Documentation and records Findings

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.

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)). Complaint Handling Your QU did not adequately ensure procedures were established and followed. For example, your procedure for customer complaints and inquiries is inadequate. Your approach to determining severity and adverse events resulted in delayed and incomplete investigations. Additionally, investigations were based on the client and not the severity of the complaint. Also, adequate complaint investigations were not completed in a timely manner. In your response, you commit to revising your procedure and reviewing past complaints to ensure serious events are properly investigated. Your response is inadequate. You did not provide the status of open complaint investigations or whether additional complaints have been received since the close of the inspection. Stability Program Your QU failed to ensure stability testing was conducted according to your program procedures. Your firm missed stability time points, missed stability tests, or performed incorrect tests on batches placed into your stability program. In your response, you acknowledge the lack of proper QU oversight of the stability program. You commit to performing an impact assessment with the assistance of external consultants and revising your stability program procedure. Your response is inadequate. You did not provide details on how the impact of incomplete stability testing will be assessed for product batches that have been distributed to the US. market. In response to this letter, provide: A comprehensive, independent review of your overall complaint system, 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: o Nature of complaint, and potential associated risk. o Date of first notification and subsequent contacts with complainant. o Timing and sufficiency of followups with complainant to obtain photographs and the complaint sample, as well as to obtain any additional contextual information. Determine relevant complaint samples were available and extent of efforts to obtain the complaint sample. If insufficient attempts were made, identify the root cause(s) for not adequately pursuing their return. o Review of long-term history for similar or same defects. o Identification of potential causes of the defect that led to the complaint, including evaluation whether the scientific justification and evidence relating to the identified root cause(s) were adequately documented. In the event a complaint was attributed to factors outside of the firm’s control (e.g., user error), assess the strength of this determination and whether it was based on conclusive or inconclusive information. o CAPA steps taken, including but not limited to manufacturing/quality improvements (e.g., manufacturing operation, raw materials, supplier, quality control), as well as recalls or heightened quality surveillance (additional testing/examinations, adding batch to stability program). o For all complaint investigations found by the retrospective review to be deficient due to insufficient root cause or CAPA, perform a thorough analysis of production (e.g., batch manufacturing records, adequacy of the manufacturing steps, suitability of equipment/facilities, variability of raw materials, process capability, deviation history, complaint history, out-of-specification history, batch failure history). o Based upon this independent review, provide a comprehensive assessment of the complaint system that identifies all deficiencies and needed improvements. o The status of your review of open complaint investigations and whether additional complaints have been received since the procedure has been revised. A comprehensive, independent assessment and CAPA plan to ensure the adequacy of your stability program. Your remediated program should include, but not be limited to: o Stability indicating methods. o Stability studies for each drug product in its marketed container-closure system before distribution is permitted. o An ongoing program in which representative batches of each product are added each year to the program to determine whether the shelf-life claim remains valid. o Detailed definition of the specific attributes to be tested at each station (timepoint), as part of a program that encompasses each quality attribute that may change over the product shelf-life. o All procedures that describe these and other elements of your remediated stability program. 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. Quality Unit Authority Your inspectional history indicates that your QU is not able to fully exercise its authority and/or responsibilities. Your firm must provide the QU with the appropriate authority and sufficient resources to carry out its responsibilities and consistently ensure drug quality. Drug Production Suspended We acknowledge your commitment to suspend production of all OTC (b)(4) drug products at this facility. If you plan to resume any manufacturing operations regulated under the FD&C Act, notify this office before resuming your drug manufacturing operations. You are responsible for resolving all deficiencies and systemic flaws to ensure your firm is capable of ongoing CGMP compliance. In your notification to the Agency, provide a summary of your remediations to demonstrate that you have appropriately completed all CAPA.…

Failure to prepare and use master production and control records. Your batch record for (b)(4) lacked some of the critical processing information necessary to ensure consistent manufacturing and product quality. For example, you did not list (b)(4) and major equipment used in the manufacturing process. You did not provide a batch record for (b)(4) , despite being asked to provide this documentation multiple times. Without suitable batch records, you cannot adequately monitor and analyze both intra-batch and inter-batch variations to ensure that manufacturing processes remain in a state of control. In response to this letter, provide: A comprehensive, independent global review of the adequacy of the design, control, monitoring, and documentation of the production processes used for all your APIs. Appropriately detailed master batch records that capture all the significant manufacturing steps for each of your APIs.

