FDA – Warning Letter -September 1

FDA – Warning Letter -September 1

The U.S. Food and Drug Administration (FDA) conducted an inspection of your facility, from March 8, 2023 through March 15, 2023. Based on inspectional findings and review of the labels collected during the inspection, we identified significant 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 FDA’s home page at www.fda.gov.

We received written correspondence from you dated March 30, 2023 to the Form FDA 483, Inspectional Observations, issued to you at the close of the inspection. We address your response below, in relation to the applicable violation.

Adulterated Dietary Supplements

During the inspection, our investigators found significant violations of Title 21, Code of Federal Regulations (CFR), Part 111 (21 CFR Part 111), Current Good Manufacturing Practice (cGMP) in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements. These violations cause the (b)(4), and (b)(4) sticks dietary supplements manufactured at your facility 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.

FDA - Warning Letter -September 1

Your significant violations of the cGMP requirements are as follows:

1. You failed to, for each dietary supplement that you manufacture, establish product specifications for the strength and composition of the finished batch of the dietary supplement, as required by 21 CFR 111.70(e). Specifically, your finished product specification sheet for the (b)(4) dietary supplement finished product failed to include specifications for the strength and composition of each ingredient in the finished product.

Once you have established the required specifications, you must take specific actions to determine whether those specifications are met, as required by 21 CFR 111.73 and 21 CFR 111.75, and you must make and keep records of all activities relating to such specifications, in accordance with 21 CFR 111.95.

2. You failed to establish component specifications that are necessary to ensure that specifications for the strength and composition of dietary supplements manufactured using the components are met, as required by 21 CFR 111.70(b)(2). Specifically, your component specifications sheet you provided for the component (b)(4), an ingredient blend you use in the manufacture of (b)(4) sticks, did not include strength and composition specifications for the (b)(4) ingredients the product label lists as present in the blend.

Once you have established the required specifications, you must take specific actions to determine whether those specifications are met, as required by 21 CFR 111.73 and 21 CFR 111.75, and you must make and keep records of all activities relating to such specifications, in accordance with 21 CFR 111.95.

We received your March 30, 2023, response, in which you said, “meetings have been conducted in researching HPLC [High Performance Liquid Chromatography] units” for use in testing, “current action is sending raw material samples to a third-party laboratory . . . to obtain the information for purity and strength and to update specification sheets for each ingredient raw material,” and that you have added into your associated procedure “a clause where we will ask our vendor for a third-party testing COA [Certificate of Analysis]” for blended raw material ingredients (i.e., (b)(4)). In your response, you did not provide evidence that the lacking component specifications have been established; thus, we are unable to assess the adequacy of your corrective action.

3. You failed to conduct at least one appropriate test or examination to verify the identity of any component that is a dietary ingredient before using such component, as required by 21 CFR 111.75(a)(1)(i). For example, your specification sheets you provided for the following components all list Fourier transform infrared spectroscopy (FTIR) testing as the method for verifying identity: (b)(4) and (b)(4) (used in the manufacture of the (b)(4) product) and (b)(4) (used in the manufacture of the (b)(4) product). However, during our inspection, you said your FTIR instrument has been broken since June 29, 2021 and you have not used it for identity testing since that time.

We received your March 30, 2023, response, in which you said your FTIR is still not functioning, you are sending raw material samples (including for the component (b)(4)) to a third-party laboratory for testing, and corrective actions will be completed within (b)(4) to (b)(4) to test all your existing ingredients. Although your response included a quotation from a third-party laboratory and you said you sent the component (b)(4) to the laboratory for testing, you did not include evidence that you have sent out samples to a third-party laboratory for testing, nor did you include any testing results. Therefore, we are unable to assess the adequacy of your corrective action.

4. You failed to confirm that the components you use meet the limits you have established on the 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(a)(2). When relying on a COA from the supplier of the component that you receive, you failed to first qualify the supplier by establishing the reliability of the supplier’s COA through confirmation of the results of the supplier’s tests or examinations, as required by 21 CFR 111.75(a)(2)(ii)(A).

Specifically, during the inspection, you stated to our investigator that, to determine that the components you use meet the limits you have established on the types of contamination that may adulterate or lead to adulteration of the finished batch of the dietary supplement, your firm relies on supplier COAs for raw materials, including dietary ingredients, because your firm does not conduct testing for limits on certain contaminants, such as heavy metals and pesticides for powdered components and microbial specifications for liquid components. However, you have not established the reliability of the supplier COAs.

