Findings citing 21 CFR 211.100

Your firm failed to establish adequate written responsibilities and procedures applicable to the quality control unit (21 CFR 211.22(d)). Your QU did not provide adequate oversight for the manufacture of your drug products. For example, your QU failed to ensure: Documentation of all interventions during filling of sterile drug products. Our investigators observed multiple batch records in which operators failed to document most aseptic interventions. For example, the batch record for (b)(4) injection (b)(4) mg/ (b)(4) ml, on February 6, 2026, documented that 12 interventions had occurred during filling. However, records indicated approximately 200 interventions were conducted. Notably, critical interventions, including but not limited to removing vials from the filling zone and removing fallen vials from (b)(4) , were not documented. (21 CFR 211.188) Performance of adequate disinfectant efficacy studies. You failed to adequately evaluate your environmental isolates for inclusion in your disinfectant efficacy studies. Studies failed to adequately represent the full spectrum of microbes in your facility. (21 CFR 211.42(c)(10)(v)) Reproducible manufacturing processes in the production of sterile (b)(4) drug products. You did not perform a process validation study after implementing a new production step nor provide stability data within your response. (21 CFR 211.100(a)). In your response, you state you will ensure the QU has a role in verifying intervention documentation in batch records and establish a procedure to periodically evaluate disinfectant efficacy. Your response is inadequate because you fail to provide sufficient details on how interventions in your aseptic process simulations will be captured, simulated, and verified. You also do not describe the QU's oversight of the disinfection practices or identify the environmental isolates to be challenged in the disinfection efficacy studies. Complete and accurate batch production and control records are necessary to ensure that manufacturing processes are consistently followed and are reproducible. Additionally, incomplete manufacturing records fundamentally compromise your ability to reliably conduct batch record review, to adequately investigate deviations and batch failures, and to ensure a continued state of control. Your firm’s quality systems are inadequate. You may refer to 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 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 A CAPA plan, based on the retrospective assessment of your disinfection program, that includes appropriate remediations to your disinfection processes and practices, and timelines for completion. Include the following as part of the assessment and CAPA plan: o a detailed summary of vulnerabilities in your process for lifecycle management of equipment disinfection o a list of improvements, with an explanation how each will enhance disinfection effectiveness o improved ongoing verification of proper disinfection execution for all products and equipment o and, any other needed remediations. 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 timeline for performing appropriate process performance qualification 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 prior to performing any process validation studies. A comprehensive review of your complaints received for (b)(4) injection, including a retrospective review of all complaints for the last three years from the initial date of the inspection, with an assessment that includes but is not limited to evaluating and comparing the (b)(4) complaints received before and after the (b)(4) step. 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 must 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.

Failure to establish written procedures for production and process control designed to assure that the drug products have the identity, strength, quality, and purity that they are purported or represented to possess, as required by 21 CFR 211.100(a). For example, your firm has not validated the manufacturing processes for your umbilical cord derived products with respect to identity, strength, quality, and purity.

