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(4) equipment utilized in the mw drug substance manufacturing process is deficient.

Specifically, Multiple deviations of bag leaks have been identified in 2024 and 2025 involving various bag siZes gm 0) etc.) of mw bags. The calculated bag defect rates range from 0.45% to 5.88% for 2025. These bags perform critical functions throughout the manufacturing process, including oH) @) etc. Change control PR 218330 was initiated on Dec 1, 2025, proposing to implement a@ (4) bags as a corrective measure. However, this change control is currently under board review and pending approval. The effectiveness of this proposed change control in reducing the bag leakage rate is currently unclear.

Laboratory controls are inadequate to ensure reliable analytical testing of critical quality and safety attributes.

Specifically, Critical analytical methods showed high invalid assay rates froma@ to current: m@ fora @@ ALaboratory Investigation Report (LIR) has been initiated, and operator training was identified as the main root cause. While some methods have shown improvement following enhanced training programs O@ invalid rates for the following critical analytical methods remain high in @@ for o@ @@ |!n addition, invalid rates are also high fotg@ iNey

10903 New Hampshire Avenue; White Oak Building 51, Room 2269 12/08/2025-12/16/2025 Silver Spring, MD 20993 Email: OPMABLA [email protected] 3026506583 SUED Brendan McGrath, VP of Manufacturing and Ireland Site Lead Wuxi Biologics Ireland Limited Dundalk Science and Technology Park CITY, STATE, ZIP CODE, COUNTRY TYPE ESTABLISHMENT INSPECTED Mullagharlin, Dundalk, County Louth, A91 X56F, Ireland Drug Substance Manufacturer Written documents are inadequate to ensure proper documentation of manufacturing operations.

Specifically, During walk-through of the manufacturing area for o@ @) step, it was observed that the logbook reflected a completed gw cycles while the SAP system showedg@ cycles. This discrepancy between physical records and SAP system represents inadequate documentation practices.

Laboratory investigation procedures for Out of Specification (OOS) results are inadequate.

Specifically, In WX-SOP-10217: Laboratory Investigation Report Procedure, Section 5.5.9.1, states: "If no root cause is identified through phase 1 and 2 investigations, upon consultation with QA, the investigation may progress to retesting.". Section 5.5.9.5 specifies: "If all results meet specification, are within system suitability and sample acceptance criteria the re-testing can be reported and the original analysis invalidated.". This SOP allows retesting and subsequently invalidate the original results if no root cause has been identified, which is inappropriate. When no clear laboratory error has been identified, the initial results may constitute valid analytical findings that should be reported and considered in the batch release decisions. SEE

Procedures for corrective and preventive action have not been adequately established.

Specifically, you have not fully documented and implemented written procedures for analysis of complaints to identify existing and potential quality problems. For example, A. You have not fully implemented Section 4.7 of your Complaints Management procedure requiring that you document the justification as to whether or not additional actions are required following your analysis to determine if there is a trend in the compliant data. B.You do not have written procedures defining your monthly complaint data trend analysis and evaluation. Further, your records of trend analysis for complaint data in December 2023, January 2024, and February 2024 do not list an evaluation covering Alert Limit deviations which were identified during these reviews.

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

Specifically, your firm has not conducted at least one specific identity test and has not established the reliability of the suppliers analyses through appropriate validation of the supplier's test result at appropriate intervals for © vial used as primary container for Adstiladrin drug product. Between ” (b) (4) , your firm has shipped/distributed approximately (©) (4) Adstiladrin vials to the US market. In addition, you have not established a written procedure describing the sampling and testing of© vial.

The quality control unit lacks responsibility to approve all procedures or specifications impacting on the identity, strength, quality and purity of drug products.

Specifically, your quality control unit has not established a procedure that governs the performance of visual inspection on reserve samples from representative sample lots at least once a year for evidence of deterioration.

Written procedures for cleaning and maintenance fail to include maintenance and cleaning schedules.

Your firm has not adequately validated your adherent (b) (4) regarding cell infection in that certain combinations of critical parameters have not been assessed.

The Multiplicity of Infection (MOI) is used in a calculation in step ©@ of master batch record (b) (4) (b) (4) , for determining a correct volume of virus particle concentrate. The MOI is a critical process parameter with a target of ™® viral particles per cell (VP/Cell) and a range of (b) (4) VP/Cell. The Duration of Infection (DOI) pertains to the time taken from infection to harvest and has a normal/acceptable range of (1b) (4) = (page 157, master batch record (b) (4) )) The DOI is a critical process parameter. Although the MOI target is 163 VP/Cell, there is no prohibition on using any other value within the range. Your firm has not validated combinations (including extremes) of MOls and DOls for acceptability regarding two (b) (4) , which were observed in operation in building (6) (4) and include (b) (4) and (b) (4) (b) (4). (b) (4) was observed but reported undergoing an upgrade. Drug products batches

Failure to check the reliability of Certificate of Analysis (COA) at Regular Intervals.

Specifically, your firm has not established the reliability of suppliers COA through appropriate validation of the supplier’s test result at appropriate intervals for the following components/excipients: pecification Number Material Name (b) (4) (b) (4) (b) (4) (b) (4) ” (4) (b) (4) (b) (4) (b) (4) (b) (4) (b) (4) (b) (4) (b) (4)

Deviations during production have not been thoroughly investigated.

Specifically, a. (b) (4) documented in deviation DEV-1498 did not trigger impact assessment on previous batches manufactured (b) (4) The impact on product quality of (BD) (4) hat might have been damaged | . Add Contirwation Page

Preventative maintenance ofcritical equipment is not performed per written procedures.

Specifically, a. Preventative maintenance for (b} (4) was not performed as scheduled. Daily tasks are not documented, Between June 7, 2015 and April 21, 2016, of 47 required weekly PM activities, eight that were late, 15 were missed, and two were not scheduled. Over the ten month period, only one ofthree quarterly j Maintenance activities was performed, due on August 31, 2015, completed on April 19, 2016, Semi-annual }preventative maintenance performance was two months overdue,

Failure to follow standard operating procedure for deviation management, Specifically, a.

Critical deviations DEV-1484, DEV-1632, and DEV-2081 were initiated, respectively, 1, 5, and 2, days past the yoy 4 * . ® : . (DY (4) window as required by the deviation management procedure, GMP-0263, Rev 16. In all cases, the client was notified and initial investigations started within (0) (4) but the official documentation of the deviations were not initiated within the (8) (4) window. Wie - : ee ee tae Peete Tree 1

Your firm failed to establish 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 has not demonstrated a state of control over the CASGEVY manufacturing process: a) ()() Aseptic Process Simulation (APS) runs were executed from (b) (4) in Grade ® suites (b) (4) _ APS runs (®)@) were executed in Suite ©)@ with results that met specifications, however, these runs were repeated due to a trend of aseptic lapses and inconsistent aseptic practices that were not considered representative of your firm’s process quality standards. Additionally, a total of 4) deviations (including major) were initiated during execution ofthe®™APs runs. b) © healthy donor (HD) (b) (4) runs were executed in (b) (4) to support (b) (4) CASGEVY production capacity. HD Batch Nos. (b) (4) were ™rejected for failure to meet production control specifications in the HD protocol. The (©) @) disposition for Batch No. (b) (4) was also rejected due to an out of specification (OOS) result for (BD) (4). c) Commercial production of CASGEVY was initiated in November 2025 with manufacture of®® batches. Batch No. (b) (4) was rejected for ©) observed in the BSC (6) (4)

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

Specifically, a)DEV-1358321 was initiated on 5/30/2025 for an identified trend of particulates (b) (4) for the CASGEVY manufacturing process. In response to this event, CAPA-1420656 was opened on 10/2/2025 for initiation of a (b) (4) for (b) (4) was created on (Bb) (4) to update (b) (4). the software for (Bb) (4) in-process monitoring of particulates and develop an SOP for governing (b) (4) . However, in-process monitoring of particulates is still being implemented, and updates to (Bb) (4) and creation of a| (Bb) (4) SOP have yet to be completed. Additionally, ©)@ other deviations have been initiated (subsequent to the trend investigation) for investigation of particulates identified in APS runs and commercial batches. b)DEV-1435080 was initiated on 10/29/2025 after a trend was identified for EM good documentation practices (GDP) assay errors and incorrect performance of critical in operation (CIO) EM. CAPA-1447250 was opened on 11/18/2025 to include an action plan for initiation of a (b) (4) for establishment of a| (B) (4) SOP for (b) (4) and training guidelines. However, a has yet to be initiated for development and implementation of a (b) (4) SOP and training guidelines. Additio

Procedures describing the warehousing of drug products are not followed.

Specifically, a review of the use log form (_ (Db) (4) _ ) for (b) (4) of CASGEVY final drug product vials in’ (b) (4) revealed that your firm failed to capture the number of vials transferred to this unit for Batch Nos. (b) (4) . Additionally, the’ (1b) (4) __ inventory list for CASGEVY final drug product vials (1B) (4) — units only reports the final product batch number and not the actual number of vials placed in the (0) units.

Discrepancy and failure investigations related to manufacturing were not expanded to assess worst case conditions.

Specifically, a) Deviation 201042740 initiated on 09JAN2024, pertaining to particulate contamination of was not adequately investigated. Your (b) (4) identified an within a (b) (4) sent for analysis during the deviation investigation. However, you failed to perform an adequate risk analysis that included worst case conditions to support the utilization of during manufacturing of (6)i(4)i ll lll | lll batch “This batch was released and distributed for further manufacture of final drug products INFANRIX (lots (BY (4) 9) and BOOSTRIX (lot(6))). b) Deviation 201079963 was initiated on 25JUL2024 pertaining to a (b) (4) 7) This batch was identified as out of controlled temperature fol) hrs with the warmest temperature reachin ). You failed to evaluate product impact for all 17 and failed to adequately investigate and justify your viability testing sample was representative of worst-case conditions. This was released for further manufacture of and (6) 4) batches ad

Procedures for the acceptance and rejection of components and materials utilized within drug substance manufacturing are not adequate.

Procedure LSOP 9000087267 (ver. 01 — approved 20MAR2024), titled “FILT.UF (B)(4) Pi was implemented as a corrective action in response to deviation 201042740 and requires visual inspection of the prior to use within manufacturing. The procedure allows for the acceptance and use o containing ,” however, no risk assessment or study was conducted to assess the impact of utilizing with (b) (4) ” within your process.

Input to and output from the computer and related systems of formulas are not checked for accuracy.

Specifically, b) (4 A. Your firm utilizes electronic formats/recipes configured within the ( ) ( ) (b) (4) systems to control critical manufacturing parameters for the drug products, including but not limited to fill volume. Your firm manufactured drug product batches using non-validated formats/recipes, as follows: J __—il Filling lines (b) (4) wavre site) Syringe Syringe ,,..| Vials filling line | Vial fillin ae yy m8) filling line _ filling line line | Format Format Format Format Adjuvant ASO1s (b) (4) (Shingrix) Aso1(b) (4) Adjuvant ASO1: (b) (4) Pediatric Pediatric (Arexvy) aso1 () (4) ©) 4), (4) as03 VIAL weonesvon]|||)

Your firm failed to establish 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, A. The Master Batch Record, MBR, No. (b) (4) and executed production batch, (4) records for SHINGRIX® specify the use of format/recipe (b) (4) with a target fill volume of () However, actual manufacturing operations utilized format/recipe (b) (4) witha target fill volume of(b) (4), representing a (5) (4) deviation from the specified fill volume. Your firm failed to follow the batch record specifications during manufacturing for (b) (4) lots of SHINGRIX® PFS- Pre-Filled Syringe drug products, of which (b) (4)have been released since March 16, 2024. The actual fill volume and format/recipe used in production did not match the fill volume and format/recipe documented in the batch record. For example, your firm manufactured and released SHINGRIX® Batch No. ASFLA026A, release date September 1, 2025, on filling line using format/recipe IIMA with a fill volume of (Bb) (4). However, the MBR and production batch record reflect the use of format/recipe (1) (4) with a target fill volume of (b) (4) B. Filling parameters are modified and adjusted during production and process control in the (b)Oy the operator as needed. Your firm has not established procedures governing operator c

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

Specifically, A.Your current APS (Aseptic Process Simulation) design does not challenge or represent worst-case conditions for routine commercial fill volumes and container sizes. Commercial products, such as Boostrix, Engerix, Havrix, Twinrix, Fluarix, FluLaval, Infanrix, Kinrix, Pediarix, Rotarix, Shinerix. Svnflorix. Penmenvy, Arexvy, and Hiberix are filled at volumes ranging from (b) (4) (b) (4) syringe containers, (b) (4) syringe containers, and (b) (4) (b) (4) vial containers. However, your APS program uses only the (b) (4) syringe container filled to a target volume of (b) (4) for filling line" and vial container filled to a target volumeo or (b) (4) | container filledto a target vol f b) (4 f filling line (1) (4) . B.Your LSOP 9000002087, version 17, “Validation of Aseptic Operations — Aseptic Process Simulation (APS)”, section 6.2.5.2 requires justification and validation of the (b) (4) (b) (4) media fill volumes for each container and validation of incubation conditions. Section 6.2.5.4 requires development and justification of a container (6) (4) _ ; otherwise, all container sizes must be (b) (4) during (b) (4) APS requalification. Section 6.2.5.4 further requires that w

Deviations from written production and process control procedures are not justified.

Specifically, your firm failed to evaluate unexpected events during drug product manufacturing to determine whether they constitute deviations from established procedures. There is no documentation demonstrating that your firm assessed these events or provided justification for why they were not classified and investigated as deviations. For example, your firm manufactured SHINGRIX® Lot No. ASFLAO18A on (b) (4) , During the manufacturing process, the operator detected a failure of the (b) (4) ), which monitors the Grade o filling line. This event was documented in the batch record as defect code (b) (4) However, your firm failed to evaluate whether this PEMS failure constituted a deviation from established procedures or requirements.

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

Specifically, A.Inadequate Environmental Monitoring Following Planned and Unplanned Shutdowns ol Your |, (b) (4) and (b) (4) units are classified as Grade (ISO “) during operations and declassified during shutdown. These Grade "” areas are used for

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

Specifically, ©) (4) wey . . . . _— me) Your Grade and Grade classified areas, which provide direct and indirect support to Grade (b) (4) aseptic processing operations, are not monitored for (b) (4) via an environmental management system (e.g., (2) (4)). Your firm monitors (b) (4) in classified areas; however, (b) (4) parameters are not monitored, recorded, trended, or ‘ (D) (4) (b) (4) evaluated in Grade and Grade “ areas. Furthermore, your firm has not established a documented scientific justification demonstrating that the

Your firm failed to establish 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, A. Your multiple materials such as 0541 PIP Me% For example, the Ib/141 'process is not required to run continuously and is allowed to be completed over 51(41 until the OM 18)141 15141 . The are held process is finished. (0141 and other or for 51+0 (WI before resuming was paused on Ibif41 , the materials were placed on hold from on (.1(.) 81141 at batch were held on . Due to a power outage, the with other - Your process for batch resumed on , and was completed on, batch lwas released to your - Ifor further! OM) . Palforzi a _Ito the U.S market. Your firm has not established an appropriate hold time or validated the non -continuous

There is a failure to thoroughly review any unexplained discrepancy and the failure of a batch or any of its components to meet any of its specifications whether or not the batch has been already distributed.

Specifically, A. Incident No. INC-24-00219, was initiated on July 8, 2024, for a site wide unplanned power outage that occurred on July 3, 2024. During this outage, manufacturing of Palforzia 20mg batch number was interrupted during the batch was placed on hold for the 111(4) ow) ( process. The and completed on. process for Palforzia I Additionally, experienced a temperature excursion due to the outage Your investigation concluded that there was no product impact; however, no product impact in the Palforzia batch was released to your client for further

Written procedures are not established and followed for the cleaning and maintenance of equipment, including ,used in the manufacture, jof a drug product.

Specifically, A. On March 12, 2025, multiple dissembled equipment parts of the , including the om fb1 were observed to have visible (EE of a B. You failed to establish cleaning instructions and documentation logs for the connecting to the used in the of excessive during the production of finished drug product. C. On March 12, 2025, equipment including: RE4I (1 of the was used in multiple location on surfaces of production PIRO

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

Specifically, you fail to establish a procedure to adequately address the control of documents in your manufacturing suite when not in use. The following blank documents and records were observed in the common support area of the manufacturing suites during the walkthrough on March 12 2025 i. - 1-0147 "Line Clerance Form for - Manufacturing Operations" ii. Attachment 3 of SOP -0342 " Operation, Maintenance, and Calibration of the MN System, including Page 29-44 iii. Attachment 2 of SOP -0368" - Cleaning of MN for the 00I ", Major Cleaning of - (Page 1-3)

Buildings used in the manufacture, in a clean and sanitary condition.

of drug products are not maintained Specifically, during our inspection walkthrough on March 12 2025, we observed the following deficiency: A. Multiple cracks on the oxo on the - - , used for the of 0.5mg, 10mg, and 20mg of finished drug product Palforzia B. A hole on the MM 0841 ofthel were observed in production suite - for the manufacturing and no work order having been initiated for repair. ! of the C. Paint peeling off the - inside production suite - , which is used for the used for the manufacturing of 20mg and 100mg of finished thug product Palforzia.

