Between November 15, 2018 and December 12, 2018, the U.S. Food and Drug Administration (FDA) inspected your dietary supplement facility located at 44 Miller Lane Suite 10, Williston, VT, 05495. During the inspection, our investigators found significant violations of the Current Good Manufacturing Practice (CGMP) regulations for Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements, Title 21, Code of Federal Regulations, 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 the dietary supplement products have been prepared, packed, or held under conditions that do not meet CGMP requirements for dietary supplements.
In addition, we have reviewed product labels collected during the inspection and have determined that your ThermoCaps product is misbranded within the meaning of section 403 of the Act [21 U.S.C. § 343].
You can find the Act and the FDA’s regulations through links on FDA’s home page at
www.fda.gov
.
We received your firm’s response, dated January 2, 2019, concerning the observations noted on the Form FDA 483, Inspectional Observations, which was issued to your firm on December 12, 2018. We address your response below, in relation to each of the noted violations.
Adulterated Dietary Supplements: CGMP Violations
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, and composition, as required by 21 CFR 111.75(c). To meet this requirement, you must provide adequate documentation of your basis for why meeting 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 supplement meets all product specifications for identity, purity, strength, and composition, as required by 21 CFR 111.75(c)(3) and 21 CFR 111.95(b)(4). Specifically, you stated that you do not have documentation of your basis for determining that your (b)(4)testing program will ensure each batch meets all product specifications.
We have reviewed your response, dated January 2, 2019; however, we are unable to evaluate the adequacy of your corrective actions. Your response includes a Material Review Process SOP and Material Review Report form but does not provide an explanation as to the scientific rationale behind your (b)(4) testing program to ensure that all finished batches of dietary supplements meet established specifications.
2. You failed to confirm the identity of other components and determine whether other applicable component specifications established in accordance with 21 CFR 111.70(b) are met, as required by 21 CFR 111.75(a)(2). This requirement may be met by either conducting appropriate tests or examinations in accordance with 21 CFR 111.75(a)(2)(i), unless you petition the agency under 21 CFR 111.75(a)(1)(ii) and the agency exempts you from such testing, or by relying on a certificate of analysis (COA) from the supplier of the component that you receive, provided that certain requirements are met to establish the reliability of the supplier’s COA in accordance with 21 CFR 111.75(a)(2)(ii). However, when relying on a COA from a component supplier, you failed to qualify the suppliers by establishing the reliability of the suppliers' COA through confirmation of the results of the suppliers' tests or examinations, before using those components, as required by 21 CFR 111.75(a)(2)(ii)(A), and failed to maintain documentation of how the supplier was qualified, as required by 21 CFR 111.75(a)(2)(ii)(C). In order to rely on a COA from a supplier of the component, the following requirements of 21 CFR 111.75(a)(2)(ii) must be met: (A) qualify the supplier by establishing the reliability of the supplier's COA through confirmation of the results of the supplier's tests or examinations; (B) the COA must include a description of the test or examination method(s) used, limits of the test or examinations, and actual results of the tests or examinations; (C) maintain documentation of how you qualified the supplier; (D) periodically reconfirm the supplier's COA; and (E) the documentation setting forth the basis for qualification (and re-qualification) of any supplier must be reviewed and approved by quality control personnel. Specifically, you stated to our investigator that you do not have written documents covering how you qualified component suppliers by establishing the reliability of the suppliers’ COAs, which your quality control unit relied on to release the components for manufacturing of your finished dietary supplement products.
We have reviewed your response, dated January 2, 2019; however, we are unable to evaluate the adequacy of your corrective actions. Your response indicates that you are in the process of revising and implementing a documentation strategy, with regards to your suppliers but does not provide any supporting documentation regarding your corrective actions.
3. Your quality control personnel failed to reject a component or dietary supplement when that component or dietary supplement failed to meet an established specification; 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 was packaged and labeled as specified in your master manufacturing record (MMR), as required by 21 CFR 111.77(a) and 111.113(b)(2). Your firm’s quality control personnel also failed to conduct a material review and make a disposition decision when the established specification was not met, as required by 21 CFR 111.113(a)(1).
Specifically, out of specification results were received for the component green tea, lot number (b)(4), which was tested by a third-party laboratory. Your quality control unit failed to reject green tea, lot number (b)(4), which was released from quarantine and used in the manufacturing of a finished product, and failed to reject the finished product, ((b)(4)) product, lot number (b)(4) (also labeled as a (b)(4)), which was released for distribution.
In addition, the finished product specification regarding the weight for your ((b)(4)) product is listed as between (b)(4). Your COA for your ((b)(4)) product, lot number (b)(4), which you provided to our investigator, demonstrated a fill weight of 501.9 mg. Furthermore, your ((b)(4)) product, lot number (b)(4), has a specification of ≥ (b)(4) (mg) (b)(4) but testing results demonstrated 9.7 mg was present in the finished product. No material review or disposition decision was performed by your firm in these examples where the dietary supplements failed to meet established specifications, and these dietary supplements were released into distribution.
We have reviewed your response, dated January 2, 2019; however, we are unable to evaluate the adequacy of your corrective actions. Your response includes a Material Review Process SOP and Material Review Report form that only address instances where an out of specification occurs for any component used in the packaging of a dietary supplement.
