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The U.S. Food and Drug Administration (FDA) conducted an inspection of your facility located at 300 N. Macarthur Blvd, Oklahoma City, Oklahoma, from June 7, 2022, through June 13, 2022. Based on inspectional findings and a review of your product labels, 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 on the FDA’s home page at www.fda.gov.
We received your written response, dated July 5, 2022, to the Form FDA 483, Inspectional Observations, issued to you at the close of the inspection. We have reviewed that document and our comments are listed following each of the significant violations.
Adulterated Dietary Supplements
The inspection of your facility revealed serious violations of the 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). Based on the inspection, we determined that your products, including your (b)(4), and (b)(4) products 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 CGMP requirements for dietary supplements.
The significant violations documented during the inspection include, but are not limited to the following:
1. You failed to establish product specifications for the identity and purity of the finished batch of the dietary supplement as required by 21 CFR 111.70(e). Specifically, you told our investigator that you have created finished product specifications for your (b)(4) and (b)(4) products; however, these specifications fail to include established specifications for the identity and purity of each of the products.
We acknowledge your response, which states, “Raw materials and finished product shall be tested for identity, purity, or composition as stated in the revised SOP…The Quality Department will be working with the labs to establish specifications for identity, purity, and composition for finished products.” However, we are unable to evaluate the adequacy of your corrective action because you did not provide finished product specifications for our review.
2. You failed to prepare and follow a written 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, as required by 21 CFR 111.205(a). Specifically, you provided MMRs for the (b)(4) and (b)(4). You also provided batch production records (BPR) for two lots of (b)(4) and two lots of (b)(4). With the exception of one lot of the (b)(4), none of the BPRs matched the MMRs for the products. As such, the BPRs do not support that you are preparing and following written MMRs for each unique formulation and batch size of dietary supplement that you manufacture. In preparing the MMRs, they must include the required elements of 21 CFR 111.210.
We reviewed your response in which you state, “Quality Supplement Manufacturing will have the SOP revised and implement the new process in place within the next 90 days.” We are unable to evaluate the adequacy of your corrective action because you did not provide any MMRs for any manufactured dietary supplement for our review.
3. You failed to verify, for a subset of finished dietary supplement batches that you identify through a sound statistical sampling plan (or for every finished batch), that your finished batch of the dietary supplement meets product specifications for identity, purity, strength, and composition, as required by 21 CFR 111.75(c). Specifically, your firm’s BPRs for the (b)(4) (lots (b)(4) and (b)(4)) and (b)(4) (lots (b)(4) and (b)(4)) indicate that the supplement products contain multiple dietary ingredients; however, during inspection, you stated that you verify the strength for only one dietary ingredient in each of the dietary supplements. Selecting only one of multiple dietary ingredients in the supplement products does not verify your production and process control system is producing a dietary supplement that meets the required product specifications for identity, purity, strength, and composition of the dietary supplement.
We reviewed your response in which you state, “Quality Supplement Manufacturing will have the SOP revised and implement the new process in place within the next 90 days.” We are unable to evaluate the adequacy of your corrective action because you did not provide any standard operating procedures for review.
4. You failed to ensure all tests and examinations that are used to determine whether a specification is met are appropriate and scientifically valid in accordance with 21 CFR 111.75(h)(1). Specifically, you stated “the only analysis for the finished product is by input and a (b)(4) test.” The input of the various dietary ingredients during production and subsequent analysis of a single dietary ingredient alone in the finished product is not sufficient to verify specifications for identity, purity, strength, and composition in a finished product because inputting specific amounts of various ingredients during manufacturing does not ensure that specifications are met in the finished product, nor does later testing for a single dietary ingredient assess any other components within the finished product.
5. Your quality control personnel did not reject a component and dietary supplement for which a specification was not met, as required by 21 CFR 111.77(a), nor did they approve a treatment, an in-process adjustment, or reprocessing that would ensure the quality of the finished dietary supplement and that the dietary supplement would be packaged and labeled as specified in the MMR. You have in-process specifications within your MMR for fill weights of capsules and tablets to ensure that the finished product meets the label declarations. In several instances, your product neither met these specifications nor were they approved for an appropriate treatment, in-process adjustment, or reprocessing. For example:
o The tablet run sheet for (b)(4) (lot (b)(4)) includes out of specification fill weights. The BPR states the fill weight range is (b)(4) mg. The tablet run sheet has weights throughout in the (b)(4) range and notes “tablet won’t hit the weight so running (b)(4).” A corrective action approved by the firm’s quality unit was not documented.
o The capsule run sheet for (b)(4) (lot (b)(4)) includes out of specification fill weights. The BPR states the fill weight range as (b)(4) mg. The QC capsule run sheet has fill weights listed at (b)(4) mg, (b)(4) mg, (b)(4) mg and (b)(4) mg. There are several notes that adjustments are being made but no corrective action approved by the firm’s quality unit addresses the underweight capsules.
