Findings citing 21 CFR 211.165

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 quality unit (QU) did not adequately oversee your drug manufacturing operations. For example, your QU failed to ensure: Adequate documentation of production and process control functions executed at the time of performance (21 CFR 211.100(b)) Adequate validation of manufacturing processes and the (b)(4) system (21 CFR 211.100(a) Adequate written procedures for production and process control (21 CFR 211.100(a)) Adequate stability testing program (21 CFR 211.166) Adequate finished product testing (21 CFR 211.165(a), 211.165(b)) 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/regulatory-information/search-fda-guidance-documents/q10-pharmaceutical-quality-system and https://www.fda.gov/regulatory-information/search-fda-guidance-documents/quality-systems-approach-pharmaceutical-current-good-manufacturing-practice-regulations, respectively. 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 Lot Identification CGMPs define a lot number, control number, or batch number as any distinctive combination of letters, numbers, or symbols, or any combination of them, from which the complete history of the manufacture, processing, packing, holding, and distribution of a batch or lot of drug product or other material can be determined. Upon further review of your records and information, it appears that you assign the same batch number to different products fulfilled on a single Purchase Order. You have identified drug products with different active ingredients, routes of administration, use instructions, and dates of manufacture with the same batch number. You must establish written procedures to apply unique identification of the drug product with a lot or control number that permits determination of the history of the manufacture and control of the batch. (21 CFR 211.130(c)). Drug Recall On February 3, 4, and 5, 2026, FDA attempted to contact you requesting a teleconference to discuss recalling your (b)(4) labeled as sterile, within expiry, and currently in distribution to the U.S. market. We have also attempted to contact your listed U.S. Agent. To date, neither you or your U.S. Agent have responded to any of our attempts for direct contact. We recommend you remove any batches of (b)(4) labeled as sterile currently in distribution and within expiry from the U.S. market. 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.

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 failed to adequately test your OTC drug products prior to release and distribution to the U.S. market. For example, your firm did not perform assay testing of the API as part of finished product release testing of your (b)(4) product (b)(4) batches (b)(4) . These batches were released and distributed to the U.S. market without appropriate testing. Without adequate testing, you do not have adequate scientific evidence to assure that drug product batches conform to appropriate specifications before release. In your response you state you will confirm the definitions of raw material and product specification standards with your customer and explicitly verify whether the assay test is included. Your response is inadequate. Your firm’s quality system does not ensure that all required tests are identified, documented, and performed before product is released to your customers. You do not have a written procedure or a quality agreement describing the roles and responsibilities between you, as the contract manufacturing organization, and your customer regarding testing requirements and established product specifications. You are responsible for the quality of drugs you produce as a contract facility regardless of agreements in place with product owners. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act for safety, identity, strength, quality, and purity. See FDA’s guidance document Contract Manufacturing Arrangements for Drugs: Quality Agreements at https://www.fda.gov/downloads/drugs/guidances/ucm353925.pdf. In response to this letter, provide the following: A comprehensive quality agreement describing the responsibilities of each party regarding drug products testing and release, establishing drug product specifications, initiating investigations, and batch disposition. The quality agreement should define the manufacturing responsibilities and communication processes for quality related activities. A list of chemical and microbial test methods and specifications used to analyze each lot of your drug product before making a lot disposition decisions.

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 appropriate laboratory testing, as necessary, for each batch of drug product required to be free of objectionable microorganisms (21 CFR 211.165(a) and 211.165(b)). Based on the records and information you provided, you did not demonstrate that you adequately test your finished OTC drug products prior to release and distribution to the United States. For example, the finished product testing reports you provided did not include appropriate assay testing for the identity and strength of each active ingredient or for impurities prior to release. Additionally, the records you provided failed to demonstrate adequate microbiological testing for each batch of your drug product prior to release. Testing is an essential part of CGMP to ensure that the drug products you manufacture conform to all predetermined 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.

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 failed to perform adequate analytical and microbiological release testing for each batch of your over the counter (OTC) drug products prior to distribution. For example, your “ (b)(4) ” batch (b)(4) , was manufactured on October 3, 2024. Samples were collected for pH, microbiological and assay testing between October 3 and October 7, 2024. Two months later, on December 23, 2024, this bulk batch underwent additional manufacturing by (b)(4) . No testing of the resulting final drug product, “ (b)(4) ” batch (b)(4) , was conducted. In addition, you released the same finished drug product batch prior to obtaining documented product release approval by the quality unit. Drug product batches must be tested for identity, strength, quality, and purity prior to release. Testing is an essential part of ensuring that the drug products you manufacture conform to all predetermined quality attributes and are appropriate for their intended use. Without adequate testing, you lack basic data to support that each drug product batch conforms to appropriate specifications before release. In your response, you acknowledge lack of understanding of the regulations. You commit to implement a comprehensive finished drug product testing plan. You state that all active finished drug products in-house have been sent for microbial testing and active pharmaceutical ingredient (API) analytical testing. You also commit to perform retrospective testing for all active and recently distributed lots using third-party analytical and microbiological verification. Your response is inadequate because your firm did not provide a procedure describing how you will ensure your finished drug products, not only the bulk products, meet the appropriate quality standards prior to release. You did not provide details on the acceptance criteria of the tests performed by the third party and did not provide an impact assessment for products on the market and within expiry. 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 product before making a batch disposition decision and the associated written procedures.