For example, you stated you have not confirmed the reliability of the COAs for (b)(4) and (b)(4) used in the (b)(4) Juice finished product, or of the COA for (b)(4) used in the manufacture of the (b)(4) finished product.

Additionally, you rely on supplier COAs that do not include test results for the contamination limits you have established, as required by 21 CFR 111.75(a)(2)(ii)(B). Specifically, the (b)(4) juice concentrate component specification includes limits for heavy metals, pesticides, and microbial content (including Salmonella and S. aureus); however, the COA for lot (b)(4) does not include test results for heavy metals, pesticides, Salmonella, or S. aureus. Likewise, the (b)(4) component specification includes limits for S. aureus; however, the COA for lot (b)(4) does not include test results for S. aureus.

The (b)(4) concentrate and (b)(4) components were both used in the manufacture of (b)(4), lot (b)(4). Furthermore, the (b)(4) and (b)(4) component specifications include pesticide limits; however, the supplier COAs for lot (b)(4) of (b)(4) and for lot (b)(4) of (b)(4) do not include test results for pesticides. These components were used in the manufacture of (b)(4), lot (b)(4), and (b)(4), lot (b)(4), respectively.

We received your March 30, 2023, response. Your response stated you will be confirming the reliability of COAs using a third-party laboratory, but you did not include evidence of this being implemented. Therefore, we are unable to assess the adequacy of your corrective action.

5. Your quality control personnel failed to 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, as required by 21 CFR 111.105. Specifically, the ingredients listed on the finished product labels of the dietary supplements you manufacture are inconsistent with the ingredients listed in the Master Manufacturing Records (MMRs) and batch production records (BPRs) for those finished products. For example, the (b)(4), batch record number (b)(4), lists (b)(4), and (b)(4) ingredients being added to the batch, but these ingredients are not declared on the finished product label.

In addition, the (b)(4), batch record number (b)(4), lists (b)(4) being added to the batch, but these ingredients are not listed on the finished product label.

6. Your MMRs for the (b)(4) Stick (b)(4), and (b)(4) USA finished dietary supplement products you manufacture failed to include all required information, in accordance with 21 CFR 111.210. Specifically, the MMRs fail to include the following information:

  • A statement of any intentional overage amount of a dietary ingredient [21 CFR 111.210(e)];
  • A statement of theoretical yield of a manufactured dietary supplement expected at each point, step, or stage of the manufacturing process where control is needed to ensure the quality of the dietary supplement, and the expected yield when you finish manufacturing the dietary supplement, including the maximum and minimum percentages of theoretical yield beyond which a deviation investigation of a batch is necessary and material review is conducted and disposition decision is made [21 CFR 111.210(f)];
  • Written instructions [21 CFR 111.210(h)], including the following:
  • Specifications for each point, step, or stage in the manufacturing process where control is necessary to ensure the quality of the dietary supplement and that the dietary supplement is packed and labeled as specified in the MMR [21 CFR 111.210(h)(1)].
  • Written procedure for sampling and a cross-reference to procedures for tests or examinations [21 CFR 111.210(h)(2)].
  • Specific actions necessary to perform and verify points, steps, or stages in the manufacturing process where control is necessary to ensure the quality of the dietary supplement and that the dietary supplement is packaged and labeled as specified in the MMR [21 CFR 111.210(h)(3)].
  • Such specific actions must include verifying the weight or measure of any component and verifying the addition of any component [21 CFR 111.210(h)(3)(i)]; and For manual operations, such specific actions must include [21 CFR 111.210(h)(3)(ii)]:

A. (b)(4) weighing or measuring a component and another person verifying the weight or measure [21 CFR 111.210(h)(3)(ii)(A)]; and
B. (b)(4) adding the component and another person verifying the addition [21 CFR 111.210(h)(3)(ii)(B)].
o Corrective action plans for use when specifications are not met. [21 CFR 111.210(h)(5)]

We received your March 30, 2023, response. Your response stated you will be revising your MMRs and you provided a checklist stating what you intend to include in your MMRs, but you did not include any revised MMRs for review. Therefore, we are unable to assess the adequacy of your corrective action.

