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March 27, 2024

WARNING LETTER
CASE #673930

Dear Dr. Abouhalkah:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Vintage Chemical, Inc., FEI 3002718545, at 2007 Bremer Road, Fort Wayne, Indiana, from November 13 to 20, 2023.

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 December 8, 2023 response to our Form FDA 483 in detail.

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

1. Your firm failed to perform operations within specifically defined areas of adequate size and to have separate or defined areas or such other control systems necessary to prevent contamination or mix-ups (21 CFR 211.42(c)).

Your firm manufactures over-the-counter (OTC) antibacterial hand soap and hand sanitizer drug products. End of
Translation You manufacture these drug products using the same equipment that you use to manufacture numerous non-pharmaceutical materials in your facility, including industrial detergents and degreasing products. It is unacceptable as a matter of CGMP to continue manufacturing drugs using the same equipment that you use to manufacture these non-pharmaceutical products due to the risk of cross-contamination.

In response to this letter, confirm whether you will discontinue manufacturing drugs on shared equipment in your facility. If you intend to continue manufacturing both pharmaceutical and non-pharmaceutical products at your facility, provide a plan showing how you will separate the areas that will maintain dedicated manufacturing equipment for your pharmaceutical manufacturing and industrial product manufacturing operations.

In addition, provide a risk assessment for all drugs you have previously produced on equipment shared with industrial products. For each product, assess the risk of potential contamination due to the shared equipment, and provide your plans for addressing the product quality and patient safety risks for any product still in distribution, including potential recalls or market withdrawals.

2. Your firm failed to have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release, and conduct for each batch of drug product, appropriate laboratory testing, as necessary, required to be free of objectionable microorganisms (21 CFR 211.165(a) and 211.165(b)).

You failed to perform potency and microbiological testing on your hand sanitizer and antibacterial hand soap products prior to release for distribution. Your batch record for the benzalkonium chloride (BZK) based hand sanitizer only lists finished drug product tests for pH, color, odor, and clarity.

Testing is essential to ensure that the drug products you manufacture conform to all pre-determined quality attributes appropriate for their intended use. Because you lacked adequate testing of each batch of your drug products, you do not know whether they conform to all appropriate finished product specifications and are suitable for release to consumers.

In your response, you state that your batch record was updated to “show the (b)(4) procedure and the results of the drug (BZK).” You also state that you have identified contract testing laboratories and will test for active ingredient para-chloro-meta-xylenol (PCMX) prior to release. Your response is inadequate because you did not provide sufficient information to establish that your testing is equivalent or better than applicable United States Pharmacopeia (USP) compendial methods, nor provide sufficient details as to how you will ensure adequate release testing is performed on all OTC finished drug products performed by contract testing laboratories.

In response to this letter, provide the following:

• A list of chemical and microbiological specifications, including test methods, used to analyze each batch of your drug products before batch disposition decisions.

    o An action plan and timelines for conducting full chemical and microbiological testing of retain samples to determine the quality of all batches of drug products distributed in the United States that are within expiry as of the date of this letter.
    o A summary of all results obtained from retain samples from each batch. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.

• A comprehensive independent third-party assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. This assessment should include, but not be limited to, a review of method suitability criteria, and validation (or verification, for USP compendial methods) to determine whether they are fit for their intended use. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.

3. Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality. Your firm also failed to validate and establish the reliability of your component supplier's test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2)).

Your firm manufactures OTC drug products without adequate assurance of the quality of raw materials. For example, you did not conduct identity testing of each component lot used in the manufacture of your OTC drug products. During the inspection, our investigator noted that you perform only pH testing on incoming (b)(4) raw materials without establishing the reliability of your component suppliers’ certificates of analysis (COA) at appropriate intervals. Without adequate testing, you do not have scientific evidence that the components conform to appropriate specifications prior to use in the manufacture of your drug products.

In your response, you acknowledge that you perform “a minimum of one test (pH) to verify the raw material” and ensure a COA is received from your suppliers. You also state that you would “formally visit and audit our vendors to establish their product reliability.” Your response is inadequate. You failed to provide sufficient details regarding how you will ensure at least one identity test for each lot of each shipment of incoming raw materials is performed and how you will validate your suppliers’ COAs. You also did not address how you will assess the quality of your components used in your distributed drug products that are within expiry.

In response to this letter, provide the following:

• A comprehensive 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 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 suppliers’ COA instead of testing each component lot for strength, quality, and purity, specify how you will robustly establish the reliability of your suppliers’ results through initial validation as well as periodic revalidation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot.
• A summary of results obtained from testing all components to evaluate the reliability of the COA from each component manufacturer. Include your standard operating procedure that describes this COA validation program.
• A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture.

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 evaluate your operations and to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with FDA. 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 # 673930. 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
Director of Investigations Branch
Division of Pharmaceutical Quality Operation III
Office of Regulatory Affairs

/S/
Jeffrey D. Meng
Program Division Director
Division of Pharmaceutical Quality Operation III
Office of Regulatory Affairs