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 post-fill visual inspection of aseptically filled over-the-counter (OTC) (b)(4) drug products was insufficient to identify particulate matter and defects which may be present in each unit. Your drug product containers are (b)(4) , and only very slightly (b)(4) , and particulates can be seen through them readily, which does not meet the criteria for “difficult to inspect.” For example, your firm only conducted subvisible particulate testing on a sample of units based on your assertion that the bottles were (b)(4) and not suitable for visual inspection. Further, your Acceptable Quality Limit (AQL) testing was designed to examine for filling, labeling, and packaging defects only, and did not include defect categories for particulates or foreign matter. Your firm’s inadequate visual inspection program provides insufficient assurance to prevent release of (b)(4) drug products with particulate matter or foreign material defects. In your response, you acknowledge that 100% visual inspection is not performed and that you lack the proper procedures and/or equipment. You commit to modifying your visual inspection program to include the reliable detection of particulate contamination and other visible defects prior to resuming production operations. Your response is inadequate. Although you commit to evaluating the visual inspection program and replacing the (b)(4) , you did not consider a combination of (b)(4) inspection methods to ensure detection of the wide array of potential visible product defects. Also, you did not consider the impact of particulates or foreign matter in (b)(4) drug products that were distributed to the U.S. market. We encourage the use of suitable (b)(4) visual inspection for particulates to augment the 100% (b)(4) visual inspection program. (b)(4) methods should be rigorously studied, and qualified, to assess their capability and robustness under various conditions, machine settings, container-closure sizes, defect types, product characteristic, and other variables. In addition, any use of (b)(4) particulate inspection as an adjunct method does not supplant the need for 100% (b)(4) visual inspection, for various other attributes (e.g., cracks, deformities, closure issues, volume, insufficient crimping, leaks, (b)(4) , discoloration, turbidity, other appearance defects). In addition, your firm failed to provide adequate data to demonstrate manufacturing systems were adequately maintained, operated, and monitored. For example, you lacked a formalized process and procedure for responding to your (b)(4) alarms. Alarms occurred at multiple timepoints from 2024 to 2026 without documented evidence of a systematic or appropriate response. OTC (b)(4) drug products manufactured at your firm use (b)(4) as the main component for each formulation. Further, your firm has not completed commitments made during the Regulatory Meeting held January 10, 2025. In your response, you commit to creating new procedures for the (b)(4) maintenance and operation, including responding to alarms and performing a comprehensive review of alarm histories to determine if notable alarms require further investigation. Your response is inadequate. You did not provide documentation or details on the review of alarms for potential impact to drug products made with (b)(4) from your (b)(4) . We acknowledge that you are using an independent third-party consultant to evaluate your visual inspection program. You should consider performing a comprehensive assessment and remediation plan for your visual inspection program to ensure compliance with CGMP. The remediation plan should incorporate U.S. Pharmacopeia (USP) <790> Visible Particulates in Injections and USP <771> (b)(4) Products-Quality Tests, including container-specific testing protocols (e.g., (b)(4) ) for each container type. Your strategy should include: Implementing 100% visible inspection using enhanced lighting with background contrast methods, as appropriate, for difficult-to-inspect products (DIP) (e.g., (b)(4) containers) that allow visual inspection. For drug products that preclude visual inspection (e.g., products packaged in (b)(4) containers), using destructive testing (e.g., subvisible particulate matter) with appropriate, statistically significant sample sizes to test for critical defects. Where traditional visual inspection methods cannot be used, establishing periodic in-process visible particulate matter testing for both bulk solution and fill/finish operations to ensure process control, and implementing enhanced manufacturing controls, including strengthened (b)(4) and environmental controls. Developing a product-specific, risk-based visual inspection approach incorporating product knowledge, process experience, deviation investigation analysis, and recall/complaint data to ensure ongoing compliance with USP <790>, USP <771>, and CGMP requirements. Additionally, in response to this letter, provide: An evaluation of customer and clients’ complaints received for potential particulates that were overlooked due to use of inadequate defect criteria during visual inspection. A comprehensive remediation plan for the design, control, and maintenance of the (b)(4) , including: o 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. Your total microbial count limits to monitor whether this system is producing (b)(4) suitable for the intended uses for each of your drug products. A detailed risk assessment addressing the potential effects of the observed (b)(4) failures on the quality of all drug product lots currently in U.S. distribution or within expiry.…

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 QU with the responsibilities and authority to oversee the manufacturing of drug products. For example, the QU failed to ensure: Establishment of appropriate written procedures for production and process controls, including appropriate qualification of the (b)(4) system (21 CFR 211.100(a)). Establishment of an appropriate written testing program designed to assess the stability characteristics of drug products and to use results of stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)). Establishment of adequate written procedures defining QU responsibilities and controls (21 CFR 211.22(d)). An adequate number of qualified personnel to perform and supervise the manufacturing, processing, packing, or holding of each drug product (21 CFR 211.25(c)). 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, Q9(R1) Quality Risk Management at https://www.fda.gov/media/167721/download, and ICH Q10 Pharmaceutical Quality System at https://www.fda.gov/media/71553/download. 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. 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 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. Drug Listing Violations Section 510(j) of the FD&C Act and 21 CFR Part 207 set forth the requirements for the listing of drugs. In addition to listing a drug that you manufacture under your own labeler code, under 21 CFR 207.41(c)(1), you are required to list each drug you manufacture for commercial distribution under the trade name or label of a PLD using an NDC that includes such PLD’s labeler code. Evidence from the most recent inspection of your site and a search of eDRLS confirms that you are manufacturing KleenLine Alcohol-Free Sanitizing Wipes for a PLD, Brady Industries, Inc., but you did not list this drug under the PLD’s trade name and labeler code as required. Therefore, you failed to fulfill your drug listing obligations in accordance with section 510 of the FD&C Act. Failure to provide listing information for a drug in accordance with 510(j) of the FD&C Act is prohibited under section 301(p) of the FD&C Act. Under section 502(o), a drug is misbranded if it is not included in a list required by section 510(j). Under section 301(a), the introduction or delivery for introduction, or the causing thereof, into interstate commerce of any drug that is misbranded is prohibited. Complete, accurate, and up-to-date establishment registration and drug listing information is essential to promote and protect patient safety. FDA relies on establishment registration and drug listing information for several key programs, including drug establishment inspections, supply chain security, and post-market surveillance. Establishment registration and drug listing information is also widely used outside FDA for purposes such as electronic prescribing and electronic health records, insurance reimbursement, and patient education. We note that the labeling provided in your drug listing for Hand Sanitizing Alcohol-Free Wipes, NDC 84111-000, bears the trade name of what appears to be another PLD. Please update your labeling accordingly. It is your responsibility to ensure that all drugs manufactured at your establishment 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. Registration and listing information and instructions on how to properly register an establishment or submit drug listings can be found at Electronic Drug Registration and Listing Instructions .

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, and your firm’s quality control unit did not review and approve those procedures, including any changes (21 CFR 211.100(a)). You failed to validate your manufacturing process for your OTC drug products. During the inspection, you…

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 the processes used to manufacture your OTC drug products. You have not performed process performance qualification (PPQ) studies, nor do you have an adequate ongoing program…