Findings citing 21 CFR 211.100

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 establish 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)]. Outsourcing facilities must comply with CGMP requirements under section 501(a)(2)(B) of the FDCA. FDA’s regulations regarding CGMP requirements for the preparation of drug products have been established in 21 CFR parts 210 and 211. FDA intends to promulgate more specific CGMP regulations for outsourcing facilities. FDA has issued a revised draft guidance, Current Good Manufacturing Practice — Guidance for Human Drug Compounding Outsourcing Facilities under Section 503B of the FD&C Act . This draft guidance, when finalized, will describe FDA’s expectations regarding outsourcing facilities and the CGMP requirements in 21 CFR parts 210 and 211 until more specific CGMP regulations for outsourcing facilities are promulgated. Under section 301(a) of the FDCA [21 U.S.C. § 331(a)], the introduction or delivery for introduction into interstate commerce of any drug that is adulterated is a prohibited act. Further, it is a prohibited act under section 301(k) of the FDCA [21 U.S.C. § 331(k)] to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being adulterated. C. Corrective Actions We have reviewed your firm’s responses to the Form FDA 483. We are unable to fully evaluate some of your corrective actions due to lack of adequate supporting documentation…

Your firm failed to establish adequate written procedures for production and process controls designed to assure that the drug products have the identity, strength, purity, and quality that they are purported or represented to possess (21 CFR 211.100(a)). Inadequate Process Validation for Drugs Your firm did not adequately validate the manufacturing processes you used to manufacture your (b)(4) drug products to demonstrate that your processes are reproducible and controlled to consistently yield drugs of uniform character and quality. Your Process Validation for Cosmetic Products document indicates that you use it to validate your manufacturing process for your OTC (b)(4) mL bottle. During the inspection, your firm confirmed that this process validation is intended to support the manufacture of (b)(4) . However, our investigator confirmed that the (b)(4) is not manufactured in accordance with the validated process. For example, the process validation includes a (b)(4) step that is absent from the (b)(4) batch record. Furthermore, you failed to conduct process validation for your (b)(4) . Your firm confirmed during the inspection that your firm relies on the process validation performed for (b)(4) to support the manufacturing of (b)(4) . However, the manufacturing processes for these products differ. We acknowledge your commitment to perform process validation for all your products moving forward. It remains your responsibility to maintain all supporting documentation, including your defined critical manufacturing process parameters. 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. Your validation program should identify sources of process variability and assure that manufacturing operations meet appropriate parameters and quality standards. This includes, but is not limited to, evaluating suitability of equipment for its intended use, ensuring quality of input materials, determining the capability and reliability of each manufacturing process step with ongoing monitoring of process performance and product quality. Inadequate Validation of (b)(4) You used (b)(4) as a component to manufacture multiple batches of OTC (b)(4) drug products and distributed these batches to the U.S. market. However, your firm failed to adequately qualify your (b)(4) to ensure it produces (b)(4) that meets appropriate chemical and microbial attributes and meets the (b)(4) monograph. Specifically, your (b)(4) qualification protocol and report lacked total organic carbon (TOC) testing, conductivity, or microbial content to ensure the (b)(4) is fit for its intended use. Additionally, you use this (b)(4) for cleaning drug manufacturing equipment. (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. In your response, you state you increased microbial sampling frequency to (b)(4) , revised the (b)(4) facility inspection record form to include TOC for routine monitoring, and established a trend analysis mechanism. Your response is inadequate because it fails to include the current action and alert limits for total counts and objectionable microorganisms used for your (b)(4) . Without defined limits, increased sampling frequency alone does not constitute a robust monitoring mechanism. See FDA's guidance for industry, Process Validation: General Principles and Practices at https://www.fda.gov/downloads/drugs/guidances/ucm070336.pdf for general principles and approaches that FDA considers appropriate elements of process validation. In response to this letter, provide the following: A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle along with associated procedures. Describe your program for process performance qualification and ongoing vigilant monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control. Also, describe your equipment and facility qualification program. A procedure for your (b)(4) monitoring that specifies routine microbial testing of (b)(4) to ensure its acceptability for use in each batch of drug products produced by your firm. The current action/alert limits for total counts and objectionable organisms used for your (b)(4) . Ensure that the total count limits for your (b)(4) are appropriately stringent in view of the intended use of each of the drug products produced by your firm. A procedure governing your program for ongoing control, maintenance, and monitoring that ensures the remediated system consistently produces (b)(4) that meets (b)(4) specifications and appropriate microbial limits.

