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2026년 7월 2주차 규제뉴스

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

Specifically, A.During review of your firm’s airflow visualization (smoke) study, document ID VFU315T, entitled, “Rokstudie modifiering @@ *. dated 2024/07/03. conducted on the filling line used to fill the m@ @@ drug, oe the following was observed: 1.Your, airflow visualization study is deficient as it was only conducted under static conditions. The study fails to evaluate but is not limited to the following: i.aseptic filling process under dynamic conditions ii.set-up activities iii.expected and unexpected operator interventions 2.The static study performed shows air turbulence in the Grade A filling area of filling machine @@ at the level of the HEPA filter where the ceiling meets the surrounding @@ barrier. The HEPA in the ceiling is surrounded by ag@ that is approximately q@ from the edge of the HEPA filter to the Grade A barrier. Turbulence was observed around this @@ . 3.The study failed to show smoke that is uniformly supplied and distributed covering the entire airflow cascade from the HEPA filter to the working area. 4.There is no evidence to show that the smoke generated is neutrally buoyant. Smoke used for the airflow visualization study is generated by using handheld d

Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not established, written and followed.

Specifically, Examples of poor aseptic behavior were observed during review of the aseptic process simulation study, media fill batchay@ and batch@@ on the ampoule lineg used to fill the gy@ drug a)@ 0) 4) 1. During line set up for both media fill batches an operator was observed setting up the@@ using their gloved hands where their hands came in direct contact with the components used to hold the m@ @@ _‘«in place on the line and components that the m@ They were observed physically manipulating multiple machine parts around the @@ and touching the upper part of the a@ with their hands when placing the g@@ —onto the machine. 2. An operator was observed using their gloved hands to secure and arrange unfilled ampoules onto the q@ @) (4) (ampoule loading area) in the Grade A filling machine.

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

Specifically, A. Your firm does not have a risk assessment to justify the environmental monitoring and personal monitoring locations and frequencies. 1. There is no surface monitoring on the Grade A aseptic filling line, aw used to fill the a)@ drug, ©@ While reviewing machine set up of the media fill dated September 15, 2025, and while observing machine set up on January 23, 2026, it was noted that area of the line that houses the @@ requires multiple manual manipulations and adjustments during set up and operation which are performed with the operator’s gloved hands. Environmental monitoring of these surfaces and associated @@ has never been performed. 2. While observing machine set up and filling of filling line m@ on January 23, 2026, the operators were observed leaning their head and torso over the gy@ and surrounding area of the machine.

The batch production and control records are deficient in that they do not include documentation of the accomplishment of each significant step in manufacturing and processing.

Specifically, Batch records do not contain documentation of all interventions performed in the Grade Aor the length of time taken to perform each intervention. Routine interventions not recorded include but are not limited to the following

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

Specifically, 1.The m@ is located above the end of the filling line m@ at the ceiling level. HEPA filtered air is drawn up and directly off the line when a m@ on the end is removed for the duration of machine set up. @@ are located on each side of the line and extend down from the top of the line to approximately @@ above the table holding the filling line. The aseptic filling line is not equipped with RABS technology or @@ and is not fully enclosed on all sides. The front and back are partially covered with ag)@ that extends from the top of the line downward. The front g@ stops approximately @@ before the table that holds the filling line and the line is open from the end of this g@ down to the table. 2.The w@ (ampoule loading area) extends out of the Grade A into the surrounding Grade B room. @) sterilized ampoules are loaded onto the g@ protruding out of the Grade A prior

Appropriate controls are not exercised over computers or related systems to assure that changes in master production and control records or other records are instituted only by authorized personnel.

Specifically, your firm’s @@ Equipment ID @m@ does not save testing data generated from ag@ nor is it attached to any type of system that will print or save the generated raw data. The current process relies on a single analyst to manually transcribe results from the equipment display into the laboratory record without independent verification or electronic capture of raw data. Two person verification is not required. This @@ ow is used to conduct assay and impurity testing on the ew drug

Laboratory controls do not include the establishment of scientifically sound and appropriate test procedures designed to assure that drug products conform to appropriate standards of identity, strength, quality and purity.

Specifically, your firm has omitted the @@ °C incubation step during incubation of the plates used to conduct environmental monitoring of all classified areas and operators. No method suitability study was performed or able to be provided that demonstrates that eliminating this incubation temperature does not have a negative impact on recovery of mold and yeast in the EM samples being tested.

Your firm failed to establish adequate written procedures for production and process controls designed to assure that the drug products have the identity, strength, purity, and quality that they are purported or represented to possess.

Each batch of drug product purporting to be sterile and pyrogen-free is not laboratory tested to determine conformance to such requirements.