Written procedures are not followed for the storage of components and dnig product Specifically, MO) MWD A.

On March 18' 2025, we observed that material was placed in the incorrect location in the including: Material Name and Batch !Location Assigned iniLocation observed in Number e 00.1 11310) Microcrystalline Powder

There is a failure to thoroughly review any unexplained discrepancy and the failure of a batch or any of its components to meet any of its specifications whether or not the batch has been already distributed.

Specifically, the following was observed: a) Covering the time period of January 2021, to the present, invalid test rates for release testing assays pertaining to Menveo and Bexsero drug substance (DS) and drug product (DP) batches were observed to routinely exceed the firm’s QC trending investigation threshold of) x. ia Within 2023, multiple assays were observed to have invalid rates exceeding _,,, - During review of 2023 data, it was observed that CAPAs were only opened or Menveo (DS & DP) and Bexsero (DS) zm assay (3 CAPAs and Menveo (DS) and Bexsero(DS)) sw ~=—S—S—s=é<C«s~*«‘«C:*«CSWLCSSay (1 CAPA). Innvaalid rates werre observed as high as}. for'~ and we assay. It was observed that no CAPAs were initiated to implement corrective action and prevent future occurrence ofran trending excursions for the following assays observed at over|~ _ invalid rate during| | analysis (this list is not all inclusive). * Menveo (DS & DP) - on conjugated bulks (b)(4)

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

specifically, the following was observed: a) The firm reported over 5500 deviations between January 2021 through December 2023. For 2023, root causes were classified as; “ method,|- |machine, and | manpower (human error). The firm does not assign most deviations as recurrences due to a reported limited definition in| - The firm has not performed analysis of the deviations per related topics, similar root cause, manufacturing production unit, or product to determine if there are clusters of similar deviations that may be recurrences and if there may need to be a general or master deviation or master CAPA to address these similar events. A review of the deviations revealed clusters of deviations under similar topics: | - for equipment;|. _|for HEPA and other filter failures; . —_|for water, wm Sw for training; [- | interventions (including maintenance | gy interventions). The firm has not established CAPA effectiveness checks to determine if corrections to similar events are correcting the issues. b) Deviation UE 201022310, opened on 19 September 2023, was for a failed HEPA filter leak test

Employees engaged in the manufacture and processing of a drug product lack the training required to perform their assigned functions.

Specifically, a) Critical cGMP training and operator qualifications are sometimes lapsed to be expired. The training qualifications are not always managed effectively to prevent gaps or lapses in training for operators who perform critical functions including aseptic operations and visual inspections and to ensure retraining is planned in a timely manner. Expired operator qualifications were

Not all adverse drug experiences that are both serious and unexpected have been reported to FDA within 15 calendar days of initial receipt of the information.

Specifically, a. The firm's pharmacovigilance reporting of adverse drug events in year 2023 listed the following number of events were reported to the agency later than the required time. Vaccine Number of events reported Number of Days Late ate to agency in 2023 1 to 122 The firm reported that some of the events for Shingrix were due to a common social media information event, but this was not defined. No explanation was given to why other adverse events were reported late or to the extent of number of days. b. The following additional vaccine adverse events were reported to the agency later than the 30- day requirement. Number of events reported (Number of Days Late ate to agency in 2023

Established laboratory control mechanisms are not followed.

Specifically, the following was observed: e While observing QC release testing pertaining to the Menveo Full Liquid (DP) Quantitative determination of se on bos assay for batches | we | ww on 01/18/2024, it was observed that testing analyst = |did not lock|~ _|laptop workstation utilized to record the assay within|- _|on multiple occasions when leaving ~ |workbench while conducting the assay. This activity does not follow firm procedure QC LSOP 9000054316 v10 “Good practices for computerized lab system” part 4.2 stating) - e While observing QC release testing pertaining to Bexsero (DS) Quantitative Determinations of wo inae aa on 01/19/2024, it was observed that testing analyst |= | did not lock!~ _|laptop workstation utilized to record the assay within|-_| when leaving '~_|workbench while conducting the assay. This activity does not follow firm procedure QC LSOP 9000054316 v10 “Good practices for computerized lab system” part 4.2 stating)=

An MDR report was not submitted within 30 days of receiving or otherwise becoming aware of information that reasonably suggests that a marketed device has malfunctioned and would be likely to cause or contribute to a death or serious injury if the malfunction were to recur.

Specifically, You received multiple customer complaints that reasonably suggest MDR reportable events where a device malfunction likely occurred. For example, at least two (2) False Positive Customer Complaints (Cases: 2021-01270852, 2022- 01583216) ofan Rh mistype, and an Rh C mistype (Case 2022-01867083). Also, there were multiple False Negative results for which various antigens were mistyped. For example, an anti-E (Rh3) provided a false negative (Customer Complaint # WO000283663).

Failure to submit a biological deviation report.

Specifically, A. Customer complaint numbers, 1. WO-00333475, received on 11/8/2022, stated that unopened vials, Ref. 210532 Anti-Fyb

Risk analysis is inadequate and is incomplete.

Specifically, Your (6)(4) , Appendix 1, (6)(4y- 4), Version 16, Effective 02/02/2018, documents your firm’s risk analysis in the (6)4y Use of (b) (4) . However, your (6)(4)§)} Process does not include risk assessments for your (6)K4) used to generate Blood Grouping Reagents (BGRs) and Anti- Human Globulin (AHG) antibodies, (6)4) of your firm’s BGR and AHG (64) including (b) (4) , which your firm uses to (6)K4) in ©) of (6)K4) (b) (4) in Site that requires (6)(4) processes. Additionally, your firm has not established a Design Risk Analysis for your firm’s BGRs, AHG, and

Procedures for the control of storage areas and stock rooms have not been adequately established.

Specifically, You have not defined proper temperature excursion procedures and what is an acceptable and unacceptable departure from acceptable storage temperatures. Your (6/4) located at Site % used to store blood grouping reagents and reagent red blood cells had a temperature excursion (B)(4)) degrees Celsius on September 5, 2023 and January 1, 2024. You did not initiate a non-conformance or document any action(s) taken due to the temperature being out of an acceptable range for more than (6)(4) ' Your procedure "Use/Verification of Temperature Loggers, Alarm Probes and Thermobuttons" does not establish the (6)(4) out-of-range acceptability. Currently, you have no procedure that defines when action or documentation should be initiated when the temperature of the (6)(4) deviates from its defined acceptable range.

The written MDR procedure does not include documentation and recordkeeping requirements for all information that was evaluated to determine if an event was reportable.

In-process inspections, tests, or other verification activities and approvals were not documented.

Specifically, On 04/12/2024, your firm formulated a batch offpy4yy of Anti-D Blood Grouping Reagent (Catalog No. (649); Lot 734000) to be processed into )@ kits @@cassettes ofml) of finished Anti-D BGR for automated systems for the U.S. market. During an in-process formulation quality control check for pH, your firm’s formulation technician §@%) measured the pH twice, discarding the paper record of the first pH measurement into biohazardous waste without retaining the pH measurement paper record and

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

Although your firm's Quality Unit approved a written procedure, SOP-11058.33, entitled “Nonconformance Reporting," effective August 9, 2025, which defines the nonconformance management process, investigation, assessment of impact, determination of root cause, implementation of corrections, identification of corrective actions, documentation, and reporting of process nonconformities, your firm failed to thoroughly investigate the following: a) Non-conformance NC-2025-0053, initiated on May 23, 2025, investigated the visual inspection failure of final product bags with lot number (b) (4) the final product bags from this lot did not meet the required visual inspection criteria: (b) (4) units contained embedded particulates on the product (b) (4) surface, and | (B) (4) units contained embedded particulates on the (b) (4) product (b) (4) surface. Despite these findings, the lot was approved for use by Supplier Quality Assurance (SQA). This lot was subsequently used in the manufacturing of __ final product batches of Sipuleucel-T and remains the current lot in use for finished product. a ; . 4 4 b) For critical material, (b) (4) , Lot # (b) (4) were rejected during the ex packaging opera

Laboratory records do not include the initials or signature of a second person showing that the original records have been reviewed for accuracy.

Your firm's test method, (b) (4) entitled (b) (4) effective June 29, 2022, for Sipuleucel-T release lacks adequate independent verification of microbial contamination results. The procedure _reauires () (4) (b) (4) entitled “(b) (4) ” effective March 10, 2026, no microscopic examinationof(b) (4) by QC reviewers. On March 19, 2026, this was confirmed when an analyst performed (b) (4) for batches (b) (4) and (b) (4) , and a (b) (4) analyst stated reviewers verify only (b) (4) . This test is used for product release before final sterility testing is completed.

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

‘ 4 : ” ; ss 1. Your written procedures mre 1100448.13, entitled, “Cleaning of the ISO Classified and CNC Areas at the Seal Beach Facility,” effective July 19, 2025, and (©) 400168. 12, entitled “Cleanroom Behavior at the...Manufacturing Facilities,” effective May 23, 2024, are inadequate in that they lack detailed instructions to prevent contamination of sterile biological drug products and to perform aseptic manufacturing and cleaning of classified areas. The following deficiencies were observed during manufacturing activities for Sipuleucel-T: A. On March 18, 2026, we observed the following deficiencies during the culture bag filling operation of a Sipuleucel-T, Day processing for batch (D) (4) at workstation ™®

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

A. Your firm uses a contract manufacturer to (b) (4) (b) (4) of your (b) (4) . Your firm’s quality control unit does not ensure that the final visual inspection for the ©) solution is completed and acceptable for release. For example, your quality control unit did not document the reason for rejection provided by the contract manufacturer for the following and did not conduct investigations of the rejections. Your contract manufacturer rejected the following: 1. (b) (4) rejected (b) (approximately 16% total batch) 2. (b) (4) rejected (©) @approximately 8% of total batch) 3: (b) (4) rejected (>) approximately 30% of total batch) 4. (b) (4) rejected ©) approximately 99% of total batch) 5. (b) (4) rejected ©) @)(approximately 34% of total batch) B. Your firm uses a (b) (4) with (b) (4) solution for manufacturing of your (b) (4) . The information for use (71500870 AF V:6 09/2020) states “the products are intended for (b) (4)

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

Electronic records are used, but they do not meet requirements to ensure that they are trustworthy, reliable and generally equivalent to paper records. A. On March 17, 2026, it was observed that the workstation used in the manufacturing process have a (b) (4) to document in the electronic batch record for Sipuleucel-T manufacturing (Master Batch record number (D) (4). The (b) (4) make it potentially impossible to identify the employee that performed each step during manufacturing. Additionally, the Manager for Manufacturing Operations explained that (5) (4) verifier can assist © workstations simultaneously performing manufacturing operations for Sipuleucel-T. B. The (b) (4) batch record does not contain detailed documentation describing the reason (b) (4)are rejected during filling and capping. For example: 1, (b) (4) had (b) (4) rejected due to “volume filling error,” the batch record does not describe what the reason for the error was or how the error occurred. 2. (b) (4) haa (b) (4) rejected due to “volume filling error,” the batch record does not describe what the reason for the error was or how the error occurred. 3. (b) (4) haa (b) (4) rejected due to “volume filling error,”

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

Specifically, since February 2024, your firm has manufactured (b) (4) and (b) (4) in house. A comparison study was conducted to demonstrate the comparability between your in-house manufacturing process and the prior contract manufacturer’s process. Your current manufacturing process significantly differs from the contract manufacturer’s process in the following parameters: 1. Lot Size ll. Mixing Conditions Ill. Hold times IV. Elimination of (DB) (4) step a V. Filling Environment ISO “to ISO # VI. Method of (8) (4) sterilization VII. Different() (4) Composition The manufacturing validation and comparability study did not fully address the impact of the changes above. Your firm did not ensure the reproducibility and effectiveness of the manufacture of the (b) (4) solutions, (b) (4) . Your (b) (4) are a critical component in your Sipuleucel-T manufacturing process as they are used to (b) (4) the target cells. Since February 2024, your firm has manufactured approximately (b) (4) of (b) (4) and approximately

Drug product (b) (4) are (b) (4) so as to alter the safety, identity, strength, quality, and purity of the drug beyond the official or established requirements.

Specifically, since February 2024, your firm started using (b) (4) for the in-house manufacturing of (b) (4) instead of (B) (4) (b) (4) which were used by the CMO’s formulation. However, your stability study with (b) (4) in the (B) (4) position does not evaluate potential leachable, extractables, and seal integrity or if the formulation degrades when in direct, long-term contact with the (b) (4) or over time.

Employees engaged in the manufacture, processing and packing of a drug product lack the experience required to perform their assigned functions.

Your firm's quality unit approved written procedure, SOP-10046.20, entitled "General Visual Inspection," effective June 13, 2025, outlines the training and qualification requirements for personnel performing visual inspections. The quality unit failed to provide documents and demonstrate visual inspection test kits or library of defective samples as part of visual inspection training for employees performing 100% visual inspection. Furthermore, your firm relies on visual inspection to ensure the following materials do not contain particulates and are acceptable for use in manufacturing of your Sipuleucel-T drug product: 1;(b) (4 3: 4.

Reprocessing was performed without the review and approval of the quality control unit.

Specifically, employees engaging in the manufacturing operation of your (b) (4) determines whether ashould be reprocessed during packaging operations. Reprocessing can occur because of (b) (4) , (b) (4) , or incorrect color () (4), Furthermore, your firm does not have a written procedure for reprocess or rework. For example: a) (b) (4) Lot # (b) (4) had (b) (4) reprocessed inline during the packaging operation. b) (b) (4) Lot # (b) (4) had (b) (4) reprocessed inline during the packaging operation. c) (b) (4) Lot # (b) (4) had (b) (4) reprocessed inline during the packaging operation. = There is no quality unit oversight for approval of reprocessing of the ae

Laboratory controls do not include the establishment of scientifically sound and appropriate specifications and test procedures designed to assure that components and raw materials conform to appropriate standards of identity.

Specifically, A.Laboratory control procedures are not followed: -During review of electronic data for m@ USP API, we observed multiple unreported sample injections prior to or after the official reported sample injections for Related Substances and Assay by HPLC testing that were not documented in laboratory batch records. API batches involved ; - o@ included batch numbers . Batches oe were approved by QA and shipped to the U.S. market. -During the current inspection we requested your firm to perform calculations for all unreported Related Substances and Assay injections, where at least one batch, @@ revealed an unreported injection with an OOS result. Specifically, on 12/20/2024, your analyst injected a blank and single injection for sample @@ , with calculations during the current inspection resulting in OOS for assay, with calculated result as@@ % versus specification ofm@ %. The official reported result documented in your laboratory batch records for m@ was performed on 12/22/2024, with reported result asy@ %. This batch was shipped to the U.S. Market.

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 has failed to establish adequate process validation and production control procedures. Your process validation for @@ USP API and key starting materials does not accurately reflect actual manufacturing, making production non-replicable. A.Your firm’s process validation does not clearly identify the batch records used, their execution sequence, or how records are@m@ during the manufacture ofm@ USP API anda@ 0) , a key starting material. For example, each m@ USP API batch produced following m@ manufacture was o@ a practice not addressed in the process validation documentation. In addition, production occurs through the m@ @) execution of@ batch records—manufacture of oe oe however, this approach was not addressed in the process validation.

Batch production and control records do not include complete information relating to the production and control of each batch.

Specifically, A.Your firm fails to maintain accurate and consistent cleaning logs and batch records, demonstrating significant data integrity deficiencies in the documentation ofy@ 001 cleaning and 0) ofme USP API @@ batches form@ Review of the following batch

Procedures for the cleaning and maintenance of equipment and its release for use in the manufacture of intermediates and API are deficient regarding sufficient detail of the methods, equipment, and materials used in the cleaning and maintenance operation, and the methods of disassembly and reassembly of equipment as necessary to assure proper cleaning and maintenance.