During our inspection, our investigators observed specific violations, including but not limited to the following: 1. Your firm failed to establish an adequate quality unit and the responsibilities and procedures applicable to the quality unit are not in writing and fully followed (21 CFR 211.22(a) and 21 CFR 211.22(d)). Your firm, which holds, labels 1 , releases, and distributes over the counter (OTC) drug products under your own label (b)(4) , lacks adequate quality unit (QU) oversight and procedures for the drug products you distribute. During the inspection, you stated that no QU oversight is performed for your suppliers and contract manufacturers, including packagers. Specific failures observed during the inspection include but are not limited to the following: The absence of procedures describing how you ensure that the drug products you receive meet quality specifications, and the roles and responsibilities of each party for each of your suppliers (for example, quality agreements). Also, you do not request, receive, or maintain Certificates of Analysis (CoAs) for incoming bulk and finished OTC drug products. Notably, one of your contract manufacturers, (b)(4) , has been considered noncompliant with CGMP across multiple FDA inspections. Improper segregation of drug products throughout your warehouse to prevent mix-ups. For example, boxes of finished drug products designated as “Unlabeled, No Lot, No Exp” were observed to contain unlabeled, filled product containers stored in the same general area as labeled drug products. Your firm has no written procedures describing how finished drug products are to be received, quarantined before release, stored under appropriate conditions, and approved for distribution. This is also a violation of 21 CFR 211.42. A lack of procedures by which the distribution of each lot of drug product can be readily determined, to facilitate its recall if necessary. In your response, you state that a QU was formally established, and that a quality manual and several SOPs have been created or revised. Your response is inadequate. You did not provide a comprehensive evaluation of the current state of your QU’s actual capabilities, nor did you include an assessment of the potential impact on the quality of drug products already distributed. Additionally, your response did not appear to address the systemic nature of your QU failures. While you indicate that a supplier qualification program is being implemented and that quality agreements will be executed with all suppliers, you did not provide adequate details to determine how you will ensure that incoming drug products meet appropriate quality specifications or how you will detect, monitor for, and identify CGMP noncompliance by your contract manufacturers. With respect to warehousing, your commitment to designate areas for quarantined, released, and rejected materials did not include a timeline for implementation, and you did not conduct a risk assessment for drug products currently held at or previously distributed from your facility under these conditions. Regarding traceability, while you commit to updating shipping records to include lot numbers and to creating a new distribution SOP, you did not provide sufficient detail to demonstrate that your proposed system will be capable of achieving adequate traceability (for example, lot-level). 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 document Quality Systems Approach to Pharmaceutical CGMP Regulations 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. A comprehensive review of your suppliers and contract manufacturers, including but not limited to: o Evaluating all suppliers and contract manufacturers to determine if they are reliable and appropriately qualified. o An assessment of all drug products to determine whether they are consistently of acceptable quality. o A review to ensure assigned expiration dates are appropriate (supported by data). o Adequacy of the supplier and contract manufacturer qualification program, and its selection, qualification, and disqualification provisions. A comprehensive review of your warehousing of drug products, including but not limited to: o Procedures relating to the receipt of drug product, quarantine before release, storage under appropriate conditions, and approval for distribution. o A list of the different types of drug products and related materials you store in your warehouse (for example, finished drug products, unlabeled drug products, expired drug products, raw materials and components) and a current inventory, including manufacturer-assigned expiration dates and status (for example, released, quarantined, rejected). A comprehensive assessment of documentation systems used throughout your manufacturing operations to determine where documentation practices are insufficient, including lot traceability from receipt through distribution. Operations Observed During the Inspection During the inspection, your firm stated that packaging and labeling activities conducted at the Dayton, New Jersey facility were limited to equipment functionality trials using rejected and expired materials, and that these materials were not intended for distribution. Your firm, however, was unable to provide documentation to support the disposition of the materials used in these trials. Our investigators observed the following: Multiple boxes with labels stating, “ (b)(4) ,” and a handwritten note affixed, stating, “Needs to Change Expiry”. Multiple boxes of bottled, unlabeled drug products observed throughout the facility (for example, boxes labeled “ (b)(4) ”). (b)(4) boxes, each with a label stating, “ (b)(4) ,” containing bulk tablets imprinted with “ (b)(4) ” on one side and “ (b)(4) ” on the other side. An operational packaging and labeling line with a (b)(4) product-label roll loaded onto the labeling equipment, accompanied by approximately (b)(4) boxes of corresponding bulk (b)(4) Tablets (Batch No. (b)(4) , manufactured in (b)(4) ), and empty plastic bottles and caps positioned in the vicinity of the line. Numerous large rolls of (b)(4) -branded drug product labels for multiple OTC drug products stored within the office area of the facility. Your firm was unable to provide documentation of your packaging and labeling operations. As a result, FDA is unable to verify the nature, scope, and disposition of materials and activities conducted at this facility. Use of Contract Manufacturers Drugs must be manufactured in conformance with CGMP. FDA is aware that many drug manufacturers use independent contractors such as production facilities, testing laboratories, packagers, and labelers. FDA regards contractors as extensions of the manufacturer. You are responsible for the quality of your drugs regardless of agreements in place with your contract facilities. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act to ensure safety, identity, strength, quality, and purity. See FDA’s guidance document Contract Manufacturing Arrangements for Drugs: Quality Agreements at https://www.fda.gov/media/86193/download. 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 assist your firm in meeting CGMP requirements.

