.” “Conforms to standard” does not specify the extent to which the component must conform. “Eurofins or eq.” is not a test method and “Rotational” does not describe the frequency of when testing is to occur.
Similarly, the finished product specification for your (b)(4) brand (b)(4) product states testing “Frequency” as “Rotation” for several components, and does not describe the frequency of when testing is to occur.
3. You failed to establish and follow laboratory control processes that are reviewed and approved by quality control personnel, for use of criteria for selecting standard reference materials used in performing tests and examinations, as required by 21 CFR 111.315(d). Specifically, the FTIR analysis performed by your third-party laboratory uses previous shipments of components as the reference for testing and they do not own a reference library for the FTIR tests. Testing components against previous shipments of the component may confirm receipt of the same component but this does not ensure the identity, purity, quality, and strength of the component is thoroughly characterized .
4. Your quality control operations did not approve and release, or reject, each finished batch for distribution as required by 21 CFR 111.123(a)(8). Specifically, your firm distributed (b)(4) brand (b)(4) product, Lot # (b)(4), without quality control review, approval and release of the finished batch for distribution.
5. Your quality control personnel must not approve and release for distribution any batch of dietary supplement, including any reprocessed batch, that does not meet all product specifications established in accordance with 21 CFR 111.70(e), as required by 21 CFR 111.123(b)(2). Your quality control personnel released (b)(4) brand (b)(4), Lot # (b)(4), when the specification for pH was not met. Specifically, your established finished product specification for pH for the (b)(4) brand (b)(4) product is (b)(4) and the pH of the product in Lot # (b)(4) released for distribution was 6.34.
6. Your quality control personnel neither rejected a component or dietary supplement when that component or dietary supplement failed to meet a specification established in accordance with 21 CFR 111.70, nor did they approve a treatment, an in-process adjustment, or reprocessing, as permitted in 21 CFR 111.77, in accordance with 21 CFR 111.113(b)(2). Specifically, (b)(4) brand (b)(4), Lot # (b)(4), uses (b)(4) and (b)(4) as components. Testing of these two components by a third-party laboratory found both were not within your established specifications. Your quality control personnel failed to reject these components used in the manufacturing of your finished product and failed to reject the (b)(4) brand (b)(4) product, Lot # (b)(4).
7. Your quality control operations failed to approve, and release from quarantine, all components, before they are used as required by 21 CFR 111.120(e). Specifically, your quality control operations approved, and released from quarantine several components used in the manufacture of (b)(4) brand (b)(4) product, Lot # (b)(4), and components used in the manufacture of (b)(4) brand (b)(4), Lot # (b)(4). For example, the raw material data sheets for the components (b)(4), and (b)(4) used in the manufacture of your (b)(4) brand (b)(4), Lot # (b)(4), and the raw material data sheets for the (b)(4) and the (b)(4) used in the manufacture of your (b)(4) brand (b)(4) product, Lot # (b)(4) do not show a disposition by your quality control operations to approve, and release these components for use in manufacturing your finished products.
8. You failed to prepare and follow a master manufacturing record (MMR) for each unique formulation of dietary supplement that you manufacture, and for each batch size, to ensure uniformity in the finished batch from batch to batch, which includes all required information, as required by 21 CFR 111.205(a) and 21 CFR 111.210. Specifically, the Master Manufacturing Records for the following (b)(4) brand products which you manufacture were missing the following required elements:
a. (b)(4) Item # (b)(4):
i. A statement of theoretical yield of a manufactured dietary supplement expected at each point, step, or stage of the manufacturing process and the maximum and minimum percentages of theoretical yield beyond which a deviation investigation of a batch is necessary. (21 CFR 111.210(f)).
ii. Procedures for sampling and a cross-reference to procedures for tests or examinations. (21 CFR 111.210(h)(2)).
b. (b)(4) Item # (b)(4):
i. A statement of theoretical yield of a manufactured dietary supplement expected at each point, step, or stage of the manufacturing process and the maximum and minimum percentages of theoretical yield beyond which a deviation investigation of a batch is necessary. (21 CFR 111.210(f)).
ii. Procedures for sampling and a cross-reference to procedures for tests or examinations. (21 CFR 111.210(h)(2)).