Specifically, A.Your firm has not performed cleaning validation studies to address microbiological and residue contamination for processes where such contamination could be of concern during manufacture of 0) Equipment used in the manufacture ofw@ USP API includes Cleaning procedures for equipment used to manufacture o@ USP API for the U.S. market lack adequate detail and do not reflect actual practices. Your firm's cleaning procedures and batch records do not specify cleaning methods or techniques, materials used, contact times, acceptance criteria, or verification requirements. For example, while the cleaning SOPs for the m@ indicate that mw water/solvent is used for cleaning, the firm stated that they use onlym@ water for all equipment cleaning, without differentiation by product, batch, or stage of manufacture. The firm confirmed that the specific type of solvent is not documented in any procedure and that operators determine which solvents to use based on memory. An undocumented exception to the use ofm@ water for cleaning was identified for equipment »@ 1, which is cleaned with@ during processing. Per your firm's Production in Charge, during Step® of production for batches O@

Drug products do not bear an expiration date determined by appropriate stability data to assure they meet applicable standards of identity, strength, quality and purity at the time of use.

Specifically, A.Stability study reports provided during the inspection in support of»@ USP API do not adequately support the statedw@ shelf life/expiry date. During our review of your completed long-term 2015 stability study reports and recorded results, we observed that your firm did not have supporting raw test data, both electronic and physical laboratory batch records, for stated results for the long-terme@ stability study. Furthermore, the current ongoing long-term

There is a failure to thoroughly review any unexplained discrepancy and the failure of a batch or any of its components to meet any of its specifications whether or not the batch has been already distributed.

Specifically, A.Complaint CMe@@ 002/25 was received via email on January 16, 2025, from a customer regarding an out-of-specification (OOS) result for an unspecified impurity in the Related Substances by HPLC test during analysis of ©® ~~ intermediate, batch numbero@ @@ Your firm's investigation, documented in CM@@ /002/25 dated January 16, 2025, determined that your firm did not use the specified column required by the customer, despite the Method of Analysis (MOA) requiring use of that column or equivalent. The CAPA included your firm

The accuracy, sensitivity, specificity and reproducibility of test methods have not been established and documented.

Specifically, Your firm has not established or documented method verification studies for the USP compendial assay and residual solvent test methods used for m@ USP API. The methods lack

Buildings used in the holding of active pharmaceutical ingredient do not have the suitable construction to facilitate cleaning, maintenance, and proper operations.

Specifically, During our walkthrough of the production area on January 19, 2026, we observed multiple deficiencies withe @ equipment and surrounding areas where m@ API is manufactured. Equipment and piping located on and above m@ where product material is H@ showed visible rust. M@ identified as clean or in operation had missing or removed bolts scattered around or placed on top of theq@ .-Am@ and hose assembly used to transfer product from the m@ 0 to theme was held together with tape and metal wiring. Plastic tarps positioned below the m@ to catch material during m@ operations were visibly soiled. These conditions demonstrate inadequate equipment maintenance and cleaning practices that present a risk of contamination to the API.

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

Failure to ensure training is regularly conducted by qualified individuals and covers, at a minimum, the particular operations that each employee performs and CGMP as they relate to the employee’s functions.

Specifically, Your firm failed to ensure that personnel involved in drug manufacture operations were adequately trained. Per your firm's QA Executive, induction and@@ _training were not consistently performed, as outlined in your training procedure. For example, operators performing »@ operations for 0) USP API batchese@ lacked documented training for the

Written production and process control procedures are not followed in the execution of production and process control functions.

Specifically, A. Your firm failed to follow written procedure, ‘BOS-SOP-0249, Aseptic Sampling Technique’ which states for(b) (4) samples using (b) (4) the samples are to be taken from sufficient locations to obtain(b) (4) . In addition, the procedure states to (b) (4) . On 04/02/2026, we observed a Manufacturing Associate, and a Manufacturing Supervisor obtain (b) (4) for (b) (4) Bulk Powder batch # (b) (4) During discussion of the sampling technique, the operators referred to section 8.4 of the procedure on obtaining (b) (4) using (b) (4) however we observed the operator only obtain (b) (4) _ from the (b) (4) , into the IBC (Intermediate Bulk Container). Your firm failed to provide adequate justification for not following your procedure on taking a work-in progress / in-process (b) (4) of(b) (4) Bulk Powder batch # (b) (4) at sufficient locations to obtain (b) (4) of the bulk powder within the IBC. B. Your firm failed to follow your written procedure ‘SOP-BST-000043, DIA Data Integrity and Security’, which states the use of generic accounts is prohibited. During review of previous (b) (4) tests performed on the (b) (4) instrument, Asset ID: Sys-0084, multiple instances of a manuf

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

Specifically, laboratory investigations into aberrant or Out of Specification (OOS) results were not conducted thoroughly to identify root cause(s). Investigations failed to identify potential sources of the OOS results and insufficient justifications were provided to explain the observed aberrant test results. For example, laboratory OOS investigation #02LINV-166 was initiated for observed (b) (4) assay value of 112.5%, outside the specification limit of(b) (4) %. Retesting performed by (b) (4) , ©) @) reported (b) (4) values of 96.0% and 102.1%. The laboratory OOS investigations did not identify potential root causes for the initial OOS result and no justifications were provided for the high (~6%) testing variabilities observed during the retesting by the (b) (4) . As no root cause(s) were identified, no CAPAs were implemented to prevent reoccurrence.

Laboratory records do not include a complete record of all data secured in the course of each test, including all charts and spectra from laboratory instrumentation, properly identified to show the.

Specifically, generated electronic data from your (b) (4) laboratory instruments are not controlled to ensure security and integrity. For example, A.Original electronic data stored on the (b) (4) of the (b) (4) instrument was able to be modified and deleted with the Windows File Explorer. During the data integrity demonstrations on the instrument computer, analytical data file names for previously analyzed samples were able to be modified with the Windows File Explorer. Additionally, the demonstrations revealed original data files could be deleted from the instrument file folders by the manager level users. Deleted files were recovered in the system Recycle Bin and restored. As per the site management, the instrument software ‘(b) (4) ” was identified as 21 CFR Part-11 Compliant. Bb) (4) Analyzer instrument (b) (4) was not configured to maintain security and integrity of the generated electronic data. Electronic data on the instrument computer was not restricted to prevent modifications and the

Failure to maintain a backup file of data entered into the computer or related system.

Specifically (b) (4) system backup of electronic data from the (b) (4) UV-VIS Spectrophotometer was not executed for paces and the firm’s IT group failed to take corrective actions for the identified data backup failures, as defined in the written procedure. According to the system logs, the last successful (6) (4) data backup was executed on March 30, 2026. At time of the facility walkthrough on April 8, 2026, the instrument computer was observed to have been powered off, in contrary to the label on the instrument, “DO NOT TURN OFF THIS COMPUTER”.

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, the(b) (4) Microbial Limits/Bioburden testing procedure do not contain sufficient control to ensure (b) (4) have reached the required (b) (4) , prior to use. There are no defined methods to identify the (b) (4) of the (b) (4) and insufficient controls to ensure sufficient (b) (4) . Exceeding the (b) (4) requirements could destroy/attenuate the microorganisms on test, resulting in reduced or false negative test results.

Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to aseptic processing of drug products.

Specifically, A.Your firm repackages sterile (b) (4) drug product(b) (4) , in an unclassified office environment using a (6) (4) laminar airflow hood. The area lacks appropriate cleanroom classifications (e.g., ISO 5 conditions), and your firm has not demonstrated that aseptic conditions are maintained during processing. Further, the laminar airflow hood used during repackaging has not been qualified, certified, or routinely maintained. Your firm has no documentation demonstrating that the hood provides adequate HEPA filtration or unidirectional airflow. B.Your firm does not perform viable or non-viable environmental monitoring, surface sampling, or personnel monitoring in areas where sterile drug products are repackaged. Your firm lacks data to demonstrate control of the aseptic processing environment. These conditions create a significant risk of contamination of drug products intended to be sterile.

Testing and release of drug product for distribution do not include appropriate laboratory determination of satisfactory conformance to the final specifications prior to release.

The identity of each component of a drug product is not verified by conducting at least one test to verify the identity, using specific identity tests if they exist.

Specifically, Your firm receives sterile drug product, (b) (4) , from a compounding pharmacy and repackages them without performing identity testing. Your firm also fails to obtain or review Certificate of Analysis (COAs) to verify the identity, strength, quality, and purity of the received drug products.

There is no quality control unit.

Specifically, Your firm has not been effective in carrying out its duties of ensuring drug product purported to be sterile are manufactured in accordance with current good manufacturing practices (CGMP) to ensure safety, efficacy, purity, and overall quality at your firm. This is evident by the following deficiencies: A. Failure to qualify the following vendors

There is no quality control unit.

Specifically, Your quality control unit has not been effectively carrying out its duties to ensure that drug products are manufactured in accordance with current good manufacturing practices (CGMP). Since January 2025 your firm has released and distributed about batches of (b) (4) , under the following conditions: a. The Quality Control Manager performs and approves all laboratory tests without independent review. The testing and batch release approval executed by the same individual, which represents a lack of segregation of duties in the quality control process. b. Your firm has not qualified or validated its manufacturing equipment, including the (b) (4) system, the blending tank for finished product bulk blend, and the storage tank for product storage and transfer to packaging. c.The labels for the product (b) (4) are not reviewed by Quality Control. There is no inventory of drug labels used in production. Drug labels are used and returned without any type of accountability, documentation or record keeping. There is no oversight for potential discrepancies.

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

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.

Testing and release of drug product for distribution do not include appropriate laboratory determination of satisfactory conformance to the identity and strength of each active ingredient prior to release.

Specifically, a. Potency is not performed on the finished product (b) (4) . Potency is performed on the bulk blend before it is transferred into the (b) (4), packaged and distributed. b. Raw materials used in the manufacture of finished product are not tested for identification, and the active ingredient, (b) (4) , is not tested for potency.

There is a failure to thoroughly review any unexplained discrepancy whether or not the batch has been already distributed.

Specifically, Your firm's investigations of deviations are not always adequate. a. Quality Event QE-239020 was initiated 16NOV2025 following the identification of foreign particles ile@ batches ofmw tablets. Analytical characterization identified the particles as containing (b)@) Your investigation proposed the potential source as excipient/API @@ —«material). The following batches were affected: Strength | Batch Expiration Quantity of Quantity of Quantity of Tablets Date oe tablets ©) (4) Tablets manufactured found with foreign Inspected &)@) R S, bytownss

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

Specifically, Your firm's CAPA system is not always adequate to ensure deviations have appropriate measures implemented to prevent recurrence. During the manufacturing ofm@ mg tablets, Batch m@ o@ ,QTY:@@ tablets, EXP: m@ , manufactured from m@ through OX) , IN-process appearance testing revealed four tablets containing foreign particulate matter. This was from the inspection ofm@ tablets. Laboratory analysis identified the contaminant as@@ _ _. Quality Event QE-239020 was initiated 16NOV2025, and your investigation attributed the defect to a worn tablet press. However, the preventative maintenance program was not updated to address the equipment wear condition that caused this deviation.

Equipment used in the manufacture and processing of a drug substance shall be suitably located to facilitate operations for its intended use.

Specifically, During the inspection, 4) 4)batch @ a for batch § failed to meet the well-controlled critical process parameter (WC-CPP) 9, 4) ofw@ due to the firm not havingo@ units in order to perform the unit operation. The firm opened up deviation 22-016 to investigate the root cause. The deviation investigation is ongoing and the impact on product quality is being assessed.

Material Management is inadequate.

Specifically, the supplier of critical process equipment ®@ that are needed to performo@® essential unit operations, did not deliver the promised number of gy _in your purchase order in December 2021 and missed several agreed upon delivery dates in January 2022 resulting in deviation 22-016.

Written records of investigations into unexplained discrepancies do not always include conclusions and follow-up which are adequately justified.

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

Specifically, A. Investigations do not always include complete data derived from all tests necessary to assure compliance with established specifications and standards. During review of laboratory data, we observed multiple sequences where interrupted sample injections were injected and showed that the sample did not run, instead showing “Data Incomplete”. Your firm was not aware that data from these injections are retrievable. Samples injected were not documented to be performed, in order to determine whether the samples injected had any discrepancies or appeared to be out of trend. This discrepancy in your firm’s ability to retrieve, review and investigate all electronic raw data is a gap in your Data Integrity system. B. QC Review of chromatographic and non-chromatographic electronic raw data generated by analysts in the QC laboratory is not adequate. QC technicians responsible for electronic data review do no perform a comprehensive review of all potential electronic data generated for all test items in your stand alone and network softwares. C. Your firm has identified Research and Development laboratory stand alone equipment as back-up testing equipment for QC analysts. There

Drug Substance filling is inadequate.

Specifically, we observed drug substance bottles filled at a rate which caused splashing and extensive 4 ») 4) The nature of the®® have not been characterized to date.

havens cleaning is inadequate.

Specifically, a discoloration in the Oa _was observed during the walk through of the downstream operations. The nature of the discoloration is unknown at this time.

Cell Bank Storage is inadequate.

Specifically, all master cell bank and working cell bank vials are located in a single location, room wwe in the manufacturing building.

a) The instructions to add antifoam in the production bioreactor are unclear and open to operator interpretation.

Anti-foam addition has varied gq) across batches in 2021. b) The instructions to sequentially add g) 4 during ow oa are unclear and not specified in the batch record.

Class D area cleaning is inadequate.

Specifically, ag)4 area used to movew@ between®@® in the manufacturing facility had debris on the floor. 4.

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, This is a REPEAT OBSERVATION from the inspection conducted 10/22/2018 to 10/26/2018. Unqualified and Undefined: When Process Validation Fails to Deliver During a regulatory compliance review of your validation program on 05/13/2025, your Quality Unit provided several process validation (PV) reports for the following OTC m@ drug products: oO While reviewing the reports, several critical quality failures demonstrate the inadequate of your validation program for OTC m@ drugs. Issues identified include

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

Specifically, This is a REPEAT OBSERVATION from the inspection conducted 10/22/2018 to 10/26/2018. Your firm neglected to adequately clean and maintain non-dedicated equipment used for manufacturing over-the-counter a@ drug products. Elevated Risk of Cross-Contamination On 05/12/2025, I conducted an extensive inspection ofyour @@ tank 11 and@w filler m@ equipment previously used by your Production Manager during the cleaning validation of lot m@ for oe on 03/27/2025. Since then, your Production Manager confirmed that these equipment have not been used to make any commercial products. Given the current state of

Batch production and control records do not include complete information relating to the production and control of each batch.

Specifically, Batch production and control records for OTC @@ drug products lack essential CGMP requirements necessary for process reproducibility. Additionally, your quality unit uses non-validated Excel spreadsheets to make changes for all master batch records. Missing Paper Trail: When »@ Sanitization Goes Unverified On 05/14/2025, while reviewing batch record of lot ©@ , your Production Manager detailed that »@ sanitization had been carried out before operating m@ tank Tandww filler 3. To explain how the filler’s attached tubing is sanitized, a written justification narrative was provided outlining the sanitization process for filleim@ Referring to the batch record, there are no supporting documents to corroborate that m@ sanitization was performed contemporaneously prior to using any production equipment. Compliance in Question: When Cleaning Guidelines Lack Clarity The cleaning and sanitization form (VC-025) lacks explicit directives regarding equipment disassembly. It instructs production staff to dismantlea@ utensils, »@ pipes, gaskets, m@ andM@ “if necessary” but fails to define the conditions requiring disassembly. Without clear criteria, your production team cannot relia

The written stability testing program is not followed.

Specifically, This is a REPEAT VERBAL OBSERVATION from the inspection conducted 10/22/2018 to 10/26/2018. Customer Satisfaction Over Compliance: Stability Testing Vanished Your firm’s stability program (VC-SOP-Q-303.2) states that once long-term data confirms a product’s shelf life, one lot each year is selected for continuous stability testing. Despite this requirement, your Quality Unit prioritized customer satisfaction over fulfilling regulatory compliance, which led to the omission of the required stability testing for every marketed OTC m@ product since 2023. Examples of the commercial batches were reviewed with your quality unit to identify which timepoints your contract laboratory had last completed. OC)

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

Written records of investigations into unexplained discrepancies do not always include the conclusions and follow-up.

Specifically, Your investigations into elevated microbial counts for the »@ samples lacked sufficient root

Procedures to control environmental conditions have not been adequately established.

