글로벌 규제 모니터
2026년 7월 2주차 규제뉴스

Written records of investigations into the failure of a batch or any of its components to meet specifications do not always include the conclusions and follow-up.

Specifically, A. Extrinsic biological particulates (mammalian hair) have continued to be identified in finished sterile drug products. However, investigations into these events have not been completed in a timely manner and do not demonstrate that the root cause has been adequately identified and corrected. From approximately 08/30/2025 to present, you have identified mammalian hair in finished units in at least <Redacted B4> batches, including three identified in 2026, representing a recurring contamination issue (approximately <Redacted B4>) <Redacted B4> batches out of <Redacted B4> inspected in 2026). Probable root cause has been attributed to stopper components; however, this conclusion is based on an ongoing, aggregated trend investigation (REC 1093464), that was opened on 08/28/2025, and has not been substantiated through complete, batch specific investigations. All <Redacted B4> deviations are currently open. You stated that closure of those deviations is pending completion of this trend investigation. Despite implementation of multiple corrective and preventative actions, you continue to observe mammalian hair in finished drug products. I EMPi.OY1:E($) SIGJ'IAl\lRE /I SEE

Control procedures are not established which monitor the output and validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in­process material and the drug product.

Specifically, A. Visual inspection methods have been implemented without adequately qualifying inspection sensitivity, defect detectability, or comparability between methods. For example: Your threshold <Redacted B4> studies failed to generate <Redacted B4> across the full visible range of defects and failed to establish <Redacted B4> based on defect size at which defects become reliably detectable. Without establishing <Redacted B4> supported by <Redacted B4> you have not demonstrated that inspection sensitivity has been adequately qualified or that the visual inspection process is capable of consistently detecting and rejecting critical defects. Additionally, MVI studies were conducted using aggregated "particulate" defect categories that combined multiple particulate defect types (ex: glass, metal, rubber, fibers). Further, defect units were characterized by using broad size ranges rather than actual measured particle sizes, which does not allow for evaluation of detection capability as function of particle size. Review of your threshold studies supporting the manual baseline demonstrated that certain particulate defect types, such as glass, black fiber, and hair, exhibited low

Procedures designed to prevent microbiological contamination of drug products purporting to be sterile did not include adequate validation of the aseptic and sterilization processes.

The number of containers and amount of material taken from each container is not based upon appropriate criteria.

Aseptic processing areas are deficient regarding the system for monitoring environmental conditions.

Specifically, Environmental monitoring is not always performed in response to interventions located and/ or impacting critical surfaces. Examples include but are not limited to: <Redacted B4>, tools to include <Redacted B4>.

The responsibilities and procedures applicable to the quaJity unit are not in writing and fully followed.

Specifically, You lack comprehensive trending analysis regarding your environmental monitoring program as well as your <Redacted B4> and <Redacted B4> decontamination <Redacted B4> program. Both programs lack adequate spatial analysis such as intra and inter location requirements over justified periods.

Master production and control records lack complete manufacturing and control instructions.

Equipment used in the manufacture, processing, packing, or holding of drug products is not of appropriate design to facilitate operations for its intended use.

Specifically, The <Redacted B4> Assembly Machine (Equipment ID# <Redacted B4>) is utilized to assemble and label sterile drug product <Redacted B4> into <Redacted B4>. The firm assembles and labels the sterile drug roducts <Redacted B4> and <Redacted B4> on the <Redacted B4> assembly machine <Redacted B4> The equipment performance qualification studies titled' <Redacted B4> Assembly Machine (System <Redacted B4> Performance Qualification Protocol Summary Report-VL-087 JUN2 l, VPQ- <Redacted B4> S-VL-087JUN21, Client <Redacted B4>" effective: 01/23/2023,' b 4 Assembly Machine System <Redacted B4> Performance Qualification Protocol Summary Report-VL-087JUN21, Client <Redacted B4> Addendum 11, VP 6 4 -00019-S-VL-087JUN21-ADD1 l," effective: 01/27/2026, and <Redacted B4> Assembly and Labeling Machine (System <Redacted B4> Performance Qualification Protocol, A-VPQ-00061-P," effective: 04/08/2025, do not assess the assembly and labeling functionality as indicated in the production of <Redacted B4> and <Redacted B4> for the production batch sizes of <Redacted B4> and <Redacted B4> finished drug product <Redacted B4> EMPt..oYEECS) SIGNATURE SEE Joohi Castelvetere, Investigator 04/24/2026 R

Personnel were observed conducting aseptic manipulations where the movement of "first air" in the ISO 5 area is blocked or disrupted.

