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  5. TJA Health, LLC - 678539 - 07/17/2024
  1. Warning Letters

WARNING LETTER

TJA Health, LLC MARCS-CMS 678539 —

Delivery Method:
UPS
Product:
Drugs
Recipient:
Recipient Name
Mr. Behnam (Ben) Vaziri
Recipient Title
Chief Operating Officer
TJA Health, LLC

2501 Reeves Road
Joliet, IL 60436-9523
United States

Bvaziri@plaquehd.com
Issuing Office:
Division of Pharmaceutical Quality Operations III

United States

July 17, 2024

WARNING LETTER
CASE #678539

Dear Mr. Vaziri:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, TJA Health LLC, FEI 3010203410, located at 2501 & 2505 Reeves Road, Joliet, IL 60436, from January 25 to 29, 2024.

This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).

We reviewed your response dated February 8, 2024, to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.

During our inspection, our investigator observed specific violations including, but not limited to, the following.

1. Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality (21 CFR 211.84(d)(1) and 211.84(d)(2)).

Your firm failed to adequately test incoming raw materials used for the manufacture of your drug products, including active pharmaceutical ingredients (API) and other high-risk components. Instead, your firm released API and other materials for use in drug product manufacturing based on your supplier’s certificate of analysis (COA) without performing at least one specific identity test on each component.

Component testing is fundamental to quality. Without adequate testing, you do not have scientific evidence that your incoming components conform to appropriate specifications before use in the manufacture of your drug products.

Products Contain High Risk Components

You failed to adequately test each shipment of each lot of incoming components at high-risk of diethylene glycol (DEG) or ethylene glycol (EG) contamination. This includes, but is not limited to, testing of the glycerin and sorbitol you used in manufacturing of Plaque HD Toothpaste and Plaque Remineralizing Mouth Rinse drug products to determine their appropriate identity. Identity testing for these and certain other high-risk drug components include a limit test in the United States Pharmacopeia (USP), to ensure that the component meets the relevant safety limits for levels of DEG or EG. Because you did not perform identity testing on each shipment of each lot using the USP identification test that detects these hazardous impurities, you failed to assure the acceptability of these components for use in manufacture of your drug products.

The use of ingredients contaminated with DEG or EG has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document Testing of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and Other High-Risk Drug Components for Diethylene Glycol and Ethylene Glycol to help you meet the CGMP requirements when manufacturing drugs containing ingredients at high risk for DEG or EG contamination at https://www.fda.gov/media/167974/download.

(b)(4) Water

Your firm produced (b)(4) water that was used as a component in the production of your drug products. Your firm has not demonstrated that the (b)(4) water was suitable for manufacturing of your aqueous-based OTC drug products due to lack of routine monitoring for Burkholderia cepacia complex (BCC).

BCC poses a risk of contamination in non-sterile, water-based drug products. For more information regarding the significance of BCC contamination in drug products, see the FDA’s July 7, 2021, advisory for drug manufacturers.1

Because water is used as a component in your non-sterile drug products, the lack of data regarding the state of control of your water system poses a potential risk of introducing objectionable microbial contamination into your products. Pharmaceutical water must be suitable for its intended use and routinely tested to ensure ongoing conformance with appropriate chemical and microbiological attributes.

In your response, you provide (b)(4) identity test summary reports of components, including glycerin and sorbitol, and commit to perform at least one identity test for the components used in the manufacture of your drug products.

You also include your updated procedure for water system maintenance and testing that requires all (b)(4) water samples to be routinely tested per USP Chapters <60>, <61> and <62>. You indicate that you have started testing (b)(4) water as per USP Chapter <60> since February 1, 2024.

Your response is inadequate. You did not perform a limit test for DEG and EG for glycerin and sorbitol as required by USP to ensure that the component meets the relevant safety limits for the levels. Additionally, you do not provide a comprehensive assessment of your water system describing whether all ports are free of objectionable microorganisms and the frequency of water testing, including sampling from all ports. You also do not include supporting documentation of microorganism identification testing.

