US FDA Aseptic processing and sterility assurance findings

Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)). Poor Aseptic Practices Our inspection identified aseptic processing design deficiencies that pose significant hazards to drug product sterility. During a mock filling operation and during review of your unidirectional smoke studies, our investigators observed multiple instances of inappropriate aseptic behavior in which operators blocked unidirectional airflow at critical locations without implementing appropriate corrective measures, including discarding potentially compromised vials. Specific examples include: Blocking airflow over the stopper bowl and (b)(4) vials while refilling the stopper bowl Passing forceps over the (b)(4) and removing fallen vials from the (b)(4) and (b)(4) over (b)(4) vials Blocking airflow during (b)(4) transfer operations, including (b)(4) repositioning of filled vials onto a (b)(4) and mechanical displacement of (b)(4) vials into the (b)(4) via forceps Any compromise of first-air protection exposes sterile drug products to potential microbiological contamination. Cleaning, Decontamination, and Maintenance You failed to adequately clean, decontaminate, and maintain your (b)(4) used for aseptic drug product manufacturing. For example, our investigator observed multiple instances of deterioration and damage inside the (b)(4) used for manufacturing sterile drug products. These instances of deterioration and damage were not adequately addressed through your cleaning, decontamination, and maintenance programs. For example, our investigator observed: Deteriorated (b)(4) used to support the (b)(4) tank Excess sealant adjacent to the HEPA filters in the filling and (b)(4) areas Use of nonsterile wipes soaked in (b)(4) to clean (b)(4) In addition, our investigator observed accumulation of standing water and unknown (b)(4) staining on the wall surface adjacent to the (b)(4) pipelines, located outside the (b)(4) room within the HVAC area. All equipment and associated operational areas should follow a reliable, comprehensive preventive maintenance program. This program should be designed to ensure sustained operational integrity through the systematic implementation of validated cleaning and disinfection protocols, as well as the proactive replacement of components before they deteriorate or degrade. Maintenance and change management procedures should prevent practices that may compromise equipment or introduce contamination risks. Aseptic processes need to be designed to minimize exposure of sterile articles to potential contamination hazards. A suitable monitoring system is critical to maintain appropriate environmental conditions throughout your (b)(4) and cleanrooms. Prompt detection of an emerging problem is essential to preventing contamination of your aseptic production operations. Your response states existing procedures "did not adequately define acceptable hand positioning, intervention speed, first-air protection requirements, rejection criteria for potentially affected exposed units, or required actions following airflow interruption" and acknowledges “equipment design and ergonomic limitations within the (b)(4) ”. Additionally, you state you will not resume operations until “successful aseptic process simulation run incorporating all listed interventions under worst-case conditions are completed”. Furthermore, you commit to updating procedures for (b)(4) sanitization and cleaning to include sterile (b)(4) and sterile wipes. Your response also states that remediations were made to equipment, including repairing all sealant joints in the (b)(4) , smoothing internal machine surfaces to meet cleanability requirements, and updating maintenance checklists to include criteria for wear, damage, smoothness, cleanability, and material suitability. Your response is inadequate. You do not provide sufficient detail including deliverables on your third-party risk assessment of all aseptic filling lines. Additionally, your response does not sufficiently address the lack of oversight of operator aseptic behavior, equipment cleaning and maintenance, various manual activities, and intervention ergonomics. 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. In your response to this letter, provide the following: Your CAPA plan to implement routine, vigilant operations management oversight of facilities and equipment. This plan should incorporate oversight from a qualified independent consultant and ensure, among other things, prompt detection of equipment/facilities performance issues, effective execution of repairs, adherence to appropriate preventive maintenance schedules, timely technological upgrades to the equipment/facility infrastructure, and improved systems for ongoing management review. A CAPA plan, based on the retrospective assessment of your cleaning and disinfection program, that includes appropriate remediations to your cleaning and disinfection processes and practices, and timelines for completion. Provide a detailed summary of vulnerabilities in your process for lifecycle management of equipment cleaning and disinfection. Describe improvements to your cleaning and disinfection program, including enhancements to cleaning effectiveness; improved ongoing verification of proper cleaning and disinfection execution for all products and equipment; and all other needed remediations.…

Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes. Your firm also failed to maintain buildings used in the manufacture, processing, packing, or holding of drug products in a good state of repair (21 CFR 211.113(b) and 21 CFR 211.58). Airflow Visualization (AFV) Smoke Study Deficiencies Our inspection noted deficient smoke studies. Our investigators determined you did not perform AFV smoke studies after modifying your (b)(4) Restricted Access Barrier Systems ( (b)(4) RABS) unit by removing the (b)(4) and remounting the nonviable particulate probe in suite (b)(4) of the (b)(4) filling line. Your validation department determined smoke studies were not necessary after the modification, despite your engineers proposing smoke studies be conducted. As another example, two interventions, including product spillage cleaning at the filling station and (b)(4) adjustment lacked adequate smoke to visualize unidirectional airflow. It is not clear whether airflow is adequate to protect the aseptic processing line. In your response, you state you will re-execute AFV studies, develop a standardized AFV protocol template, and revise the change control procedure. Your response is inadequate because you do not explain how you will ensure satisfactory conduct of smoke studies in the future. Thorough smoke studies are essential to evaluate the effects of such interventions on unidirectional airflow and suitability of design modifications. We also note that your Grade A suites (b)(4) are described as (b)(4) RABS. Although your firm characterizes these processing lines as (b)(4) RABS, their design and operation involve an excessive number of interventions and do not meet the minimum standards of a restricted access barrier system. The Grade A area is critical because sterile products are exposed during aseptic production and therefore are vulnerable to contamination if operations are not well designed and diligently controlled. Your aseptic processes should be designed, and operations executed, to prevent contamination hazards to your sterile product. Flaws in the design of cleanrooms and aseptic processing lines, or improper execution of operations, can promote influx of contamination into the critical processing area in which sterile drugs are exposed. Inadequate Environmental Monitoring We observed inadequate EM technique and insufficient EM locations. Our investigators observed the surface swabbing of the (b)(4) did not include the (b)(4) . Additionally, the analyst did not swab the maximum accessible area of the (b)(4) of each (b)(4) . In your response, you state the procedures will be updated and a retrospective EM review will be performed. You also performed a historical review of your EM data since 2024 which you indicate has no adverse trends. Your response is inadequate because the quality of the data was compromised by insufficient technique and locations. Environmental monitoring is only as meaningful as the quality of its sampling technique and locations. The purpose of environmental monitoring in an aseptic processing facility is to apply a risk-based approach to reliably detect routes of contamination. Facility Maintenance Deficiencies Your firm did not properly maintain classified areas used in the manufacture of drug products. Our inspection noted peeling paint on the walls and plastic debris on the floors within your Grade C hallway and product transfer room (b)(4) in Suite (b)(4) . In your response, you commit to implement post-cleaning visual inspection, require cleaning verification in the cleaning logs, and repair the facility. Your response is inadequate because your product impact evaluation states “…types of debris observed (e.g., paint, plastic) are non-viable particulates...” However, you do not explain the basis for the assertion that paint debris could not harbor microorganisms. In addition, your response does not adequately evaluate the cause of the paint bubbling and peeling from the walls and whether this has contributed to mold identified throughout all your classified areas. Deteriorating surfaces such as peeling paint are potential sources of particulate and microbial contamination. It is critical that the building is maintained to prevent exposure of sterile articles to potential contamination hazards in the manufacturing operation. In response to this letter, provide: Your systematic plan to assure adherence to appropriate aseptic practices, cleanroom behavior, and written procedures, including but not limited to an independent assessment of the following with accompanying CAPA: o suitability of actual practices based on extensive retrospective review and prospective observation of aseptic processing operations o deficiencies in production management oversight, and identification of specific improvements to ensure effective and routine supervisory oversight for all batches o frequency and depth of quality unit oversight (e.g., audit, ad hoc, daily interactions) of aseptic processing and its support operations o adequacy of written procedures o evaluate how poor aseptic technique and cleanroom behavior may have affected the quality and sterility of your drugs A thorough, independent evaluation of airflow unidirectionality in your aseptic process. Ensure smoke studies are conducted under dynamic conditions, with thorough and complete evaluations of aseptic processing line airflow unidirectionality, including the impact of dynamic interactions and aseptic interventions. These thorough smoke studies should be performed after you remediate your aseptic operation and be conducted using proper practices (e.g., neutrally buoyant media) to appropriately visualize airflow. Your CAPA plan to implement routine, vigilant operations management oversight of facilities and equipment.…

Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192). Your firm operates as a contract manufacturer of sterile injectables for (b)(4) . You failed to adequately investigate a sterility test failure as well as recurring mold recoveries in the ISO 5 (Grade A) filling area. Sterility Failure You did not adequately investigate a failed sterility test result for your aseptically filled (b)(4) mg/ (b)(4) ml. Your firm identified Ustilago spermophora , a fungi, in (b)(4) medium. Your investigation’s root cause finding of “undetermined” was inadequate. Although your firm rejected this batch, your investigation did not thoroughly examine all possible root causes including but not limited to potential routes of fungi migration through your classified areas (e.g., personnel/material flow hazards, HVAC hazards, inadequate disinfection). Additionally, your investigation lacked adequate corrective action and preventive action (CAPA) responses. In your response, we acknowledge your intentions to strengthen investigation requirements, perform a retrospective review of investigations, and review the facility’s contamination control strategy. However, your response does not specifically address the sterility failure investigation. Environmental Monitoring (EM) Action Level Excursions Your firm’s investigations into multiple instances of fungi contamination on and below the (b)(4) of aseptic processing lines have been inadequate. For example: On March 20, 2024, Chaetomium globosum was recovered below the (b)(4) of the (b)(4) vial machine in suite (b)(4) after filling a batch of (b)(4) mg/ (b)(4) ml. Your investigation was inadequate as it did not adequately evaluate potential root causes, including whether the mold was introduced during filling operations. You released the product without sufficient investigation. On May 16, 2025, fungi was recovered in two locations within the (b)(4) filling line in suite (b)(4) . The passive air sample recovered Didymella glomerata during the filling of (b)(4) injection. You attributed the mold recovery to a power failure that occurred during filling. Notably, surface monitoring below the (b)(4) also recovered Mycosphaerella africana after the power was restored. The investigation lacked sufficient CAPA. On June 4, 2025, Chaetomium cruentum/globosum was recovered from the (b)(4) of the (b)(4) vial machine in suite (b)(4) after filling a batch of (b)(4) mg/ (b)(4) ml. Your firm rejected the batch but failed to adequately investigate likely root causes. You stated within the investigation, “historically there has never been a mold hit isolated on the grade A space on the (b)(4) filling Line,” however the same mold, Chaetomium globosum , had been recovered, on March 20, 2024, on the same line. The investigation lacked CAPA. Overall, trends of fungal recoveries within your suites (b)(4) , and supporting cleanrooms, have significantly increased since 2023. Your firm has closed investigations without implementing robust CAPA. Your firm also has not adequately evaluated the ongoing trend of adverse findings of fungi within your aseptic production area, directly within product, and on product contact surfaces over time. In your response you commit to revise your procedures to perform routine trend analysis and strengthen your investigations. Your response is inadequate because you indicate that product impact conclusions in investigations were appropriate based on a lack of sterility failures, adverse environmental monitoring trends, and complaints, but fail to sufficiently address contamination sources. Your firm has not demonstrated that you have remediated your investigational capabilities to ensure scientifically rigorous investigations to effectively identify root causes so that appropriate CAPA can be implemented. To ensure proper root cause analysis and appropriate CAPA implementation, investigations must be thorough, well-documented, scientifically sound, and timely. Procedural updates and training alone do not address the systemic failures that allowed deficient investigations to persist undetected by quality unit (QU) oversight. In response to this letter, provide: A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, out-of-specification results, and failures. Provide a detailed action plan to remediate this system. Your action plan should include, but not be limited to, significant improvements in investigation competencies, scope determination, root cause evaluation, CAPA effectiveness, QU oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted. An independent assessment and remediation plan for your CAPA program. Provide a report that evaluates whether the program includes effective root cause analysis, ensures CAPA effectiveness, analyzes investigation trends, improves the CAPA program wherever needed, ensures final QU decision authority, and is fully supported by executive management. A comprehensive, independent risk assessment of all contamination hazards with respect to your aseptic processes, equipment, and facilities, including but not limited to, the following: o All human interactions within the ISO 5 area (e.g., risk reduction or elimination of manual interventions wherever possible) o Equipment suitability (e.g.…