Specifically, there is no requirement for stratification or distinct timepoints throughout the filling process at which BET samples are to be collected. A single vial is randomly collected from each batch ofgy and is used for Bacterial Endotoxin Testing (BET) per SOP 1525, “Kontrollomfattning Steril Produktion”. There are approximately@g)@ ampoules filled in one commercial scale batch ofg@ *DATES OF INSPECTION 1/21/2026(Wed), 1/22/2026(Thu), 1/23/2026(Fri), 1/26/2026(Mon), 1/27/2026(Tue), 1/28/2026(Wed), 1/29/2026(Thu)

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

Specifically, A. Your quality unit failed to ensure that the stability protocol Doc. No. (b) (4) or stability commitments for (b) (4) are being followed, in that, allows that all (fb) (4) long-term stability studies (total of” stability studies placed from 7/7/2020 to 10/5/2023, equivalent to (b) (4) ) from (b) (4) climate chamber room ID # (b) (4) (located in room (b) (4) and dedicated to (b) (4) ) at storage condition at (b) (4) °C and (b) (4)% RH to be transferred to retained sample room, in which there is no assurance or document to ensure if moved to sample retained room # (b) (4) with a temperature control at (b) (4) °C (most likely to be as per management) or sample retained room 4(b) (4) (dedicated for (b) (4) ) with a temperature control at (b) (4) °C. As per change control or assessment form FRM-12414 approved by QC and QA units on 3/21/2024, the samples were to be allocated in location ©) @) (6) (4), asset (b) (4) _ in which is a(b) (4) room (temperature control at (®) (4) °C), Either of the retain sample rooms are not intended or qualified for the stability sample studies conditions. The quality unit did not provide any scientific rational for the use of the retained ro

Reserve drug product samples are not representative of each lot or batch of drug product and retained and stored under conditions consistent with product labeling.

Specifically, retain samples for the US market were found stored in (b) (4) bins with (b) (4) covers. In some instances, samples were additionally wrapped in (b) (4) bags and/or sealed in (b) (4) bags, with some samples double-wrapped. However, these additional protective components added to the product and/or primary/ secondary packaging closure system do not represent the product and container closure system as marketed or received by consumers. This practice is inconsistent across all products and container closure and is not required or specified in the firm’s control procedure Doc. No. SOP-08511, Version 54, Reserve/Retain Sample Collection and Retention Procedure at Gilead LA Verne, Effective Date: 20 Aug 2025. The current practice of adding extra protection to the products/containers closure may delay or mask any deterioration that would otherwise be detected during annual visual inspections. Examples of this discrepancies were observed for the following finished products: REVERSE x OFTHIS feteCla 02/18/2026 PAGE DISTRICT ADDRESS AND PHONE NUMBER Fairchild 3013189568 SUED Jean G. Allaume, Vice President La Verne Manufacturing Operations STREET AODRESS CITY, STATE, ZIP CODE,

Test procedures relative to appropriate laboratory testing for sterility are not followed.

Specifically, ‘ 1. The firm’s analyst was observed to not performing adequate procedural step for bacterial endotoxin testing according to document number SODMTD-510 of(b) (4) sample preparation on February 13th, 2026, to ensure testing does not yield false negative results. a. During bacterial endotoxin testing for samples of(b) (4) taken on February 13, 2026, a total of(b) (4) samples were tested. The analyst attempted to (b) (4) each sample by placing each test tube on a (b) (4) for (b) (4) 3 however, the majority, if not all (b) (4) samples were not properly (b) (4) _ to establish proper (b) (4) formation throughout the test tube to ensure uniformity, homogeneity, and prevention of endotoxin adsorption. This occurred due to each test tube being overfilled. The (b) (4) .

Established sampling plans are not followed.

Specifically, 1. The firm's Standard Operating Procedure SOP-10912, revision 19.0, for Sampling and Monitoring of(6) (4) Systems specified that no (b) (4) | is required for (b) (4) in controlled areas. However, during the investigation of quality event QE-174808 (exceeded bioburden alert and action limit), the interview section noted that most samplers () (4) the (®) (4), (b) (4) prior to sample collection. SOP-10912 was not sufficiently clear to ensure that (b) (4) , except for (b) (4) , are not to be (b) (4)!. The current version 31.0 of SOP-10912 still contains the same language as revision 19.0. a. During a conversation with the firm, the firm could not determine the definition of "required" and whether (b) (4) require (b) (4) , or not. However, the firm stated that samples should not include (b) (4) | ofthe (b) (4) in order to maintain consistency with actual manufacturing conditions, where production personnel do not (®) (4) the (b) (4) prior to use. b. According to SOP-10912, multiple sample() (4) are designated as (b) (4) operation specifically (b) (4) which are used for (b) (4) formulation, cleaning for (b) (4) holding tanks, as well as cleaning of dedicated (4) worby ay.

Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not followed.

