WARNING LETTER
Brand Packaging Group, Inc.
MARCS-CMS 633651 —
March 17, 2023
Delivery Method:
VIA UNITED PARCEL SERVICE
Product:
Food & Beverages
Recipient:
Recipient Name
Lawrence S. Sayage
Recipient Title
President
Brand Packaging Group, Inc.
85 Price Parkway
Farmingdale
,
NY
11735-1305
United States
Issuing Office:
Division of Human and Animal Food Operations East I
United States
WARNING LETTER
CMS# 633651
March 17, 2023
Dear Mr. Sayage:
Between March 29, 2022, and April 8, 2022, the U.S. Food and Drug Administration (FDA) inspected your facilities located at 75 & 85 Price Parkway, Farmingdale, NY 11735-1305. The inspection of your facilities revealed significant violations of the Current Good Manufacturing Practice (CGMP) regulations for Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements, under Title 21, Code of Federal Regulations, Part 111 (21 CFR Part 111). These violations cause your dietary supplement products, including your
(b)(4)
, and
(b)(4)
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. You can find the Act and the FDA’s regulations through links on FDA’s home page at www.fda.gov.
We received your correspondence dated April 25, 2022, in response to the Form FDA 483, Inspectional Observations, issued to you at the close of the inspection. We address your response below, in relation to each of the noted violations.
Your significant violations of CGMP requirements are as follows:
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, and for limits on those types of contamination that may adulterate or that may lead to adulteration of the finished batch of the dietary supplement as required by 21 CFR 111.75(c). Specifically, your firm's certificates of analysis for finished products
(b)(4)
, and
(b)(4)
indicate assay testing was based on production input rather than on any type of analytical testing of the finished product. This was confirmed in discussions with management stating that product specifications are determined to be met based on product input during manufacturing for all products manufactured. The input of a dietary ingredient alone is not sufficient to verify its specifications and composition because the addition of a dietary ingredient into a product formulation is a manufacturing step; it is not a definitive test method that yields a measured result, nor is it able to assess the ingredient in the finished dietary supplement product when other components are present. All tests and examinations that are employed to determine whether a specification has been met must be scientifically valid in accordance with 21 CFR 111.75(h)(1).
We have reviewed your response dated April 25, 2022, and find it to be inadequate because it does not include specifications and test methods for performing microbiological testing for pathogenic microbes, which is required under 21 CFR 111.75(c). We note your corrective action plans for implementing the use of
(b)(4)
to test presence and strength of active ingredients for all finished products, installation of a
(b)(4)
, creation/improvement of procedures and personnel training.
2. Your firm failed to conduct at least one appropriate test or examination to verify the identity of any component that is a dietary ingredient, prior to its use, as required by 21 CFR 111.75(a)(1)(i), unless you petition the agency under 21 CFR 111.75(a)(1)(ii), which you have not, and the agency exempts you from such testing. Specifically, you failed to verify the identity of:
Dietary ingredients Zembrin (Sceletium tortuosum (aerial parts) extract) Lot
(b)(4)
and Agmatine Sulfate Lot
(b)(4)
before they were used to manufacture the finished dietary supplement product
(b)(4)
, Lot
(b)(4)
, Exp 0723;
Dietary ingredient Camellia Sinensis Extract (leaf) (Epicatechin) Lot
(b)(4)
before it was used to manufacture the finished dietary supplement product
(b)(4)
, Lot
(b)(4)
, Exp 0723;
Dietary ingredient Betaine HCl Lot
(b)(4)
before it was used to manufacture thefinished dietary supplement product
(b)(4)
, Lot
(b)(4)
, Exp 05/2024;
Dietary ingredient Organic Chaga Mushroom Extract (Inonotus obliquus) Lot
(b)(4)
before it was used to manufacture the finished dietary supplement product
(b)(4)
, Lot
(b)(4)
, Exp 04/2024; and
Dietary ingredients Zinc (as Zinc Gluconate) Lot
(b)(4)
, Echinacea Purpurea Lot
(b)(4)
, and Elderberry Fruit Extract (as Sambucus Nigra) Lot
(b)(4)
before they were used to manufacture the finished dietary supplement product
(b)(4)
, Lot
(b)(4)
, Exp 06/2022.
Discussions with management during our inspection confirmed that no testing is conducted on new dietary ingredients when they are first received by your firm. Instead, your firm uses
(b)(4)
and
(b)(4)
to test these ingredients and then use the results as the standard moving forward.
We have reviewed your response dated April 25, 2022, and we are unable to evaluate the adequacy of your corrective actions. We note your corrective action plan for incoming raw materials is to purchase a scientific database to obtain standards for botanicals and to obtain physical standards and testing on your equipment to build a library.