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 validate your manufacturing processes for OTC drug products. You did not revalidate your manufacturing processes after making major process changes, nor did you fully execute validation protocols through the completion of all batches. For example, you changed the manufacturing process for (b)(4) to rephase the formulation without revalidation and outside of your change management system. Also, for (b)(4) , your process validation execution deviated from your Validation Master Plan (VMP) which requires validating your manufacturing processes with three batches. Furthermore, you did not retain stability samples from any of the three batches. Your firm also failed to adequately validate your cleaning processes for non-dedicated equipment used to manufacture (b)(4) . For the two validation batches where cleaning validation swab samples were collected, OOS results for residual of active pharmaceutical ingredients were not adequately investigated. In your response, you state a change control will be conducted for the (b)(4) and, if required, a process validation will be performed for the revised process. You also state you will complete the validation for the (b)(4) and will update your VMP as well as applicable standard operating procedures (SOPs). Your response is inadequate because you do not commit to revalidating the (b)(4) process. Additionally, you do not evaluate the roles and responsibilities of your QU, including change management and document control, to ensure comprehensive oversight functions. Also, it appears that you used a maximum allowable carryover limit of (b)(4) ppm in your cleaning validation calculations without adequate scientific justification. Without adequate process validation that incorporates all manufacturing inputs and parameters that can affect product quality, your firm lacks basic assurance that you can reproducibly deliver products that meet specifications. 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 include intensive monitoring and testing throughout each significant process stage to characterize intra-batch variation and evaluate batches to 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 document Process Validation: General Principles and Practices 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 for process performance qualification, and ongoing vigilant monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control. A timeline for performing appropriate process performance qualification for each of your marketed drug products. A risk assessment for the distributed drug products produced using inadequately validated processes. Appropriate improvements to your cleaning validation program, with special emphasis on incorporating conditions identified as worst case in your drug manufacturing operation. This should include, but not be limited to, identification and evaluation of all worst-case: o drugs with higher toxicities o drugs with higher drug potencies o drugs of lower solubility in their cleaning solvents o drugs with characteristics that make their manufacturing equipment difficult to clean o swabbing locations for areas that are most difficult to clean o maximum hold times before cleaning A description of the steps that will be taken in your change management system before introduction of new manufacturing equipment or a new product. A summary of updated SOPs that ensure an appropriate program is in place for verification and validation of cleaning procedures for products, processes, and equipment. A comprehensive, independent retrospective assessment of your cleaning effectiveness to evaluate the scope of cross-contamination hazards. Include the identity of residues, other manufacturing equipment that may have been improperly cleaned, and an assessment whether cross-contaminated products may have been released for distribution. The assessment should identify any inadequacies of cleaning procedures and practices, and encompass each piece of manufacturing equipment used to manufacture more than one product. Quality Systems Your firm’s quality systems are inadequate. For help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211, see FDA’s guidance documents Quality Systems Approach to Pharmaceutical CGMP Regulations at https://www.fda.gov/media/71023/download. Significant findings in this letter demonstrate that your firm does not operate an effective quality system in accord with CGMP. In addition to the lack of effective management oversight of your production and laboratory operations, we found your quality unit is not enabled to exercise proper authority and/or has insufficiently implemented its responsibilities.…

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 QU did not adequately exercise its authority and responsibilities, including but not limited to, implementing effective procedures and conducting adequate oversight of the drug products you manufacture. For example, your QU failed to ensure: Establishment of adequate procedures describing their roles, responsibilities, authorities, and oversight (e.g., production personnel perform functions that should be QA responsibilities (21 CFR 211.22(a) and 21 CFR 211.22(d)). That production and process control procedures are designed to assure the quality of drug products (e.g., completion of bulk hold time validation studies) (21 CFR 211.100(a)). 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/media/71023/download. In response to this letter, provide a comprehensive assessment and remediation plan to ensure that your QU is given the authority and resources to function effectively. The assessment should also include but not be limited to: A determination of whether procedures used by your firm are robust and appropriate Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices A complete and final review of each batch and its related information before the QU disposition decision Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products (b)(4) FDA identified significant concerns regarding the (b)(4) , which appear to operate as closely integrated entities despite maintaining separate corporate identities. Both firms share the same physical location, use common manufacturing operations (utilities, equipment, document management system), and employ overlapping personnel, including key management oversight positions. This level of operational integration raises questions about the independence of your respective quality systems and regulatory compliance programs. Given that (b)(4) , the shared resources and management structure between your firms create the potential for a risk that compliance deficiencies may be transferred or propagated across both organizations. The lack of clear operational separation between (b)(4) diminishes confidence in your ability to maintain independent quality-assurance functions and to implement effective corrective-action systems. Clarify the nature of this relationship and demonstrate how each entity maintains distinct and adequate control over its manufacturing operations, quality systems, and regulatory compliance responsibilities. CGMP Consultant Recommended We acknowledge that you have engaged a consultant to evaluate your operations and to assist your firm in meeting CGMP requirements. The qualified consultant should be qualified as set forth in 21 CFR 211.34 and should 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’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). Based on the records and information you provided, you did not demonstrate that your quality unit (QU) adequately exercised its authority and responsibilities for the manufacture of your OTC drug products. For example, your QU failed to ensure the following: Establishing appropriate written procedures for production and process controls to qualify process performance and for qualification of your (b)(4) system, which produces (b)(4) used as a component in your drug products (21 CFR 211.100(a)). Maintaining complete manufacturing information relating to the production and control in batch records (21 CFR 211.188). Providing appropriate stability data to support the labeled drug product expiration date (21 CFR 211.137(a)). Establishing adequate QU authority and procedures (21 CFR 211.22(a) & 211.22(d)). Your firm’s quality systems are inadequate. For help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211, see FDA guidance documents Quality Systems Approach to Pharmaceuticals CGMP Regulations at https://www.fda.gov/media/71023/download. Drug Registration and Listing We note that two separate establishments are referenced in this warning letter. Under section 510(i) of the FD&C Act and 21 CFR 207.17(a) any establishment within any foreign country engaged in the manufacture, preparation, propagation, compounding, or processing of a drug that is imported or offered for import into the United States must be registered with FDA. Under section 301(p) of the FD&C Act, 21 U.S.C. 331(p), it is a prohibited act to fail to register an establishment as required by section 510 of the FD&C Act. Additionally, a drug may be considered misbranded within the meaning of section 502(o) of the FD&C Act, 21 U.S.C. 352(o) if it was manufactured in an establishment not duly registered under section 510 of the FD&C Act. It is your responsibility to ensure that all drugs manufactured at your establishment(s) comply with all establishment registration and drug listing requirements under section 510 of the FD&C Act, 21 U.S.C. 360, 21 CFR Part 207, and all other applicable FDA regulations. CGMP Consultant Based upon the nature of the violations we identified in your response, 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.