Specifically, your firm's quality unit failed to reject inadequate airflow visualization studies that were supposed to demonstrate proper particle contro! dynamics. For example: A. Your firm's 2024 Airflow Visualization Study for the aseptic filling process area of filler line § does not show the full range ofairflow. The smoke study video in the final report ofyear 2024, "LV- RQR-A-2011-0005 Airflow Visualization Study - Video 1 — Product Pathway (Filler (b) (4) and (b) (4) (File # REC-97652), shows the turntable where depyrogenated vials accumulate but does not show the nozzles or manifolds where smoke is released. The video fails to demonstrate that smoke was introduced into the chamber perpendicularly to air flow. Although your firm had unedited ~~ lem OF THIS 02/18/2026 PAGE DISTRICT ADDRESS AND PHONE NUMBER -02/1 8/2026* 3013189568 NAMEAND TITLE OF INDIVIDUAL TOWHOM REPORT ISSUED Jean G. Allaume, Vice President La Verne Manufacturing Operations CITY, STATE, ZIP CODE, COUNTRY TYPE ESTABLISHMENT INSPECTED La Verne, CA 91750-5801 Drug Manufacturer, Packer, and Labeler . video showing the full setup and smoke introduction orientation, this footage was not included in the final vi

Failure to establish process controls designed to assure that the drug products manufactured have the identity, strength, quality, and purity that it purports or is represented to possess.

Specifically, a. On 02 March 2026, observed was the setup ofthe m@ fill line formw drug product manufacture lotea@ Including, but not limited to the vied ibs observed was the equipment sanitized in Grade D space and assembled to the@ _—+by sanitizedg _ hands, with these equipment pieces during manufacture directly above the sterile open m@ Personnel gowning during the assembly process was Grade D gowning. with exposed facial skin within theg@ You failed tog _ sterilize the equipment and assemble the equipment to the »@ ‘in a manner that provides an optimum equipment surface for manufacture that can reasonably be expected to have an impact of product quality. Furthermore, observed was they sterilized@ Stopper Bowl and © covered, where the equipment »~@ was removed in Grade D space, with the equipment transitioning and assembled tothe fill line. The remainingoo covering theya stoppering system was removed immediately at time of installation exposing the sterile @@ stopper contact surfaces. Observed was an operator with exposed face skin working near and over the exposed sterile §4» stopper contact surfaces. The @ stopper contact surfaces were not installed in a manner that maintained

Equipment and facilities ing@ drug product manufacture are not adequately designed or located.

Specificaily, a. Based on design, the fill line for)4 drug product manufacture fails to have a HEPA filter,5 » directly above they _—«sstopper bowl. You identified by risk assessment that the area did not have excellent airflow during the @ @ smoke study, with the risk assessment failing to account for the 4 4 stoppering system q@ intervention for installation and any risk mitigation. There are no & - intervention smoke studies that includes the assembly ofthe,» stoppering system, air pattern testing. There is no viable environmental monitoring at thea)« stopper bow] location, with the total non- viable particle cone at an elevated level above the work surface. b. Theyw room wall mounted signage, holder indicating Code and Lotidentification creates a gap between the wall and the holding device, a cleaning challenge. _ ~

Failure to maintain equipment and facilities in a good state of repair in g drug product manufacture.

Specially. a. Thea used in w@ drug product manufacture was observed with deteriorated sealant at@@ ow mounting. The »@ near the stoppering system was observed with extensive)... _ scoring. b. oe© was observed with 2) line to an open bucket, along with »@ below theg@ aty~@ locations. O® was observed with an unsecured electrical box, ag@ leak and absorbent pads for ay@_ leak. oe @@ was observed withg on thé floor from ag)q __ valve. c. Your laminar flow hood (LFH) #9589, used during bioburden testing on 4 March 2026, had a rust-like -Tsubstance on the screws and visible debris on the wipe cloth after wiping the LFH surfaces before testing. Additionally, LFH #9588, located adjacent to LFH #9589, had a rust-like substance on the screws, along the inside upper edges of the hood, and along the inside right edges, as well asq) _ substance adhered to several areas on the inside ceiling of the hood.

Procedures in @ @ drug product manufacture are deficient.

Specifically, a. Your firm lacks adequate procedures and training for microbiological plate reading, resulting in inconsistent practices among laboratory personnel. There are no written procedures or documented training records that define the methodology for reading environmental monitoring settle plates and touch plates for microbial growth. On 5 March 2026, laboratory personnel were observed using inconsistent techniques when reviewing environmental monitoring plates. Laboratory Technician ®® placed plates on the light table for about one second, while Laboratory Technician®® and Team Lead®® placed plates on-the light table for several seconds, rotated them, and examined them from multiple angles. These inconsistent practices compromise the reliability and accuracy of —

Your firm faited to establish adequate quality control unit oversight with the responsibility and authority to approve or reject production and quality documents.

Your firm failed to establish adequate controls to ensure documentation is complete, accurate, appropriately reviewed and traceable.

Procedures applicable to the quality unit are not fully followea ) Specifically, The firm's SOP LIG/PCD-ZL-09-E/4 "Change Control Procedure”, effective date: 10/16/2024, requires change control to be completed for all equipment used directly in production and quality control testing that impacts product quality.