Specifically, e Cleanroom specifications have not been adequately established. For example, e Specification for maximum surface viable or airborne viable contaminants are not adequately established. Per Bioburden Monitoring of Kalamazoo Cleanroom CR006K- WI Rev 01 08/17/2024 page 9 section 8.4.6, a limit ofMMMMMJ CFU is not to be exceeded. However, your firm does not have an adequate justification for the upper limit of CFU. Per Quality Inspection Requirements MN Prod Family QIR ev D 01/07/2025 page 15, each product has a pre-sterilization bioburden alert t ofal CFU and action limit ofWicru. The(b) (4) _ product family is manufactured within the cleanroom. e Specification for minimum positive pressure has not been established in| ontrolled

Procedures for corrective and preventive action have not been adequately established.

Specifically, e Corrective and preventive actions are not initiated in accordance with established procedures. Per 13 Corrective and Preventive Actions Rev 19 08/14/2025, page 4, section 2.2, review of nonconformance records can result in a decision of corrective action required; when the nonconformance evaluation indicates a recurring or systemic issue, a new CAPA will be initiated and linked to the nonconformance. Per 12 Control of Non-conforming product Rev 27 11/07/2025 page 3 section 3.2, a risk assessment to determine the need for generating a corrective action is performed b , then a Corrective Action 1s required.

Schedules for the adjustment, cleaning, and other maintenance ofequipment have not been adequately established.

Specifically, e The preventive maintenance for the equipment is not adequately established. Per Total Preventive Maintenance Form 1154 Rev A 08/16/2023 the sealer has (b) (4) maintenance tasks related to mspections for damage to equipment and equipment cleaning and(b) (4) maintenance tasks of inspections for damage to electrical cables and power adaptors. However, per Owner’s Manual pages 35 — 36, maintenance activities should include checks for the filter /regulator system and draining ofPD water and as well as periodic checks for tightness of screws, nuts and bolts to the sealing chamber, tools, and platens. Your firm does not have adequate rationale for why these preventive maintenance activities were not established in the preventive maintenance schedule for the equipment. e The 2) equipment was not installed in accordance with manufacturer requirements. Per tallation Qualificationi Rev A 06/15/2023 page 1, the equipment is installed with electrical requirements established as(b) (4) VAC, iheBPhase, Ml Amp.

The inspection or other activities necessary for ensuring that purchased product meets specified purchasing requirements were not adequately established and implemented.

Specifically, incoming inspections are not consistently performed in accordance with the established AQL sampling plan, as described in procedures #SP-28-01, "Receiving Inspection", and #WI-SP-28-01, "Inspection and AQL Sampling Plan". For example, * Hydratherm Deluxe: Sampling Plan: a Sample size : were (b)4) sampled (out ofra * O2 Concentrators: Sampling Plan: »« Sample size = aw Sse sampled (out of fois)

A process whose results cannot be fully verified by subsequent inspection and test has not been adequately validated according to established procedures.

Specifically, change request CR.24.S0.027 was opened to change the nitrogen line and regulator to a PSV and reduce the nitrogen pressure from ~——SSS_—sin thee sterilization chambers. The Chamber 4 CR.24.80.027, Chamber 5 Nitrogen Flow Control document, Section 6.1, Chamber 5 Nitrogen Flow, states " - The calculated pressure change was 47.2 mB/min. which wasa failing result. No work was done to rectify the nitrogen flowrate.

Corrective and preventive action activities and/or results have not been adequately documented.

Specifical corrective action CA-8134, opened due to|- | customer loads impacted as a result of the temperature within the aeration room falling below the minimum temperature for more than 30 minutes. Two root causes have been identified as part of the CAPA Investigation. They are “Equipment” due to the failure of the Air Handling

Procedures for management review have not been adequately established.

Specifically, the Management Review Procedure, STG-WI-1470, Section B, Facility Management Review Meeting states under 2.a, For facility/laboratory management review, facility/laboratory managers/supervisors must be present. The management review conducted 9/27/2024, covering the period from 1/1/2024 through 6/1/2024 only had four people present, the Production Manager, General Manager, EHS Manager, and Laboratory Manager. The QA Manager, Customer Service Manager, and Maintenance Managers were not present.

Outsourced processes that affect product conformity to requirements were not adequately monitored and controlled.

Specifically, your firm did not conduct an adequate evaluation of your contract manufacturer for the CardiaMend device to ensure control. The acceptance of the supplier's own internal audit report as a substitute for an audit was not adequately justified, and did not evaluate critical controls such as performance against your established Quality Agreement. Your procedure, SOP004 "Supplier Management," Section 5.2.9 and Attachment 1 requires an ((D) (4) (6) (4)as part of the Initial Evaluation for a Major supplier.

There is a failure to thoroughly review any unexplained discrepancy and the failure of a batch or any of its components to meet any of its specifications whether or not the batch has been already distributed.

Specifically, your firm failed to adequately investigate recurring stability failures for (Bb) (4) (b) (4) Capsules (©) 4) under (b) (4) stability conditions and did not fully characterize the unknown impurity causing the failures. For example, (B) (4) Capsules (©) (4) lot (b) (4) had stability failures under (b) (4) conditions (b) (4) ) between April 2025 and July 2025. At (b) (4) ) (b) (4) conditions, this lot exhibited assay degradation to 89.8% (below the (>) (4) specification), as documented in Incident Report (IR): IR-25-042. At (b) (4) ) accelerated conditions, this lot exhibited assay degradation to 88.7% (below the () (4) specification), as documented in Incident Report (IR): IR-25-077 and this lot was found to be OOS for unknown impurity (RRT 0.5 minutes), and total impurity limit (NMT (®) (4), as documented in IR-25-080. Additionally, (b) (4) Capsules (©) @) Jot (b) (4) exhibited an assay OOS failure (88.2%) at the(b) (4) (IR- 25-077) and an unknown impurity and total impurity OOS at the (BD) (4) timepoint (IR-25-080). Your firm's investigations remain incomplete as the unknown impurity has not been fully characterized, or toxicologically qualified.

The written stability testing program is not followed.

Batch production and control records do not include complete information relating to the production and control of each batch.

Buildings used in the holding of a drug product are not maintained in a good state of repair.

Specifically, your firm failed to adequately maintain critical HVAC equipment supporting GMP storage areas.

There is no quality unit.

Specifically, Your firm has not established, documented, or implemented an effective quality management system and current good manufacturing practice (CGMP) that involves the active participation of management, quality, and appropriate manufacturing personnel. Your firm's quality unit lacks sufficient resources to carry out its responsibilities and consistently ensure medical gas quality. For example: A. Your firm has not designated any personnel to serve in quality assurance roles. B. Your firm failed to establish written procedures that define the roles, responsibilities, and procedures of quality unit personnel. It was observed on batch records that the filler, tester, and product release approver were the same person, demonstrating a lack of independent verification and segregation of duties, as shown on batch records dated (b) (4) dot (©) (4)) (b) (4) dots (b) (4) ). () (4) Coil) (4)). (1b) (4) dots (fb) (4) . (b) (4)). and (b) (4) (lots (b) (4) ). Your firm distributed these lots to customers. C. Your firm failed to provide cGMP training to employees involved in cGMP manufacturing and failed to establish a standard operating procedure (SOP) for training management. D. Your f

Batch production records do not include documentation that each significant step in the packaging of the medical gas was performed.

Specifically, Source bulk() (4) lot numbers were not recorded on batch records dated (b) (4) (lots(b) (4) (lots (b) (4) ), and (b) (4) (lots (b) (4) ). These lots were distributed to customers.

The quality unit failed to review and approve manufacturing production and control records, including those for packaging and labeling, to determine compliance with all established, approved written procedures before batches were released or distributed.

Specifically, The product release approver signature line was blank on batch records dated (b) (4) (lots (b) (4) ), and the batches were released without any documented approval. These lots were distributed to customers.

Your firm failed to perform required tests on bulk medical(b) (4) USP received for production.

Specifically, No testing was performed on any bulk lot of medical (6) (4) USP received from your supplier. Your firm has not established and maintained a program to ensure the reliability of the supplier's capabilities through appropriate assessment and testing procedures.

Your firm failed to establish a written program designed to ensure proper performance of automatic, mechanical, and electronic equipment used to produce medical (b) (4) Specifically, The new (b) (4) equipment (Db) (4) Pumping System) used for production and the (DB) (4) used for testing lack a written program to ensure proper performance and maintenance.

Your firm uses this equipment to fill and test medical () (4)gas distributed to customers. Tenothy HVo » 4 Bae Sigted: 04 022026 11:02:21

Laboratory controls do not include the establishment of scientifically sound and appropriate sampling plans designed to assure that in-process materials and drug products conform to appropriate standards of identity, strength, quality and purity.

Specifically, your firm’s sampling plan is inadequate for bulk drug product and in-process materials. For example, A. Bulk batch sizes range from approximately(b) (4) to (b) (4) pounds; however, sampling is limited to ©) @locations ((b) (4) of the tank), with (b) (4) samples collected. Your firm does not sample from the (b) (4) of the tank, and therefore does not ensure that samples are representative of the entire batch. Bulk (b) (4) batch (b) (4) consisted of approximately (b) (4) pounds of product and was sampled from only the (b) (4) of the mixing tank using a sample collection (b) (4) — method). This approach does not adequately assess content uniformity throughout the batch, particularly in the (b) (4) portion of the tank. Additionally, for microbiological testing, a (b) (4) is collected from (b) (4)the (b) (4) of the tank. Your firm did not provide scientific justification for this limited sampling approach or for the reduced sample size relative to chemical and analytical testing.

Drug products are not stored under appropriate conditions of temperature, humidity and light so that their identity, strength, quality, and purity are not affected.

Specifically, your firm failed to adequately evaluate, test, or control returned drug products to ensure product quality. Your firm’s procedure for accepting returned products does not include analytical, chemical, or microbiological testing, nor does it assess or verify the environmental or storage conditions in which the product was exposed while outside your control. For example, your firm shipped batch (b) (4) — ot(b) (4) on(b) (4) _ and(b) (4) and subsequently received a return ofcases on 01/07/2026. During this period, the product was outside your control, and your firm has no assurance that appropriate storage conditions were maintained. Despite this, the returned product was inspected in accordance with WIS-QAM-1018, ©) @ RGA Inspection Type Z18, effective date 3/30/22, revision 06, and released back into inventory for distribution. In 2025 your firm processed approximately 328 returned drug products (each consisting of more than ®cases) and returned these products to saleable stock

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

Specifically, your firm’s procedure for cleaning the dispensing rooms is inadequate. This procedure, WIS-OPM-1029, Dispensing and Mix General Housekeeping and Sanitation, 1/31/2025, revision 11, does not require documentation when dispensing activities occur where multiple APIs and excipients are portioned out for manufacturing drug product purposes, i.e. (b) (4) and (b) (4) (b) (4) Additionally, your firm’s procedure, does not provide cleaning instructions to ensure no cross contamination among products, such as when an API is dispensed on the same day that another API or excipient is dispensed. The current procedure only requires cleaning to be performed (b) (4) . On 01/06/2026 dispensing bay __ was observed with remains of apparent white powder residue on the walls, floor, and on the dust snorkel which sits above the product being weighed out. This practice could lead to cross contamination of drug products.

There is a failure to thoroughly review the failure of a batch or any of its components to meet any of its specifications whether or not the batch has been already distributed.

Specifically, your firm released (b) (4) lof®) @)| in which visual inspection defect rates exceeded action level specification in all defect categories (critical, major, and minor). Your firm works with a contract manufacturing organization (CMO) that produces approximately ©@ of(b) (4) lots. (b) (4) lot ©) @) was manufactured by the CMO. The lot was visually inspected(®) (4) by the CMO andl®) @) at Lantheus prior to release. The following visual inspection results were obtained for lot (b) (4) 1. CMO initial inspection: Critical rejects 1.9%, (action level oe 0) . ° (b) (4) *, . . Overall rejects 2.9%, (action level %). Most critical defects were for vial overseal crimp defects (e.g., loose crimp). 2. CMO reinspection: Critical rejects 0.8% Overall rejects 6%. Because the alert and action levels for reinspection differ from those for initial inspection, the lot was deemed passing per the CMO’s procedures and released to your firm. The root cause of the

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

Component testing is deficient in that each component is not tested for conformity with all appropriate written specifications for purity, strength, and quality.

Specifically, A.Your firm lacks scientific justification for your sampling specification for release testing of incoming raw material (b) (4) . Your firm samples in accordance with the (b) (4) raw material specification, which requires Identification (DB) (4) content) and Assay testing to be performed on (b) (4) of each received lot regardless of the size of the received lot. Your firm lacks data to demonstrate that(b) (4) would be representative of a lot, and your (b) (4) raw material specification fails to meet your procedural requirement on the number of containers necessary to be representative of a lot. Your firm uses (b) (4) as an excipient for production of all lots of drug product (b) (4). For example, for (b) (4) lot (b) (4), your firm received (b) (4) bottles of(b) (4) and sampled (b) (4) to : : (o) (4) . perform Identification and Assay testing. Your firm used (BD) (4) loi(b) (4) to manufacture (b) (4) lot(b) (4). expiry(b) (4) —_, which your quality unit released for distribution on 12/17/2025. Your firm received approximately ots of(b) (4) in 2024-2025.

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

Specifically, a. Foi(b) (4) ) to which(®) (4) are attached for transfer of(®) (4)during production operations, (©) (4)is sampled for QC testing directly from the (©) @)sample port instead of from the) (4) Your firm utilizes a (®) (4)system to produce(®) (4) that feeds the (Bb) (4) system. The @) is used for manufacturing and cleaning. (b) (4) _ points of use have a(®) @) attached for transfer of(©) (4) during operations: (b) (4) ; and (b) (4) . “BLDG. 110 Utilities Sampling Instructions” SOP 005552 does not require attachment of the) @) during QC sampling and instead specifies drawing the sample directly from the sample port of the) @). b. Your firm uses a(b) (4) to) @) the API for the

Strict control is not exercised over labeling issued for use in drug product labeling operations.

Specifically, A. Cartons bearing lot numbers and expiry dates for drug product (1) (4) are staged in cages without locks in an unsecured area of the controlled room temperature (CRT) warehouse, designated Room (b) (4), for extended periods during the packaging process. For example, on 3/18/2026, I observed cartons bearing lot number (BD) (4) in an unlocked cage in an unsecured area of Room (Db) (4). Status documentation on the cage indicated that cartons had been moved to that location on 2/27/2026. Personnel from your operations, manufacturing, aa packaging, supply chain, facilities, engineering, validation, quality control, and metrology departments have access to warehouse (1) (4).

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, manufacturing operators have access to administrator privileges, including data deletion and date/time modification, on your firm’s(D) (4) particulate counters. Your firm uses the particulate counters to perform nonviable particulate sampling in your environmental monitoring program.

Access to the storage area for labels and labeling materials is not limited to authorized personnel.

Specifically, A. Your firm stores vial labels for drug product (b) (4) in a badge-access cage, designated Room (6) (4) jocated in the rear of the controlled room temperature (CRT) warehouse. Personnel from your operations, manufacturing, kit packaging, supply chain, facilities, engineering, validation, quality control, and metrology departments have access to this label cage. B. Your firm stores product package inserts for drug product (1b) (4) in the (b) (4) CRT warehouse, designated Room (6) (4) and(b) A), outside of the label cage. Personnel from your operations, manufacturing, kit packaging, supply chain, facilities, engineering, validation, quality control, and metrology departments have access to this warehouse.

Written records of investigations into unexplained discrepancies do not always include the conclusions and follow-up.

A root cause and corrective/preventative actions have not been pursued for two batches that failed testing for environmental viable air at the location while filling batches on®@ machine ®)@ Deviation investigation # 13305 was opened in J;anuary 2015, finding that) 4 batch #4) failed to meet viable air specifications, detecting@ cfu of yeast. Similarly, Deviation investigation # 13442 was opened in Fe, nary 2015, finding that © batch # ©@ yy failed to meet viable air specifications, detecting® cfu of mold. These two batches were released to the US market, as 4) procedures require two environmental failures of a batch before quarantine is required, per SOP document KBPROC-00263. A root cause and corrective/preventative actions have not been pursued for three © is used as an ingredient for ®@ manufacturing, for cleaning process equipment and as 4) for @@) used in sanitization/sterilization) samples that failed testing for microbial specifications. Deviation investigation # 13833 was opened in April 2015, finding that failed to meet specifications, detecting ®@) cfu and) cfu ato sampling locations. Similarly, Deviation investigation # 14135 was opened in June 2015, finding that failed

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

Viable air and particulate monitoring are not regularly conducted in the Grade A areas of the © (b) (4) to show that environmental conditions conform to requirements. There are ®@) (b) (4) that are used to aseptically fill OM 4) was tested once for Viable air and particulates in 2009, but ©@ have no record of monitoring, nor is there a schedule for any regular verification that these™ filling machines are operating in Grade A conditions as intended.