4. 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). Under 21 CFR 111.205, you must prepare an MMR that (1) identifies specifications for the 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 master manufacturing record and (2) establishes controls and procedures to ensure that each batch of dietary supplement that you manufacture meets these specifications. In addition, each MMR must conform to the requirements as described in 21 CFR 111.210. Specifically, the MMRs you provided to our investigator for your ((b)(4)), ((b)(4)), and (b)(4) products were missing several of these requirements under 21 CFR 111.205 and 21 CFR 111.210, including:
- 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, as required by 21 CFR 111.210(f);
- Written instructions as required by 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 packaged and labeled as specified in the master manufacturing record in accordance with CFR 111.210(h)(1);
- Procedures for sampling and a cross-reference to procedures for tests or examinations in accordance with 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 master manufacturing record in accordance with 21 CFR 111.210(h)(3);
- Special notations and precautions to be followed, as required by 21 CFR 111.210(h)(4);
- Corrective action plans for use when a specification is not met, as required by 21 CFR 111.210(h)(5).
We have reviewed your response, dated January 2, 2019; however, we are unable to evaluate the adequacy of your corrective actions. Your response included an “updated” MMR only for your (b)(4) product which continues to not meet the requirements of 21 CFR 111.205 and 21 CFR 111.210.
5. You failed to approve, and release from quarantine, all components before they were used, as required by 21 CFR 111.120(e). Specifically, your quality control personnel did not approve and release from quarantine all components, including dietary ingredients, before they were used in the manufacture of your dietary supplement products. For example, your quality control personnel did not approve and release from quarantine Green Tea, Bitter Orange, and Sweet Scented Geranium before they were used to manufacture Lot #(b)(4) of your (b)(4) product.
We have reviewed your response dated January 2, 2019; however, we are unable to evaluate the adequacy of your corrective actions. As part of your response, you submitted a Material Review Process SOP, but the SOP does not address the approval and release all components from quarantine. You also indicated that you will utilize and complete a standardized check list form, but your response did not provide documentation demonstrating that quality control personnel approve and release all components before they are used in the manufacture of dietary supplements
6. Your quality control operations for packaging and labeling failed to approve for release, or reject, any packaged and labeled dietary supplement (including a repackaged or relabeled dietary supplement) for distribution, as required by 21 CFR 111.127(h). Specifically, you released your ((b)(4)) product, lot number (b)(4), into distribution during June 2018 even though your quality control unit did not review and approve the release of this product because you had not received finished product testing results, which were not provided until July 2018. In addition, you released your (b)(4)) product, lot number (b)(4), into distribution during July 2018 even though your quality control unit did not review and approve the release of this product because you had not received finished product testing results, which were not provided until August 3, 2018. These two lots were released without approval by your quality control unit.
7. You failed to follow written procedures for fulfilling the requirements for returned dietary supplements, as required by 21 CFR 111.503. Specifically, you do not always follow your "Returned Goods" SOP Version SPH450-04, which states, "The Quality Unit will evaluate the condition of the returned good(s) and determine if there is evidence of tampering or damage and if the product(s) have been compromised or if the good(s) can be repaired and returned to stock". Our investigator observed that 23 of 53 of your "Returned Good Forms" covering 2017 and 2018 year to date did not include a quality control review and approval before product was "Return[ed] to stock" or "Repaired," or the form was left blank.
We have reviewed your response dated January 2, 2019; however, we are unable to evaluate the sufficiency of your corrective actions. Your response indicates that you are conducting reviews and training sessions but does not provide any documentation that demonstrates that you are following your written procedures for returned dietary supplements.
Misbranded Dietary Supplements
Additionally, your ThermoCaps product is misbranded within the meaning of section 403 [21 U.S.C. § 343] of the Act because it does not comply with the labeling requirements for dietary supplements as required by 21 CFR 101. For example:
1. Your ThermoCaps product is 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 does not comply with 21 CFR 101.36. Specifically, the Supplement Facts label fails to provide the amount per serving as required by 21 CFR 101.36(b)(2)(ii). The label lists the quantitative amount of the dietary ingredients (proprietary blend) as the “amount per capsule” whereas the serving size is 2 capsules.
The violations cited in this letter are not intended to be an all-inclusive statement of violations that exist at your facility or 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. Failure to promptly correct these violations may result in legal action without further notice, including, without limitation, seizure and injunction.
Within fifteen working days of the receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct 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 action within fifteen working days, state the reason for the delay and the time within which you will complete the correction. If you believe that your products are not in violation of the Act, include your reasoning and any supporting information for our consideration.
Section 743 of the Act (21 U.S.C. § 379j-31) authorizes FDA to assess and collect fees to cover FDA’s costs for certain activities, including re-inspection-related costs. A re-inspection 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. Re-inspection-related costs means all expenses, including administrative expenses, incurred in connection with FDA’s arranging, conducting, and evaluating the results of the re-inspection and assessing and collecting the reinspection fees (21 U.S.C. § 379j-31(a)(2)(B)). For a domestic facility, FDA will assess and collect fees for re-inspection-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 re-inspection-related costs.