However, your firm did not have a change control documentation for the Potentiometric Titrator (ID: HY-121) and pH Meter (ID; HY-120), which are used to iest the assay and pH offinished over-the-counter drug (OTC) drug products, including me oO

Written records of major equipment use are not included in individual equipment logs.

Specifically, Your firm does not maintain equipment use logs for equipmen: used in the manufacturing process of over-the- counter drug products. This includes, but is not limited to, the following equipment: Name ofManufacturing Equipment Equipment ID(s) o@

Equipment and utensils are not cleaned, maintained and sanitized at appropriate intervals to prevent contamination that would alter the safety, identity, strength, quality or purity of the drug product.

Specifically, A.Workshop Room§y “Utensil Storage Room” contains cleaned equipment, utensils, and hoses storage. Examples of cleaning deficiencies 1 observed in this room on March 20, 2025 include: 1.I observed unknown residue inside all ports of the shared-use,, .. used to hold bulk MT) ; Ow OO) drug product during filling for multiple a) products. which is a hazardous drug, arcay ofthe approximately,,, ,,., commercial and R&D drugs filled using this,,,,, This aarmn _ Was designated as clean. Four firm filled threeay process validation lots0) ww using this @¢y 11. Approximately bd shared-use @ that operators use to transfer API and other raw ,.erials from bulk packaging to temporary vessels during weighing operations for all drugs manufactured in Workshop®) vere inside a tote. I observed unknown at the bottom of the tote with several visibly soiled ® © “oe . (&)4) with the unknownow . All the utensils in the tote were designated clean. B.Workshop hy Room, contains equipment used during formulation ofow products. Theow >) equipment ID 1) , was designated as clean when I examined its interior surfaces on March 17, $025. Examples of cleaning deficiencies include

Routine checking of automatic and electronic equipment is not performed according to a written program designed to assure proper performance.

Specifically, I reviewed qualification, mapping, and routine monitoring records for the long-term (25° C/60% RH) stability chamber, ID 911C49003. I observed the following deficiencies: A. Stability chamber requalification protocol VP1026-24-01-00 and report VR1026-24-01-00 indicate the chamber must be ina full load configuration prior to initiating the temperature and humidity mapping forow : Validation personnel confirmed they added large boxes to the chamber to fill the shelves before the most recent qualification in about June 2024. Your firm did not provide written scientific justification to add non-stability study materials to the chamber instead of requalifying the chamber in its as-is condition which would be most representative. Stability samples from the three6 process validation lotsPy were placed into this long-term stabality chamber in February 2024 and were inside the chamber during this requalification. B. I observed the monitoring and control sensors for temperature and humidity were located directly in front of the circulation fans at the top rear ofchamber 911C49003 when I examined the interior on March 17, 2025. Stability chamber requalification

The written stability testing program is not followed.

Specifically. your firm assigned aow shelf-life to the threeow process validation lots w manutactured in January 2024. There was no accelerated stability study conducted at 40° Celsius and bis relative humidity for six months to support theoa expiration date. Your firm released,p process validation lot 4) expiration dateo@ “Me and distributed the drug on about©

Your firm failed to establish adequate written procedures for production and process controls designed to assure that the drug products have the identity, strength, purity, and quality that they are purported or represented to possess.

Specifically, Your firm failed to retain records to support your process validation for OTC manufacturing. You did not maintain batch production records used as part of you process performance qualification for your OTC liquid at and OTC gel ‘i. The following batches were used to for your process validation; however, your firm did not retain these records in support of your validation: roduct Batch] Batch2___ [Batch 3 a |

There is no written testing program designed to assess the stability characteristics of drug products.

Specifically, Your firm’s stability program is deficient. For example: (a) You did not maintain batch production r pport your stability testing used to establish AOA) spiration date for your OTC liqui i. and OTCmo to The following batches were used for your accelerated and long-term stability study, however your firm did not maintain the batch records and destroyed them on February 10, 2023. atch i Batch2 Batch 3 ear 11/7/2022 (b) Your firm failed to evaluate the stability of OTC n the container-closure system in which they are being marketed. You manufacture liquid roducts in the following { configuration z. However, you only conducted stability testing for liquid I) n the z configuration and you do not have data to support the expiration date in your liqui productsiA configurations.

Drug product component testing is deficient in that at least one specific test to verify the identity of each component is not performed, Specifically, Drug components used in the manufacture of QAI oducts lack identification testing.

For example, your firm does not perform spectroscopic identification tests and limit of o) or spectroscopic identification tests and limit o or Each assessment is described as an identification test per the material’s USP monograph. SNe ene eee eee ee

Establishment of the reliability of the component supplier's report of analyses is deficient in that the test results are not appropriately validated at appropriate intervals.

