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Warning Letter 320-26-29

December 16, 2025

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 April 28, 2025 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, Guangdong Renhe Guozhuang Biotechnology Co., Ltd, FEI 3030384816 at No. 5, Tongfu Road, Xicheng Industrial Area, Renhe Town, Baiyun District, Guangzhou Guangdong, China.

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

1. 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. Your firm also failed to 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)).

Your firm manufactures over-the-counter (OTC) drug products including sterile (b)(4). Based on the records and information you provided, you did not demonstrate that you adequately test your OTC finished drug products prior to release for distribution to the United States.

In your initial response, you state that you test each batch of your finished drug products before release. On June 23, 2025, FDA specifically requested that you provide the test data; however, in response to this request, you failed to provide the requested information to demonstrate that your finished products are tested prior to release.

Full release testing, including for identity, strength, and impurities, must be performed prior to drug release and distribution. Without adequate testing, there is no scientific evidence to assure that your drug products conform to appropriate specifications before release.

In response to this letter, provide:

• A list of chemical and microbial specifications, including test methods, used to analyze each lot of your drug products before a batch disposition decision.
  o An action plan and timelines for conducting full chemical and microbiological testing of reserve samples to determine the quality of all batches of drug product distributed to the United States that are within expiry as of the date of this letter.
  o A summary of all results obtained from testing reserve 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 assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.

2. Your firm failed to conduct at least one test to verify the identity of each component of a drug product (21 CFR 211.84(d)(1)).

Based on the records and information you provided, you did not demonstrate that you adequately performed identity testing on incoming components including, but not limited to, (b)(4), which are at high-risk of (b)(4) contamination. Identity testing for these and certain other high-risk drug components includes a limit test in the United States Pharmacopeia (USP) to ensure that the component meets the relevant safety limits for levels of (b)(4). Because you did not perform sufficient identity testing, you failed to assure the acceptability of these components for use in manufacture of your drug products.

The use of ingredients contaminated with (b)(4) has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document (b)(4).

In your initial response, you state that you or your contract laboratory performed identity testing on each shipment of each lot of components before they were released for use in manufacturing. On June 23, 2025, FDA specifically requested that you provide the test data; however, in response to this communication you failed to provide any records demonstrating that you tested your incoming components before use in manufacturing.

Without adequate testing, you do not have scientific evidence that incoming components conform to appropriate specifications prior to use in the manufacture of your drugs. As a manufacturer, you have a responsibility to sample, test, and examine incoming materials before use in production to assure adequate quality.

In response to this letter, provide:

• A commitment to provide (b)(4) test results, no later than 30 calendar days from the date of this letter, from testing retains for all lots of high-risk drug components used in the manufacture of drug products. Alternatively, if a retain of a component lot is unavailable, perform retain sample testing of all implicated finished drug product batches for the presence of (b)(4).
• A full risk assessment for drug products that are within expiry which contain any ingredient at risk for (b)(4) contamination (including, but not limited to, (b)(4)). Take prompt and appropriate actions to determine the safety of all lots of the component(s) and any related drug product that could contain (b)(4), including customer notifications and product recalls for any contaminated lots. Identify additional appropriate corrective actions and preventive actions that secure supply chains in the future, including, but not limited to, ensuring that all incoming raw material lots are from fully qualified manufacturers and free from unsafe impurities. Detail these actions in your response to this letter.
• A comprehensive, independent review of your material system to determine whether all suppliers of incoming materials 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 materials.
• 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 incoming material lot for conformity with all appropriate specifications for identity. If you intend to accept any results from your supplier’s certificate of analysis (COA) instead of testing each incoming material lot for other tests, specify how you will ensure that you have adequate evidence to establish that the supplier consistently provides material meeting specifications. In addition, include a commitment to always conduct at least one specific identity test for each incoming material lot.
• A summary of results obtained from testing all incoming materials to evaluate the reliability of the COA from each incoming materials 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 drugs you manufacture.

3. Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100 (a)).

Lack of Process Validation

In your response, you stated that no validation activities have been performed for your drug products.

Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately and assure the quality of raw material inputs, in-process materials, and finished drugs. Process qualification studies determine whether an initial state of control has been established. Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality is necessary to ensure you maintain a stable manufacturing operation throughout the product lifecycle.

See FDA’s guidance for industry Process Validation: General Principles and Practices for general principles and approaches that the FDA considers appropriate elements of process validation at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/process-validation-general-principles-and-practices.

Inadequate (b)(4) System

In your initial response, you state that you qualified your (b)(4) system. On June 23, 2025, FDA specifically requested that you provide the test data; however, in response to this communication you failed to provide any records demonstrating that the (b)(4) system has been qualified or appropriately tested. Also, it appears that you do not perform adequate chemical or microbiological analysis to determine suitability of or monitor the (b)(4) generated for use in drug manufacturing.

(b)(4) is an ingredient in your drug products. (b)(4) must be suitable for its intended use and routinely tested to ensure ongoing conformance with appropriate chemical and microbiological attributes. See FDA’s (b)(4)

In response to this letter, provide:

• A timeline for performing appropriate process performance qualification for each of your marketed drug products. Also include an explanation how you will ensure proper satisfactory process performance qualification studies are performed prior to future distribution of any drug products.
• Your process performance protocol(s) and written procedures for qualification of equipment and facilities.
• A (b)(4) system validation report. Also include the summary of any improvements made to system design and to the program for ongoing control and maintenance.
• A procedure governing your program for ongoing control, maintenance, and monitoring that ensures the remediated system consistently produce (b)(4) that meets (b)(4) USP monograph specifications and appropriate microbiological limits. Include action/alert limits for total counts and objectionable organisms used for your (b)(4) system.
• A procedure for your (b)(4) system monitoring that specifies routine chemical and microbiological testing of (b)(4) to ensure its acceptability for use in each batch of drug products produced by your firm. Ensure that the total microbiological count limits for your (b)(4) are appropriately stringent in view of the intended use of each of the products produced by your firm.

Quality Systems

Your firm’s quality systems are inadequate. 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/regulatory-information/search-fda-guidance-documents/quality-systems-approach-pharmaceutical-current-good-manufacturing-practice-regulations.

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.

FDA placed all drugs and drug products offered for import into the United States from your firm on Import Alert 66-40 on November 12, 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 Guangdong Renhe Guozhuang Biotechnology Co., Ltd., No. 5, Tongfu Road, Xicheng Industrial Area, Renhe Town, Guangzhou, 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, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).

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 3030384816 and ATTN: Chhaya Shetty.

Sincerely,
/S/

Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research