Your firm failed to establish adequate written responsibilities and procedures applicable to the quality control unit (21 CFR 211.22(d)). Your QU is inadequate as demonstrated through its oversight of investigations. Your QU reviewed and approved investigations that did not thoroughly investigate unexplained discrepancies or failures of a drug product to meet any of its specifications. For example, your QU failed to adequately ensure root causes were appropriately supported and CAPA were justified and implemented for the following: Concerning an out-of-specification (OOS) investigation for assay of (b)(4) , after failing the initial test, hypothesis and two repeat tests, you changed your autotitrator instrument and reported passing results. You failed to scientifically justify the root cause, electrode sensing issue, and your investigation failed to include a CAPA. Concerning an OOS investigation for assay of (b)(4) after failing the initial test, hypothesis, and five repeat tests, you invalidated all these results. You failed to scientifically justify the root cause, which you attributed as a sample weighing error and insufficient electrode saturation. Your preventive action was inadequate as you only verbally made “concerned analysts” aware. Concerning an OOS investigation for a specified impurity, (b)(4) , in stability samples, you accepted passing results by testing retain samples in triplicate. You failed to scientifically justify the root cause, which you attributed as contamination of the “MS source.” Your preventive action was inadequate as you only instructed the analyst to clean the source before the initiation of the analysis without revising your procedure. This strategy of using repeated testing until you obtain a passing result, then disregarding the OOS results without scientific justification (“testing into compliance”) is unscientific and objectionable under CGMP. In your response, you state you are revising your OOS investigation procedure to mandate your hypothesis plan with scientific justification. Your response is inadequate because you are revising procedures without performing a gap analysis of your investigations. Additionally, you have failed to address the authority, responsibility, and competency of your QU which had reviewed and approved all your out-of-specification investigations. 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 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 o Also describe how top management supports quality assurance and reliable operations including, but not limited to, timely provision of resources to proactively address emerging quality issues and to assure a continuing state of control. A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, OOS 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, quality unit 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 investigations trends, improves the CAPA program whenever needed, ensures final quality unit decision authority, and is fully supported by executive management. A retrospective, independent review of all OOS including in-process and release/stability testing) results for U.S. products irrespective of whether the batch was ultimately distributed in the U.S. for the last three years from the initial date of inspection and a report summarizing the findings of the analysis, including the following for each OOS: o Determine whether the scientific justification and evidence relating to the invalidated OOS result conclusively or inconclusively demonstrates causative laboratory error. o For investigations that conclusively establish laboratory root cause, provide rationale and ensure that all other laboratory methods vulnerable to the same or similar root cause are identified for remediation. o For all OOS results found by the retrospective review to have an inconclusive or no root cause identified in the laboratory, include a thorough review of production (e.g., batch manufacturing records, adequacy of the manufacturing steps, suitability of equipment/facilities, variability of raw materials, process capability, deviation history, complaint history, batch failure history). o Provide whether customers were notified of each OOS. Responsibilities of a Contract Testing Lab FDA considers contractors as extensions of the manufacturer’s own facility. Your failure to comply with CGMP may affect the quality, safety, and efficacy of the drugs you test for your clients.…