Specifically, On 05/05/2026, a compounding technician was observed preparing the following prescription in Buffer Room lH-ll0A: R R X <Redacted B4> TPN, 2000 mL IV Bag During the preparation of RX# <Redacted B4> the following deficiency was observed: While injecting components into the 2000mL IV bag, the technician's hand placement was observed blocking the bag port and needle. The technician's hands were positioned in a manner that obstructed the unidirectional first air between the HEPA filter face and the critical work surface, thereby compromising the sterility assurance of the critical area.

Personnel performed aseptic manipulations with exposed hair or skin.

Specifically, a. The compounding technician was observed leaning into the ISO 5 Laminar Airflow Workbench (LAFW). with exposed skin around the eyes and forehead while performing aseptic manipulations of <Redacted B4> TPN, 2000 mL IV Bag, increasing the risk of contamination to the critical work surface.

Lack of disinfection of equipment at each transition from areas of lower quality air to areas of higher quality air.

Specifically, On 05/05/2026, compounding technician was observed preparing the following prescription in Sterile Buffer Room lH-ll0A: • RX# <Redacted B4> TPN, 2000mL IV bag During TPN compounding, the technician was observed operating a <Redacted B4> scanner connected to the <Redacted B4> TPN Compounder Computer while entering multiple times into and out of the ISO 5 LAFW without disinfecting the scanner or gloves each time. Additionally, the technician was observed touching the TPN formulation via the <Redacted B4> (Control Panel (Version <Redacted B4>) touchscreen on the <Redacted B4> TPN Compounder Computer touchscreen, which is located outside of the ISO 5 LAFW, then going back into the ISO 5 hood to perform aseptic manipulations without disinfecting their gloves.

Personnel were observed moving quickly in a critical area or in an area immediately adjacent to a critical area likely causing disruption of unidirectional airflow.

Specifically, On 05/05/2026, compounding technician was observed preparing the following prescriptions in Buffer Room l H-ll0A: • RX# <Redacted B4> Remicade (Infliximab) 500mg/0.9%NS, 250mL IV bag The compounding technician was observed moving quickly within the ISO 5 LAFW workspace during aseptic manipulations, disrupting unidirectional airflow and increasing the risk of introducing lesser-quality air into the ISO 5 critical area.

Use of a disinfectant in a manner insufficient to achieve adequate levels of disinfection.

Specifically, On 5/6/2026 during <Redacted B4> cleaning operations, cleaning performed within the ISO 5 classified laminar airflow hood (LAFH), cleaning procedures were found to be inadequate in the following respects: a. A compounding technician was observed wiping the interior surfaces of the ISO 5 LAFH without using overlapping wipe passes during the cleaning procedure. The absence of overlapping strokes resulted in visible gaps in surface contact, with some interior surface areas visibly not contacted or wetted by the disinfectant wipe. b. The compounding technician was observed using a back-and-forth scrubbing motion while wiping the interior surfaces of the ISO 5 classified LAFH, rather than the required unidirectional wiping technique potentially spreading contaminants to previously cleaned areas and negating the effectiveness o fthe disinfection process.

Use of a sporicidal agent in the facility's ISO 5 areas was improper.

Specifically, The compounding technician was observed performing the <Redacted B4> cleaning of the ISO 5 classified laminar airflow hoods and ISO 7 classified buffer room. The technician applied a wetted sterile wipes treated with sterile <Redacted B4> (manufactured by <Redacted B4> to the <Redacted B4> ) workbench and the <Redacted B4> and <Redacted B4> or surfaces of the laminar airflow hoods. Following application, all treated surfaces were observed to air-dry within a couple of seconds. This is inconsistent with the sterile <Redacted B4> manufacturer's <Redacted B4> specified dwell time of <Redacted B4> for sporicidal effect.. r17

Failure to appropriately and regularly clean and disinfect or sterilize equipment located in the ISO 5 area.