There is a lack of written procedures describing in sufficient detail the methods, equipment and materials to be used for sanitation.

Procedures for sanitization do not always reflect contact times that were determined in your "Report of Qualification of the Efficacy of Disinfectants on Surfaces of the Manufacturing Facility According to Requirements of USP <1072>." For example, when using the the sporicide®@) procedures (SOP- KBPROC-00083) specify to apply for then spray with© and wipe. The efficacy report indicates that it may take up te of contact time with®@) to deactivate certain tested species.

Written procedures for cleaning and maintenance fail to include description in sufficient detail of methods, equipment and materials used and parameters relevant to the operation.

Cleaning validation documents process parameters for cleaning © from ®)@) equipment) to include av cleaning cycle with ®@

Routine calibration of mechanical equipment is not performed according to a written program designed to assure proper performance.

Calibration of O@ speeds (rpm) for processing tanks used to make) is not always conducted following a scheduled program, such as for theo # 3, C 40, and C 26 tanks.

Written production and process control procedures are not documented at the time of performance.

Although ®@ 9 times are documented during the manufacturing of , na) speeds for formulation, which are critical process parameters, are not recorded in batch records during production.

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 in- process material and the drug product.

For 4) manufacturing (used as an ingredient in drug production and used for cleaning), operating ranges for process parameters are not fully established, such as determining acceptable levels of pressures and flow during routine production, in order to sufficiently validate and control this manufacturing process. For example, appropriate ranges (upper and lower limits) for the monitoring of flow/pressure for retention time and proper filtering and manufacturing have not been fully established for processing ®@ through the? filter (only a delta P is observed, no pressure or flow is recorded), @@ is recorded, but no flow/pressure), ®@) (only a delta P is observed, no pressure or flow is recorded), (no monitoring of pressure/flow), ©@ filter (only a delta P

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

Microbial analysis of © (SOP-KBPROC-00370) utilizes only abi pl portion via ®@) (b) (4) method. Larger sample portion quantities, e.g., mil, are not following your firm's analytical method, in order to gain assurance that colony counts detected are statistically representative, especially when results are low to undetectable using® | ml volumes.

The firm failed to maintain adequate quality control systems, including data integrity controls and procedural oversight, Specifically, a.

Your firm failed to ensure that laboratory records include complete data derived from all tests conducted on GMP materials and failed to maintain adequate documentation of laboratory testing activities. Review ofHPLC sample injection testing data from instruments (b)(4) and) (b)(4) (software:| (b)(4) ) revealed that analysts performed 35 undocumented HPLC sample injections on GMP materials under the non-GMP testing project name "test" and the GMP testing project name (b)(4) between April 2023and December 2024. Both instruments are used for testing GMP and non-GMP samples. This practice is also performed on the firm’s other laboratory equipment: GC, IR/UV, and (b)(4) For example, analysts conducted sample testing without recording the activities in laboratory logbooks and analyst notebooks. The undocumented analyses fall into the following categories with the reasoning behind each injection

The firm failed to have an ongoing testing program designed to monitor the stability characteristics of active pharmaceutical ingredients.

Specifically, Your firm has not performed an ongoing stability testing program that is established to monitor the stability characteristics ofAPI (b)(4) to establish or verify retest dates. For example: Your firm manufactured (b)(4) batches ofAPI (b)(4) in (b)(4) (batches (b)(4) ). Although these batches have been tested and approved for release, they have not been placed on stability studies.

Materials are not handled and stored in a manner to prevent contamination and ensure proper identification.

Additionally, there is inadequate separation between materials of different statuses. Specifically, Your firm does not have material log-in records for your refrigerators and freezers used to store critical production materials. On March 30, 2026, during a facility walkthrough, it was observed that the firm stores intermediates in refrigerators (b)(4) and freezers (b)(4) but could not demonstrate adequate knowledge ofthe materials stored in specific units. For example, an unidentified bag of failed research and development intermediate IM-(6)(4) was found in Freezer /)(6)(4)), which is also used to store GMP intermediates for (b)(4) production. The firm was unable to explain the reason for storing this material in the freezer or the duration of storage. The presence ofthis unidentified, failed research and development material in the same storage unit as approved GMP intermediates creates a risk of cross-contamination or mix-up between rejected materials and materials intended for use in drug product manufacturing.

Buildings used in the manufacture, processing, packing, or holding of intermediates and API are not maintained in a good state of repair and kept in a clean condition.

Specifically, Your firm has not maintained facility ceilings in critical GMP areas in a good state of repair. For example, during a facility walkthrough on 03/30/2026, it was observed that Room (M4), designated as "GMP Raw Material (Quarantine)," had damaged and discolored ceiling tiles above the sampling area. The ceiling tiles showed discolored stain marks and a crack approximately two feet long. Your QA staff observed a water leak in this room

Procedures for the cleaning and maintenance of equipment are deficient regarding the protection of clean equipment from contamination prior to use.

Specifically, your firm has not performed any cleaning validation studies to assess the effectiveness of your cleaning procedures for equipment and rooms used in the packaging operations for| wu woe drug products. Additionally, no disinfectant efficacy studies have been conducted to ensure the effectiveness of your disinfectants used during cleaning operations.

Requirements that must be met by suppliers have not been adequately established.

Specifically, = ws components off am -__\drug product are not adequately controlled for bioburden levels. Specifications for ii | ww do not include a bioburden requirement and incoming certificates of conformity do not certify that components meet a bioburden requirement.

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

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

Specifically Supervisory oversight over quality/production unit operations and laboratory/production electronic system and data is deficient. For Example A. The Quality Unit lacks adequate control over the issuance of production batch records purported to be controlled under your batch issuance procedures. During the inspection, it was observed that copies ofofficial batch records for dru uctsPe | | tae ithout adequately controlling each page. For example, (b)(4) B. There are no requirements for the Quality Unit oversight of Master Batch Record storage and copying for use in manufacturing to ensure executed record instructions are accurate reproductions of the master records. Your firm does not maintain adequate master batch records for the above- mentioned drug products. During the inspection, we observed at least two recent deviations where incorrect batch record documents were issued and used by the production unit. C. Your firm does not have adequate Quality Unit oversight of visual inspection qualification test kits and the qualification process for operators performing vi i i ations during packaging of drug products wi For example, per = firm’s procedure, th (b)(4) SEE

Each lot in shipment received was not identified with a distinctive code for each container or grouping of containers for components, Specifically, The firm does not assign unique lot number for each lot in each shipment received for all drug components.

Currently, the firmusesthe[ws MEDICAL DEVICE

A process whose results cannot be fully verified by subsequent inspection and test has not been adequately validated.

he firm failed to conduct thorough and adequate annual product reviews.

Specifically, our document PD.OPS-0026, Revision 7, Internal Quality System Assessments and Product reviews, effective /2/2026, does not include specific requirements for conducting product-specific reviews ofmedical gases, including evaluation of batch records, testing results and stability data. Additionally, the 2023 - 2025 Quality Management reviews lacked Out-of-specification (OOS) investigations, process capability trends and change controls made during he review period for each specific product.

here is no written testing program designed to assess the stability characteristic of USP grade Air, (b) (4) and (b) (4) Specifically, ‘Your firm has not established a stability program, nor have you performed stability studies to assess the stability characteristics of USP grade Air: (b) (4) as well as (b) (4) .

Currently you have manufactured, released and distributed approximately ©) @) lots since 12/01/2025.

There is a failure to establish the reliability of the component supplier's report of analyses.

Specifically, A) There is no supplier qualification or quality agreement established for the following non-USP solvents used for manufacturing APIs: B) Certificate ofAnalysis (COA) test results provided by the supplier of non-USP solvents have not been validated. This includes the lack of verification for Identity test results, jg -—«Limit test results, wwLimit test results, Residue on Evaporation test results, pH test results, Solvent Acidity test results, Denaturant Level test results, and/or Impurity test results. In addition, the non-USP in-house test method used for Gas Chromatography (GC) purity testing has not been validated. According to the QA Manager, the test parameters for the in-house methods were solely determined based on the firm's laboratory capability.

There is a failure to thoroughly review any unexplained discrepancy whether or not the API batch has already been distributed.

A) According to the QA Manager, there have been no deviations or non-conformances reported since the previous 2019 inspection. However, the following equipment breakdowns recorded in the Breakdown Maintenance Record Logbook, Format No.: UNI/MAIN/006 and 2024-2025 CAPA logs did not include thorough investigation of the API equipment breakdown incident (e.g., during which stage in activities), root cause analysis and product quality impact details on distributed API batches: Machine/Equipment Breakdown Restart Date Root Cause Corrective Action No./Plant Location | Date ae Jan 06, 2025 Jan 06, 2025 | (yy New J) Fitting | Leakage Problem for Work Completed a em. oO Dec 01, 2024 Dec 01, 2024 an Vessel om New valve fitted in | | eae Valve Leakage Ayn

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

Specifically, The following deficiencies were observed during my inspectional walkthrough of the Quality Assurance (QA) area on February 23, 2026: A. 2025 Quality Control API test results (e.g. pH and Assay test results) were observed to be documented on loose uncontrolled template paper for commercial API batches. According to the Production Manager, this document template is no longer in use as of 2026 and all the remaining uncontrolled documents previously filled with similar GMP data have already been shredded. There is no record of which GMP documents have been previously shredded in 2025 and the , years prior. B. The Microbiology Department's Cleaning Record of Equipment Log No. F/MIC/008 was pre- dated with equipment cleaning (Frequency: g@ _) already completed on g ; which is & @ since the last equipment cleaning documented for completion on poe The logbook entry pre-dated for g4 also included Done By, Checked By, and Reviewed By signatures that were already filled in as ofa C. According to the QA Manager, the Done By signature in Cleaning Record of Equipments Logbook is not signed by the actual person doing the work (Production Worker) due to English language barrier. The

GMP training is not conducted with sufficient frequency to assure that employees remain familiar with cGMP requirements applicable to them.

Specifically, There is no documented GMP training (e.g. on Good Documentation Practices) and training on standard operating procedures applicable to the job functions of the Quality Control (QC) Lab Assistant, who is routinely involved with QC sampling activities and functions involving QC instrument cleaning and equipment upkeep. There is also a lack GMP and SOP training for the Production Worker responsible for routinely cleaning microbiology and QC laboratory equipment. Guerlain Ulysse

There is a failure to clean equipment and utensils to prevent contamination or carry-over of a material that would alter the quality of the API beyond the official or other established specifications.

Specifically, There are no standard operating procedures or established instructions to perform and document a visual inspection of equipment subsequent to cleaning operations. For example: During my walkthrough of the Bulk Drug (API) Manufacturing Area on February 23, 2026, I observed that thes, ofBi UNI)@ 06 had visible g)4) | residue product material all throughout the surfaces and gq gasket area. This is despite full equipment cleaning documented as already being completed on February 16, 2026. . ***This is a Repeat Observation***

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

Specifically, The transfer hoses used to transfer bulk drug products to the filling lines are cleaned and reused without an established replacement interval or life cycle management program (A) Your firm has not conducted tubing lezchable studies or tubing material compatibility studies for the transfer hoses used in the filling of the following drug products: - (b) (4) Solution, (b) (4) - (b) (4) Solution, USP ((b) (4) __) - (b) (4) Solution, USP, °@ (B) Your firm has not established written procedures governing the use of transfer hoses that define the maximum number of uses or duration ofuse for© solution/suspension and (b) (4) solution drug products.

There is a failure to thoroughly review the failure of a batch or any of its components to meet any of its specifications whether or not the batch has been already distributed.

Specifically, A.Your firm's OOS investigation practices do not conduct a thorough investigation to determine root causes, leading to repeated failures including out-of-specification results for active pharmaceutical ingredients and content uniformity. Currently you are releasing product despite specification failures based on retest results without proper investigation or justification to invalidate the initial OOS failures. Review of your OOS investigation log from the last 3 years revealed at least 25 investigations concluding with "possible" root causes without definitive determination. Examples include: 1.00S-946-QC concluding "possible root cause may have been sample preparation error" with no verification 2.00S-0019-QC concluding "Possible root cause may have been incorrect (b) (4) ” 3.00S-0022-QC concluding "Possible root cause may have been standard preparation". Additionally, at least 6 investigations (OOS-003 1-QC, OOS-0049-QC, OOS-0051-QC, OOS-0067-QC, OOS- 0069-QC, OOS-0107-QC) conclude "Possible root cause could be the age of the material" without assessing potential supplier or storage issues. B.Your OOS files from 2023-2026 revealed investigation root causes without

Laboratory records do not include the quantity of the sample.

Specifically, During live evaluation of raw material release testing of (b) (4) (Batch # (6) (4) _—+) performed on 3/19/2026, your analyst was observed performing method Q-1045, (b) (4) Assay determination by Gas Chromotography, Version 1.0, Effective Date: 5/18/2022. The analyst was observed: 1.Weighing USP Reference Standard material with weights recorded it Notebook Number 861, Page 51 (weight (b) (4) . weight (b) (4) ) 2.(b) (4) volumetric flask 3.Assuming (b) (4) volume without measuring or recording the actual volume added 4.Entering the unconfirmed concentration of(b) (4) _ into the GC software without written verification of calculations The test method requires to "accurately weigh standard known sample to (b) (4) _" which necessitates precise measurement and documentation of both weight and volume to calculate concentration. However, no written calculation was recorded to confirm the known standard solution concentration ((b) (4) __) prior to entry into the GC system. When questioned, the analyst stated: "J always add exactly (b) (4).” Additionally, historical data review of the analysts Laboratory notebook and raw data from the same method performed by the same analyst o

Determinations of conformance to appropriate written specifications for acceptance are deficient for drug products.

Specifically, Your firm changed batch release specifications in response to out-of-specification (OOS) results without providing adequate scientific rationale, and without following formal change control procedures. Review of the OOS log identified at least specification changes made in response to OOS results over 3 years (OOS-0002, OOS-0005-QC, OOS-0009-QC, OOS-0021-QC, OOS-0024-QC, OOS-0030-QC, OOS-0041-QC, OOS-0053-QC, OOS-0055-QC, OOS-0080-QC) allowing substandard batches to be released to the market. For example: A. OOS-0021-QC - (b) (4) , Lot (6) (4)- Deficiencies in OOS-0021-QC Investigation: Your firm explicitly states "”o root causefor the high (b) (4) values has been determined" yet proceeded to change the specification and release the batch. However, the specification was widened from (b) (4) % to (b) (4) % specifically to accommodate the 107.3% failing result. No scientific rationale was provided for why®% (b) (4) is acceptable when % was previously the upper limit, or what quality attributes are affected by higher (b) (4) levels. The investigation committed to "review ofstability data providing proofthat the (b) (4) analysis is stable throughout the expiry" yet the ba

Records are not maintained so that data therein can be reviewed at least annually to evaluate the quality standards of each drug product to determine the need for changes in specifications or manufacturing or control procedures.

Specifically, Your firm's Annual Product Review (APR) procedures and execution are inadequate to identify trends and drive continuous improvement. For example: A Deficiencies in 2024 APR for Formula (©) @) 1.The 2024 APR states "no significant trends on assay resultsfor (b) (4) , and (b) (4) " despite three documented OOS investigations (OOS-0012-QC at(b) (4) stability, OOS-0017-QC at (b) (4) stability and OOS-0064 for finished product) all involving (b) (4) degradation and low OOS. OOS-0017-QC noted "historically, there have been various OOS investigationsfor thisformulation container closure system ((b) (4) )," yet there is no mention to corrective actions taken to address recurrence. 2.The APR states "no trends were noted" in deviations despite documenting 10 deviations where 50% were labeling/packaging issues, 30% were process control issues, and 20% were material accountability failures - clear patterns that were not identified or addressed. 3.The APR identified that (b) (4) has a Cpk of 0.91 (below the specification, indicating the process is not in control) and states "assay resultsfor (b) (4) are at the upper end ofthe specification range" but took no corrective action. No

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

Specifically, Your firm failed to have adequate data and procedures to support the use of hoses that are not product dedicated or used in multi-day campaign during manufacturing and filling operations of your drug products: ||(b) (4) hoses used during manufacturing are not product-dedicated and are used interchangeably across multiple products. (b) (4) hoses used during filling operations are product-dedicated but are used during campaign runs lasting up to (b) (4) . ((b) (4) hoses used during filling operations are (6) (4) use but are used throughout campaign runs lasting up to (b) (4) .

The written stability testing program is not followed.