Specifically, a) has never fully tested a drug component supplier’s certificate of analysis for an | rug comp b) Your firm qualified uppliers despite not having fully performed testing of drug components per USP. eee =" J

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.

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>

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.

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.

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).

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.

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.

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.

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.

Failure to investigate all out of specification test results.

Specifically, a review of(b) (4) test results from March 2024 to February 2026 revealed four (4) instances where your firm received an out of specification test result for endotoxins. Your firm has no documentation to show that these out of specification test results were investigated nor did you perform any product impact assessment. Per MIDL-SOP-307 (b) (4) , effective January 1, 2024, the specification for endotoxin is (6) (4) EU/mL. * Sample from © system collected 05/29/2024 - test result was 0.430 EU/mL * Sample from© system collected 09/25/2024 - test result was 1.508 EU/mL * Sample from© system — QC Laboratory collected 09/25/2024 - test result was 0.439 EU/mL * Sample from© system — QC Laboratory collected 03/3 1/2025 - test result was 17.589 EU/mL * Sample from © system collected 05/27/2025 - test result was 0.418 EU/mL In addition, several of the lab reports for the testing of the (b) (4) _ indicate that the sample for endotoxin testing was received outside of the recommended temperature range. The laboratory report does not state the temperature the samples were received at nor does it state what the recommended temperature range is. There is no evaluation of this issue

Failure of the Quality Unit to fulfill its oversight responsibilities.

Specifically, a) CAPAs are not fully documented in accordance with your established procedure entitled Corrective and Preventative Actions (MIDL-SOP-124) effective January 1, 2024; they also are not closed out in a timely manner. For example: * CP25-014 (initiated 8/15/2025), CP25-010 (initiated 7/01/2025), CP25-019 (initiated 11/17/2025), CP24-12 (initiated 10/11/2024), and CP24-13 (initiated 9/24/204), either lack or have insufficient documentation of an effectiveness check. * CP24-12, CP24-13 and CP25-019 have not been finalized and signed off as completed or reviewed by quality. b) Your firm does not have written procedures for the issuance, use and reconciliation of loose-leaf forms used for documentation of manufacturing (e.g. batch record) and laboratory testing. Examples of these forms include: - All forms and documents that are part ofthe batch record * Form 239A Reagent/Solution Preparation Log * Form 120A Label Control Form * Form 121A Label Issuance ¢ Form 112B ©)@) Pre-Shipment Review Log ¢ Form 133D Total Unacceptable (b) (4) Count c) There is a failure to review and approve all quality-related documents. The analytical testing lab books (data collection form) used fo

Your firm failed to conduct an annual product quality review of your API.

During the current inspection ofyour facility we observed that you had not conducted your 2024 annual product quality review for your API (b) (4) , USP. On August 6, 2025, your firm initiated a deviation report however, no content was provided in the report explaining why the 2024 review had not been completed or when it would be finalized. The deviation is still open.

Failure to perform testing of the (b) (4) used in production and in the QC Laboratory.

You did not exclude pests from your food plant to protect against contamination of food.

Specifically, your facility stores multiple food products under ambient conditions, including but not limited to bottled and canned beverages, pickles in a pouch, powder infant formula, candy, cereals, ramen, canned foods, beans, rice, food oils, baby food, plastic resealable storage bags, and snack food. These products are commingled throughout the facility with other commodity types including cosmetics, animal food, medical products, cleaning chemicals and automobile products. During the inspection between 11/17/2025 — 12/18/2025, multiple walkthroughs ofyour facility were conducted. Your (6b) (4) raised dock doors were observed to be open most ofthe day during the inspections on 11/17— 19/2025. While in your facility, observations of pest activity within your facility included, but are not limited to, the following: (5) (4) Warehouse Apparent Rodent Evidence OOne apparent live rodent was observed in a pallet ofAahubara rice located on the (b) (4) level of racking above bay © on 11/18/2025. A breakdown ofthis pallet also found apparent rodent excreta pellets (REPs) too

You did not maintain your plant in a clean and sanitary condition and in adequate repair.

Specifically, your facility stores multiple food products under ambient conditions, including but not limited to bottled and canned beverages, pickles in a pouch, powder infant formula, candy, cereals, ramen, pet food, canned foods, beans, rice, food oils, baby food, plastic resealable storage bags, and snack food. During the inspection between 11/17/2025 — 12/18/2025, multiple walkthroughs ofyour facility were conducted.

You did not keep the grounds around your plant in a condition that would protect against the contamination of food.

Specifically, during the inspection between 11/17/2025 — 12/18/2025, multiple walkthroughs of your facility were

You did not hold and store a toxic chemical in a manner that protects against contamination.