during an inspection of your drug manufacturing facility, PReye, LLC, FDA Establishment Identifier (FEI) 3031057987, at 4855 Ward Road, Wheat Ridge, from March 17 to 19, 2026. This inspection was conducted under FDA’s statutory authority and public health responsibilities to protect the public from unsafe, ineffective, and poor quality drugs. 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). In addition, violations were identified and documented during the review of your website https://essencelaser.com/vitaminsee/ in June 2026. Based on our review, “PReye Vitamin SEE” is an unapproved new drug under section 505(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355(a). As explained further below, introducing or delivering this product for introduction into interstate commerce violates sections 301(d) and 505(a) of the FD&C Act, 21 U.S.C. 331(d) and 355(a). We reviewed your March 22, 2026, response to our Form FDA 483 in detail. Violations of the Federal Food, Drug, and Cosmetic Act The following are violations identified during our inspection and review. As a reminder, this is not an all-inclusive list of violations at your facility. CGMP Violations 1. Your firm failed to perform operations within specifically defined areas of adequate size and to have separate or defined areas or such other control systems necessary to prevent contamination or mix-ups in aseptic processing areas. Your firm also failed to use equipment in the manufacture, processing, packing, or holding of drug products that is of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance (21 CFR 211.42(c)(10) and 21 CFR 211.63). Your firm was registered as a drug repacker and produced drug products solely for distribution through the co-located med spa, Essence Laser and Wellness, which you own. Your repackaging operations consisted of a small flow hood on a desk in your office. These operations were performed in a non-certified, non-qualified flow hood within an unclassified office space that lacked a high-efficiency particulate air (HEPA) filtration system. You obtained bulk liquid drug and manually filled multiple (b)(4) drug products. The drug product was labeled with directions to use “ (b)(4) ”. Your (b)(4) products were filled under unsuitable aseptic processing conditions, in that they lacked appropriate facilities, equipment, and process controls to protect the drug product from microbiological contamination. Your manufacturing facility, equipment, and process must be designed, and operations must be executed, to prevent contamination risks to sterile drug products (e.g., (b)(4) drug products). 2. 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's quality systems are inadequate. Your firm lacked a quality unit (QU) function and associated written procedures defining QU responsibilities and controls. You failed to establish basic procedures including, but not limited to, complaint review, supplier qualification, release testing, change management, cleaning, disinfection, and deviation handling. In addition, your ophthalmic drug products lack traceability because you did not issue batch numbers for all sterile drug products manufactured since 2024. An adequate QU overseeing all manufacturing operations is necessary to consistently ensure drug quality. You failed to implement fundamental procedures and practices to ensure the safety, identity, strength, quality, and purity of your drug products. 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. Unapproved New Drug Violations Based on a review of your website, “PReye Vitamin SEE” is a drug under section 201(g)(1) of the FD&C Act, 21 U.S.C. 321(g)(1), because it is intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or intended to affect the structure or any function of the body. Examples from your product labeling, including on your website, that provide evidence of the intended use (as defined in 21 CFR 201.128) of the product as a drug include, but may not be limited to, the following: PReye Vitamin SEE On the webpage https://essencelaser.com/vitaminsee/: “Antioxidant Vitamins provide protection against the damaging effects of UV light from sun exposure. . . . In the eye, UV light ages all the structures. Ocular surface damage, cataracts and macular degeneration are all possible effects from UV exposure and can ultimately lead to decreased vision, and blindness.” “Both Ascorbic Acid and Acetylcysteine have been used independently to treat pathology in the eye, including corneal alkali burns and filamentary keratitis in severe dry eye. But, never have they been combined as a vitamin supplement eyedrop to prevent eye disease related to UV exposure, including cataracts and macular degeneration.” “PReye Vitamin SEE” is a "new drug" under section 201(p) of the FD&C Act, 21 U.S.C. 321(p), because it is not generally recognized as safe and effective (GRASE) for use under the conditions prescribed, recommended, or suggested in the labeling. With certain exceptions not applicable here, a new drug may not be introduced or delivered for introduction into interstate commerce without an approved application from FDA in effect, as described in section 505(a) of the FD&C Act, 21 U.S.C. 355(a). No approved application pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, is in effect for this product. Accordingly, this product is an unapproved new drug. The introduction or delivery for introduction into interstate commerce of this unapproved new drug product violates sections 301(d) and 505(a) of the FD&C Act, 21 U.S.C. 331(d) and 355(a). Additional Guidance on Drug Listing We note that your firm’s drug listing for “PReye Vitamin SEE” has not been updated or certified as required and therefore has been inactivated by FDA. Please update the listing information for this drug to reflect its current status. If you no longer manufacture and distribute this drug, it must be discontinued by adding an end