The United States Food and Drug Administration (FDA) conducted an inspection of your dietary supplement manufacturing facility located at 1019 Grand Boulevard, Deer Park, NY 11729-5709, on March 21, 25, 28, 29, and April 3, 5, and 9, 2019. During the inspection, you informed our investigator that your firm is manufacturing, packaging, and labeling dietary supplements for contract customers who then market and distribute the dietary supplements. The inspection revealed serious violations of FDA’s regulations for the Current Good Manufacturing Practice (CGMP) in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements, found in Title 21, Code of Federal Regulations, Part 111 (21 CFR Part 111). These CGMP violations cause the dietary supplement products manufactured by your firm, including (b)(4) and (b)(4) 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)] because they have been prepared, packed, or held under conditions that do not meet CGMP requirements for dietary supplements. You may find the Act and the FDA regulations through links at FDA’s homepage at
www.fda.gov
.
We acknowledge receipt of a written response from your firm on April 24, 2019, responding to the Form FDA-483, Inspectional Observations, that was issued to your firm on April 9, 2019. Our comments regarding your corrective actions, as applicable to the violations noted below, are provided below.
The significant violations are as follows:
1. You failed to establish product specifications for the identity and purity of the finished batch of dietary supplement that you manufacture, as required by 21 CFR 111.70(e). For example, your product specification in the master manufacturing records for (b)(4) and (b)(4) do not include specifications for identity and purity.
Your written response received April 24, 2019, does not specifically address this violation.
2. You failed to establish an identity specification for each component that you use in the manufacture of a dietary supplement, as required by 21 CFR 111.70(b)(1). For example, the raw material specification and release documents for ingredients such as L-Selemonethionine, Vitamin E, and Chlorella do not include identity specifications.
We acknowledge your written response received April 24, 2019, in which you provided UV Spectra for 12 dietary ingredients (L-Selenomethionine Lot# 4935, Vitamin E Lot# 6031, Chlorella Lot# 3720, Zinc Glycinate Chelate Lot# 5513, L-Tyrosine Lot# 5865, 5-HTP Lot# 5597/5584, L-Theanine Lot# 4166, L-Theanine Lot# 4871, Vitamin C as Ascorbic Acid Lot# 8078, L-Glutamine Lot# 8023, and Vitamin A as Beta Carotene 20% Lot# 8014). However, although you provided spectra as evidence of identity testing for each of the 12 dietary ingredients, the records do not include an identity specification to determine the results are adequate.
3. Your quality control operations failed to determine whether all in-process specifications established in accordance with 21 CFR 111.70(c) are met, as required by 21 CFR 111.123(a)(6). For example,
- The product (b)(4) with finished lot number (b)(4) has a specification for the yield after encapsulation of (b)(4). Your firm’s encapsulation yield record and reconciliation for February 14, 2019, documents that your firm calculated the yield as 105.8%.
- The product (b)(4) with finished lot number (b)(4) has a specification for tablet hardness of no less than (b)(4) and no more than (b)(4). Your firm’s compression record for January 8, 2019, documents that the tablet hardness was less than (b)(4) for 9 out of (b)(4) entries, and your firm’s compression record for January 10, 2019, documents that the tablet hardness was less than (b)(4) for 6 out of (b)(4) entries.
However, there is no documentation to support that your quality control operations determined whether the in-process specification were met. For example, they did not conduct an investigation or complete a deviation report for the non-conformances as stated in your Standard Operating Procedures titled “Responsibilities of Quality Unit” and “Deviation Management,” both dated August 1, 2016.
We acknowledge your written response received April 24, 2019, in which you describe how personnel were re-trained, and you provided copies of training records for three employees. However, we are unable to determine the adequacy of your response because while the training may prevent recurrence, you did not provide documentation to show the investigation and subsequent corrective actions for the specific out of specification results observed during production of the (b)(4) and (b)(4) dietary supplements.
4. You failed to examine, before packaging and labeling operations, packaging and labels for each batch of dietary supplement to determine whether the packaging and labels conform to the master manufacturing record, as required by 21 CFR 111.410(c). Specifically, your firm released product label for use in the packaging and labeling operations for (b)(4) Dietary Supplement Lot (b)(4) that listed silicon dioxide as an ingredient; however, your master manufacturing record did not list silicon dioxide as an ingredient in the product.
We acknowledge your written response received April 24, 2019, in which you state that employees were re-trained and which provided documentation for the recall of (b)(4) product. You provided evidence of QC Associate training dated April 23, 2019, on PL5-04 “Label Verification & Control Procedure;” however, we are unable to evaluate the adequacy of your response because you did not provide a copy of the “Label Verification & Control Procedure” so that we could review your corrective actions to ensure this deviation does not recur.
5. Your firm’s master manufacturing record (MMR) fails to include all the information required by 21 CFR 111.210. Specifically, your MMR for (b)(4) does not include the following:
- A statement of theoretical yield in your Bottle Count Check Procedure. You state a Yield Limit = ± (b)(4) but you do not state the theoretical target [21 CFR 111.210(f)];
- Written instructions, including 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 [21 CFR 111.210(h)(1)]. For example, your MMR refers to specifications for preparing empty bottles and packaging finished bottles but these specifications are not in your records;
- Procedures for sampling and a cross-reference to procedures for tests or examinations [21 CFR 111.210(h)(2)]. For example, your written instruction “Take sample sample [sic] (b)(4), submit to lab” does not explain how to take the sample or what tests or examinations should be performed.
Your written response received April 24, 2019, does not specifically address this violation.
6. Your batch production record failed to include complete information relating to the production and control of each batch, as required by 21 CFR 111.255(b). For example, your firm performed blend reconciliation on December 23, 2018, for (b)(4). You documented the total amount of product received for compression after blending operations as (b)(4); however, your firm’s compression records document that a total of (b)(4) of (b)(4) blend was received for compression during the January 5, 7, 8, and 10, 2019 production dates. The additional (b)(4) added to the batch is not documented.
Your written response received April 24, 2019, does not specifically address this violation.
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 and FDA regulations, including the dietary supplement CGMP regulation (21 CFR 111). 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 (15) working days of receipt of this letter, please notify this office in writing of the specific actions that you have taken to correct these 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 15 working days, state the reason for the delay and the time frame within which you will complete the correction. If you do not believe your products are in violation of the FD&C 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 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 noncompliance materially related to a food safety requirement of the Act. Accordingly, FDA may assess fees to cover any re-inspection-related costs.