CGMP Violations 1. Your firm failed to have buildings used in the manufacture, processing, packing, or holding of drug products with adequate space for the orderly placement of equipment and materials to prevent mix-ups and contamination; and failed to have separate or defined areas or such other control systems necessary to prevent contamination or mix-ups (21 CFR 211.42(b) and 21 CFR 211.42(c)). Your firm contract manufactures over-the-counter (OTC) drug products as well as non-drug products. Your firm lacked adequate space and defined areas for equipment and materials to prevent mix-ups and contamination in the manufacturing of drug products. For example, our investigators observed inadequate material storage throughout your facility, with components and raw materials stored haphazardly on floors, along walls, and in hallways between packaging lines used for the manufacturing of drug products. In addition, materials lacked clear identification of contents, designated status (e.g., quarantined, approved, or rejected), intended use, or production run association. Your facility also lacked designated areas for quarantining incoming materials and segregating approved from rejected materials. Your lack of designated areas further compromises inventory control and increases the risk of mix-ups and contamination. Also, you conduct your drug manufacturing operations in a warehouse environment unsuitable for drug product manufacturing. For example, your drug manufacturing environment consisted of concrete floors, metal sheeting over cinderblock walls, exposed ceiling vents, exposed piping, exposed joists, and ceiling fans. Additionally, your lack of adequate ventilation systems for drug manufacturing areas can create risks for microbial and particulate contamination of drug products. While you state that you plan to acquire a new warehouse by Autumn 2026 for additional room expansion, your current environment is not of suitable construction or design to facilitate adequate cleaning and maintenance for drug manufacturing operations. In response to this letter, provide: A comprehensive, independent evaluation of your manufacturing, storage, packaging, labeling operations, and facility’s suitability for drug manufacturing. Provide an analysis including but not limited to the following factors: o Retrospective review of batches (i.e., defect types and frequencies; deviations; complaints; related investigations) o Facility layout and personnel/material flow o Equipment design, maintenance and repair history, and suitability for intended use o Assessment of whether current infrastructure (e.g., floors, walls, ceilings) can be adequately remediated or whether expansion, renovation, or relocation is necessary o Adequacy of ventilation and air handling systems for all manufacturing and packaging areas, including appropriate controls for airborne particulate and microbial contamination o Capability of facility surfaces to be adequately cleaned and sanitized in support of drug manufacturing operations A comprehensive, independent evaluation of your material control and segregation practices. Provide an analysis including but not limited to the following factors: o Appropriately designated areas for quarantined, approved, and rejected components and in-process materials o Procedures for material identification, segregation, and status control throughout the facility with applicable training 2. Your firm failed to clean, maintain, and, as appropriate for the nature of the drug, sanitize and/or sterilize equipment and utensils at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements; and failed to establish and follow adequate written procedures for cleaning and maintenance of equipment (21 CFR 211.67(a) and 21 CFR 211.67(b)). Your firm failed to ensure that appropriate procedures are established and followed for cleaning and maintenance of your equipment used to manufacture drug products. Specifically, your firm’s cleaning and maintenance procedure lacked critical details, including types of cleaning agents, cleaning agent concentrations or dilutions, contact times, sampling requirements, and testing specifications. This deficiency is particularly concerning because your firm manufactures OTC drug products on the same non-dedicated equipment used to manufacture non-drug products. Additionally, per your cleaning procedure, equipment cleaning should be documented in a designated logbook and verified by a supervisor. However, your firm could not provide any cleaning or sanitization logs to demonstrate that cleaning was performed on your equipment. Additionally, while your batch records contained a designated step for documenting equipment cleaning, this step was not completed for multiple drug product lots. You lacked appropriate evidence that cleaning was performed or verified, including when cleaning was performed, who performed the cleaning, and what product was cleaned from the equipment. Furthermore, your cleaning practices were inadequate. For example, the (b)(4) you used in equipment cleaning repeatedly yielded too-numerous-to-count bioburden results during routine sampling. Despite these recurring out-of-limit bioburden results, your firm failed to take appropriate corrective actions and continued using this (b)(4) for equipment cleaning without remediation. Inadequate cleaning procedures and the use of microbiologically contaminated (b)(4) for equipment cleaning create a significant risk of microbial contamination and cross-contamination of drug products subsequently manufactured on that equipment. In response to this letter, provide: 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 them difficult to clean o Swabbing locations for areas that are most difficult to clean o Maximum hold times before cleaning In addition, describe 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 standard operating procedures that ensure an appropriate program is in place for