글로벌 규제 모니터
2026년 10월 3주차 규제뉴스

1. 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 conducts microbiological analyses of components and drug products for your customers. You perform (b)(4) pour plate methods for microbial enumeration of (b)(4) samples. During the inspection, our investigator observed that your microbiologist failed to record the (b)(4) results when they were assessed as too numerous to count (TNTC), recording only the pour plate counts. The investigator also noted that while the (b)(4) for the pour plate samples was cracked and desiccated, the pour plate counts were recorded as within acceptable limits. When (b)(4) plates are desiccated and cracked, the media can no longer reliably support uniform microbial growth. A result recorded from a compromised plate, even one that falls within specification, cannot be considered valid, as the physical condition of the media may have suppressed or obscured actual microbial recovery. Additionally, your data review procedure is deficient in that it does not require secondary verification when an initial plate count is recorded as 0 colony forming units (CFU), creating a systemic gap where microbial growth can go undetected. During the inspection, the investigator identified a colony on a plate recorded as 0 CFU by your analyst. Further, several samples with desiccated and cracked (b)(4) were recorded as 0 CFU and discarded without secondary analyst review. The practice of non-reporting of TNTC (b)(4) results, and the investigator's direct observation of a colony on a plate recorded as 0 CFU illustrates the unreliability of your data, and further demonstrates that lack of secondary verification is unacceptable.

2. 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 failed to investigate aberrant media conditions (e.g., cracked or desiccated (b)(4) plates) used for testing raw material and drug product samples in your microbiological laboratory. In your response, you state that you opened an investigation to determine the scope of affected samples and adequacy of results and transferred microbial samples into an alternative incubator as an interim measure. Based on analyst interviews and a limited records review, you concluded that the results are valid. We acknowledge your plan to retest affected samples as a means of confirming your initial test results. Your response is inadequate. Without photographic evidence of plate conditions at the time of reading, there is no basis to retroactively confirm any result. Your conclusions rely solely on analyst interviews and data records that you acknowledged are unreliable. Furthermore, you did not commit to discontinuing the use of damaged plates for microbiological testing.

3. Your firm’s quality unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22). Your QU lacked adequate oversight and control over your laboratory operations to ensure a state of control and adherence to applicable quality standards. Significant findings in this letter demonstrate that your firm does not operate an effective quality system in accord with CGMP. In addition to the lack of effective management oversight of your laboratory operations, we found your QU is not enabled to exercise proper authority and/or has insufficiently implemented its responsibilities.

1. 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 contract manufactures non-sterile over-the-counter (OTC) (b)(4) drug products, including those labeled for use in (b)(4) . You failed to adequately investigate out-of-specification (OOS) microbiological testing results for components used to manufacture your drug products. For example, in November 2025, you obtained OOS microbiological results for (b)(4) lots (b)(4) . You prepared (b)(4) independent samples from each lot. You tested (b)(4) of the samples for total aerobic microbial count and the (b)(4) samples for total yeast and mold count. One sample from each lot exceeded your total yeast and mold count acceptance criterion of no more than (b)(4) colony forming units per gram. You did not perform an appropriate investigation into the OOS results. Rather, you invalidated the OOS results by averaging the (b)(4) total yeast and mold count sample results to obtain a passing result. You also revised your microbiological sampling plan to allow for averaging of test results for component testing. This practice is not in accordance with the United States Pharmacopeia <61> test method and is unacceptable as it obscures the detection of non-uniform microbiological contamination within a lot. You subsequently released (b)(4) lots and used them in the manufacture of (b)(4) Lot (b)(4) , distributed in (b)(4) .

Notably, on (b)(4) , your customer, (b)(4) , initiated a Class I recall of (b)(4) lots of (b)(4) manufactured at your facility due to potential fungal contamination in your (b)(4) . The investigation associated with this recall is inadequate. For example, you implemented (b)(4) of incoming (b)(4) prior to filling to reduce bioburden, but subsequent OOS microbiological results obtained from (b)(4) lots demonstrate this corrective action was ineffective. Additionally, your change control associated with the (b)(4) process did not include ensuring appropriate validation of the process as well as evaluation of the (b)(4) . Further, you lacked cleaning procedures for the (b)(4) line, did not conduct cleaning validation of the (b)(4) line, and failed to include yeast and mold microbiological testing as part of your environmental monitoring program. Though your investigation into the potential fungal contamination documented an evaluation of the cleaning procedures and environmental monitoring, it did not identify nor appropriately follow-up on these risks related to potential mold contamination.