Misbrand Dietary Supplements
1. Your (b)(4) brand (b)(4) and (b)(4) brand (b)(4) and (b)(4) sizes) products are misbranded within the meaning of section 403(q)(5)(F) of the Act (21 U.S.C. 343 (q)(5)(F)) in that the presentation of the nutrition information on the labeling of your product does not comply with 21 CFR 101.36. For example,
a. Your (b)(4) brand (b)(4) ((b)(4)) includes a Supplement Facts label with columns for “Amount per Serving (29.6 mL),” “Ages 4+ yrs,” “Pregnant and Lactating,” “Per serving (2.5 mL),” and “Ages 2-3 yrs.” Your “Suggested Use” panel includes different serving instructions for “2-3 Years,” “4-10 Years,” “11-17 Years,” “18 Years+,” and “Pregnant/Lactating & Seniors (65+).” Therefore, your Supplement Facts label fails to list all of the groups of individuals, by age or status (Pregnant/Lactating). for which the products are intended.
b. Your (b)(4) brand (b)(4) ((b)(4)) includes a Supplement Facts label with columns for “Amount per Serving” and “% DV” for unspecified intended consumers; however, your “Suggested Use” panel lists several intended consumers, including “children, 1-3 years,” “Children, 4-13 years,” “Adults, 14-64 years” (the serving size indicated on the Supplement Facts label), and “Pregnant/Lactating and Seniors, 65+.” Therefore, your Supplement Facts label fails to list all of the groups of individuals, by age or status (Pregnant/Lactating), for which the products are intended.
c. Your (b)(4) brand (b)(4) ((b)(4)) product labels use the incorrect unit of measurement for copper for the (b)(4) serving size. The amount must use the unit of measurement given in 21 CFR 101.9(c)(8)(iv), as required by 21 CFR 101.36(b)(2)(ii)(B).
2. Your (b)(4) brand (b)(4) ((b)(4) and (b)(4)) and (b)(4) brand (b)(4) ((b)(4) and (b)(4) sizes) products are misbranded within the meaning of section 403(q)(1)(A) of the Act [21 U.S.C. § 343(q)(1)(A)] because the serving size declared on the label is incorrect. Specifically, your product labels only list the serving size for one of the intended consumer groups listed in the “Suggested Use” panel. As your products are intended for several other age groups/categories of individual (Pregnant/Lactating or Senior), you must list the serving size for each group/category in your Supplement Facts label.
3. Your (b)(4) brand (b)(4) ((b)(4)) and (b)(4) brand (b)(4) ((b)(4) and (b)(4)) products are misbranded within the meaning of section 403(q)(1)(B) of the Act [21 U.S.C. § 343(q)(1)(B)] because the number of servings per container declared on the label is incorrect. Specifically, your product labels only list the number of servings for one of the intended consumer groups listed in the “Suggested Use” panel. As your products are intended for several other age groups/categories of individuals, you must list the number of servings for each group/category in your Supplement Facts label.
4. Your (b)(4) brand (b)(4) ((b)(4)) are misbranded within the meaning of section 403(i)(2) of the Act [21 U.S.C. § 343(i)(2)] in that the product label fails to declare the common or usual names of each ingredient used as required by 21 CFR 101.36 and 21 CFR 101.4. Specifically, the label declares trace minerals as part of the proprietary blend, but this is not the common or usual name of a dietary ingredient.
This letter is not intended to be an all-inclusive statement of violations that may exist in connection with your products. You are responsible for investigating and determining the causes of any violations 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.
This letter notifies you of our concerns and provides you an opportunity to address them. Failure to adequately address this matter may result in legal action including, without limitation, seizure, and injunction.
We also have the following comment:
Based on further review of your product and process information, your firm’s “(b)(4)” products appear to meet the definition of an acidified food (AF) and your firm’s “(b)(4)” products appear to meet the definition of a low-acid canned food (LACF) as defined in 21 CFR Parts 108, 113 and 114. Consequently, your firm may be required to register as an LACF/AF processor and file the necessary scheduled processes with FDA. We recommend working with a process authority to further evaluate your products in order to establish and file scheduled processes in accordance with 21 CFR Part 108.
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