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 establish and follow an adequate written stability testing program that included reliable, meaningful, and specific test methods for assessing the stability characteristics of these drug products (21 CFR 211.165(a) and 211.166(a)). Your firm manufactures various (b)(4) over-the-counter (OTC) drug products, including those containing the active ingredient (b)(4) and the inactive ingredient (b)(4) . You failed to establish scientifically sound and appropriate finished product specifications. For example, you did not include (b)(4) testing as a release or stability requirement. Under certain conditions, (b)(4) can degrade through a known mechanism to form (b)(4) , a known carcinogen. Also, when (b)(4) is present in a drug formulation in combination with certain chemicals such as (b)(4) , it may react under certain conditions to generate (b)(4) . Over the drug product's shelf life, (b)(4) can accumulate and increase in concentration. Despite these known degradation and reaction pathways, you distributed at least (b)(4) batch of an OTC (b)(4) -containing drug product into interstate commerce without (b)(4) testing. Your quality unit is responsible for ensuring that appropriate testing and procedures are in place and followed prior to releasing drug products for distribution. Your firm’s inadequate response to a known contamination event further compounds these failures. Your firm was aware that your customer voluntarily recalled (b)(4) products in Canada on (b)(4) , due to potential (b)(4) contamination. The recalled batches were manufactured at your facility using the same formulation, packaging, and labeling used for products distributed in both the United States and Canada. Despite being notified of (b)(4) contamination in your product, your firm failed to determine whether the recalled batches were also distributed in the United States and did not evaluate the potential risk to U.S. consumers. During the inspection, your firm confirmed that you do not test OTC drug products that contain (b)(4) or (b)(4) for (b)(4) before release or during stability testing. Your written risk assessments for (b)(4) contamination are inadequate. In your response, you commit to discontinue your manufacturing of (b)(4) and (b)(4) and to deactivate the drug listing for (b)(4) and (b)(4) . You also commit to engaging a third-party laboratory for (b)(4) testing, updating release and stability specifications, and completing comprehensive risk assessments for all currently marketed OTC drug products. Your response is inadequate. You did not provide test results to show products still in the market are below the recommended (b)(4) levels. Most critically, your firm failed to evaluate the impact of (b)(4) contamination identified in (b)(4) , which was recalled in other markets. You also failed to identify other potentially affected batches or conduct appropriate market action assessments. Further, your response does not demonstrate that your third-party laboratory is qualified to perform (b)(4) testing on your drug products. FDA has alerted drug manufacturers of products at risk for presence of (b)(4) that they should be testing those drug products for (b)(4) . For more information see (b)(4) . In response to this letter, provide: A list of chemical and microbial specifications, including test methods, used to analyze each lot of your drug product before a batch disposition decision. A detailed description of the method you establish to test for (b)(4) in finished products prior to release. 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. A summary of all results obtained from testing retain samples from each lot of (b)(4) products and (b)(4) products that are currently on the U.S. market within expiry. If retain samples of component lots are unavailable, perform retain sample testing of all implicated finished drug product batches for the presence of (b)(4) . If testing reveals substandard-quality drug products, take rapid corrective actions, such as notifying customers and initiating product recalls. Provide your market action plan to ensure that no batches potentially contaminated with (b)(4) remain in the U.S. market. 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 comprehensive assessment and corrective action and preventive action (CAPA) plan to ensure the adequacy of your stability program. Your remediated program should include, but not be limited to, the following: o Stability indicating methods o Stability studies for each drug product in its marketed container-closure system before distribution is permitted o An ongoing program in which representative batches of each product are added each year to the program to determine whether the shelf-life claim remains valid o Detailed definition of the specific attributes to be tested at each station (timepoint), as part of a program that encompasses each quality attribute that may change over the product shelf-life All procedures that describe these and other elements of your remediated stability program.

Your firm failed to conduct appropriate laboratory testing, as necessary, for each batch of drug product required to be free of objectionable microorganisms (21 CFR 211.165(b)). You failed to ensure adequate microbiological testing for each batch of your drug product prior to release. Your non-compendial test method used to determine microbiological attributes (e.g., total count, objectionable microorganisms) for your finished OTC drug product was inadequate. Specifically, you lacked appropriate incubation times, lacked appropriate method suitability, and lacked positive and negative controls. In addition, you did not validate this non-compendial method. Your response is inadequate. You state that a contract laboratory will perform validation of United States Pharmacopeia (USP) <61> and <62> test methods for future release testing. While you submitted your Laboratory Controls and Test Method Management procedure and CAPA-2026-005, which references validation planning for microbiological methods, your response does not demonstrate adequate corrective actions to ensure that distributed product was appropriately tested prior to release, nor does it include a retrospective assessment of product quality. Testing is essential to ensure that the drug product you manufacture conform to all predetermined quality attributes appropriate for their intended use. Because you lacked adequate testing of each batch of your drug products, you do not know whether they conform to all appropriate finished-product specifications and are suitable for release to consumers. In response to this letter, provide: A list of chemical and microbial specifications, including test methods, used to analyze each batch of your drug products before a batch disposition decision. 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. 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.