Natuzen Co., Ltd.

Warning Letter 320-24-36

May 3, 2024 Dear Mr. Cho:

Your facility is 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 29, May 9, July 8, 2022, and October 6, 2023 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, Natuzen Co., Ltd., FEI 3006731547, at 289 Namdongdong-Ro, Namdong-gu, Incheon 21639, South Korea.

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 response to our 704(a)(4) request 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)).

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:

Your firm manufactures OTC drug products including Atoren Hand Sanitizer.1 Based on the records and information you provided, you did not demonstrate that you are testing your active ingredient ethanol for methanol. For example, you stated that hand sanitizers containing ethanol are not tested for methanol in accordance with a “notification of the Korean Ministry of Food and Drug Safety.”

Without adequate testing you do not have scientific evidence that your raw materials conform to appropriate specifications prior to use in the manufacture of your drug products. As a manufacturer, you have a responsibility to sample, test, and examine drug components before use in production to assure adequate quality, including testing for the presence of methanol in ethanol.

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, at: https://www.fda.gov/media/173005/download.

The records and information you provided did not demonstrate that you have established adequate, validated procedures for cleaning of non-dedicated manufacturing equipment. Cleaning validation cannot be conducted without specific, reproducible cleaning procedures.

Inadequate removal of active ingredients and product residues from surfaces of non-dedicated manufacturing equipment can lead to contamination of drug products subsequently manufactured on that equipment.

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 you have established an adequate quality unit (QU) to oversee the quality of your drug manufacturing operations. In your response, you state that “We do not have a quality unit.”

The QU is responsible for fully exercising its authority and responsibilities. FDA is concerned that your QU may not be conducting appropriate oversight regarding CGMP operations. 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.

If your firm intends to resume manufacturing drugs for the U.S. market, you should engage a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements before resuming drug manufacturing operations. 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 all corrective action and preventive action (CAPA) before you pursue resolution of your firm’s compliance status per FDA’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations.

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 on April 29, 2024.

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 Natuzen Co., Ltd., 289 Namdongdong-Ro, Namdong-gu, Incheon 21639, South Korea, 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 3006731547 and ATTN: Joel Hustedt.