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August 5, 2022

In reply, refer to CMS 620224

WARNING LETTER

Dear Mr. Menke:

The U.S. Food and Drug Administration (FDA) inspected your facility, located at 1001 S. 3rd Street West, Missoula, Montana, on September 14-17 and 28, 2021. During the inspection, our investigators collected product labels for your products. Based on the inspectional findings and subsequent review of your product labels and labeling, 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 correspondence sent electronically on October 13, 2021, November 11, 2021, and December 22, 2021, concerning our inspectional observations listed on the FDA-483, Inspectional Observations, issued to you at the close of the inspection. We address this response below as it relates to the noted observations.

Adulterated Dietary Supplements

The inspection revealed serious violations of the 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 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 of CGMP requirements observed during the inspection include, but are not limited to, the following:

1. 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, composition, and for limits on those types of contamination that may adulterate or lead to adulteration of the finished batch of the dietary supplement, as required by 21 CFR 111.75(c). Specifically, you have not provided adequate documentation of your basis for determining that compliance with the specification(s) selected under 21 CFR 111.75(c)(1), through the use of appropriate tests or examinations conducted under 21 CFR 111.75(c)(2), will ensure that your finished batch of dietary supplements meets all product specifications for identity, purity, strength, and composition, and the limits on those types of contamination that may adulterate, or that may lead to the adulteration of, the dietary supplement, as required by 21 CFR 111.75(c)(3), for the following finished products manufactured at your facility: (b)(4).

We have received your responses dated October 13, 2021, November 11, 2021, and December 22, 2021; however, we are unable to evaluate the adequacy of your corrective action. In your responses, you provided an updated Certificate of Analysis for (b)(4) Lot Number (b)(4), an updated Certificate of Analysis for (b)(4) Lot Number (b)(4); as well as Standard Operating Procedures (SOPs) SOPQA2025, (b)(4) Testing for Finished Dietary Supplement Product, SOPPE1001 Development of Release Specifications for Components and Labeling, and SOPPE1002, Development of Finished Product and In-process Specifications. However, your responses do not provide documentation to support that you are verifying that the finished dietary supplements meet established product specifications.

2. Your quality control personnel failed to follow your written procedures for the responsibilities of the quality control operations, as required by 21 CFR 111.103. Specifically, your written procedure, SOPQA1008, Quality Assurance Authorities and Responsibilities, states your Quality Assurance (QA) authorities have the responsibility to “[r]eview and approve decisions for investigating product complaints”. The Quality Assurance sections of QA-705-C v9, Manufacturing Defect (MD) Intake and Preliminary Investigation Form, which documents the receipt and visual inspection of returned product and whether to investigate the complaint, was not completed and approved by quality assurance for complaint records 50638, 50643, 50652, 50656, and 50469.

We have received your responses dated October 13, 2021, November 11, 2021, and December 22, 2021. In your responses, you stated you have retrained applicable personnel and started addendums to the referenced complaints regarding investigations. Your corrective actions will be evaluated during the next inspection of your firm.

3. You failed to verify that the laboratory examination and testing methodologies are appropriate for their intended use, as required by 21 CFR 111.320(a). Specifically, you conducted identity tests for multiple dietary ingredients within a blend by Fourier-Transform Infrared Spectroscopy (FTIR). For the blends (b)(4) Lot (b)(4) Lot (b)(4), and (b)(4) Lot (b)(4), FTIR could not identify the individual dietary ingredients within the blend. While FTIR may be used to verify that the supplier is consistent in sending the same component, FTIR does not ensure that the component received is what it is claimed to be when the component is a blend with multiple ingredients.

We have received your responses dated October 13, 2021, November 11, 2021, and December 22, 2021; however, we are unable to evaluate the adequacy of your corrective actions. In your responses, you stated you have, or are working with a third-party laboratory to develop reference standards for components and finished products using methodologies including (b)(4), as applicable, but did not provide further evidence or documentation of the development of the reference standards.

