Findings citing 21 CFR 211.22

Your firm failed to establish adequate written responsibilities and procedures applicable to the quality control unit and to follow written procedures applicable to the quality control unit (21 CFR 211.22(d)). Specifically, our review of the data collected during the inspection revealed that your firm does not maintain the production video recordings which are used to determine root causes and corrective actions during investigations. For example, after recovering microbial contamination inside the ISO 5 classified critical area during the production of Ketamine HCl 10 mg/mL lot 1125035065, your Quality Unit evaluated the production video recording as part of excursion investigation EXC-2025-0045 to examine aseptic practices for potential root causes. However, instead of retaining the video recording as a quality related document, you only retained still images. Your Chief Quality Officer stated that video recordings are kept for approximately (b)(4) before being overwritten. 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 FDA has issued a revised draft guidance, Current Good Manufacturing Practice — Guidance for Human Drug Compounding Outsourcing Facilities under Section 503B of the FD&C Act . This draft guidance, when finalized, will describe FDA’s expectations regarding outsourcing facilities and the CGMP requirements in 21 CFR parts 210 and 211 until more specific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 also 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 facility’s responses to the Form FDA 483 dated November 21, 2025, and December 31, 2025. Some of your corrective actions appear adequate. However, we are unable to fully evaluate some of your corrective actions due to lack of adequate supporting documentation…

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’s quality 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 QU with the responsibilities and authority to oversee the manufacture of drug products. For example, you failed to ensure: Adherence to a stability program that supports the drug products’ expiration dating (21 CFR 211.166(a)). Contemporaneous documentation of EM and personnel monitoring sampling data in laboratory records (21 CFR 211.194(a)). In response to this letter, provide: A comprehensive assessment of documentation systems used throughout your manufacturing and laboratory operations to determine where documentation practices are insufficient. Include a detailed CAPA plan that comprehensively remediates your firm’s documentation practices to ensure you retain attributable, legible, complete, original, accurate, contemporaneous (ALCOA) records throughout your operation. A comprehensive assessment and remediation plan to ensure your QU is given the authority, independence, and resources to effectively function that includes, but is not limited to: o A determination of whether procedures used by your firm are robust and appropriate o Provisions for independent QU oversight throughout your operations to ensure satisfactory procedures and 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 o Also, describe how executive management will support robust quality assurance at your firm, including but not limited to timely provision of resources that enable proactive detection and resolution of emerging manufacturing/quality issues to assure a continuing state of control Ineffective Quality System 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 QU is not enabled to exercise proper authority and/or has insufficiently implemented its responsibilities. Executive management should immediately and comprehensively assess your company’s global manufacturing operations to ensure that your systems, processes, and products conform to FDA requirements. Your firm’s quality systems are inadequate. For guidance on establishing and maintaining CGMP-compliant quality systems, see FDA guidances: Q8(R2) Pharmaceutical Development at https://www.fda.gov/media/71535/download, Q9(R1) Quality Risk Management at https://www.fda.gov/media/167721/download and Q10 Pharmaceutical Quality System at https://www.fda.gov/media/71553/download. Drug Production Ceased and Suspended We acknowledge your commitment to suspend production of (b)(4) Drugs at this facility for the U.S. market and to cease production of all other (b)(4) solutions. If you plan to resume any manufacturing operations regulated under the FD&C Act, notify this office before resuming your drug manufacturing operations. If you resume CGMP activities, you are responsible for resolving all deficiencies and systemic flaws to ensure your firm is capable of ongoing CGMP compliance. In addition, 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 assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive six-system audit 1 of your entire operation for CGMP compliance and evaluate the completion and efficacy of all CAPA, 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. In your notification to the Agency, provide a summary of your remediations to demonstrate that you have appropriately completed all CAPA. Repeats Violation at Facility In a previous warning letter (WL 320-19-01), FDA cited similar CGMP violations. You proposed specific remediations for these violations in your response. Repeated failures demonstrate that executive management oversight and control over the manufacture of drugs is inadequate. Additional Guidance on Aseptic Processing See FDA’s guidance document Sterile Drug Products Produced by Aseptic Processing—Current Good Manufacturing Practice to help you meet the CGMP requirements when manufacturing sterile drugs using aseptic processing at https://www.fda.gov/media/71026/download.

Your firm’s quality 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 lacked adequate oversight and control over your laboratory operations to ensure a state of control and adherence to applicable quality standards. 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 laboratory operations, we found your QU is not enabled to exercise proper authority and/or has insufficiently implemented its responsibilities. Executive management should immediately and comprehensively assess your company’s global manufacturing operations to ensure that your systems, processes, and products conform to FDA requirements. Your firm’s quality systems are inadequate. See FDA’s guidance documents ICH Q10 Pharmaceutical Quality System and 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. 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: 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 Also describe how top management supports quality assurance and reliable operations including, but not limited to, timely provision of resources to proactively address emerging manufacturing/quality issues and to assure a continuing state of control. 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’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) lacked adequate control over your OTC drug product manufacturing operations and failed to ensure that you had adequate procedures. Your firm made changes to your manufacturing process parameters in the batch manufacturing instructions without following your Procedure for Change Management and Operational Procedures for Handling of Abnormal Situations . For example: During the manufacture of your product (b)(4) , batch (b)(4) , you changed your (b)(4) without documented justification. During the manufacture of your product (b)(4) , batches (b)(4) , you changed a (b)(4) without documented justification. Your response states that a retrospective investigation revealed that your research and development team made on-site adjustments to process parameters without following the established change procedure. In your response you commit to following the required change procedure. Your response is inadequate because your retrospective review did not include a comprehensive assessment of other possible incidents of the change procedure not being followed. Additionally, the following are examples of poor QU oversight: The batch production and control records are deficient in that they do not include documentation of the accomplishment of each significant step in manufacturing. 21 CFR 211.188(b) There is no written testing program designed to assess the stability characteristics of drug products. 21 CFR 211.166(a) An adequate QU overseeing all manufacturing operations is necessary to consistently ensure drug quality. See FDA’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations at https://www.fda.gov/downloads/drugs/guidances/ucm353925.pdf for help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR parts 210 and 211 . In response to this letter, provide the following: A copy of your revised SOP, Operational Procedures for Handling of Abnormal Situations 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. Procedures to ensure if your manufacturing process parameters change your quality approves before all commercial manufacturing. Training records to confirm that all relevant personnel, including research and development staff have been trained in the change management requirements. Drug Production Suspended During the inspection you communicated your decision to allow your drug registration with the FDA to expire. Your firm stated that you will renew the drug registration if a U.S. (b)(4) order is received. If you plan to resume any manufacturing operations regulated under the FD&C Act, notify this office before resuming your drug manufacturing operations. If you resume CGMP activities, you are responsible for resolving all deficiencies and systemic flaws to ensure your firm is capable of ongoing CGMP compliance. In addition, 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 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 all 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. In your notification to the Agency, provide a summary of your remediations to demonstrate that you have appropriately completed all corrective action and preventive action (CAPA).

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.