Specifically, A <Redacted B4> light fixture housing in the ISO 5 laminar flow hood (LFH) is not properly seated, creating a gap between the housing and the surrounding surface. This gap constitutes a hard-to-clean area that may harbor particulate matter and microbial contamination, posing a risk to product quality.

Smoke studies were not performed under dynamic conditions.

Beta-lactam drugs were produced without providing adequate containment, segregation, and/or cleaning of work surfaces, utensils, and/or personnel to prevent cross-contamination.

Specifically, Beta-Lactam drug products are produced in the same ISO 5 hoods as non-beta-lactam drug products intended to be sterile. The following beta-lactam drugs were observed being produced in your LAFH hood include, but are not limited to: - - - - - - ceftaroline fosamil 300 mg in D5W 100 mL ampicillin 2 gm in Normal Saline Mini-Bag 100 mL ampicillin/sulbactam 3 gm in Normal Saline Mini-Bag I00 mL ertapenem I gm in Normal Saline Mini-Bag 50 mL meropenem 1000 mg in Normal Saline Mini-Bag 50 mL meropenem 2000 mg in Normal Saline 100 mL Your firm performs cleaning with only '(bl <41 between the production ofbeta-lactam and non-beta lactam drug products intended to be sterile in the same ISO 5 area and uses[(I:)) (4) I, with a [(I:)) (4) I~ time, as the cleaning/sanitizing agent to inactivate beta-lactam residues only[(I:)) (4) Ion[(I:)) (4) Iin the non-hazardous production area. This frequency is inadequate to prevent cross-contamination. Add Continuation Page

Contamination was observed in your production area.

Specifically, On 04/29/2026, unidentified brown staining was observed on the HEPA filter in the ISO 5 non-hazardous LAFH production hood (SN: <Redacted B4>. Your firm was unable to identify the source of the staining or confirm whether it affected filter integrity, air quality, or aseptic conditions in the ISO 5 area. The duration of this condition is unknown. Add Continuation Page

Lack of disinfection of supplies at each transition from areas of lower quality air to areas of higher quality air.

Specifically, A) On 04/27/2026, 04/28/2026, and 04/29/2026, <Redacted B4> operators in both the hazardous and non-hazardous production rooms failed to wipe down materials with an appropriate disinfectant (e.g., <Redacted B4> when transitioning those materials from the ISO 7 buffer room environment into the ISO 5 critical zone during the production of luspatercept aamt 50mg, label # <Redacted B4> B) On 04/28/2026, a re-purposed <Redacted B4> bottle, labeled <Redacted B4> used to discard leftover fluid generated during aseptic processing operations, was observed used within the ISO 5 critical zone without observed disinfection upon transfer from the ISO 7 buffer room after being emptied. The bottle was reused and stored in the ISO 5 hood over multiple days. During aseptic processing activities, the cap has to be removed by the technician, and the bottle handled each time liquid is deposited inside. The operator was observed discarding liquid into the reused bottle. On <Redacted B4> bortezomib 2.7mg, label <Redacted B4> was produced with the re-used fluid discard bottle present in the ISO 5 critical area. C) The wearable, <Redacted B4> communication device is inconsistently worn by op

An operator rested their arms on the work surface of the hood during aseptic production.

This practice may introduce contamination into the ISO 5 work area. Specifically, A) In the non-hazardous production room <Redacted B4> operators were observed resting their hands directly on the ISO 5 workbench surface on 04/29/2026 during the production of micafungin 100mg in normal saline 1OOmL. B) On 04/28/2026, the operator's elbows were observed resting on the edge of the front grille of the ISO 5 Biological Safety Cabinet (BSC). Add Continuation Page

Personnel were observed touching equipment or other surfaces located outside of the ISO 5 area with gloved hands and then proceeding with aseptic processing without changing or sanitizing gloves.