2. Your firm’s quality unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22). Your QU failed to adequately oversee your OTC (b)(4) drug product manufacturing operations. For example, your QU failed to: Validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(2)). Follow a written testing program designed to assess the stability characteristics of drug products (21 CFR 211.166(a)). Maintain written records so that the quality standards of each drug product can be evaluated at least annually to determine the need for changes in drug product specifications, manufacturing, or control procedures (21 CFR 211.180(e)).

Based on the above labeling evidence, (b)(4) intended for use as (b)(4) drug product. As such, these drug products are “new drugs” under section 201(p) of the FD&C Act, 21 U.S.C. 321(p), because they are not generally recognized as safe and effective (GRASE) for use under the conditions prescribed, recommended, or suggested in their labeling. With certain exceptions not applicable here, 1 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 applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, are in effect for these products. Accordingly, these products are unapproved new drugs. The introduction or delivery for introduction into interstate commerce of these unapproved new drug products violates sections 301(d) and 505(a) of the FD&C Act, 21 U.S.C. 331(d) and 355(a).

1. 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 and Cleanroom Behavior You manufacture sterile, (b)(4) drug products (including (b)(4) ). We observed poor aseptic practices during set-up and filling operations including, but not limited to: Operators repeatedly broke first air by reaching their arms, torsos, and heads over open sterile tubes, (b)(4) , and open (b)(4) during (b)(4) interventions. Operators used (b)(4) directly over open bottles, (b)(4) , and caps. An operator was observed working in the Grade A area of the (b)(4) line wearing a visibly stained gown.

Inadequate Smoke Studies Dynamic airflow visualization (smoke) studies demonstrated that airflow patterns failed to adequately protect the aseptic processing line, including exposed sterile product and product contact equipment, from significant contamination hazards. For example, your dynamic smoke studies did not demonstrate unidirectional airflow protection of the production line when barrier (b)(4) were open. The studies showed air moving at a sharp angle upward toward return vents, leaving critical areas of your aseptic processing lines unprotected throughout the period in which the (b)(4) are opened. This fundamental design flaw enables the entrainment of lower-quality air from the surrounding lower-classified (Class 10,000/ISO 7) cleanroom into the Class 100 (ISO 5) aseptic processing line, posing a severe risk to product sterility.

Inadequate Equipment Cleaning and Sterilization Your aseptic processing operation is inadequately designed to prevent contamination of your sterile (b)(4) drug products. For example, you did not appropriately sterilize critical container-closure contact surfaces, such as the (b)(4) , bowl, track and (b)(4) equipment, as well as the (b)(4) , bowl, track, and (b)(4) equipment. Instead, you wipe these surfaces with sporicidal disinfectants. To ensure sterility, it is imperative that only sterilized equipment comes into direct contact with the sterile formulation, containers, and closures.

3. Your firm’s quality unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22). Your firm failed to establish an adequate QU with the responsibilities and authority to oversee the manufacture of drug products. For example, you failed to ensure: Adherence to a stability program that supports the drug products’ expiration dating (21 CFR 211.166(a)). Contemporaneous documentation of EM and personnel monitoring sampling data in laboratory records (21 CFR 211.194(a)).

1. Failure to establish procedures designed to prevent micro-contamination in products purporting to be sterile (21 CFR 211.113(b). Several of your (b)(4) (e.g., (b)(4) ) are labeled as “sterile.” We note that your OTC products including (b)(4) are not sterilized. In your response to our Form FDA 483, you stated, “Our (b)(4) are manufactured under a controlled process designed to meet the microbial limits specified in the Certificate of Analysis (C of A).” Of note, your COA does not indicate your drugs are sterile, even though your labelling purports them to be so. Sterile (b)(4) may be used by (b)(4) , if labeled as sterile, must have controls in place to ensure sterility. The inspection documented that you do not perform sterility testing of the drug products at the time of release. Your Specification and Analysis Method on (b)(4) tests the Finished Product Quality Standards to the Chinese standard (b)(4) , with acceptance criteria of ≤ (b)(4) colony forming units (cfu)/gram of total aerobic bacteria, ≤ (b)(4) cfu/gram of mold and yeast, and no fecal coliforms. Your microbial count laboratory worksheet data for (b)(4) batch number (b)(4) , released (b)(4) , reported the presence of (b)(4) cfu/gram of total aerobic bacteria. This specification is unacceptable for drug products labeled sterile.