7. You failed to establish BPRs that satisfy the requirements of 21 CFR 111.255(b) and 111.260. Specifically, the BPRs for (b)(4), lot number (b)(4) Sticks, lot number (b)(4), and (b)(4), lot number (b)(4), were missing the following:

  • The date and time of the maintenance, cleaning, and sanitizing of the equipment and processing lines used in producing the batch, or a cross-reference to records, such as individual equipment logs, where this information is retained [21 CFR 111.260(c)];
  • A statement of the actual yield and a statement of the percentage of theoretical yield at appropriate phases of processing [21 CFR 111.260(f)];
  • The actual results obtained during any monitoring operation [21 CFR 111.260(g)];
  • The results of any testing or examination performed during the batch production, or a cross-reference to such results [21 CFR 111.260(h)];
  • Documentation that the finished dietary supplement meets specifications established in accordance with § 111.70(e) and (g) [21 CFR 111.260(i)];
  • Documentation, at the time of performance, of the manufacture of the batch, including [21 CFR 111.260(j)]:

o The date on which each step of the MMR was performed [21 CFR 111.260(j)(1)];

  • Documentation, at the time of performance, of packaging and labeling operations [21 CFR 111.260(k)], including:

o The unique identifier that you assigned to packaging and labels used, the quantity of the packaging and labels used, and, when label reconciliation is required, reconciliation of any discrepancies between issuance and use of labels [21 CFR 111.260(k)(1)];
o The results of any tests or examinations conducted on packaged and labeled dietary supplements (including repackaged or relabeled dietary supplements), or a cross-reference to the physical location of such results [21 CFR 111.260(k)(3)];

  • Documentation at the time of performance that quality control personnel [21 CFR 111.260(l)]:

o Reviewed the batch production record [21 CFR 111.260(l)(1)], including:
 Review of any monitoring operation required under subpart E of this part [21 CFR 111.260(l)(1)(i)]; and
 Review of the results of any tests and examinations, including tests and examinations conducted on components, in-process materials, finished batches of dietary supplements, and packaged and labeled dietary supplements [21 CFR 111.260(l)(1)(ii)]; and
o Approved and released, or rejected, the batch for distribution, including any reprocessed batch [21 CFR 111.260(l)(3)]; and
o Approved and released, or rejected, the packaged and labeled dietary supplement, including any repackaged or relabeled dietary supplement [21 CFR 111.260(l)(4)].

  • Documentation at the time of performance of any required material review and disposition decision [21 CFR 111.260(m)].

We received your March 30, 2023, response. Your response stated you will be revising your BPRs and you provided a checklist stating what you intend to include in your BPRs, but you did not include a copy of any revised BPRs for review. Therefore, we are unable to assess the adequacy of your corrective action.

Misbranded Dietary Supplements

In addition, we reviewed your product labels collected during the inspection and have determined the (b)(4) Sticks, and (b)(4) products you manufacture are misbranded under section 403 of the Act [21 U.S.C. § 343] because they do not comply with the labeling requirements for dietary supplements. Specifically, we identified the following:

1. The (b)(4) product is misbranded within the meaning of section 403(a)(1) of the Act [21 U.S.C. § 343(a)(1)] because the product label is false or misleading. Specifically, the product label states that the (b)(4) product contains “(b)(4),” and “(b)(4),” but the BPRs you provided to our investigator for (b)(4), lot number (b)(4) do not list any of these ingredients as being added to the product, demonstrating that these ingredients are not present in the (b)(4) product.

2. The (b)(4) Sitcks, and (b)(4) products are misbranded within the meaning of section 403(i)(2) of the Act [21 U.S.C. § 343(i)(2)] in that these product labels fail to declare all the common or usual names of each ingredient used as required by 21 CFR 101.36 and 21 CFR 101.4. For example:

  • According to your BPRs for (b)(4), lot number (b)(4), provided to our investigator, the (b)(4) product is formulated with (b)(4). However, none of these ingredients are declared on the (b)(4) product’s label. In addition, according to your BPRs for (b)(4), lot number (b)(4), provided to our investigator, the (b)(4) product is formulated to contain (b)(4). However, none of these ingredients are declared on either products’ label.
  • The standardized common name (SCN) for “lychee” is “litchi” according to the reference Herbs of Commerce regarding the labeling on your (b)(4) Sticks product.

3. 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 product label fails to include a serving size in accordance with 21 CFR 101.36(b). The term “serving” or “serving size” for a dietary supplement are defined in 21 CFR 101.9(b) and 21 CFR 101.12(b) Table 2, as the maximum amount recommended on the label for consumption per eating occasion.

