Source: https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2013/ucm377967.htm
Timestamp: 2019-04-23 01:57:21+00:00

Document:
On October 29-30 and November 1-2, and 14, 2012, the U.S. Food and Drug Administration (FDA) conducted an inspection of your facility located at 520 Wolf Road, Random Lake, Wisconsin. This inspection found that your firm is a manufacturer of dietary supplements. The inspection revealed serious violations of FDA’s Current Good Manufacturing Practice (CGMP) regulations 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 supplements have been prepared, packed, or held under conditions that do not meet CGMP requirements for dietary supplements. Specifically, our investigators observed violations relating to the following dietary supplement products: (b)(4) and (b)(4).
the present time. Therefore, you are still responsible for complying with 21 CFR Part 111 for these products. For example, you have a continuing obligation to comply with 21 CFR 111.605, which requires the retention of written records required under 21 CFR Part 111 for one year past the shelf life date, if shelf life dating is used, or two years beyond the date of distribution of the last batch of dietary supplements associated with the records. You also have a continuing obligation to comply with section 761 of the Act, 21 U.S.C. § 379aa-1 (“Serious Adverse Event Reporting for Dietary Supplements”), with respect to these products.
You can find the Act and related FDA regulations through links on FDA’s Internet home page at www.fda.gov.
a. You failed to establish an identity specification for each component, as required by 21 CFR 111.70(b)(1).
b. You failed to establish component specifications that are necessary to ensure that specifications for the purity, strength and composition of dietary supplements manufactured using the components are met, as required by 21 CFR 111.70(b)(2).
We have reviewed your responses dated December 6, 2012, January 15, 2013, February 15, 2013, and March 19, 2013. Your January 15, 2013, response indicated that you have developed a standard operating procedure (SOP) to address how you will comply with the requirement of establishing component specifications; however, after reviewing the SOP, the procedures lack an explanation of how you will establish identity specifications and other component specifications, but rather discuss how you will sample and test all components used in the manufacture of dietary supplements. Furthermore, while your February 15, 2013, response included several identity specifications and other component specifications, we were unable to evaluate the adequacy of your response because although you state the official compendium that you are using, you do not specify which reference standards from that compendium apply to your materials.
Your January 15, 2013, response stated that you have developed a template to be completed by your customers and attached the template and an example of a completed Finished Product Specification for your (b)(4) product. However, we were unable to evaluate the adequacy of your response because although your (b)(4) Finished Product Specification example states the official compendia that you are using, you do not specify which reference standards from those compendia apply to your materials.
As is discussed above, your February 15, 2013, response stated that you are no longer manufacturing (b)(4) products labeled as dietary supplements, nor are you manufacturing the (b)(4) dietary supplement product. You further stated that you had therefore not completed finished product specifications for your (b)(4) products. We agree that it is no longer necessary for you to establish finished product specifications for these products. As is described above, you do have a continuing obligation to comply with 21 CFR Part 111 with respect to dietary supplement products that you previously manufactured.
3. Your firm failed to prepare a written master manufacturing record (MMR) for each unique formulation of dietary supplement that you manufacture, and for each batch size, in accordance with 21 CFR 111.205(a). Specifically, at the time of our inspection you did not have MMRs for each formulation and each batch size of dietary supplement products you manufacture.
Your February 15, 2013, response provided an updated MMR template and a completed MMR for your (b)(4) dietary supplement product. However, this MMR failed to include the weight or measure of each dietary ingredient that will be declared on the Supplement Facts label, as required under 21 CFR 111.210(d). Please also note that if you include any intentional overage amount of a dietary ingredient, your MMR must include a statement of that amount in accordance with 21 CFR 111.210(e).
c. The initials of the person responsible for weighing or measuring each component used in the batch, 21 CFR 111.260(j)(2)(i).
d. The initials of the person responsible for verifying the weight or measure of each component used in the batch, 21 CFR 111.260(j)(2)(ii).
e. The initials of the person responsible for adding the component to the batch, 21 CFR 111.260(j)(2)(iii).
f. The initials of the person responsible for verifying the addition of components to the batch, 21 CFR 111.260(j)(2)(iv).
g. An actual or representative label, or a cross-reference to the physical location of the actual or representative label specified in the MMR, 21 CFR 111.260(k)(2).
In your February 15, 2013, response letter, you provided an updated Batch Production Procedure (BPR) QAM-191; however, you did not provide an actual batch production record to evaluate. Your February 15, 2013, response letter outlined a timeline for coming into compliance with the requirements regarding BPRs. We will evaluate your compliance with these requirements at our next inspection.
a. You distributed (b)(4) lot J1122KF following (b)(4) in-process line checks that documented occurrences of cooled can pressure below the established specification of (b)(4) psi. Your quality control personnel did not conduct a material review and make a disposition decision, as required by 21 CFR 111.113(a)(1) when a specification established in accordance with 21 CFR 111.70 is not met. Your firm subsequently received a complaint regarding “soft cans” from (b)(4) Company.
b. Upon a customer’s request, you released a portion of (b)(4) lot 2237KF that had not been thermally processed in accordance with the established parameters. Your quality control personnel did not conduct a material review and make a disposition decision, as required by 21 CFR 111.113(a)(2) when any step established in the master manufacturing record is not completed.
Furthermore, firm management verbally confirmed to our investigators that your firm regularly ships products prior to completion of all tests and examinations. This increases the potential for shipping products that fail to meet specifications.