4. You failed to establish and follow laboratory control processes for selecting standard reference materials used in performing tests and examinations, as required by 21 CFR 111.315(d). Specifically, previously released lots of glycerin, (b)(4) yeast, and (b)(4) powder used in manufacturing, were used as reference standards in FTIR analysis; however, you failed to establish any criteria to establish a reference standard. Further, you failed to demonstrate that the non-compendia standards originating from these lots were thoroughly characterized to ensure their identity, purity, quality, and strength. Non-compendia reference standard materials should be of the highest purity by reasonable effort and should be thoroughly characterized to ensure their identity, purity, quality, and strength. Once characterized, the official qualification documentation of these standards must be reviewed and approved by Quality Control prior to use, as required by 21 CFR 111.110(a).

We have received your responses dated October 13, 2021, November 11, 2021, and December 22, 2021. We acknowledge that you have purchased a reference standard for glycerin and discontinued the use of (b)(4) powder within products. Regarding the component (b)(4) yeast, although your responses identified that you have adopted Lot (b)(4) as a reference standard and provided supporting documentation for characterization, you did not provide an explanation as to why Lot (b)(4) was chosen as the reference standard. Further, your document DQL1010, Testing Requisition and Summary Report: Components state your identity specification for the reference standard as “conforms” without defining acceptance criteria so that a decision can be made to accept or reject test material against the reference standard.

Misbranded Dietary Supplements

In addition, the (b)(4) products are misbranded dietary supplements under Section 403 of the Act [21 U.S.C. § 343] because they do not comply with the labeling requirements for dietary supplements, as required by 21 CFR 101, and as follows:

1. The (b)(4) and (b)(4) 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. Serving size for a dietary supplement is the maximum amount consumed per eating occasion as recommended on the product label, as defined in 21 CFR 101.9(b) and 21 CFR 101.12(b) Table 2. For example:

a. The (b)(4) label’s directions state to “Take 1-2 chewable tablets daily as needed, at bedtime.”, but the serving size listed in the Supplement Facts label is 1 tablet.

b. The (b)(4) label’s directions state "Adults should take 1 tablet twice daily. Children aged 7-16 years should take 1 tablet daily." Thus, the amount recommended on the label per eating occasion is 1 tablet, but the serving size listed in the Supplement Facts label is 2 tablets.

2. The (b)(4) Calcium, and (b)(4) 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 products does not comply with 21 CFR 101.36. For example:

a. The (b)(4) Supplement Facts label declares the dietary ingredients “Vitamin B3”, “Vitamin B5”, and “Vitamin B7”. However, “Vitamin B3”, “Vitamin B5”, and “Vitamin B7” are not synonyms specified for niacin, pantothenic acid, or biotin, respectively, as noted in 21 CFR 101.9 or 101.36(b)(2)(i)(B).

b. The (b)(4) Facts label declares “Vitamin B1” and “Vitamin B2”. While each of these alternative names is an acceptable synonym for thiamine and riboflavin, respectively, the synonym must parenthetically follow the name of the nutrient in accordance with 21 CFR 101.36(b)(2)(i)(B)(2). Furthermore, the source ingredient that supplies a dietary ingredient may be identified within the nutrition label in parentheses immediately following or indented beneath the name of a dietary ingredient and preceded by the words "as" or "from", in accordance with 21 CFR 101.36(d).

c. The (b)(4) Facts label bears the following statement: “Percent daily values are based on a 2,000 calorie diet.” This statement is only permitted when the percent of Daily Value is declared for total fat, saturated fat, total carbohydrate, dietary fiber, or protein, as required by 21 CFR 101.9(c) and 21 CFR 101.36(b)(2)(iii)(D).

d. The (b)(4) Facts label fails to place pantothenic acid before biotin, as noted in 21 CFR 101.36(b)(2)(i)(B).

e. The (b)(4) Facts label (for the (b)(4) Calcium product and as included in the (b)(4) product) declares the term “Vitamin K (as (b)(4))” as a (b)(3)-dietary ingredient. We note the term Vitamin K, as stated in 21 CFR 101.9(c)(8)(iv), only applies to the (b)(2)-dietary ingredient phylloquinone [81 FR 33742, at 33905 and 33935].