marketing date. Additional Guidance on Aseptic Processing See FDA’s guidance document Sterile Drug Products Produced by Aseptic Processing—Current Good Manufacturing Practice to help you understand CGMP requirements for sterile drugs produced by aseptic processing at https://www.fda.gov/media/71026/download. Container Closure for (b)(4) Formulations When contaminated, (b)(4) drug products pose a significant risk of harm because (b)(4) administration bypasses some of the body’s natural defenses. Irreversible damage, including (b)(4) can occur, and in some cases, may progress to life-threatening systemic infection. The risk is exacerbated when (b)(4) drug products lack a (b)(4) and lack data to demonstrate that the container-closure system can prevent microbiological ingress, contamination, and proliferation. Drug Production Ceased On March 22, 2026, you communicated your commitment to cease manufacturing and distribution of PReye Vitamin SEE for the U.S. market for the future. We acknowledge your commitment to cease production of PReye Vitamin SEE drugs at this facility. If you plan to resume any drug manufacturing operations, including repackaging, notify this office before commencing 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 action and preventive action, before you pursue resolution of your firm’s compliance status with FDA. 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). Drug Recall On May 11, 2026, FDA held a teleconference with you recommending you consider removing any batches of PReye Vitamin SEE currently in distribution from the U.S. market. On May 18, 2026, you issued a voluntary recall of PReye Vitamin SEE due to lack of sterility testing.

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 visual inspection program was inadequate to ensure that sterile injectable drug products were essentially free of visible particulates. Specifically, you failed to appropriately qualify personnel who performed visual inspections of injectable products. Your visual inspection qualification kit did not include adequately representative visible particulates (e.g., size), and your qualification records lacked sufficient detail to determine the qualifications of staff who perform visual inspection of (b)(4) bags. Your response states that your visual inspection qualification kit contained representative particulates. You add that you are developing a new kit that will continue to contain such particles, and that you will periodically review production and post market data to verify the kit remains representative. Your response is inadequate. It does not address the failure of your visual inspection qualification program to demonstrate that visual inspection personnel can detect visible particles at a level that meets the appropriate standard. The example particles in your kit may not be representative of smaller particles in your drug products. Visual detection of particulates is a probabilistic process that depends on, among other things, ensuring that visible particulates can be reproducibly detected by trained personnel with appropriate visual acuity. Your qualification kit should contain particles of a size and composition that adequately challenge inspectors across the range of particulate sizes that may be present in your drug product and should be qualified to demonstrate that inspectors can reliably detect visible particulates relevant to your specific product and container/closure system. These qualification kits should typically contain particles in the range of 100-150 microns to adequately challenge inspector detection capabilities. In response to this letter, provide: A remediation plan that better assures ongoing management oversight throughout the manufacturing lifecycle of all drug products. Provide a more data-driven and scientifically sound program that identifies sources of process variability, and assures 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 and its controls, and vigilant ongoing monitoring of process performance and product quality. A comprehensive, independent assessment and remediation plan for your visual inspection program to ensure compliance with CGMP. The remediation plan should include but not be limited to: o Improved visual inspection methods, as appropriate o Improved qualification protocols and associated records for all staff performing visual inspection o Incorporation of U.S. Pharmacopeia (USP) <790> Visible Particulates in Injections standards into your procedures o Use of an appropriate range of visible particulate types and sizes, including particles of also approximately 100-150 microns, as part of staff qualification studies o All other provisions necessary to ensure appropriate qualification of visual particulate inspectors Drug Recall On April 6, 2026, you issued voluntary recalls of DELFLEX Dextrose Peritoneal Dialysis Solution due to Lack of Assurance of Sterility. The company announcements were posted to the FDA website: https://www.accessdata.fda.gov/scripts/ires/index.cfm?Product=219904 https://www.accessdata.fda.gov/scripts/ires/index.cfm?Product=219905 CGMP Consultant 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 1 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.

Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the room and equipment to produce aseptic conditions, as required by 21 CFR 211.42(c)(10)(v). For example, you have not validated your processes for cleaning and disinfecting the ISO (b)(4) biological safety cabinet (BSC) where your products are exposed to the environment during aseptic processing.