Specifically, On 04/28/2026 during the production of bortezomib 2.7mg, label # <Redacted B4> an operator failed to sanitize or change their gloved hands with <Redacted B4> after touching the computer keyboard and mouse within the ISO 7 buffer room prior to going back into the ISO 5 critical area to continue aseptically processing drug product intended to be sterile. Your SOP only specifies <Redacted B4> surfaces. We did not observe your third party cleaners cleaning and sanitizing your keyboards, mouse, and handheld scanner. Add Continuation Page

Personnel were observed moving quickly in a critical area or in an area immediately adjacent to a critical area likely causing disruption of unidirectional airflow.

Specifically, An operator was observed spraying their gloved hands with (bl <4> under the ISO 5 hood and then rapidly moved their hands to dry within the critical area, causing disruption of unidirectional airflow on 04/28/2026 during the production of bortezomib 2.7mg, label li(o) (4) The operator's hands moved rapidly over materials and components used during production.

Production areas have difficult to clean or contain porous, particle generating, or visibly dirty equipment or surfaces.

Specifically, A) The <Redacted B4> plate and washer located on the front grille of BSC SN: <Redacted B4> and <Redacted B4> (hazardous room <Redacted B4> ) are difficult to clean and may harbor and shed particulates and microbial contamination into the ISO 5 environment. This screw and washer were left by the firm's engineering to the BSC grill and not part of the smoke studies, therefore there is no assurance that this is not interfering in the functionality or causing turbulence in the BSC. B) On 04/30/2026, during the production of doxorubicin 48mg in normal saline 250 mL, chipped and protruding paint was observed on the walls ofthe ISO 7 buffer room. C) At least <Redacted B4> protruding fire sprinklers located in the ISO 7 ante and buffer rooms were observed not cleaned since around 2020. Additionally, the screw, cameras, and WiFi device on the ceilings of the buffer rooms (room <Redacted B4> were not documented as cleaned. The buffer rooms contain the ISO 5 areas that are used to produce drug products intended to be sterile. D) On 04/28/2026, Bluetooth speakers were observed on the workbench of the ISO 7 buffer room, across from the ISO 5 laminar airflow hood (LAFH) used for ha

Personnel performed aseptic manipulations with exposed hair or skin.

Specifically, A) On 04/27/2026 and 04/29/2026, multiple operators were observed aseptically processing drug products intended to be sterile in the ISO 5 laminar airflow hood (LAFH) with exposed hair, including during the production of daptomycin 670 mg in sodium chloride 0.9%, 36.6 mL, label # <Redacted B4> in room <Redacted B4> B) On 04/29/2026, one operator was observed inserting their head, including the exposed skin of their forehead, and eyeglasses into the ISO 5 critical zone during the production of luspatercept-aamt 50mg, label <Redacted B4>. These eyeglasses are only cleaned with <Redacted B4> before being brought into the ISO 7 buffer area and are worn throughout the hospital and patient care areas. No sporicidal agent was used to clean these items and no environmental monitoring was performed to assess the contamination risk they may introduce. Add Continuation Page

Materials were exposed to lower than ISO 5 quality air.

Specifically, A) Sterile, lint-fre.e wipes stored in an exposed, open condition were observed on the wall of the ISO 7 buffer rooms. At least <Redacted B4> of the transparent boxes on the wall had broken hinges and were left open during production. The wipes, which were difficult to pull from the box, were sprayed with sterile <Redacted B4> in the ISO 7 buffer and then used to clean the ISO 5 workbench surface and to wipe materials transitioning from areas of lower quality air into the ISO 5 critical areas. B) Sterile, lint-free wipes were observed on the wall of the unclassified areas of the segregated ICU room <Redacted B4> by the sink. Add Continuation Page

Personnel engaged in aseptic processing were observed wearing non-sterile gloves.

Specifically, Operators were observed using expired sterile gloves (manufactured in 01/2022) during aseptic production of bortezomib 2.7mg, label # <Redacted B4> on 04/28/2026. There is no assurance that the gloves are intact and remain sterile. Your sterile glove manufacturer suggested that the gloves be used within <Redacte d B4> of the manufacturer date. Add Continuation Page