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2026년 8월 4주차 규제뉴스

Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2)). Your firm contract manufactures over-the-counter (OTC) (b)(4) containing the active pharmaceutical ingredient (API) (b)(4) . You failed to conduct adequate identity testing of incoming components, including the API, used in the manufacturing of your drug product. Additionally, you relied on your suppliers’ certificates of analyses (COA) without establishing the reliability of each of your component suppliers’ analyses at appropriate intervals.

Your firm failed to conduct appropriate laboratory testing, as necessary, for each batch of drug product required to be free of objectionable microorganisms (21 CFR 211.165(b)). You failed to ensure adequate microbiological testing for each batch of your drug product prior to release. Your non-compendial test method used to determine microbiological attributes (e.g., total count, objectionable microorganisms) for your finished OTC drug product was inadequate. Specifically, you lacked appropriate incubation times, lacked appropriate method suitability, and lacked positive and negative controls. In addition, you did not validate this non-compendial method.

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 quality unit (QU) failed to thoroughly investigate multiple microbial count results that exceeded (b)(4) colony forming units/milliliters from your (b)(4) system. You use (b)(4) from this system as a component to manufacture your drug products. Instead, you continued to use (b)(4) from this system with out-of-limit (OOL) test results to manufacture drug products that were ultimately released, distributing potentially contaminated drug products to market.

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 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 (21 CFR 211.42(c)(10)). Inadequate Design of Facility and Equipment You manufacture sterile injectable drug products produced primarily through aseptic processing including, but not limited to, (b)(4) products for (b)(4) . Aseptic processing lines (b)(4) and (b)(4) were intended to be “ (b)(4) restricted access barrier systems.” However, segments of the line lacked sufficient restricted access barrier system (RABS) design elements (e.g., proper ergonomics, proper (b)(4) placement, and appropriate physical separation from the surrounding environment). These features are essential for minimizing or eliminating direct operator intervention into the critical (ISO 5) area during batch manufacturing. More specifically, portions of the line (b)(4) from aseptic processing on lines (b)(4) and (b)(4) are not RABS. These lines failed to provide appropriate separation and protection of the ISO 5 areas during equipment setup and routine production. Operators were allowed to physically enter the (b)(4) lifting area of the aseptic line on a frequent basis (e.g., permitted up to (b)(4) times per batch) to perform manually intensive interventions. When (b)(4) , the (b)(4) partially folded over the processing line. Appropriate ISO 5 conditions were not reliably maintained during these activities. In addition, within the RABS portion of the line, the positioning of (b)(4) disrupted unidirectional airflow to open vials during interventions. This included, but was not limited to, the removal of empty vials from the (b)(4) , which occurred up to (b)(4) times per batch. Furthermore, product contact equipment on each line was insufficiently protected or otherwise exposed to contamination hazards. For example, the processing lines lacked robust physical separation between ISO 5 and surrounding ISO 7 areas. These design flaws compromised your ability to maintain aseptic conditions. Inadequate Environmental Monitoring You failed to ensure adequate environmental monitoring (EM) of classified areas used for aseptic production. For example, you did not hold extended ISO 5 areas of processing line (b)(4) , where critical aseptic connections occurred, to ISO 5 limits.

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 Technique and Cleanroom Behavior We observed your operators using poor aseptic practices during line setup and routine production on processing lines (b)(4) and (b)(4) . These deviations included, but were not limited to: During (b)(4) installation, operators touched sterile portions of the RABS (b)(4) and brushed their gown sleeves against open (b)(4) . Operators did not typically further disinfect the (b)(4) following installation of the (b)(4) . The (b)(4) may be used for up to (b)(4) prior to (b)(4) . During production of (b)(4) injection, batch (b)(4) , on line (b)(4) : o Operators reached their upper body (e.g., head and shoulders) over an open transfer hose while executing an aseptic connection in the extended ISO 5 area. o Operators left RABS (b)(4) on opposing sides of the production line open, exposing sections of the vial conveyor to ISO 7 conditions for at least (b)(4) . During this time, the operator opened a nearby cleanroom (b)(4) into an ISO 7 corridor, creating an unnecessary heightened risk of exposing the ISO 5 area to lower quality air. Furthermore, you configured Line (b)(4) similarly, creating significant risks associated with the non-RABS sections of the line and excessive exposure of the line to multiple personnel during setup. Inadequate Process Simulation Your process simulations failed to adequately evaluate critical interventions performed during aseptic manufacturing. For example, your firm failed to include all critical interventions in the line (b)(4) process simulation requalification, such as the aseptic connection of the (b)(4) used in bulk (b)(4) of (b)(4) . You manufactured at least (b)(4) batches of (b)(4) injection since the (b)(4) requalification of this intervention.

Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to ensure compliance with established specifications and standards (21 CFR 211.194(a)). Your firm is a contract testing laboratory that conducts testing of various application and nonapplication drug products for the US market. Your laboratory records lacked complete and original data demonstrating that you performed the required testing. You did not accurately complete laboratory records contemporaneously at the time you performed the laboratory activities. Our investigator observed (b)(4) microbial test samples that lacked complete documentation on raw data test sheets (e.g., the test sheets had blank spaces where entries should have been recorded). While your summary reports included final plate counts, your raw data test sheets for some of the samples covered in these reports lacked complete documentation of plate counts.