Specifically, your firm has failed to establish and maintain an adequate stability testing program for all of your finished homeopathic drug products, as required by your Stability Standard Operating Procedure NLQA-057 “Stability Testing - Test-Sample Submission” rev 4 effective 5/15/2025, which requires submission of homeopathic drug products for (b) (4) and real time stability studies for(b) (4) =. The following identified issues state specific deficiencies: ‘1You have not placed any stability samples into the stability program since February 2021, following the implementation of Change Control CCLN-2101-1_(b) (4) Caps which changed the container closure system from a (b) (4) cap to a (6)(4) cap for your liquid formulations. This represents a five-year gap in stability testing for products with a modified container closure system. ‘|You have not generated any stability data for any of your pellet finished products intended for vulnerable populations, such as: (b) (4) (mfg #(6) (4) _, Lot #s (1) (4) ) (b) (4) (mfg #(b) (4) _, Lot #s(b) (4) ) o(b) (4) = (mfg # (6) (4), Lot #s (b) (4) ) ‘|Between February 2021 to March 2026, your firm manufactured a total of (b) (4) batches across y

Complaint procedures are deficient in that they do not include provisions that allow for the review and determination of an investigation by the quality control unit.

Specifically, your firm's complaint handling Standard Operating Procedures SOP NLQA-005 “Product-Customer Complaints” Rev 4 effective 04/01/2025 and SOP NLQA-006_ “Product Complaint Investigation” Rev 4 effective 04/01/2025 lacks sufficient detail regarding investigation requirements, root cause analysis procedures, trending analysis, and corrective and preventive action (CAPA) implementation for product quality complaints. For example, Between 2023 and 2025, the firm received 194 complaints regarding leaking bottles affecting at least 15 different batches, including but not limited to (b) (4) (Batch Record# (b) (4) ) and (b) (4) (Batch Record# (b) (4) ). Leaking/seal complaints increased from 37 in 2023 to 89 in 2024, representing a 140% increase, before decreasing to 68 in 2025. This trend was observable, yet the firm took no investigative action. The firm's response to the leaking bottle complaints consisted solely of replacing the affected product units for consumers without: investigating the underlying cause(s) of the container closure failures, evaluating the impact on affected batch(es) (b) (4) (Batch Record# (6) (4) ) and (b) (4) (Batch Record# (b) (4) ), assessing whether

Container closure systems do not provide adequate protection against foreseeable external factors in storage and use that can cause deterioration or contamination of the drug product.

Specifically, your firm has not conducted container closure integrity qualification or validation studies to demonstrate that the (®)@) bottles with (6)(4) caps adequately protect against contamination, evaporation, or leakage throughout the product shelf life. This applies to all your manufactured homeopathic drugs, including but not limited to (b) (4) (Batch# (b) (4) ), (B) (4) (Batch Record# (b) (4) _), and (b) (4) (Batch Record# (b) (4) ). This deficiency is particularly concerning given the 194 leaking bottle complaints received between 2023 and 2025 (see Observation [2]) and the absence of stability data for products with this closure system since its implementation in February 2021 (see Observation [1]). Martin M Kimani

Contamination was observed in your production area and areas adjacent to production areas.

Specifically, A)A_ pallet of used compounding equipment was observed in the non-classified Amoxicillin storage room. Items on_ this pallet included, but were not limited to, used process (b)(4) which were coated with yellow residue, (b)(4) . All equipment on this pallet appeared to be coated with a layer of white powder. Your staff stated that this pallet of used equipment had been present in this location for approximately 1.5 to 2 years. This pallet is located immediately adjacent to the door leading to Amoxicillin Room(b)(4) where finished product compounding and packaging of Amoxicillin products takes place. B) Widespread and extensive damage was observed on the painted drywall walls in the Amoxicillin processing area. This damage included an approximately 6-inch long and 3-inch deep hole punched in a wall from the handle of an over-extended door, multiple scrapes in paint and drywall ranging from | to 6 inches, and broken floor ceramic molding. This damage was noted approximately 10 feet from the chute where Amoxicillin capsules were (b)(4) _—pumped openly into IBC containers (6)(4) . C) Black stains were observed on damaged wall sections where paint and drywall had been scrap

Failure to conduct media fills that closely simulate aseptic production operations under the worst-case, most-challenging, and stressful conditions.

Specifically, Aseptic process simulations (media fills), along with the governing procedure SOP CR-02 — Aseptic Technique & Gloved Fingertip / Thumb Test—are deficient in that they do not simulate the finished product container size, number of units, or worst-case conditions that may arise during compounding activities. Media fills conducted by your firmto simulate aseptic processes utilize (b)(4) , which contain a total of (b)(4) and associated equipment. (b)(4) used by each sterile compounding technician as part of their) (b)(4) aseptic process simulation evaluation. During a review of your sterile compounding records for March 2026, a lot size of (b)(4) of Iron 20% (200 mg/ml) was noted in the compounding of Lot #V20030526 on!) (B)(4)). This batch was compounded to fulfill Rx 4 (b) (6) and shipped to your customer.on 2/11/9096. Additional hatch sizes of (b)(4) (b)(4) were also noted in compounding records from (b)(4) Additionally, Form CR-37 — Periodic Cleanroom Aseptic Evaluation — which is used to) (6)(4) qualify your sterile technicians, does not document the amount of time required to conduct the media fill using the (b)(4) . Start and stop times, along with total operationa

Deviation from the procedural requirements of a decree of injunction.

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 Process Validation (PV) for is deficient. You failed to use the system during in-process checks in stage for all strength due to lack of qualification of the system for product as required per Process Validation Protocol (# 044-00). According to the During step, the system is to be used to challenge for rejection

Written records are not always made of investigations into unexplained discrepancies.

Specifically, A. On 03/01/2025 at 15:00 hour, you observed the minimum and maximum temperatures at 25.800 C and 30.400 C (Acceptance criteria: 280 C to 320 C) and the minimum and maximum relative humidity was observed at 57.30% and 79.60 % RH (Acceptance criteria 70 to 80 %. RH) for stability chamber (#QC- E088, 30C/75%) where both humidity systems failed and lead to the chamber shutdown. Although (b) (4) (b) (4) (b) (4) (b) (4) (b) (4) (b) (4) (b) (4) (b) (4) (b) (4) (b) (4) (b) (4)

You established for Clean Hold Time (CHT) and Dirty Hold Time Study (DHT) for the following shared equipment (non-dedicated) that is used to manufacture : which was not based on the worst-case molecules.

Yet, you have not performed a Clean Hold Time (CHT) and Dirty Hold Time Study (DHT) after (as worst-case molecule in 2022) and (as worst-case molecule in 2023-2024) as required per SOP # UNIT PR/SOP/0017-02 “Cleaned and Dirty Equipment Hold Time, effective date 03/08/2026” as introduction of new product at the site. According to your Production Manager and Sr. Manager QA , is considered the worst-case molecule at the site.

Production records do not contain complete information relating to the production and control of each batch.

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, Per your Production Manager your firm does not review data, audit trails and alarm reports generated by the HMIs (GT-2708) and SCADA of your non-dedicated equipment ID #PR-E016) and (ID #MB-E030) utilized in the Micro Lab. Alarms generated for the (Production) and (Micro) including sterilization load cycles are not backed up and automatically overwritten by the system.

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

Specifically, A. Scientific evidence could not be provided demonstrating the source of the smoke used during your air flow visualization studies is neutrally buoyant. During your review of smoke study videos in your aseptic filling lines in workshops@gy as well as thefy line, the following discrepancies were noted: 1. The positioning of the ga ducts of the (4 RABS in relation to the grade B area has the potential to short circuit the grade B air flow, causing an upward movement ofair in the cleanroom. Smoke studies have not been performed in this area to demonstrate adequate airflow in aseptic filling lines workshops §y 2. Air flow videos are recorded with the smoke pointing directly upwards, not providing a uniform curtain of smoke in which to evaluate air currents.

Your firm failed to thoroughly investigate any unexplained discrepancy or failure ofa batch or any of its components to meet any of its specifications whether or not the batch has already been distributed.

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

A. Inadequate aseptic technique was observed in the review of videos and while watching the aseptic filling ofo@ Injection in workshop @@ on 20Apr2026. Discrepancies include: |. Operators block first air during the addition of stoppers. This was seen in workshopsw@ ee aseptic filling lines. 2. An operator was seen having to lean his upper body inside the RABS unit to retrieve and return forceps in workshopow 3. Reaching over ioe _ vials during the execution ofan intervention. The affected vials were not removed, B. The firm’s visual inspection qualification program is inadequate to demonstrate that inspectors can reliably detect all defect types in sterile injectable products. 1. Your visual inspection qualification program lacks adequate Quality Unit over-site and control. Production personnel maintain qualification kits, administer qualification tests, make pass/fail determination with only a Quality review of the bottle condition. This arrangement fails to ensure the proper administration of qualification tests according to a written procedure as well as fails to ensure objective evaluation ofinspector performance.

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

Specifically, the following discrepancies were noted during review of the environmental monitoring program

Your firm failed to establish an adequate system for cleaning and disinfecting the room and equipment to produce aseptic conditions.

Discrepancies were noted during the cleaning performed on 20Apr2026 in workshop®@ _ after the manufacture of M@® Injection-USP including: A. Operators were seen kneeling on the@@ as well as reaching over and leaning on equipment during cleaning. B. Using the same cloth to clean numerous pieces of equipment, including cleaning the lower parts of the @ 2ABS followed by cleaning the inside ofbe RABI C. Only the forceps used during setup or the removal of a stuck stopper areo@ All remaining forceps, including those used in the removal of O® fallen/jammed vials are not m@ These forceps remain on the aseptic filling lines

Routine calibration, inspection, checking ofautomatic, mechanical, electronic equipment is not performed according to a written program designed to assure proper performance.

The following discrepancies were noted during the review ofthe g@ weight check systems on aseptic filling lines in workshops oO A. Workshop ©® The weight checks performed on the®@ balances prior to use, do not bracket the amount being weighed. The balances are verified using a@@: weight while the approximate mass of the items being weighed is approximately @@and® 2 (empty and filled vial). No manual ‘ , : @ : : ‘ weight checks are performed throughout filling. This system ts used in the aseptic filling OXC) Injection. B. The ability ofthe system to reject over filled and under filled vials is not confirmed prior to start of manufacturing. The vials used during the functionality check, performed®® are not weighed out to confirm rejects near the upper and lower weight limits. The Validation Manager confirmed the low weight vials are made by oa , O@ and that they ®@ to the designated overfill vial so the vials are

Control procedures are not established that describe in process controls which validate the performance ofthose manufacturing processes that may be responsible for causing variably in the characteristics of in-process materials and the drug product.

A. Your firm failed to validate the in-process inspection method to evaluateoo ofaseptically e Currently you use mm ut provided no documented evidence that this method has been validated tor y; precision, or reproducibility. e There is no documented acceptance criteria frm® ° There ig no documented training program for personnel performing inspections, including no visual training aids or competency assessments to ensure consisten technique.

Analysis of data indicating the quality management system is not suitable, adequate, or effective was not used as input for improvement.

Specifically, your procedure SOP-QA016-01 Statistical Technique, dated 10/08/21, states you will use ANSI/ASQ Z1.4-2008 Sampling Procedures and Tables for Inspection By Attributes: General Inspection Level ®®, (5)X4)9 for sampling (reduced) for your receiving inspection, in-process, and final inspection ofmedical devices. In review ofyour receiving acceptance of the primary component(By (218) in device (S\N, Manufacturer Part number (S)N4)ENN (GLA) for the past 2 years, I observed that your sampling was erroneous for all records I reviewed. Most ofthe quantities received for this material come in quantities of(6)(4) tubes each, and using the above sampling plan, it would require you to sample @@tubes, notMM as noted by your "Receiving Inspection Checklist." In addition, I reviewed your sampling for your manufacturing ofthe device(SYA, Manufacturer Part number(64) (G4 that you have been manufacturing since 2020. Your DHR (GYAN an inspection sample size of ™each for lots of(6)(4) kits, which is the most common run

Procedures for the feedback process have not been documented.

Specifically, your procedure SOP-QA014-03 Complaint Handling and Nonconforming Events, dated 09-Feb-2026, states that complaints will be categorized for risk using factors of severity and frequency. In review ofyour complaint records for your material number (5)(4 , Manufacturer Part number CAI GIGI for the past 3 years, I observed that 8 of 8 complaints did not factor in risk or severity, yet a "low risk" designation was assigned for these complaints.

Written production and process control procedures are not followed in the execution of production and process control functions and documented at the time of performance.

Specifically, your firm failed to ensure that manufacturing processes are consistently performed and documented in accordance with established written procedures. Batch production records (BMR/BPR), sampling activities, deviations, and validation studies are incomplete, inaccurate, falsified, or not attributable to the personnel performing the activities. Your production system lacks adequate control over documentation, personnel accountability, and verification of critical steps. Examples include, but are not limited to: A. Batch records are deficient in that they lack attributability for multiple products, including but not limited to: © USP @®@ B.No.w@ ° ©®) B.No.o@ © o@ B. No. @@ * o@ B. No. @@ were found to be completed by supervisory personnel after operations took place and not by the operators who performed the work. Your Senior Production Supervisor, and Production Manager, confirmed they complete all batch records. Operators do not record their activities or sign the BMR/BPR.

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, your firm failed to establish and follow adequate written procedures for cleaning and maintenance of equipment to prevent contamination or carryover of materials. For example, but not limited to the following: A. Your firm failed to use adequate and validated cleaning processes to prevent cross-contamination for

Written procedures are not established and followed for the cleaning and maintenance of equipment, including utensils, used in the manufacture, processing, packing or holding of a drug product.

Specifically, your firm failed to maintain and ensure the accuracy, reliability, and integrity of records and signatures used to document equipment cleaning and maintenance activities in cleaning and use logs that are attributable to the individuals performing the work, accurate, complete, and contemporaneously documented.

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

Specifically, laboratory test methods used for raw material and finished product testing are not verified or validated to ensure accuracy, sensitivity, specificity, and reproducibility. Your firm failed to verify or validate the analytical test methods used for raw material acceptance testing. This includes, for example, assay testing of active pharmaceutical ingredients (APIs) by high- performance liquid chromatography (HPLC), which are used in the manufacture of OTC drug products. These methods have not been demonstrated to be suitable under actual conditions of use. No data was provided to support the accuracy or reproducibility of this method for its intended purpose. Additionally, none of the microbiological test methods used for finished product release testing, including total microbial enumeration testes (aerobic microbial count, total yeast and mold count), and testing for the absence of specified microorganisms, including, but not limited to, staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans have been validated or verified for any OTC drug product. Your firm failed to establish data to show these methods are appropriate for the specific product formulati

Buildings used in the manufacture, processing, packing, or holding of a drug product do not have the suitable to facilitate cleaning, maintenance, and proper operations.

Specifically, your firm failed to maintain adequate air-handling systems to ensure suitable environmental conditions are provided where drug products are processed. On 07 Apr 2025, the Air Handling Unit (AHU) in the “Liquidm@ Filling” area was observed to be non-operational. Your Manager, Production Planning, reported the AHU was “tripped” but could not provide a work order or documentation of the failure, notification, or any corrective actions. During this time, im-process bulk for filling, m@ (Batch #@ @ was being stored in this room at a temperature of 26°C, exceeding the validated upper limit of 25°C with labeled “To be Cleaned” [dirty] equipment, Filling Machine EL-003. No deviation or CAPA was initiated. Additionally, your firm failed to install AHUs in Quarantine Rooms @@ to ensure environmental control for bulk in-process material for all products which are stored in Quarantine Rooms m@ for up tom@® prior to filling operations. In another example, on 07 Apr 2025, I observed in-process bulk ©® B.No. XO} O@ B. Nom@ O® B. No. @@ , and ma o@ B. No. m@ to be stored in Quarantine room » with out of service/broken equipment, dirty equipment labeled to cleaned and for the temperat

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

Specifically, your Quality Unit failed to adequately exercise its authority and responsibilities, including but not limited to, ensuring data integrity, implementing effective procedures, and conducting adequate oversight to support the safety, effectiveness, and quality of the drug products you manufacture. For example, but not limited to: A. Your firm failed to perform Process Validation (PV), Cleaning Validation (CV), and/or Cleaning Verification for Product Changeover and Batch to Batch Cleaning for all US marketed products as confirmed by your Production Management and QA Manager. You utilize non-dedicated equipment to manufacture US marketed products. You established a clean hold time (CHT) ofe@ and a dirty hold time (DHT) of@@ for equipment without performing adequate studies to support the CHT and DHT. You currently manufactured approximately@@US marketed products and @@products for the rest of the world (ROW) at your facility. For example, but not limited to, US Marketed Products: we

Employees are not given training in the particular operations they perform as part of their function and current good manufacturing practices.

