Delivery Method: Via Email Reference #: 320-25-47 Product: Drugs Recipient:
Recipient Name
Changhui Qi
Linghai ZhanWang Biotechnology Co., Ltd
No. 7-2, Dalinghe Industrial Park
Linghai Shi
Jinzhou Shi
Liaoning Sheng, 121200
China
Issuing Office: Center for Drug Evaluation and Research (CDER)
United States
Warning Letter 320-25-47
February 25, 2025
Dear Changhui Qi:
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 February 26, 2024 request, and subsequent correspondence, 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, Linghai ZhanWang Biotechnology Co., Ltd, FEI 3015248821, at No. 7-2, Dalinghe Industrial Park, Linghai, Jinzhou, Liaoning 121200, China.
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 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:
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 manufactured OTC drug products, including anti-microbial wipes. Based on the records and information you provided, you did not demonstrate that you are adequately testing the identity of components used in the manufacture of your drug products. For example, you did not test your active ingredient, ethanol, for methanol content.
Additionally, you did not demonstrate the purity and quality of the components used in the manufacture of your drug products. For example, you did not test your glycerin and (b)(4) components for the presence of diethylene glycol (DEG) and ethylene glycol (EG).
Component testing is fundamental to quality. 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.
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 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.
2. Your firm failed to establish an adequate written testing program designed to assess the stability characteristics of drug products and to use results of stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)).
The records and information you provided did not demonstrate that your firm has an adequate stability program for the OTC anti-microbial wipes you manufacture. For example, you conducted stability studies under “accelerated aging experiments” for your anti-microbial wipes without scientific justification. These experiments were conducted over a (b)(4) period at (b)(4)°C and 75% relative humidity. In addition, you did not perform stability studies under long-term storage conditions to support the (b)(4) expiration date on the label.
Without appropriate stability studies, you do not have scientific evidence to support whether your drug products meet established specifications and retain their quality attributes through their labeled expiry.
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 demonstrate that your quality unit (QU) did not effectively exercise its responsibilities to oversee the quality of your OTC drug manufacturing operations. Your QU is responsible for fully exercising its authority and responsibilities. FDA is concerned that your QU may not be conducting appropriate oversight regarding drug 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.
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.
FDA placed all drugs and drug products offered for import into the United States from your firm on Import Alert 66-40 on February 10, 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 Linghai ZhanWang Biotechnology Co., Ltd, FEI 3015248821, located at No. 7-2, Dalinghe Industrial Park, 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 3015248821 and ATTN: Carrie Hughes.
Sincerely,
/S/
Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
