Yangzhou H&R Plastic Daily Chemical Co., Ltd.

The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Yangzhou H&R Plastic Daily Chemical Co., Ltd., FEI 3014543859, at 188 Xingyuan Road, Hangji, Guangling, Yangzhou, Jiangsu, from October 21 to 24, 2025.

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 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).

We have not received a response from your firm stating your actions to address the deficiencies identified during the inspection and cited on our Form FDA 483. We note that you continue to ship drug products to the United States.

During our inspection, our investigator observed specific violations 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 (21 CFR 211.165(a)).

Your firm contract manufactures an over-the-counter (b)(4) drug product. You failed to adequately test batches of your finished drug product for the identity and strength of your active ingredient (e.g. (b)(4)) before release and distribution. Your specification procedures only discuss appearance, color, and weight checks prior to batch release.

Full release testing, which includes strength and identity testing of the active ingredient, must be performed before drug product batch release and distribution. Without adequate testing, you do not have adequate scientific evidence to assure that drug product batches conform to appropriate specifications before release.

In response to this letter, provide:

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.

A list of chemical and microbial specifications, including test methods, used to analyze each lot of your drug products before a lot disposition decision.o An action plan and timelines for conducting full chemical and microbiological testing of retain 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 retain samples from each batch. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.

2. Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2)).

Your firm failed to conduct adequate identity testing on incoming components, including active pharmaceutical ingredients, used in the manufacturing of your drug products. Additionally, you relied on your suppliers’ certificates of analyses (COA) without establishing the reliability of each of your component suppliers’ analyses at appropriate intervals.

Without adequate testing and confirmation of reliability of supplier test results, you lack scientific evidence that the components conform to appropriate specifications prior to use in the drugs products you manufacture.

In response to this letter, provide:

A comprehensive, independent review of your material system, including but not limited to:o evaluating all suppliers of materials (components, containers, and closures) to determine if they are reliable and appropriately qualified;o an assessment of all materials to determine whether they are consistently of acceptable quality;o a review to ensure assigned expiration or retest dates are appropriate (supported by data);o adequacy of the supplier qualification program, and its selection, qualification, and disqualification provisions.

Based on a thorough review, provide a summary of your systems corrective actions and preventive actions to remediate the vendor qualification program and prevent use of unsuitable components, containers and closures.

The chemical and microbiological quality control specifications you use to test and release each incoming lot of component for use in manufacturing.

A description of how you will test each component lot for conformity with all appropriate specifications for identity, strength, quality, and purity. If you intend to accept any results from your supplier’s COA instead of testing each component lot for strength, quality, and purity, specify how you will robustly establish the reliability of your supplier’s results through initial validation as well as periodic re-validation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot.

A summary of results obtained from testing all components to evaluate the reliability of the COA from each component 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 drug products 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)).

Your firm failed to adequately qualify the equipment and validate the processes used to manufacture your (b)(4) drug product. You have not performed process performance qualification (PPQ) studies, nor do you have a meaningful ongoing program for monitoring process control, to ensure stable manufacturing operations and consistent drug quality.

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 to ensure 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 are necessary to ensure that you maintain a stable manufacturing operation throughout the product lifecycle.

See FDA’s guidance document for general principles and approaches that FDA considers appropriate elements of process validation, at https://www.fda.gov/media/71021/download.

In response to this letter, provide:

A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle, along with associated procedures. Describe your program forprocess performance qualification, and ongoing monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.

A timeline for performing appropriate PPQ for each of your marketed drug products. Also provide a risk assessment and any follow up actions to be taken for the distributed drug products produced without performing any process validation studies.

Process performance protocol(s), and written procedures for qualification of equipment and facilities.

A detailed program for designing, validating, maintaining, controlling and monitoring each of your manufacturing processes that includes vigilant monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control. Also, include your program for qualification of your equipment and facility.

4. Your firm’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).

Your firm failed to establish an adequate quality unit (QU) with the responsibilities and authority to oversee the manufacture of drug products. For example, you failed to ensure:

Adherence to an adequate stability program (21 CFR 211.166(a)).

Consistent and complete batch records (21 CFR 211.188).

Appropriate examination of labeling and packaging materials for correctness, including but not limited to sufficiently accounting for all ingredients used in manufacturing, prior to packaging operations (21 CFR 211.130(d)).

There was a fundamental failure of production management to effectively oversee the procedures, practices, and suitability of the manufacturing operations. In addition, even when a QU consists of one or only a few, those persons are still accountable for overseeing ongoing effectiveness of all systems and procedures, and review of the results of manufacture to ensure state of control and adherence to all quality standards.

In response to this letter, provide:

A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to:o A determination of whether procedures used by your firm are robust and appropriate.o Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices.o A complete and final review of each batch and its related information before the QU disposition decision.o Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products.

Your firm’s quality systems are inadequate. See FDA’s guidance document ICH Q10 Pharmaceutical Quality System, as well as 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/71553/download and https://www.fda.gov/media/71023/download, respectively.

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 if your firm intends to resume manufacturing drugs for the U.S. market. 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.

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 13, 2026.

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 re-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 188 Xingyuan Road, Hangji, Guangling, Yangzhou, Jiangsu, 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 3014543859 and ATTN: Philip Kreiter.