Specifically, your firm failed to maintain adequate records demonstrating that all laboratory employees had completed required training programs relevant to their job functions. 1. Your firm failed to tran@@ ofo@ %) current employees on cGMP training. There was no evidence that ALL employees conducting critical laboratory activities had received training in current Good Manufacturing Practices (cGMPs) and Good Laboratory Practices (GLPs). Additionally, your firm failed to integrate 21 CFR 211 into the cGMP training program. Your firm’s current cGMP training materials do not include specific requirements from 21 CFR 211, which provides critical guidance on Good Manufacturing Practices for drug manufacturing. This omission limits personnel understanding of essential quality standards specifically relevant to drug product production. Your firm failed to maintain adequate training records. Training records for employees were either incomplete or not maintained. Employees working in critical areas, such as thegy@ production and packaging »@%), do not have documented evidence of training in the operations they perform including proper documentation practices (BMR).

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

Specifically, while reviewing the dynamic smoke study videos for the [8 in Manufacturing Complex| Module“GI (HL) observed the following deficiencies: a) While assembling th connection, your operator covered the sterile opening of th and both sterile ends of the]7/® tubing with 777% b) Your operator blocked first air over the exposed indirect product-contact surface of the stopper chute and bowl during stopper addition operation. Your operator was also observed to block first air over the stoppers in the| 4 during removal of ajammed stopper.

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@

The firm’s contamination control strategy does not provide adequate assurance that @@ ©) @) are consistently contained within the upstream drug substance (DS) manufacturing areas.

Deficiencies in procedures for handling mw containment breaches and controlling personnel flow create arisk ofg@@ transfer to downstream DS and drug product (DP) manufacturing suites. A. Your procedures for managing breaches of m@ containment are inadequate. The Classo@ Microbiological Safety Cabinets (MSCs) are yourm@ containment for thegsy@ handling of )@) However, your procedures (including QMS-12492 and QMS-12331), do not require the documentation ofm@ _ failures (e.g.@@ ). This failure to record containment breaches prevents your firm from tracking, trending, or assessing the potential impact of mw on any given batch, making it impossible to ensure that containment was maintained during manufacturing. B. Your firm does not require personnel to shower after working in the upstream@@ handling suite before moving to other manufacturing areas. SOP QMS-8836 requires only a change of outer garments. Your justification for not requiring a shower, (documented in MA-38919), is based on the assumption that the MSCs provide total containment. However, your risk

Procedures designed to prevent microbiological contamination of drug products purporting to be sterile did not include adequate aseptic techniques during aseptic filling setup fora@ ©) (4) DP.

The environmental monitoring program is not adequate to ensure that the manufacturing areas for ©) (4) DS and DP are maintained in a state of microbial control.

Specifically, A. The environmental monitoring surface sampling plan for the Grade Am@ is inadequate. As detailed in procedure (QMS-12425 Form for batch-bound sampling of m@ ©) @) the plan fails to require sampling of critical product-contact and adjacent surfaces, such as the aw , stopper bowl, or stopper chute, after batch production. B. The viable air monitoring program for the Grade Aww is inadequate in its timing and location of sampling. According to procedures (QMS-12425), monitoring begins only at set-up or filling, failing to continuously assess the environment immediately aftere@ decontamination. Furthermore, sampling is confined to the filling station and does not include other critical areas of activity, such as theme C. Theme in theme used for the manufacture of m@ drug product are not sterilized. Procedures (QMS-12625 Batch related sampling and assessment manufacturing line® and QMS-1540 Instructions for microbiological environmental controls) only describe sanitization ofg@@ with o@ not sterilization. The m@ are used for approximately@ batchesme@ without sterilization. D. The incubation procedure for environmental monitoring plates (QMS-1540, Instructions for microbio

Procedures designed to simulate aseptic processes are inadequate to assure the sterility of the drug product.

A. Vials that are exposed during media fill interventions are excluded/omitted from incubation; therefore, the aseptic process simulation does not adequately evaluate the sterility of the full manufacturing process (including interventions). The intervention list for media fills (QMS

The firm’s visual inspection is inadequate to ensure that the visual inspection process is under a state of control and that recurring deviations are effectively investigated or corrected.

A. Your firm’s procedure for 100% visual inspection categorizes rejected vials only into the following categories: Critical, Major, and Minor. Details for specific defect sub-categories (e.g., cracks, scratches, damaged caps, poor grooving) are not recorded or trended. A change control to implement specific sub-categories (record CC-482203) was not implemented until March 2026, which prevented your firm from adequately investigating and identifying the sources of all prior recurring manufacturing defects.

Your firm’s cleaning and disinfection program is inadequate to decontaminate a@ ©) @) in drug substance and drug product manufacturing facilities and to address the risk of microbial contamination in controlled manufacturing environments.

Specifically, A. Your cleaning log documentation is deficient because it fails to demonstrate that cleaning and disinfection are performed according to established procedures. Your practice of using a single log entry for multiple rooms is inadequate, as it does not record room-specific times or, most

Your firm’s quality system is inadequate because the Quality Unit does not ensure control over material status and final product disposition, resulting in the use of unreleased materials for manufacturing and the distribution of incorrectly labelled drug products.

A. Notall@@ DS batches are withheld from use until the lots have been fully released by the Quality Unit. Multiple @@ DS batches have been partially released and manufactured into DP batches prior to being released by the Quality Unit. A few examples include: e DP batches m@ manufactured for comparability studies. e DP batchesm@ manufactured for PPQ. e DP batches m@ manufactured for analytical transfer submissions tom@® B. Upon reviewing your labeling procedure it was discovered that twom@ drug product batches had labelling errors.

Your firm's quality unit has failed to maintain adequate oversight, written documentation, procedural adherence, and document control.

Components and raw materials are not adequately tested and approved prior to their use in manufacturing.

A. Your firm does not perform sterility testing on incoming lots of stoppers. Specifically, your firm relies on the supplier's Certificate of Analysis (CoA) to ensure the sterility of the a@ (XC) ©) (4) Stoppers m@ , received from without performing its own sterility testing to verify the supplier's results. According to the firm's internal specification document, (QMS-12206, Justification of Specification) ,the rationale for sterility testing on incoming stoppers states, "Can not be tested, controlled during audit". While a bacterial endotoxin test is performed on a sample of stoppers from each lot, this test does not confirm the sterility of the component. Consequently, the sterility of the stoppers is accepted based solely on the supplier's validated process and documentation. B. Your firm failed to prevent the use of raw materials in manufacturing operations prior to their release from quarantine status. Specifically, the completion date for the drug substance manufacture of batchg)@ was February 25, 2021; however, thea)@ (batch ©) (4) which was used in the manufacturing of this batch, was still in quarantine. However, this @@ batch was approved by QA for use on February 12, 20

There is a failure to investigate invalid assays.

Specifically, the procedure for handling invalid assays, (QMS-15172 v.1.0, Trending of Invalid Assays in QC, effective date for this SOP is March 13, 2026), defines the condition for an investigation as the failure of two consecutive system suitability criteria for the same sample. Therefore this procedure does not ensure assay failures are adequately investigated when the assay failure rate reach as high as 50%. A review of laboratory data revealed multiple analytical methods with high rates of invalid results that did not result in an investigation per the firm's written procedure. Examples of analytical tests with high invalid rates for which no investigation was conducted include, but are not limited to: * ww , DS (QMS-14463): 53% invalid assay rate @@ invalid tests out of ©)4) e Bacterial Endotoxins, Gel-clot, DS in-process (QMS-1353): 43% invalid assay rate @@ invalid tests out ofm@ e Potency determination with LD50@@ (QMS-10268): 43% invalid test sample frequency m@ invalid samples out of m@ °* @@ concentration bywm@ (QMS-14625): 42% invalid assay rate @ invalid tests out of M@ ° wf related impurities, »@ (QMS-12468): 37% invalid assay rate m@ invalid tests out of ©) * @@ co

There are discrepancies between the information included in the w@ and the testing operations at the manufacturing facility.

Specifically, The reference standards used for the m@ method for the quantitative determination of m@ are not included in thea Upon review of SOPs (QMS-15037 and QMS-15190), it was discovered that special reference standards are used inthe@@ method(s) for the quantitative determination Ofe for m@ drug substance and drug product. However, the reference standards used for the we method are different from those that are described in theme

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

Specifically, A. Airflow visualization (Smoke Studies) of Grade A laminar flow on Line®® &) 4) . do not adequately demonstrate airflow in the Grade A m@ LAF where oO® of the filling machine, via an aseptic connection, takes place. The airflow visualization study conducted on Line®per protocol oe o@ is limited to simulation of m@ of the m@ ©) of the vial filling machine. The operator is then observed opening the canister and placing it m@ ©) via an aseptic connection. This intervention is in part performed using the m@ and in part performed through m@ intervention. This simulation does not represent this activity during commercial production. In commercial production, up to o@ were 4) ; ; ; observed of the vial fillmg machine on @m@ O® The operator was observed switching the canisters m@ 0) by removing an empty one and sliding the canisters around on the m@ LAF to switch the empty one out with a full one.

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, the software m@ software, versiong@ installed ongw used for ®@ integrity testing of the m@ and the ~~ Particle Counter (NVPC) o@ Software, version m@ used for environmental monitoring in the Grade A, B, C and D areas is not equipped and/or audit trail enabled.

Changes to written procedures are not drafted, reviewed and approved by the appropriate organizational unit.

Specifically, your m@ NVPC machines were accessible using a common user name “USER” and password until August 2024. Per SOP, PROC SSCOR SOP GQA 1196, “Change Management”, a Change Control is to be initiated when changes are made which may have direct or indirect impact on quality and documentation of the product, system, material, process, equipment or procedures. Your firm failed to open a Change Control and conduct any associated risk assessments to existing data when individual user IDs and passwords were assigned to approved operators.

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.

On January 22, 2026, your firm terminated the former Plant Manager due to repeated and ongoing data integrity violations, including, but not limited to, destruction of batch production records, destruction of laboratory-controlled records, and documentation of false production and laboratory data. According to your Quality Head, employees working in the production and laboratory areas were instructed by the former Plant Manager to destroy, alter, or manipulate records and felt compelled to comply due to his supervisory authority. This inadequate practice was also observed and confirmed by your Operations Manager to whom the former Plant Manager reported to. Despite these identified data integrity concerns, your firm did not initiate an investigation or conduct a comprehensive evaluation of manufacturing and laboratory records associated with OTC drug products manufactured for the U.S. market to determine the extent and impact of the data integrity breaches. In addition, your firm did not perform reconciliation of incoming raw materials, finished drug products manufactured and released, inventory records, equipment usage logbooks, laboratory test results, sample

Laboratory records do not include complete data derived from all tests, examinations and assay necessary to assure compliance with established specifications and standards.

Your firm failed to maintain complete laboratory records, including raw data, for laboratory analyses - | conducted on commercial drug products. Specifically, raw data supporting laboratory test results used to release commercial batches, to validate the commercial manufacturing process, and/or in house gw w@@ System were not retained or were unavailable for review.

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

Specifically, A. There is no assurance that laboratory testing used to determine raw material suitability and finished drug product quality is performed in accordance with applicable cGMP requirements. For example, your firm uses contracted laboratories that are not registered or inspected by the agency to perform incoming raw material and finished OTC drug product testing, including the Certificate of Analysis (CoA) used to support the release decision. In addition, no Quality Agreements have been established between your firm and the contracted laboratories to define roles, responsibilities, and oversight related to testing, data integrity, and compliance with cGMP requirements. Moreover, no documented evidence was provided, which demonstrates that the selected contracted laboratories have been inspected by your Quality Unit to assess their compliance with applicable cGMP requirements. SEE

Written procedures are not established for the cleaning and maintenance of equipment, including utensils, used in the manufacture, processing, packing or holding of a drug product.

Specifically, your firm failed to develop and approve cleaning procedures describing in sufficient detail the methods, equipment and materials to be used for cleaning the production equipment (i-¢., gq tank, holding tank and filling line) and utensils or auxiliary equipment (e.g., transfer lines and filling hoses) used in the manufacture ofyour @@ OTC product. As per your Quality Manager, your cleaning procedures are executed q

Your firm failed to maintain buildings used in the manufacture, processing, packing, or holding of drug products in a good state of repair.

Reserve samples from representative sample lots or batches of drug products selected by acceptable statistical procedures are not examined visually at least once a year for evidence of deterioration.

Specifically, according to your procedure titled “Procedure for Collection and Storage of Control Sample”, SOP Number: QCD/009, Version: R04, Effective Date: April 07, 2025, Section 5.1.1 states, “The control sample shall be collected from each batch of finished goods manufactured and from each batch of raw material ingredient received”. However, no examination is performed at least once a year to determine if product deterioration in U.S. marketed OTC products that include oe we has occurred. v ov

Your firm failed to establish 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 standard operating procedure Hb)(4) entitled "ALARMAS CRITICAS DE AUTOCLAVES" [Autoclaves, Critical Alarms, IG] is not detailed enough to include the steps during the autoclave malfunction when the(b) (4) is allowed to be transferred to another autoclave to continue sterilization cycle, when sterilization cycle can be stopped manually and when sterilization cycle is acceptable despite increased (B) (4) stage ofthe sterilization cycle. For example: a) on November 11, 2022, the autoclave had a ina during the stage of sterilization of lo , the cycle was stopped, and was moved from autoclave to . This lot was released on February 24, 2023. b) On March 14, 2023, sterilization cycle for lob)(4) was manually stopped by the operator without any explanation documented. c) On April 25, 2023, the(b) (4) stage exceeded allowed time o , and was documented asa on the autoclave sterilization printout for lo due to autoclave malfunction. This lot was released on June 20, 2023.

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

Specifically, uses(b) (4) | amount depending on and requires additional calculation if it is no . Calculation of(b) (4) was not documented on the batch records for all lots manufactured on lines and(4) from May 28, 2020 to July 22, 2024.

Laboratory records are deficient in that they do not include a complete record of all data obtained during testing.

Specifically, , your raw materials, and finished product,ss are tested for Endotoxin.(BY (4 reagent preparation 1s required for the Endotoxin test. Review of Endotoxin testing records for the raw materials and batches manufactured from May 28, 2020 to July 22, 2024 found that preparation of this solution is not documented.

Written procedures for cleaning and maintenance fail to include description in sufficient detail of methods, equipment and materials used.

Use of ingredients not intended for pharmaceutical use in sterile drug production.

Specifically, your firm was found to use a reduced dietaiy supplement grade APis in the compounding of finished sterile drug product, Glutathione Injection 200mg/mL. For example the API, Glutathione (L) USP (Reduced) (Dietaiy Supplement Grade), Lot <Redacted B4>, Expiry <Redacted B4> was used in the compounding of the finished sterile drug, Glutathione Injection 200mg/mL Lot 0060061826-1, BUD 09-26-2026. This lot was dispensed to fill patient-specific prescriptions. The firm continues to receive this grade of API based on a review of supplier provided COAs for Glutathione (L) USP.

Your firm produced drugs while construction was underway in an adjacent area without adequate controls to prevent contamination of the production environment and product.

Specifically, A. On 8/l7/2026, during a site walk-through, I found construction with sheet rock in areas surrounding a newly constructed ISO Classified modular Cleanroom Suite <Redacted B4> occurring at the same time as compounding activities within ISO <Redacted B4> modular cleanrooms (Suites <Redacted B4> located in the same general area separated by a wall not extended to the facility ceiling. Your firm's management reported construction activities had been occurring approximately three (3) weeks prior to the start of this FDA inspection. Your firm was compounding the sterile drugs, Tirzepatide 30mg/Bl2 0.5mg/mL (2.4mL) 30mg/0.5mg mg/mL, Lot number 0011081726-1 BUD 2026-11-25, Batch size <Redacted B4> vials and Semaglutide 10mg/B12 0.5mL (1.3mL) 10mg/0.5mg, Lot number 0005081726-1, BUD 2026-11-25, Batch size <Redacted B4> vials.

Microbial contamination was present in the ISO 5 area and areas adjacent to production areas.