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.

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)). Media Fills Your firm continued to manufacture and release sterile drug products manufactured by aseptic processing following media fill failures on June 21, 2024, September 4, 2024, and November 4, 2024 as well as inconclusive media fill results and other significant quality events. Your firm lacked timely and adequate media fill investigations. For instance, your root causes were unsupported and lacked effective corrective actions. Following the inspection, you committed to recalling (b)(4) batches of drug products made from (b)(4) which reflects the timeframe between the failing media fills. In addition, you commit to improving your quality unit (QU) escalation procedures to ensure proper awareness and to engaging an outside consultant to provide oversight of your QU for six months. Your response is inadequate. You did not provide a retrospective review of all media fills to ensure additional deviations, atypical events, and unexpected results during commercial manufacturing were adequately represented in your media fill programs. Poor Practices in the Aseptic Processing Areas We observed poor practices and behaviors in ISO 5 areas during commercial operations and media fills. These poor practices, included but are not limited to: Operators inserting their upper torso into the (b)(4) restricted access barrier system ( (b)(4) RABS) during interventions, breaching the ISO 5 barrier. An operator performing a (b)(4) RABS intervention directly with the (b)(4) RABS (b)(4) instead of using forceps. Shorter operators opening the (b)(4) RABS (b)(4) and bypassing the (b)(4) during difficult-to-reach interventions, while taller operators used the (b)(4) RABS (b)(4) . In your response, you commit to retraining the operators on appropriate aseptic behaviors. Also, you commit to revising procedures and engaging outside consultants to review practices. Your response is inadequate. You do not address how you plan to ensure operators follow appropriate procedures in the future, including supervisory and quality assurance oversight. Additionally, these poor aseptic practices were not investigated to determine the impact to sterile drug products manufactured under these conditions and distributed to the U.S. market. Your response also fails to reevaluate your aseptic processing design. Specifically, you do not identify and evaluate hazards posed by various manual activities (e.g., planned interventions, unplanned interventions, (b)(4) ) or address the risks that insufficient design poses. Airflow Visualization Studies (AVS) and Process Design Our inspection identified aseptic processing design deficiencies which pose significant hazards to drug product sterility, as well as multiple inadequacies in your airflow visualization studies (i.e., smoke studies). For example, unidirectional airflow could not be evaluated in certain AVS. There were interventions performed in which the camera is placed behind the operator and the impact of the intervention on the airflow cannot be visualized. Our inspection also noted other AVS deficiencies. For example, the smoke source was not always positioned at the HEPA filter face to confirm unidirectional airflow and uniform velocity.

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.

Your firm failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products (21 CFR 211.166(a)). Your firm has not established stability indicating methods for the OTC (b)(4) drug products you distribute to the U.S. market. For example, the validation protocol for the assay of Naphazoline HCl (NPZ) in the (b)(4) formulation detailed a stress study; however, the report stated that the stress study would be performed later and reported separately. Assay for NPZ is a test conducted for stability studies of the (b)(4) formulation. Without forced degradations studies to establish specificity, the accuracy of the test assay results cannot be assured throughout the shelf-life of the product during stability.

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.

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.

Failure to demonstrate that your manufacturing process can reproducibly manufacture an API meeting its predetermined quality attributes. Your response to our request for records or other information pursuant to section 704(a)(4) indicates that you manufactured and distributed (b)(4) APIs to the United States (U.S.) without adequate process validation, which is critical to ensure the quality and purity of the API. For example, in response to our request on July 7, 2025, that you provide the process validation summary report for all U.S.-marketed APIs, you indicated that these APIs were still in development and were not commercial products. Therefore, formal documents such as standard operating procedures had not been finalized. However, FDA data shows that your (b)(4) APIs were distributed to 503A compounding pharmacies.

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.

Failure to validate and verify the suitability of analytical methods. Based on the records and information you provided, your firm failed to perform test method validation (or verification if compendial testing is used) for each test method used for drugs distributed to the United States. Test methods must be validated to show that they are suitable for their intended use or verified to show, at a minimum, equivalence with United States Pharmacopeia (USP) compendial methods. Method validation and verification are necessary to support reliable determinations of identity, strength, quality, purity, and potency of drugs.

Failure to design a documented, ongoing stability testing program to monitor the stability characteristics of APIs and to use the results to confirm the appropriate storage conditions and the retest or expiry dates. Based on the records and information you provided, your firm failed to perform routine stability testing to demonstrate that the quality attributes of your APIs remain acceptable throughout the labeled expiry period. For example, your firm did not provide stability test data for (b)(4) manufactured at your facility.

You did not provide drug listing information for demecarium bromide and chlorambucil under your own labeler code, yet you manufactured and shipped these drugs into the United States. Although these drugs are listed in FDA’s drug listing database, they are listed under a different company’s labeler code, not your own.