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). Specifically, your firm’s stated specification for
(b)(4)
and
(b)(4)
identity testing is
(b)(4)
when compared to
(b)(4)
. The following ingredients did not meet this specification and were used to manufacture finished dietary supplement products without any documentation relaying QC investigation:
Dietary supplement ingredient Ashwagandha Powder Lot
(b)(4)
did not meet your established specification during
(b)(4)
testing on 8/09/2021 with a correlation of
(b)(4)
and was labeled “Fail”. The dietary supplement ingredient Ginseng Powder Lot
(b)(4)
also did not meet your established specification during
(b)(4)
testing on 8/09/2021 with a correlation of
(b)(4)
and was labeled “Fail”. Both of these ingredients were used to manufacture the finished dietary supplement product
(b)(4)
, Lot
(b)(4)
, Exp 0723.
Dietary supplement ingredient Triacetyuridine Powder, Lot
(b)(4)
did not meet your established specification during
(b)(4)
testing on 08/19/2021 with a correlation of
(b)(4)
and was labeled “Fail”. This ingredient tested again on 8/19/21 did not meet your established specification with a correlation of
(b)(4)
and was labeled “Fail”. A second dietary supplement ingredient Phosphatidylserine from Sunflower 50% Lot
(b)(4)
, did not meet your established specification during
(b)(4)
testing on 8/19/2021 with a correlation of
(b)(4)
and was labeled “Fail”. A third dietary supplement ingredient Synapsa Powder Lot
(b)(4)
did not meet your established specification during
(b)(4)
testing on 8/19/2021 with a correlation of
(b)(4)
and was labeled “Fail” and again on this date with a correlation of
(b)(4)
. All three of these ingredients were used to manufacture the finished dietary supplement product
(b)(4)
, Lot
(b)(4)
, Exp 0723.
Dietary supplement ingredient 7,8 Dihydroxyflavone (DHF) Powder Lot
(b)(4)
did not meet your established specification during
(b)(4)
testing on 08/26/2021 with a correlation of
(b)(4)
and was labeled “Fail”. This dietary supplement ingredient tested again on this date with a failing correlation of
(b)(4)
. A second dietary supplement ingredient Lion’s Mane Powder Lot
(b)(4)
did not meet your established specification during
(b)(4)
testing on 08/10/2021 with a correlation of
(b)(4)
and was labeled “Fail”. These ingredients were used to manufacture the finished dietary supplement product
(b)(4)
, Lot
(b)(4)
, Exp 0723.
We have reviewed your response, dated April 25, 2022, and we are unable to evaluate the adequacy of your corrective actions. We note your corrective action plans to revise SOPs QC-EU-005.01 “Operation, & Cleaning
(b)(4)
” & QC-EU-003.01 “Operation, and Cleaning
(b)(4)
” to add a calibration section and add more information on acceptable correlations and what to do if a correlation is below the acceptable limit. We also note your QC/QA meeting held on this subject. However, these corrective actions do not specifically address the out-of-specification (OOS) results noted above. In addition, an evaluation of revised and QC approved SOPs could not be conducted since they were not submitted with the response.
4. Your firm failed to establish and follow laboratory control processes that are reviewed and approved by quality control personnel, for use of criteria for selecting standard reference materials used in performing tests and examinations, as required by 21 CFR 111.315(d). Specifically, you do not have the proper laboratory controls in place to conduct appropriate testing or examination to verify the identity of a component that is a dietary ingredient prior to its use. You told our investigator that the first time an ingredient is received,
(b)(4)
and
(b)(4)
testing is conducted, and the results are used as your firm’s standard moving forward. This is not a scientifically valid method in creating a referenced standard.
We have reviewed your response dated April 25, 2022, and we are unable to evaluate the adequacy of your corrective actions. We note your corrective action plan for this observation is the same as that conveyed for Form FDA 483, observation #1. The
(b)(4)
you purchased is acceptable for some materials and not acceptable for others.
5. Your firm failed to follow written procedures for calibrating instruments and controls that you use in manufacturing or testing a component or dietary supplement as required by 21 CFR111.25(a). Specifically, your Standard Operating Procedure, “Setup and Operation
(b)(4)
,” SOP #: QC-EU-004.02, Date Issued: 07/22/2021 states, “The instrument optical reader needs to be calibrated
(b)(4)
.” Your firm is conducting this calibration approximately every
(b)(4)
.
We have reviewed your response, dated April 25, 2022, and we are unable to evaluate the adequacy of your corrective actions. We note your corrective action plans to revise SOP QC-EU-004.02 “Setup and Operation of the Soleris Next Generation System” to add a requirement to print and sign calibration reports every 30 days. We also note your QC/QA meeting held on this subject. However, an evaluation of the revised and QC approved SOP could not be conducted since it was not submitted with the response.
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 without further notice including, without limitation, seizure, and injunction.
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 response to the Food and Drug Administration, Attention: Lillian C. Aveta, Compliance Officer, 158-15 Liberty Ave., Jamaica, NY 11433 or via email at lillian.aveta@fda.hhs.gov (preferred). If you have any questions about the content of this letter, please contact Ms. Aveta at 718-662-5576 or email at lillian.aveta@fda.hhs.gov.
Sincerely,
/S/
Ronald M. Pace
Program Division Director
Office of Human and Animal Food Operations East – Division 1
Content current as of:
07/11/2023
Regulated Product(s)
Food & Beverages