Specifically, your firm stores and hold human and animal food products as well as toxic chemicals such as motor oil, fuel additives, and cleaning chemicals. During the inspection between 11/17/2025 — 12/18/2025, multiple walkthroughs ofyour facility were conducted. While in your facility, the following observations were made regarding the improper storage of toxic chemicals in proximity to food products: DA pallet stored in Bay © was observed to hold both Blue Deisel - Deisel Exhaust Fluid and (b) (4) on 11/17/2025. This pallet was also stored next to pallets of water and (b) (4) OTwo pallets ofMotor Oil were observed being stored directly next to a pallet of Foco Tamarind Drink in the floor storage of (b) (4) on 11/17/2025 OA pallet ofmotor oil was observed being stored directly next to pallets ofCheerios and Zwan Luncheon Loafin the floor storage of(1b) (4) on 11/17/2025 This is a repeat observation from the previous inspection(s) conducted on 7/20/2018 (written observation).

You did not take effective measures to exclude pests from your plant and protect against contamination ofanimal food by pests.

Specifically, your facility stores multiple animal food products under ambient conditions, including but not limited to dry bagged cat food and wet canned cat food. These products are commingled throughout the facility with other commodity types including human food, cosmetics, medical products, cleaning chemicals and automobile products. During the inspection between 11/17/2025 — 12/18/2025, multiple walkthroughs ofyour facility were conducted. Your (b) (4) , raised dock doors were observed to be open most of the day during the inspections on 1 1/17- 19/2025. While in your facility, observations of pest activity within your facility include, but are not limited to, the following: OA bag-by-bag breakdown of a pallet ofMeow Mix Tender Centers, lot (b) (4) , found an apparent gnaw hole and six apparent REPs on one bag, and as well as REPs ranging from 1/8” to 3/8” under product plastic- wrapping and urine stains on plastic-wrapping on 11/18/2025. (Sample 1313082) OMiultiple apparent REPs were observed on three of pallets of Friskies canned cat food, lots(b) (4) (b) (4) ,and(b) (4) __ stored on the floor on the ©) ) end of the (b) (4) wall storage racks on 11/20/2025 =

Buildings used in the manufacture, processing, packing or holding of drug products are not free of infestation by rodents, birds insects, and other vermin.

Specifically, your facility stores multiple OTC pharmaceutical products under ambient conditions, including but not limited to analgesics, cough syrup, cough drops, toothpaste, antihistamines, and antacids. These products are commingled throughout the facility with other commodity types including human food, cosmetics, medical products, cleaning chemicals and automobile products. During the inspection between 11/17/2025 — 12/18/2025, multiple walkthroughs ofyour facility were conducted. Extensive apparent rodent and pest activity, including but not limited to apparent REPs, insects, gnaw holes, nesting material, and live animals, were identified throughout your warehouse as well as in the (b) (4) Room directly underneath OTC drug products that are distributed. Examples ofOTC products observed in your warehouse or front room include, but are not limited to: Product Name Lot Number Expiry Date Quantity Observed Colgate Triple Action Toothpaste (2.50z/tube) (b) (4) cases (24 tubes/case) (b) (4) (2 capsules/pouch, 50 pouches/box) (b) (4) (2 tablets/pouch, 25 pouches/box)

Drug products are not stored under appropriate conditions of temperature, humidity and light so that pers

Devices have been prepared, packed, or held under insanitary conditions whereby it may have become contaminated with filth or whereby it may have been rendered injurious to health.

Specifically, your firm failed to protect medical devices from contamination due to pest activity in buildings storing medical devices and improper storage conditions. Your facility stores multiple medical device products under ambient conditions, including but not limited to menstrual pads, pregnancy tests, bandages, first aid kits, toothbrushes, and condoms. These products are commingled throughout the facility with other commodity types including human food, animals food, cosmetics, OTC pharmaceuticals, cleaning chemicals and automobile products. During the inspection between 11/17/2025 — 12/18/2025, multiple walkthroughs ofyour facility were conducted. During these walkthrough, evidence of apparent pests were observed throughout the facility, including apparent live rodents and birds, dead rodents in various states ofdecay, rodent excreta pellets (REPs), bird droppings, live insects, and gnawing indicative of rodents throughout the entirety ofyour facility. During a walkthoughs on 11/24/2025, a pallet ofmixed products was observed on the (b) (4) _ racks ofthe () (4) Warehouse which included approximately "cases of (b) (4) . Apparent REPs TNTC were observed on the lower

Your cosmetic was prepared, packed, or held under insanitary conditions whereby it may have been rendered injurious to health.

Specifically, your facility stores multiple cosmetic products under ambient conditions, including but not limited to soaps, lotions, hair glue, hair gels, shampoos, conditioners, and body spray. These products are commingled throughout the facility with other commodity types including human food, animal food, medical products, cleaning chemicals and automobile products. During the inspection between 11/17/2025 — 12/18/2025, multiple walkthroughs ofyour facility were conducted. ! While in your facility, observations ofpest activity within your facility involving cosmetic products included, but are not limited to, the following: | O\Apparent REPs TNTC were observed on the second level storage rack along the north wall ofthe (©) (4) | Warehouse by cases ofAxe Body Spray on 11/19/2025. OTwo apparent dead rodents were observed ona black glue board located between pallets of(D) (4) — soap and | (b) (4) in the () (4) Wall racks behind (b) (4) on 11/17/2025 OApparent REPs TNTC were observed ina pallet ofLucky Super Soft Aloe Vera liquid soap located near the (6) (4) Wall racks behind (b) (4) on 11/17/2025

You did not maintain your plant in a clean and sanitary condition and in adequate repair.