Your January 15, 2013, response includes a revised policy under which you state that you will hold finished product under quarantine until test results are received, reviewed, and product is accepted or rejected; however, you did not provide an explanation in your response regarding how you will address product currently in distribution that did not meet specifications. You did not include with your response any corrective actions with respect to the above mentioned products released for distribution without meeting established product specifications. Please note that under 21 CFR 111.140(b)(3)(iv), you are required to keep records that include documentation of any material review and disposition decision and follow-up, including identification of the action(s) taken to correct, and prevent a recurrence of, the deviation or the unanticipated occurrence. Such documentation must be included in the appropriate batch production record, and must be kept in accordance with 21 CFR 111.605 for one year past the shelf life date, if shelf life dating is used, or two years beyond the date of distribution of the last batch of dietary supplements associated with those records.
6. Your firm failed to have a qualified person investigate a product complaint that involved a possible failure of a dietary supplement to meet its specifications, as required by 21 CFR 111.560(a)(2). Specifically, your firm received a complaint on February 16, 2012, from (b)(4) Company regarding cans of (b)(4) (lot J1122KF) with low pressure, but your firm did not investigate this complaint.
As discussed above, your February 15, 2013, response stated that you are no longer manufacturing (b)(4) products labeled as dietary supplements. Your response indicated that you therefore had no corrective actions planned to address this violation. This response is inadequate. As described above, you have a continuing obligation to comply with 21 CFR Part 111 with respect to dietary supplement products that you previously manufactured. Furthermore, you have an obligation to take steps to ensure that similar violations do not occur in the future with respect to the dietary supplement products that your firm continues to manufacture.
7. Your (b)(4) product is misbranded within the meaning of section 403(w) of the Act, 21 U.S.C. § 343(w), in that the label fails to declare all major food allergens present in the product, as required by section 403(w)(1) of the Act. Specifically, your (b)(4) product contains whey protein hydrolysate, which is a component of milk; however you fail to declare the major food allergen.
ii. The common or usual name of the major food allergen in the list of ingredients is followed in parentheses by the name of the food source from which the major food allergen is derived, e.g. “(milk)”, except that the name of the food source is not required when either the common or usual name of the ingredient uses the name of the food source or the name of the food source appears elsewhere in the ingredient list (unless the name of the food source that appears elsewhere in the ingredient list appears as part of the name of an ingredient that is not a major food allergen), section 403(w)(1)(B) of the Act, 21 U.S.C. § 343(w)(1)(B).
8. Your (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).
i. The ordering of (b)(2) dietary ingredients for your (b)(4) is not in accordance with 21 CFR 101.36(b)(2)(i)(B). For example, all of the products list Vitamin B5 before vitamin B6. Vitamin B5, or pantothenic acid, should be listed after vitamin B12.
ii. Your (b)(4) product declares the (b)(2) dietary ingredients, Biotin and Selenium, below the listing of (b)(3) dietary ingredients, and it fails to declare the percent of the Daily Value for biotin and selenium as required by 21 CFR 101.36(b)(2)(iii).
iii. Your (b)(4) product contains “Other Ingredients” within the nutrition information label, enclosed in a box with the title “Supplement Facts.” The ingredient list on dietary supplements should be located below or immediately contiguous and to the right of the nutrition label and preceded by the words “Other ingredients” in accordance with 21 CFR 101.4(g).
iv. Your (b)(4) product lists a “Proprietary Energy Blend” of dietary ingredients, which can be only made for dietary supplement products. The title of the nutrition information should list “Supplement Facts” as a dietary supplement.
9. Your (b)(4) products are misbranded within the meaning of section 403(s)(2)(C) of the Act, 21 U.S.C. § 343(s)(2)(C) because the label fails to indicate the part of the plant from which some of the dietary ingredients are derived in accordance with 21 CFR 101.4(h)(1). For example, the label for (b)(4) fails to declare the part of the plant from which Epimedium extract and Eleutherococcus senticosus are derived, and the label for (b)(4) fails to declare the part of the plant from which Cha de Bugre is derived.
10. Your (b)(4) product is misbranded within the meaning of section 403(i)(2) of the Act, 21 U.S.C. § 343(i)(2), because it declares “MSM” and “5-HTP” in the nutrition information. The common or usual name for these dietary ingredients to be listed in the nutrition information without any intervening material should be methylsulfonylmethane and 5-hydroxytryptophan, respectively.
11. Your (b)(4) products are misbranded within the meaning of section 403(s)(2)(B) of the Act, 21 U.S.C. § 343(s)(2)(B), because the label fails to identify the product by using the term “dietary supplement” as a part of the statement of identity, in accordance with 21 CFR 101.3(g).
This letter is not intended to be an all-inclusive list of violations that exist in connection with your products. It is your responsibility to ensure that all products manufactured by your firm are in compliance with the requirements of the Act and all applicable regulations.
You should take prompt action to correct the violations described above and prevent their recurrence. Failure to implement lasting corrective action may result in regulatory action being initiated by FDA without further notice, such as seizure or injunction.
You should notify this office in writing within 15 working days from your receipt of this letter. Your response should outline the specific actions you are taking to correct these violations and the steps you are taking to prevent their recurrence. You should include in your response documentation and any other useful information that would assist us in evaluating your corrections. If you cannot complete all corrections within 15 working days, please state the reason for the delay and the date by which you will have completed the correction.
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 costs related to re-inspection. A re-inspection is one or more inspections conducted subsequent to an inspection that identified non-compliance 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 re-inspection 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 non-compliance materially related to a food safety requirement of the Act. Accordingly, FDA may assess fees to cover any costs related to re-inspection.

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