2. 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), 211.84(d)(2) and 211.110(c)). You failed to perform adequate identity testing on each shipment of each lot of the incoming components (e.g., (b)(4) ) used in the manufacture of your OTC drug products. You also purchase (b)(4) multiple components used for manufacturing your drug products, some containing (b)(4) , and you do not test the in-process materials for identity, strength, quality, and purity as appropriate. For example, you did not ensure that each of the (b)(4) components met the relevant safety limits for (b)(4) . In both cases, you relied on your suppliers’ certificate of analysis without establishing the reliability of each of the suppliers’ test analyses at appropriate intervals. Identity testing for high-risk drug components (b)(4) includes a limit test in the United States Pharmacopeia (USP) to ensure the component meets the relevant safety limits for (b)(4) levels, respectively. Because you did not perform identity testing on each shipment of each lot using the USP identification test or an equivalent validated method that detects these hazardous impurities, you failed to assure the acceptability of these components for use in the manufacture of your drug products.

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 quality unit (QU) did not adequately oversee your drug manufacturing operations. For example, your QU failed to ensure: Adequate documentation of production and process control functions executed at the time of performance (21 CFR 211.100(b)) Adequate validation of manufacturing processes and the (b)(4) system (21 CFR 211.100(a) Adequate written procedures for production and process control (21 CFR 211.100(a)) Adequate stability testing program (21 CFR 211.166) Adequate finished product testing (21 CFR 211.165(a), 211.165(b))

Upon further review of your records and information, it appears that you assign the same batch number to different products fulfilled on a single Purchase Order. You have identified drug products with different active ingredients, routes of administration, use instructions, and dates of manufacture with the same batch number. You must establish written procedures to apply unique identification of the drug product with a lot or control number that permits determination of the history of the manufacture and control of the batch. (21 CFR 211.130(c)).

4. Your compounding technicians and aseptic assistants employ poor practices which introduce risk of microbial contamination into the ISO 5 classified critical areas during production of drugs intended to be sterile. For example, during the production of Fentanyl Citrate 2 mcg/mL Bupivacaine HCl 0.125% lot #1125035913 and/or Methadone HCl 10 mg/mL lot #1125035922, your compounding technicians: a. Moved quickly in a critical area or in an area immediately adjacent to a critical area such that unidirectional airflow is likely to be disrupted. b. Leaned into the hood, allowing their head and upper body to enter the ISO 5 classified critical area, thereby disrupting unidirectional airflow. c. Blocked first pass air by placing gloved hands directly over the following: i. Hanging IV bag ports when making sterile connections. ii. The IV bag ports when disinfecting prior to filling. iii. The open filled syringes and the syringe cap trays during the process of screwing caps onto the syringes.

6. Your firm failed to perform adequate airflow visualization studies under dynamic conditions to demonstrate unidirectional airflow within the ISO 5 area. Your airflow visualization studies are deficient because: a. The studies do not clearly demonstrate that the airflow pattern sweeps over and away from the critical areas near and on the ISO 5 classified LAF hood work surface where aseptic operations occur. Instead, the smoke appears to arc out of the hood significantly higher than the critical area and then travel up toward the ceiling in the surrounding ISO 7 classified area. b. In your most recent airflow visualization study VAL-25-044-FR, you indicated that (b)(4) people are allowed in ISO 7 (b)(4) Room (b)(4) during aseptic operations; however, the smoke study videos provided during the FDA inspection only include a maximum of (b)(4) people, and fail to demonstrate that airflow patterns inside the ISO 5 classified critical areas are not impacted by a large number of personnel moving inside cleanroom Room (b)(4) .

5. Your firm failed to establish adequate written responsibilities and procedures applicable to the quality control unit and to follow written procedures applicable to the quality control unit (21 CFR 211.22(d)). Specifically, our review of the data collected during the inspection revealed that your firm does not maintain the production video recordings which are used to determine root causes and corrective actions during investigations. For example, after recovering microbial contamination inside the ISO 5 classified critical area during the production of Ketamine HCl 10 mg/mL lot 1125035065, your Quality Unit evaluated the production video recording as part of excursion investigation EXC-2025-0045 to examine aseptic practices for potential root causes. However, instead of retaining the video recording as a quality related document, you only retained still images. Your Chief Quality Officer stated that video recordings are kept for approximately (b)(4) before being overwritten.