Specifically, During the walk-through on 07/14/2022 I observed the following: 1.) An accumulation of food debris on the underside of the ' " and behind the "(6)(@)(4) ". 2.) Exposed tile above clean dishes in the ®@ room and above the ' Tunnel". 3.) The wall in the "(6)(4) Room" portion of the production area to be cracked.

You did not conduct operations under conditions and controls necessary to minimize the potential for contamination of food.

Specifically, During the walk-through on 07/14/2022 I observed the following: 1.) An accumulation of particulate matter on ceiling vents in the "((5)(4)J Room", "Load Out Dock" area, next to the extruder, over the "Retail Curve", in the "Filling" section of the production area, and the general storage area. The vent in the "Retail Curve" area is directly above ready-to-eat product. 2.) An accumulation of particulate matter on the ceiling tile near the "Retail Curve".

Your plant did not have adequate sanitary facilities and accommodations.

Specifically, During the walk-through on 07/14/2022 I observed the following: 1.) The hand sink near the "{(65)(4)) mixer" did not have soap or paper towels. A build-up of residue was also observed inside the basin and near the hot water handle. 2.) The hand sink in the front retail area had no soap. A blender was also observed to be inside the sink while a sign stating "Do not rinse dishes in this sink" was posted above the sink.

Your equipment and utensils were not designed and constructed to be adequately cleaned or maintained to protect against contamination.

Specifically, During the walk-through on 07/14/2022 I observed the following: 1.) The walk-in cooler to be leaking water on the floor at the cooler door. 2.) A clean bowl to be chipped in the P44 room.

The visual inspection procedures are inadequate to addresseecetective filled drug product trends.

a. The visual inspection procedures lack scientific justification to support defect categories such as critical, major, and minor. For example, you have classified liquid between stopper and broken container as major defect types, although these defects may compromise the integrity ofthe drug product container closure and product sterility. You allow approximately three ofthese defects per batch without the requirement to investigate during your AQL inspections. If liquid between stopper and broken container defects were categorized as critical defects, seven out of"(batches would exceed the critical defect limit ofom. b. The visual inspection procedures do not support identifying atypical defective product trends. For example, there have been liquid between stopper fer [2 out of“@batches of(yee rug product filled ou manufactured and up tol ofthe filled | had liquid between the stopper. Also, there have been black/white articles, fibers, glass, or other foreign particles in 12 out of Bbatches ofoe product filled 9) @@you manufactured. However, you tailed to investigate these atypical defective product trends. c. The records ofmanual visual inspection results lack details such as th

The air flow pattern testing studies did not include all operations such as setup and assembly, normal and unusual interventions, unassisted equipment operation including filling to demonstrate unidirectional airflow within the Class A classified Restricted Assess Barrier System (RABS).

Therefore, your products intended to be sterile are produced in an environment that may not provide adequate protection against the risk of contamination. For example, the following operations and practices were not performed during air flow pattern testing studies: a. Making critical aseptic connections b. PlacingSN NUNNNTNTNEassemblyWe sterilized secondary product contact items such as stopper lanes, stopper ools inside the RABS c. Setup inside the RABS d. Assembling ofthe sterilized secondary product contact items e. Assembly of stopper and removing the cover f. Actual filling of a liquid.

The I arug product manufacturing process is not adequately controlled or monitored to ensure that process limits conform to specifications.

a. The position of the is not adequately controlled. The position ofthe is determined by the during the stoppering step. The qualification ine acceptable range for the when af)7@®@ filling machine setting for stoppering parameter) is applied. b. The is not controlled or monitored during sterile The sterile is controlled as a process parameter by ting. Thei" ofthe sterilea. not detect c. The endotoxin limits have not been established for the formulation e preparation of the formulation involves herefore, contaminants could be intr during formulation preparation. Therefore, endotoxin excursion in formulation ill not be detected and thus, will not prevent endotoxin entering the product stream prior toMO viththe drug substance. SEP/21/2023 09:43 DISTRICT ADDRESS AND PHONE NUMBER CDER/OPQ/OPMA/ Division of Biotechnology Manufacturin Silver Spring, MD 20993 FEMME E-mail: [email protected] NAME AND TITLE OF INDIVIDUAL TO WHOM REFORT ISSUED STREET AODRESS. Taichung, 428 CITY, STATE, ZIP CODE, COUNTRY TYPE ESTABLISHMENT INSPECTED

Procedures designed to prevent microbiological contamination ofPM arug product purporting to be sterile are not established and followed.