  • The serving size for the (b)(4) is 1 fluid one (fl oz) (30 milliliters [mL]) but recommended use on the product label states one to four fluid ounces (b)(4) daily
  • The serving size for (b)(4) is one (1) fl oz, but directions for use on the product label states (b)(4) fl oz one to (b)(4) times daily

4. The (b)(4) Sticks, 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 is not in accordance with 21 CFR 101.36 and 101.9. For example:

  • Any (b)(2)-dietary ingredient not present, or in amounts that can be declared as zero in section 101.9(c), shall not be declared, in accordance with 21 CFR 101.36(b)(2)(i).
  • The presentation of (b)(2)-dietary ingredients is not listed in accordance with 21 CFR 101.36(b)(2)(i)(B).
  • A heavy bar is placed underneath the (b)(2)-ingredient “Calories”, which is not in accordance with 21 CFR 101.36(e)(5).
  • The type size of the (b)(2)-ingredient “Calories” in the (b)(4) product’s Supplement Facts label is not uniform with the other (b)(2)-ingredients, which is not in accordance with 21 CFR 101.36(e).
  • The (b)(4) product fails to declare the percentage DV for sodium in accordance with 21 CFR 101.36(b)(2)(iii)(C).
  • There is no provision in the regulation to provide a description of the (b)(4) within the ingredient list.
  • The (b)(4) product does not have a footnote linking the proprietary blend to the statement “Daily Value not established”, which is not in accordance with 21 CFR 101.36(b)(3)(iv).
  • There is no provision in the regulation for the (b)(4) product to bear the statement “The % Daily Value … general nutrition advice.” in the Supplement Facts label.
  • The Supplement Facts label on the (b)(4) product fails to express the Proprietary (b)(4) using metric measures in appropriate units (i.e., 1000 units must be declared in the next higher set of units, e.g., 1,100 mg must be expressed as 1.1 g) in accordance with 21 CFR 101.36(b)(3)(ii)(A).

5. The individual packet of (b)(4) Stick is misbranded within the meaning of sections 403(y) of the Act [21 U.S.C. § 403(y)] because the packet 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 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 offer the following comments:

1. During the manufacture of your 100% juice product, (b)(4), the (b)(4) temperature recording charts and (b)(4) records showed that lots (b)(4), and (b)(4) deviated from your critical limits of fill temperature ≥ (b)(4)°F and (b)(4) temperature of ≥ (b)(4)°F for ≥ (b)(4) at the (b)(4) critical control point, but no corrective actions were taken. As discussed during a Regulatory Meeting with your firm on November 14, 2018, it appears your firm uses a single thermal processing step sufficient to produce a shelf stable juice product,

therefore your firm could be exempt from including control measures to produce a minimum 5-log reduction in their HACCP plan. Under 21 CFR 120.24(a)(2), a firm claiming such an exemption must include a copy of the thermal process in its written hazard analysis. You may work with a processing authority or otherwise maintain scientific and technical documents showing that the thermal process is sufficient to provide a shelf stable product.

2. The (b)(4) and (b)(4) product labels do not bear a symbol next to the structure/function claim linking the claim to the disclaimer, in accordance with 21 CFR 101.93(d). Furthermore, the disclaimer fails to be enclosed in a box on the (b)(4) product, in accordance with 21 CFR 101.93(d).

3. Regarding the ingredient list on the (b)(4) product label, FDA’s view is that “evaporated cane juice” is not the common or usual name for sugar or cane sugar. For additional information, see: https://www.fda.gov/media/97827/download

4. According to the COA for the stevia ingredient, this product appears to be an extract from the stevia leaf. Stevia must be listed in the Supplement Facts label as a botanical with a plant part designated if it is used as a dietary ingredient. If being used as a sweetener, only a GRAS ingredient may be added to a dietary supplement, such as a purified stevia extract (e.g., “rebaudioside A”).

5. The (b)(4) and (b)(4) products’ information panels include nutrition, ingredient information, and manufacturer information intermingled with information that is considered intervening material. Examples of intervening material are “(b)(4) … analysis”, “Contains no added sugar …”, and “(b)(4) … antioxidants.” [21 CFR 101.2(e)].

6. Your use of “Best Used By” dates on the product labels should be supported by data that demonstrates the product’s shelf life.

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