In response to this letter, provide the following:

  • A comprehensive, independent review of your material system to determine whether all suppliers of components, containers, and closures are each qualified and the materials are assigned appropriate expiration or retest dates. The review should also determine whether incoming material controls are adequate to prevent use of unsuitable components, containers, and closures.
  • The chemical and microbiological quality control specifications you use to test and release each incoming lot of components including high-risk drug components to determine acceptability for use in manufacturing.
  • A description of how you will test each component lot for conformity with all appropriate specifications for identity, strength, quality, and purity. If you intend to accept any results from your supplier’s COA instead of testing each component lot for strength, quality, and purity, specify how you will robustly establish the reliability of your supplier’s results through initial validation as well as periodic re-validation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot. In the case of glycerin, sorbitol, and certain additional high-risk components we note that this includes the performance of parts A, B, and C of the United States Pharmacopeia (USP) monograph.
  • A commitment to provide DEG and EG test results, no later than 30 calendar days from the date of this letter, from testing reserve samples for all lots of high-risk drug components used in the manufacture of your drug products. Alternatively, if a reserve of a component lot is unavailable, perform reserve sample testing of all implicated finished drug product batches for the presence of DEG and EG.
  • A full risk assessment for drug products that are within expiry which contain any ingredient at risk for DEG or EG contamination (including, but not limited to, glycerin). Take prompt and appropriate actions to determine the safety of all lots of the ingredient(s) and any related drug product that could contain DEG or EG, including customer notifications and product recalls for any contaminated lots. Identify additional appropriate corrective actions and preventive actions (CAPA) that secure supply chains in the future, including but not limited to, ensuring that all incoming raw material lots are from fully qualified manufacturers and free from unsafe impurities. Detail these actions in your response to this letter.
  • Your total microbial count limits to monitor whether this system is producing water suitable for the intended uses for each of your drug products.

2. Your firm failed to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products (21 CFR 211.22(a)).

Your quality unit (QU) did not effectively exercise its responsibilities to oversee the quality of your drug manufacturing operations. Specifically, your QU did not adequately exercise its authority in the approval or rejection of components in your Materials System.

Your QU is responsible for fully exercising its authority and responsibilities. FDA is concerned that your QU may also not be conducting appropriate oversight regarding other CGMP operations, including Production, Facilities & Equipment, Laboratory Controls, and Packaging & Labeling Systems.

See FDA’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations for help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211 at https://www.fda.gov/media/71023/download.

In response to this letter, provide:

  • A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to:

    o A determination of whether procedures used by your firm are robust and appropriate.
    o Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices.
    o A complete and final review of each batch and its related information before the QU disposition decision.
    o Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products.

CGMP Consultant Recommended

Based upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements.

Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.

Conclusion

The violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.

Correct any violations promptly. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure and injunction. Unresolved violations may also prevent other Federal agencies from awarding contracts.

Failure to address violations may also cause FDA to withhold issuance of Export Certificates. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to address any violations.

This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.

Your response should refer to Case # 678539. Please address your reply via email to: ORAPHARM3_RESPONSES@fda.hhs.gov

Attention: Sneha Patel, Compliance Officer
U.S. Food and Drug Administration
Division of Pharmaceutical Quality Operations III

If you have questions regarding the contents of this letter, please contact Compliance Officer, Sneha Patel at (313) 393-8254.

Sincerely,
/S/

Rebecca E. Dowd
Program Division Director
Division of Pharmaceutical Quality Operation III
Office of Regulatory Affairs

Cc:

L. Hier
Chief Executive Officer
TJA Health, LLC
2501 Reeves Road
Joliet, IL 60436-9523

_______________

1 https://www.fda.gov/drugs/drug-safety-and-availability/fda-advises-drug-manufacturers-burkholderia-cepacia-complex-poses-contamination-risk-non-sterile

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