Hangzhou Huiji Biotechnology Co., Ltd.

Warning Letter 320-25-16

November 18, 2024 Dear Mr. Libin:

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 4, 2024 request 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, Hangzhou Huiji Biotechnology Co., Ltd., FEI 3010461961, at No. 3 Shunshuiqiao Road, Renhe Street, Yuhang District, Hangzhou, Zhejiang.

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 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 gel hand sanitizers containing ethyl alcohol. 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. For example, in your response, you state that you do not verify the identity of each shipment of drug ingredients prior to use in manufacturing. Additionally, you state that you do not utilize appropriate raw material tests described in USP, including the limit tests for DEG/EG and methanol, despite your records indicating that you manufacture products containing glycerin and ethanol.

Glycerin

Information provided indicates that you failed to adequately test each shipment of each lot of glycerin for identity, a component at higher risk for diethylene glycol (DEG) and ethylene glycol (EG) contamination. We note that glycerin is an ingredient used in your hand sanitizer drug products. Identity testing for glycerin and certain 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 lot using the USP identification test that detects 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 adequately test your incoming ethanol, which is used as an active ingredient in your hand sanitizer, 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 finished drug products for the identity and strength of the active ingredient, ethanol prior to release and distribution. For example, the “content of ethanol solutes” test procedure that you provided is not an appropriate laboratory determination of the identity and strength of your ethanol active ingredient. Additionally, you did not demonstrate the suitability of this test procedure per 21 CFR 211.165(e).

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, demonstrate that your quality unit (QU) did not effectively exercise its responsibilities to oversee the quality of your drug manufacturing operations. For example, your QU failed to ensure that appropriate batch production records were used during the manufacturing of your drug products. Your QU also failed to ensure that adequate stability data supported the expiry of your drug products. In addition, your QU failed to ensure that your water system used in the manufacture of your OTC hand sanitizers, is appropriately designed and monitored in light of its intended use.

Your 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.

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.

In addition, we note that some of the drug products you manufacture may also be regulated as cosmetics, as defined in section 201(i) of the FD&C Act. Any cosmetics you manufacture must comply with applicable statutory and regulatory requirements, including the FD&C Act. Under section 301(a) of the FD&C Act (21 U.S.C. 331(a)), it is a prohibited act to introduce or deliver for introduction into interstate commerce a cosmetic that is adulterated or misbranded. Further, your facility may be subject to requirements of the Modernization of Cosmetic Regulations Act of 2022 (MoCRA). Information on MoCRA requirements may be found at https://www.fda.gov/cosmetics/cosmetics-laws-regulations/modernization-cosmetics-regulationact-2022-mocra.

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 November 15, 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 Hangzhou Huiji Biotechnology Co., Ltd., No. 3 Shunshuiqiao Road, Renhe Street, Yuhang District, Hangzhou Zhejiang, 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 3017005720 and ATTN: Daniel W. Brisker.