verification and validation of cleaning procedures for products, processes, and equipment. A corrective action and preventive action (CAPA) plan, based on the retrospective assessment of your cleaning program, that includes appropriate remediations to your cleaning processes and practices, and timelines for completion. Provide a detailed summary of vulnerabilities in your process for lifecycle management of equipment cleaning. Describe improvements to your cleaning program, including enhancements to cleaning effectiveness; improved ongoing verification of proper cleaning execution for all products and equipment; and all other needed remediations. A comprehensive remediation plan for the design, control, and maintenance of the (b)(4) system. Include a comprehensive evaluation of vulnerabilities of (b)(4) system design and control, and summarize all deficiencies found in the system. The summary should, at minimum, describe various system characteristics that were assessed for adequacy (system (b)(4) , materials of construction, slope, any identified dead-legs, any stagnant locations, any unsanitary fittings, flow velocity, etc.) A procedure for your (b)(4) system 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. Include the current action/alert limits for total counts and objectionable organisms used for your (b)(4) system. A procedure governing your program for ongoing control, maintenance, and monitoring that ensures the remediated system consistently produces (b)(4) that meets (b)(4) , USP monograph specifications and appropriate microbial limits. 3. 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 quality unit (QU) with the responsibilities and authority to oversee the manufacturing of drug products. For example, your QU failed to ensure: Adequate procedures ensuring appropriate production and process controls for drug product manufacturing and qualification of equipment used to manufacture drug products (21 CFR 211.100(a)). Establishment of an adequate, ongoing stability program (21 CFR 211.166(a)). Establishment of adequate written responsibilities and procedures applicable to the quality control unit (21 CFR 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’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations at https://www.fda.gov/media/71023/download, as well as 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 o 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. 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. A timeline for performing 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 without performing any process validation studies. A comprehensive, independent assessment and CAPA plan to ensure the adequacy of your stability program. Your remediated program should include, but not be limited to: o Stability-indicating methods o Stability studies for each drug product in its marketed container-closure system before distribution is permitted o An ongoing program in which representative batches of each product are added each year to the program to determine if the shelf-life claim remains valid o Detailed definition of the specific attributes to be tested at each station (timepoint) o All procedures that describe these and other elements of your remediated stability program. Violations of the Federal Food, Drug, and Cosmetic Act The following are violations identified during our review. As a reminder, this is not an all-inclusive list of violations that may exist in connection with these products or operations. Unapproved New Drug Violations Based on a review of product labels/labeling, “FROYA, Instant Rosacea, Acne & Redness Stopper,” “[Norse], ACNE SCARS HEALER & PREVENTER 2.0, FACE BALM,” “[Norse], BODY ACNE KILLER, BODY BALM,” “FROYA, Hyper Fast Eczema & Psoriasis Stopper for Body & Face,” and “PRIMAL VIKING, ULTIMATE JOINT & MUSCLE REPAIR BALM” are drugs under section 201(g)(1) of the FD&C Act, 21 U.S.C. 321(g)(1), because they are 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 product labeling that provide evidence of the intended use (as defined in 21 CFR 201.128) of these products as a drug include, but may not be limited to, the following: FROYA, Instant Rosacea, Acne & Redness Stopper “… Instant Rosacea, Acne … Stopper” [from product carton] [Norse], ACNE SCARS HEALER & PREVENTER 2.0, FACE BALM “ACNE SCARS HEALER & PREVENTER … FACE BALM [from product carton] [Norse], BODY ACNE KILLER, BODY BALM “BODY ACNE KILLER.