f. The (b)(4) Facts label declares the serving size as 2 tablets. However, the Supplement Facts label fails to include the nutrition information for children aged 7-16 years for which the serving size is 1 tablet, per the Directions for Use. The percent of Daily Value shall be based on Recommended Daily Intake (RDI) or Daily Reference Value (DRV) values for adults and children 4 or more years of age, unless the product is represented or purported to be specifically for infants through 12 months of age, children 1 through 3 years of age, pregnant women, or lactating women, in which case the column heading shall clearly state the intended group. If the product is for persons within more than one group, the percent of Daily Value for each group shall be presented in separate columns as shown in paragraph (e)(11)(ii) of this section, as required by 21 CFR 101.36(b)(2)(iii)(E).

g. The (b)(4) Facts label fails to place a % mark following each of the numerical values pertaining to the % DVs, as noted in 21 CFR 101.36(b)(2)(iii)(B).

3. The (b)(4) Calcium, 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 source ingredients and a dietary ingredient fail to be declared on the label by the common or usual name, in accordance with 21 CFR 101.4 and 21 CFR 101.36. For example:

a. The (b)(4) Facts label (for the (b)(4) Calcium product and as included in the (b)(4) product) declare the names “(b)(4) minerals” and “(b)(4)”.

b. The Vitamin Code Growth Factor product included in the (b)(4) product declares “(b)(4)” on the Supplement Facts label.

c. The (b)(4) Facts label (for the (b)(4) Calcium product and as included in the (b)(4) product) declares the source ingredient “(b)(4)” as well as the (b)(3)-dietary ingredient “(b)(4)”, each of which is not the common or usual name of an 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 offer the following comment:

1. Regarding Deviation MDD(b)(4)’s out of specification result for your product (b)(4), Lot (b)(4), your initial result for the subject sample was 3650 colony forming units per gram (cfu/g), which exceeded the specification of No More Than (NMT) (b)(4) cfu/g. Your retest of this product yielded a result of 725 cfu/g, which is within specification; however, we observed the following:

• According to your procedure SOPQL3004, Total Aerobic Plate Count, “if a plate contains less than (b)(4) cfu, record number of cfu, but do NOT use these counts to determine the final average cfu/g. Plates with <(b)(4) cfu may be inaccurate”. You averaged a plate count of 1 in the final average result for the retest.
• You stated that the result of (b)(4) cfu/g is acceptable (b)(4). The results show that the colony count did not exceed the maximum acceptable count of (b)(4) colonies established by (b)(4). Furthermore, the maximum acceptable count does not negate meeting the established specification of (b)(4) cfu/g.

In addition, regarding Deviation MDD(b)(4)’s out of specification result for the product Turmeric (b)(4) Caps Lot (b)(4), your initial result for the sample was 8200 cfu/g, which exceeded the specification of (b)(4) cfu/g. Your retest yielded a result of 250 cfu/g; however, in your procedure SOPQL3069, Microbial Data Deviation Investigation, it states “[i]f one or more of the test results do not confirm the original result, further investigation may be necessary.” You did not document that a further investigation was performed, and you did not document why further investigation was not necessary. Despite this, new samples were prepared and analyzed. The result of the new sample was 300 cfu/g, which was accepted.

We ask for clarification regarding these noted items regarding the deviation investigations related to (b)(4), Lot (b)(4) and Turmeric (b)(4) Capsules, Lot (b)(4).

Please notify FDA in writing, within 15 working days of receipt of this letter, of the specific steps you have taken to address any 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 actions within 15 working days, state the reason for the delay and the time within which you will do so. If you believe that your products are not in violation of the Act, include your reasoning and any supporting information for our consideration.

Please send your reply to the Food and Drug Administration, Attention: Amy R. Glynn, Compliance Officer, 22215 26th Avenue SE, Suite 210, Bothell, Washington 98021-4421. If you have any questions regarding this letter, please contact Compliance Officer Glynn at 425-302-0411.

Sincerely,
/S/

Miriam R. Burbach
District Director
Program Division Director
Office of Human and Animal Food
Operations – West Division 6