Kardesler Ucan Yaglar Sanayi Anonim Sirketi

Your facility was recently registered with the United States Food and Drug Administration (FDA) as a manufacturer of over-the-counter (OTC) drug products. FDA has reviewed the records you submitted in response to our March 15, 2024 request, and subsequent requests, for records and other information pursuant to section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) for your facility, Kardesler Ucan Yaglar Sanayi Anonim Sirketi, FEI 3012634391, at Inonu Mah Gebze Plastikciler OSB, Mah 42 Sokak No: 1, Gebze/Kocaeli 41400, Turkey.

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

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding of drugs as described in your responses to our 704(a)(4) requests do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the FD&C Act (21 U.S.C. 351(a)(2)(B)).

Following review of records and other information provided pursuant to section 704(a)(4) of the FD&C Act, significant violations were observed including, but not limited to, the following:

You manufacture OTC drug products such as hand sanitizing wipes. Based on the records and information you provided, you did not demonstrate that you adequately tested the identity of incoming components used in the manufacture of your drug products.

Glycerin & Propylene Glycol

Information provided indicated that you failed to adequately test each shipment of each lot of glycerin and propylene glycol for identity, components at higher risk for diethylene glycol (DEG) and ethylene glycol (EG) contamination. Identity testing of glycerin and propylene glycol, along with other high-risk drug components1, 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 glycerin and propylene glycol lot using the USP identification tests that detect these hazardous impurities, you failed to assure the acceptability of these components for use in the 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.

Ethanol

You failed to demonstrate that you adequately test your incoming ethanol, used as an active ingredient, for methanol. The use of ethanol contaminated with methanol has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol to help you meet the CGMP requirements when manufacturing drugs containing ethanol at https://www.fda.gov/media/173005/download

Without adequate testing, you do not have scientific evidence that your components conform to appropriate specifications prior to use in the manufacture of your drug products.

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 (21 CFR 211.165(a)).

Based on the records and information you provided, you did not demonstrate that you adequately tested your drug products for the identity and strength of the active ingredients prior to release and distribution. For example, your responses did not demonstrate that you tested the identity or strength of ethanol or benzalkonium chloride in your finished drug products.

Testing is an essential part of CGMP to ensure that the drug products you manufacture conform to all pre-determined quality attributes appropriate for their intended use. Drug products must be tested for identity and strength of the active ingredient, prior to release and distribution. Without adequate testing, you do not have scientific evidence to assure that your drug products conform to appropriate specifications before release.

3. 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)).

The records and information you provided did not demonstrate that your quality unit (QU) effectively exercised its responsibilities to oversee the quality of your drug manufacturing operations. For example, 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 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.

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.

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.

FDA placed your firm on Import Alert 66-40 January 14, 2025.

Correct any violations promptly. 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 inspect to verify that you have completed corrective actions to any violations.

Failure to address any violations may also result in the FDA continuing to refuse admission of articles manufactured at Kardesler Ucan Yaglar Sanayi Anonim Sirketi, Inonu Mah Gebze Plastikciler OSB, Mah 42 Sokak No: 1, Gebze/Kocaeli 41400, Turkey, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be adulterated may be detained or refused admission.

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.

Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3012634391 and ATTN: Joel Hustedt.