We have reviewed your written response in which you state that the root cause for the out of specification fill weights for your (b)(4) product was “lack of training” and that you would be “revising your sample run process” along with “[a] new SOP…to explain the sample run process and how to run deviations.” We are unable to evaluate the adequacy of your corrective action because you did not provide any training records for review, new SOPs, or other documentation on your new sample run or deviation process.
6. Your quality control personnel failed to reject the component, dietary supplement, package, or label, when a specification established in accordance with 21 CFR 111.70 is not met, nor did they approve a permitted treatment, an in-process adjustment, or reprocessing, as required by 21 CFR 111.113(b)(2). For example, your finished product test for your (b)(4)(lot (b)(4)) includes strength analysis for the dietary ingredient (b)(4). The product specification for the ingredient in the supplement products is (b)(4) mg/tablet. An out of specification result of (b)(4) mg/tablet was reported by your contract lab (b)(4). A corrective action approved by the firm’s quality unit was not documented.
We have reviewed your written response in which you state that “[the] Quality Department will be signing off on all finished product test results.” We are unable to evaluate the adequacy of your corrective action because you did not provide any test result records or other documentation to show the implementation of the new procedure.
7. Your quality control operations for the MMR, the BPR, and manufacturing operations failed to include approving or rejecting any reprocessing, as required by 21 CFR 111.123(a)(5). For example, (b)(4) barrels of (b)(4) tablets (lot (b)(4)) were returned to the blending stage for grinding; however, the BPR does not include documentation showing that your quality control operations approved or rejected any reprocessing.
8. Your quality control failed to document in the BPR at the time of performance the approval and release, or the rejection of a batch of dietary supplement for distribution, as required by 21 CFR 111.260(l)(3). For example, BPRs for (b)(4) (lot (b)(4) and (b)(4)) do not include documentation that your quality control personnel approved and released, or rejected, the batches for distribution.
Misbranded Dietary Supplements
In addition, even if your (b)(4) product was not an unapproved new and misbranded drug, this product and others would be misbranded under section 403 of the Act because it does not comply with the labeling requirements for dietary supplements.
Specifically, we identified the following:
1. Your (b)(4) and (b)(4) dietary supplement products are misbranded under section 403(q)(5)(F) of the Act [21 U.S.C. § 343(q)(5)(F)] in that the presentation of nutrition information on the labeling for your products does not comply with the labeling requirements for dietary supplements in 21 CFR 101.36. For example,
o Your (b)(4) Facts label fails to declare the source of the (b)(4). (21 CFR 101.36(d))
o Your (b)(4) Facts label incorrectly declares as a (b)(2)-dietary ingredient, “(b)(4)”. 21 CFR 101.9(c)(8)(iv) lists an RDI for (b)(4) of (b)(4) mcg based on the AI (adequate intake) that pertains only to (b)(4). (b)(4) should be listed as a (b)(3)-dietary ingredient.
o Your (b)(4) product fails to declare the source of the (b)(4) as indicated in the master manufacturing record; e.g., (b)(4) (as (b)(4)). (21 CFR 101.36(d))
o Your (b)(4) fails to express the metric quantitative amounts by weight per serving of other dietary ingredients in accordance with 21 CFR 101.36(b)(3)(ii)(A); for example, (b)(4) mg should be (b)(4)g.
o Your (b)(4) fails to declare the quantitative amount of (b)(4) with the % Daily Value based upon the presence of (b)(4) in the product formula, as required by 21 CFR 101.36(b)(2)
2. Your (b)(4) product is misbranded within the meaning of section 403(w)(2) of the Act [21 U.S.C. § 343(w)(2)], in that the finished product labels fail to declare the major food allergen, shrimp and crab, as required by section 403(w)(1) of the Act. Specifically, as you have chosen to use a “Contains” statement, you must declare the specific type of Crustacean shellfish.
3. Your (b)(4) product and (b)(4) products are each misbranded within the meaning of section 403(i)(2) of the Act [21 U.S.C. § 343(i)(2)] in that each 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,
o Your (b)(4) Facts label declares the (b)(4) but fails to state the standardized common name “(b)(4)” as listed in the reference Herbs of Commerce, as incorporated by 21 CFR 101.4(h).
o Your (b)(4) product’s ingredient list declares “flavorless coating (Yellow 5, Red 40, Blue 1)” which is not the common or usual name of an ingredient. Furthermore, your batch production records for the product indicate “(b)(4)” as an ingredient but this ingredient does not appear in the ingredient list of your product label.
o Your (b)(4) Facts label declares the (b)(4) but fails to state the standardized common name “(b)(4)” as listed in Herbs of Commerce. [See 21 CFR 101.4(h)] Furthermore, the source ingredient (b)(4) fails to be listed first within the parentheses, and then followed by the (b)(4) name within parentheses; for example, (b)(4)
4. Your (b)(4) product label is misbranded within the meaning of section 403(y) of the Act [21 U.S.C. § 343(y)] in that the label fails to bear a domestic address or domestic phone number through which the responsible person (as described in section 761 of the Act) may receive a report of a serious adverse event with such dietary supplement.
This letter is not intended to be an all-inclusive statement of violations that may exist at your facility or 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.
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