…” [from product carton] FROYA, Hyper Fast Eczema & Psoriasis Stopper for Body & Face “… Hyper Fast Eczema & Psoriasis Stopper for Body & Face” [from product labeling] PRIMAL VIKING, ULTIMATE JOINT & MUSCLE REPAIR BALM “… ULTIMATE JOINT & MUSCLE REPAIR BALM” [from product carton] Based on the above labeling evidence, “FROYA, Instant Rosacea, Acne & Redness Stopper,” “[Norse], ACNE SCARS HEALER & PREVENTER 2.0, FACE BALM,” “[Norse], BODY ACNE KILLER, BODY BALM,” “FROYA, Hyper Fast Eczema & Psoriasis Stopper for Body & Face,” and “PRIMAL VIKING, ULTIMATE JOINT & MUSCLE REPAIR BALM” are intended for various nonprescription drug uses. As described below, these drug products are unapproved new drugs marketed in violation of sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C 355(a) and 331(d). A drug product is a “new drug” within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), if it is not generally recognized as safe and effective (GRASE) for use under the conditions prescribed, recommended, or suggested in its 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 FDA-approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, are in effect for these drug products identified above. Under section 505G of the FD&C Act, certain nonprescription drugs marketed without an approved application —commonly referred to as "OTC monograph drugs"—may be legally marketed if they meet applicable requirements. However, “FROYA, Instant Rosacea, Acne & Redness Stopper,” “[Norse], ACNE SCARS HEALER & PREVENTER 2.0, FACE BALM,” “[Norse], BODY ACNE KILLER, BODY BALM,” “FROYA, Hyper Fast Eczema & Psoriasis Stopper for Body & Face,” and “PRIMAL VIKING, ULTIMATE JOINT & MUSCLE REPAIR BALM” do not conform to the conditions specified in their respective monographs for the reasons described below. Acne Drug Products Based on the above labeling claims, “FROYA, Instant Rosacea, Acne & Redness Stopper,” “[Norse], ACNE SCARS HEALER & PREVENTER 2.0, FACE BALM” and “[Norse], BODY ACNE KILLER, BODY BALM” are intended for use as over-the-counter (OTC) acne drug products and must conform to OTC Monograph M006: Topical Acne Drug Products for OTC Human Use (M006) in order to be GRASE and not new drugs. 1 However, as formulated and labeled these acne drug products do not comply with the conditions specified under M006. Specifically, none of these products labeled ingredients are acceptable active ingredients for OTC topical acne drug products under M006. Skin Protectant Product and Drug Products for the Control of Dandruff, Seborrheic Dermatitis, and Psoriasis Drug Product Based on the above labeling claims, “FROYA, Hyper Fast Eczema & Psoriasis Stopper for Body & Face” is intended for use as an OTC skin protectant and for the control of psoriasis and must conform to OTC Monograph M016: Skin Protectant Drug Products for Over-the-Counter Human Use and OTC Monograph M032: Drug Products for the Control of Dandruff, Seborrheic Dermatitis, and Psoriasis for OTC Use in order to be GRASE and not a new drugs. 2 However, as formulated and labeled this drug product does not comply with the conditions specified under M016 and M032. Specifically, none of “FROYA, Hyper Fast Eczema & Psoriasis Stopper for Body & Face” labeled ingredients are acceptable active ingredients for OTC psoriasis drug products and/or OTC skin protectant drug products for eczema relief. External Analgesic Drug Products Based on the above labeling claims, “PRIMAL VIKING, ULTIMATE JOINT & MUSCLE REPAIR BALM” is intended for use as an OTC external analgesic drug product and must confirm to the OTC Monograph M017: External Analgesic Drug Products for OTC Human Use in order to be GRASE and not a new drug. 3 However, as formulated and labeled this drug product does not comply with the conditions specified under M017. Specifically, the product labeling includes intended uses that are not permitted for OTC external analgesic products in M017. Claims such as “joint & muscle repair” go beyond the general intended uses for an OTC external analgesic drug product and do not conform to the permitted uses set forth in M017. Thus, “FROYA, Instant Rosacea, Acne & Redness Stopper,” “[Norse], ACNE SCARS HEALER & PREVENTER 2.0, FACE BALM,” “[Norse], BODY ACNE KILLER, BODY BALM,” “FROYA, Hyper Fast Eczema & Psoriasis Stopper for Body & Face,” and “PRIMAL VIKING, ULTIMATE JOINT & MUSCLE REPAIR BALM” products do not comply with the applicable conditions specified in their corresponding monographs, nor have they otherwise been found to be GRASE. 4 Accordingly, these products are new drugs within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), and there is no basis under section 505G of the FD&C Act under which these products would be legally marketed without an approved application. Because there are no applications in effect for these products, these products are unapproved new drugs. The introduction or delivery for introduction of these unapproved new drug products into interstate commerce violates sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C. 355(a) and 331(d). Misbranded Drug Violations “FROYA, Instant Rosacea, Acne & Redness Stopper,” “[Norse], ACNE SCARS HEALER & PREVENTER 2.0, FACE BALM,” “[Norse], BODY ACNE KILLER, BODY BALM,” “FROYA, Hyper Fast Eczema & Psoriasis Stopper for Body & Face,” and “PRIMAL VIKING, ULTIMATE JOINT & MUSCLE REPAIR BALM” are misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee), because these products are nonprescription drugs subject to section 505G of the FD&C Act, 21 U.S.C. 355h, but do not comply with the requirements for marketing under that section and are not the subject of an application approved under section 505 of the FD&C Act, 21 U.S.C. 355. The introduction or delivery for introduction of a misbranded drug into interstate commerce violates section 301(a) of the FD&C Act, 21 U.S.C. 331(a). 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 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.