Specifically, a. The econdary product contact items such as stopper lanes, stopper er ‘ools are placed inside the RABS and outer packaging are removed or cut rior to filling to expose these items. However, environmental monitoring is not performed during these[Mfto assure that the exposed items are protected by the GradeA air. b. The sterility of the could not be assured as a ay was placed very close to ic a th illing to collect the fthete the liquid in the tray could splash from the tray. In addition, there is no assurance that the tray is sterile as there is no documentation in the batch records that the tray isWE with other items before placing in the RABS. c. Operators did not practice aseptic techniques such as changing into a new pair of steri gloves/sterile sleeves prior to performing the sterile connection between the sein assembly and sampling bag assembly in Grade B and sampling bag assembly in Grade B and the inside the RABS. These sterile connections were made onseein the Grade B area. In addition, the was not cleaned immediately prior to performing the operations and EM samples from the was not taken after the operations.

The|) sterilization validation ofdirect and indirect sterile product-contact items is not sufficient to demonstrate sterility assurance: a.

Bioindicators (BIs) incubation conditions used during sterile drug product contact equipment PE validation studies are inadequate to demonstrate that the [ummmPcycle provides a sterility assurance level ofat leastPe and, thus, there is no assurance that the direct and indirect sterile drug product contact equipment is sterilized duringee the Bls used for the product contactset and indirect product contact stopper bowl, SEE We t Agee”

The deviations and/or investigations are not always raised due to nonconformance events or incidents are not adequately investigated.

For example, » a. During the manufacturing oftre operator noted on the master batch record that fivePP @were not stoppered and removed by the operator. However, no deviation or incident report was raised to investigate the root cause for this event. b. During the manufacturing of[IPE Sthe operator noted on the master batch record that five| 7 @in the rub could not be stoppered, and theseenn removed. The operator noted that this was probably due to missingrein the tub and, thus, the yee otWB cout not be maintained. However, no investigation was performed to investigate the root cause for the missing— c. During the manufacturing ofDW the operator noted on the master batch record that five in) ©@ub could not be stoppered, and these/// PM @were removed. The operator noted that this was probably due to ith broken flange in the last row ofthe tub and, thus, the |) @@ofool weed not be maintained. However, no investigation was performed to determine root cause for the broken ange. d. During the manufacturing ofPB the operator noted thatae rejected by the filling machine. However, no investigation was performed to determine root cause for the tub rejection.

Procedures to control environmental conditions have not been adequately established.

Specifically, a. The personnel monitoring limits established for operators performing operations in the) 7° RABS are inadequate to meet acceptance criteria for Grade A (ISO 5). During the filling operation setup on September 15, 2023, the operator did not wear sterile sleeve covers and the operator’s lower forearms and the upper arms moved inside the RABS when placing the stopper bowl. However, operator’s right- and left-hand finger monitoring limits meet the requirements for Grade B (ISO 7). The operators right and left lower forearm are not monitored. The operator’s monitoring did not occur immediately following the intervention. Instead, SEP/21/2023 09:43 7

Adequate procedural controls to protect the electronic data acquisition systems have not been established.

Specifically, a. Data files from Lonza equipment L-346 and L-009 for the kinetic turbidimetric LAL method are saved locally on the C drive ofthe computers connected to the Lonza reader. Data files are saved to the servermere: HP rowever, data files from the C drive can be accessed by QA and IT staffand are therefore not controlled adequately.

The incoming material are released for manufacturing operations prior to completing the final testing and, thus, there is no assurance that incoming material meets the specification and suitable for manufacturing.

For example, a. The stopperLS been pre-released for use in filling operations prior to final testing were completed. [hese stopper lots were pre-released for filling operations to manufacture) @media fillsJ/Mengineering, andWMP batches and subsequently obtained full release. b. Theee ae been pre-released for use in filling operations prior to final testing was completed. e ots were pre- SEE

Your firm failed to properly maintain buildings and facilities used in the manufacture of API in a clean condition.

Specifically, during a walkthrough ofyour facility on March 18, 2024, I observed what appeared to be water staining and unknown residue on ceiling tiles located above retain samples, as well as on the baseboard behind the retains, in your API Reserve Sample Storage Room. Examples of retain samples stored in the API : oa ow Reserve Sample Storage Room on March 18, 2024 include: lot OO, OC) OX) OG) ot and © \ot On March 18, 2024, I also observed what appeared to be water staining on ceiling tiles above retain samples in your KSM and Intermediate Reserve Sample Storage Room, which your firm uses to store retain samples from lots of key starting raw material and from lots of intermediates during API production. *DATES OF INSPECTION 03/18/2024(Mon), 03/19/2024(Tue), 03/20/2024(Wed), 03/21/2024(Thu), 03/22/2024(Fri)