Specifically, during my review of your firm's environmental monitoring (EM) records, I found the following deficiencies: A. During a review of your fnm's 2025 <Redacted B4> EM monitor sampling of the ISO Classified Cleanroom Suite found two (2) different occurrences where I CFU was found during ISO 5 LAFC surface sampling (Acceptance Limits ISO Class 5: <Redacted B4>. These include: 1. 10/9/2025: ISO 5 <Redacted B4> Buffer Hood -1 CFU; Compounded sterile product include; a. SEMAGLUTIDE IMG, Bl2 0.5/ML, Lot 0002-100925-A, BUD 1/17/2026 b. SEMAGLUTIDE IMG, B12 0.5MG/ML, Lot 0002 -100925-A c. SEMAGLUTIDE 4MG, Bl2 0.5MG/ML, Lot 0003-100925-A d. SEMAGLUTIDE 6MG, B12 0.5MG/ML, Lot 0004-100925-A e. BPC-157 3mg/mL, Lot 019-1 00925-A f. BPC157/TB500/KPV 3/3/3MG/ML (NO COPPER), Lot 0021-100925-A, BUD 1/17/2026 g. GHK-CU l 0mg/mL, Lot 0027-100925-A, BUD 1/17/2026 h. BPC, TB500, KPV 3mg/3mg/3mg/mL, Lot 0021-100925-A 1. BPC-1 57 3mg/mL, Lot 0019-1 00925-A J. TIRZEPATIDE l 0MG, B12 0.5/ML, Lot 0007-100925-A

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

Specifically, during compounding observations of your firm's technicians, I observed your firm's technicians reaching over open vials while filling and stoppering filled sterile vials using their sterile gloved hands in the processing of sterile finished drug products, Tirzepatide 30mg/B 12 0.5mg/mL (2.4mL) 30mg/0.5mg mg/mL, Lot number 0011081726-1 BUD 2026-11-25; and Semaglutide 10mg/B12 0.5mg/mL (1.3mL) 10mg/0.5mg, Lot number 0005081726-1, BUD 2026-11-25 having the potential of blocking first air within the ISO 5 LAFC. The rubber stoppers were removed from a non-sterile. <Redacted B4> bag that were originally stored in the approved supplier's sterile packaging.

A pattern of frequent or acute pressure reversals was observed from areas of less clean air to areas of higher air cleanliness.

Specifically, during a review of your firm's 2026 <Redacted B4> ISO Classified Cleanroom differential pressure monitoring logs approved by the firm's pharmacist for Cleanrooms Suite <Redacted B4> found differential pressure reversals that occurred in the following months for Cleanroom <Redacted B4>. a. February 2026 (18 out 22 Differential pressures equal; 1 missing data for Garbing Rooms; 1 pressure reversals) b. March 2026 (17 out of 24 Differential pressures equal; 6 pressure reversals) C. April 2026 (20 out of25 Differential pressures equal; 1 missing data for <Redacted B4> & Garbing Rooms; 1 pressure reversals) J d. May 2026 (22 out of27 Differential pressures equal; 1 missing data for Clean Room <Redacted B4> pressure reversals)

The facility design was observed to allow the influx of lesser quality air into a classified area containing higher quality air.

Specifically, A. Your firm was found to be using 2 separate modular ISO classified cleanrooms designed with open vents existing into non-controlled/non-classified areas of the facility. I found ISO 8 Anteroom for Suite <Redacted B4> vent appeared to contain white foreign particulates in the flow path. The vent was being held open using a yellow/black handle screwdriver, which was on the opposite side of the ISO 8 Anteroom Cleanroom for Cleanroom Suite. Your firm's Compounding Manager reported that the contract cleanroom certifier had used the screwdriver to hold open the vent during an issue with balancing the ISO 8 Anteroom differential pressure. B. I found what appeared to be white foreign particulates on the floor within your firm's ISO 8 gowning room of Cleanroom Suite along with the vent remaining in the open position directly in front of the outside shoe storage rack.

Personnel were observed moving quickly in a critical area or in an area immediately adjacent to a critical area likely causing disrnption ofunidirectional airflow.

Specifically, I found during aseptic processing involving stoppering and capping using sterile gloves, your firm's technicians were using a <Redacted B4> disrupting unidirectional airflow within <Redacted B4> ISO 5 LAFC units within Cleanroom Suites <Redacted B4> during the processing of sterile drug products, Tirzepatide 30mg/Bl2 0.5mg/mL (2.4mL) 30mg/0.5mg mg/mL, Lot number 0011081726-1 BUD 2026-11-25; and Semaglutide 10mg/Bl2 0.5mg/mL (1.3mL) 10mg/0.5mg, Lot number 0005081726-1, BUD 2026-11-25.

Personnel infrequently changed and sanitized gloves to prevent contamination.

Specifically, your firm's technician was observed pushing trash into trashcan using their sterile gloves without performing a sterile glove change afterword. The technician disinfected their gloves and returned to the ISO 5 LAFC within ISO 7 Buffer Room to continue aseptic processing activities.

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

Specifically, A. Your firm's technician was observed failing to disinfect components located within the ISO 7 Buffer Rooms <Redacted B4> prior to placing them into the ISO 5 LAFC unit. B. Your firm's technicians in both ISO 7 Buffer Rooms suites during the aseptic processing of the sterile drug products, Tirzepatide 30mg/Bl2 0.5mg/mL (2.4mL) 30mg/0.5mg mg/mL, Lot number 0011081726-1 BUD 2026-11-25; and Semaglutide 10mg/Bl2 0.5mg/mL (1.3mL) 10mg/0.5mg, Lot number 0005081726-1, BUD 2026-11-25, was observed transfering stoppered trays of vials from LAFcQ (ISO 5 filling LAFC) through the ISO 7 Buffer Room, and into ISO 5 LAFqj (ISO 5 LAFC capping and crimping) without disinfecting the trays.

Inadequate <Redacted B4> testing on <Redacted B4> used to sterilize drug products.

I S pecifically, during a review of your firm's <Redacted B4> test of <Redacted B4> used in the compounding of finished drug sterile products, your firm failed to use calibrated gauge(s) and equipment to ensure adequate testing and <Redacted B4> were capable of meeting their intended use.

Compounding with components, containers or other materials that have not been verified to assure that they do not contribute endotoxin contamination that may be objectionable given the product's intended use.

Specifically, your fnm fail to <Redacted B4> glass beakers used in the formulation of bulk non-sterile drug products that undergo sterile <Redacted B4> to render bulk product sterile. Your firm's management reported that glassware is <Redacted B4> used. It is <Redacted B4> and wiped with sterile <Redacted B4> prior to use. Your firm's cleanroom manager reported a <Redacted B4> has been purchased for the processing of glassware. I found your firm's washed glassware used in the formulation and compounding of bulk non-sterile drug products are stored on a wire shelf in a non-controlled non-classified area directly in from of the entiy door of the facility. The glassware is positioned <Redacted B4> on the rack with no covering over the opening of the glassware.

Failure to conduct media fills that closely simulate aseptic production operations under the worst-case, most-challenging, and stressful conditions.

Specifically, your firm failed to provide adequate rational evidence in support that media fills that closely simulate aseptic production operations under the worst-case, most-challenging, and stressful conditions.

Personnel donned gowning apparel improperly, in a way that may have caused the gowning apparel to become contaminated.

Specifically, on 8/19/2026, two (2) technicians were observed donning their sterile gowns to enter the ISO 7 Cleanroom to strut aseptic processing. Sterile gowns worn by both technicians contacted the floor while donning rendering the gowns non-sterile. Additionally, poor sterile gloving techniques were found inadequate by the technicians contacting the non-sterile side of the glove using the sterile fingers of the opposite sterile glove.

Smoke studies were not performed under dynamic conditions.

Specifically, A. Your firm's PIC and cleanroom manager, reported that they neither received <Redacted B4> viewed, nor approved any static or dynamic smoke studies for either Cleanroom Suites, <Redacted B4> following original certifications or recertifications since the firm began operating in June 2025 for the <Redacted B4> cleanrooms. B. Your firm's compounding manager reported that no smoke studies during media fills were performed to assess laminar air flow conditions within any of the ISO 5 LAFCs, during aseptic manipulations and interventions to determine impact on finished sterile drug products.

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, in 2024 your firm conducted studies to qualify the defect standards for your visible particulate container challenge™®. However, you failed to assess the appropriateness of your current (b) (4) sterile vial inspection process after these Visual Inspection Method Qualification studies revealed significant degradation in visual inspection quality and capabilities when the vials were inspected by the (b) (4) method compared to 100% manual visual inspection. Your firm’s current (b) (4) visual inspection process entails vials which are presented to inspectors via a conveyor system at pre-determined speeds (without ever determining how conveyor speed impacts visual inspection performance). For example: 1. Protocol #US-PU-1027-MVD-EQP-000116815 (Determination of Probability of Detection (b) (4) with (b) (4) Fill of(b) (4) ), initiated in 8/2024. Examples of results from 100% manual inspection vs. the firm’s current (b) (4) inspection, are as follows: a. (b) (4) stopper particulate (Unit ID:©@): 93.3% vs. 10.0% b. (b) (4) stopper particulate (Unit ID: © @): 83.3% vs. 0.0% c. (b) (4) fiber particulate (Unit ID: © @): 70.0% vs.13.3% d. (b) (4) particulate (Unit ID:®): 70.0% vs.

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

Specifically, (A) The qualification™™® used to qualify visual inspectors do not always include defect samples at the lower limits of visual detection established during threshold studies. For example, Test (b) (4) ((b) (4) vial), which was used to requalify visual inspector fim on 1/21/2026, contains (b) (4) accept units and defect units. Of the defect units, "contain foreign material particulates of the following types and sizes: (b) (4) . Your threshold study established a PoD of >(®)(4) % for (b) (4) (po stopper) particulates; however, defects at this size are not represented in Test (b) (4) (B) Your firm uses fog generated from (b) (4) and (b) (4) for airflow visualization studies in cleanrooms, including sterile drug product filling lines. However, Study/CC # (03) 26-016.V6, conducted on March 13, 2026, does not provide adequate evidence that the fog is neutrally buoyant. Video observations show the fog was discharged upward in bursts, reversed direction, and fell back. (C) Your(b) (4) _ Sterilization Qualification Study #(©))17-025 for the (b) (4) vial established a minimum validated Fo of (b) (4) and (b) (4) at the worst-case location. However, per SOP US-PU-1027-SOP-OT-0000

Verification of the suitability of the testing methods is deficient in that they are not performed under actual conditions of use.

Specifically, your firm does not perform comparative testing for all in-house analytical method transfer studies that compare analytical results between the transferring lab and your receiving lab to determine a successful method transfer. For example, you did not compare the results of the transferring lab with the results of your receiving lab for the transfer of the external labs in-house method ((b) (4) ) for the Determination of Impurities in (b) (4) Injection ((b) (4) ) frorr(b) (4) to FK Grand Island, executed under Protocol: NAM-MVD-FG-000111207.

Each laboratory used to conduct testing of finished PET drug products does not follow written procedures for the conduct of each test.

Specifically, Your firm failed to follow established incubation procedures for sterility testing and environmental monitoring. A.) Your firm's procedure, Product Testing: Sterility Test (Doc# D0001993, Revision U, effective date: 09/05/2025), specifies a (b)(4) incubation period for sterility test samples. However, sterility test samples for the following batches were inspected and results recorded before completing the required_ (DMA) incubation period (incubation periods ranged from more than (b)(4) to less than(b)(4 ): (D)(4) injection, Batch# (b)(4) (b)(4) Iniection, Batch? (b)(4) Injection, Batch# _ (B)(4) B.) Your firm's procedure, Microbiological Environmental Monitoring of the ISO 5 Area of the Hot Cell (Doc# D0012139, Revision I, effective date: 11/01/2020), requires |(B)(4) plates

You did not take appropriate action to correct any identified problems to prevent recurrence of a nonconforming product or other quality problem.

Specifically, During review of the quality system related incidents, we observed the following: A. There were at least five occurrences of QC analytical chromatography testing involving operator error resulting in no blank injected during finished product testing of (b)(4) Injection in a period of approximately four months from 05/29/2025 — 10/01/2025. For each occurrence, the testing was re-performed with blank and met specification. For each occurrence, awareness training was conducted. The action taken was inadequate in preventing recurrence. In one example, a repeat incident was logged for the same operator on two consecutive days. B. There were at least three occurrences of QC analytical chromatography testing involving operator error resulting in sample injected without nroduct or no product injected during drug product testing of (b)(4) and (b)(4) Injections in a period of approximately 9 months from 02/25/2025 — 11/16/2025. For two of the incidents, the testing was re-performed and met

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

Specifically, A. Your firm's procedure SOP-00013 ("Batch Review and Release Process," v. 5, effective 10/31/2025) for shipping drug products under quarantine is inadequate. The procedure allows shipment of sterile injectable drug products to end customers before the completion of analytical tests and quality review of batch manufacturing records, but it does not specify the steps to be taken if the product fails to meet finished product quality specification(s). This procedure does not ensure the quality of products prior to distribution. B. Your firm lacked a procedure for recalls that details the steps to follow, within the shelf life of the products, in the case of batch failures due to analytical test failures or manufacturing deviations. C. Per SOP-00012 ("Corrective and Preventive Action (CAPA) Handling," v. 2, effective 04/14/2025), Quality Assurance (QA) is responsible for tracking CAPA quality events, and CAPA due dates can be extended during the Implementation phase with appropriate justification. A review of the firm's list of CAPAs revealed that many remain open past their due dates without justification. For example

There is a failure to thoroughly review any unexplained discrepancy and the failure of a batch or any of its components to meet to any of its specifications Specifically, A.

A review of the EMPQ (REC-00703, "Environmental Performance Qualification Summary Report," v0, approved 08/23/2024) showed that protocol deviations were inadequately investigated. Protocol Deviation Reports 11-16 identified 14 samples exceeding CFU action limits, totaling 315 CFUs. The Quality Unit failed to adequately investigate and implement corrective actions after identifying the CFUs, determine microorganism sources or trace them to

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

Specifically: 1) Review of the firm's qualification report for bottle packaging line® found that the performance qualification failed to identify the lot number ofproduct used in the qualification operations. Further, when the rejection log was examined for a recording of the lot used in the qualification, there was no record of the rejected product. Finally, review of the inventory card which was requested found that the responsible individual reportedly recorded the wrong lot number. 2) The firm has had a large number of complaints of cloudiness/ crystallization in the softgel product (b)(4) and for specific lots such as manufacturer lot (64) there was a large percentage of rejects and four customer complaints for lot (6)(4) However, although Spirit Pharmaceuticals, LLC internal communication dated April 5, 2016 states in reference to the supplier efforts that "Based on the evaluation done so far they have found the root cause that might be causing the re-crystallization and are in the process of making permissible manufacturing changes on (6)(4) and will implement the required changes to manufacturing process after evaluating pilot scale batches", review of quality system files

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

Specifically: (6)(4)) checking of the metal detectors employed on packaging lines does not employ non-ferrous metal challenges.

The written record did not include the reason an investigation was found not to be necessary when an investigation into unexplained discrepancies was not conducted.

: : - : (b) (6). (©) (7XC) : Specifically, your firm received a consumer complaint on 05/03/16 regarding a year old child that had an allergic reaction while using your (b) (4) product. Per the documentation on the record, "child allergic to (b) (4) which is not in our product." Although the complainant provided the batch number (8) (4) used to formulate this product, you concluded that it was not necessary to inspect and retest the retain sample for this product and advised the complainant to avoid (b) (4) and (b) (4) Additionally, you instructed the complainant to test the product on a small patch on the child and to communicate the results, despite your awareness of the potential risk of the product.

Employees are not given training in the particular operations they perform as part of their function and written procedures required by current good manufacturing practice regulations.

Specifically, you stated on 05/24/18 that your staff ((""") is responsible for maintaining the document : : (b) (6). (b)(7S) control system and has the authority to issue product labels. You stated your staff ) has the

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

Specifically, 1. On 05/21/18, I observed foreign material that appeared to be rust ona clip that secures the (6) (4) scraper for a (b) (4) kettle (Kettle “. This foreign material appeared to have discolored the scraper. The clip and scraper are internal components of the kettle that come into direct contact with (b) (4) products while batching. Additionally, because there is discoloration of the scaper, there is concern that this component is displaying reactive/absorptive properties. 2. On 05/21/18, I observed a toxic chemical spray can intended to loosen metal parts, stored on the same counter next to product contact utensils designated as "clean". Due to its close proximity, clean utensils could be exposed to toxic chemicals not intended for the finished product. 3. On 05/21/18, I observed a hose designated as "clean" hanging from a tank with the hose ends resting on the floor. Hoses are used to transfer (1) (4) products from the mixers/kettles to holding containers for filling.

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

Specifically, 1. Finished drug product testing for aerobic microbes is deficient in that the preservatives used in each product are not neutralized or deactivated so that the test results are accurate. Preservatives used include (b) (4) and (b) (4) for Spray products and (b) (4) for all other over the counter drug products. 2. Microbial testing for aerobic microbes is deficient in that growth promotion testing is not performed on each lot ofmedia prepared to ensure the media is capable of growth. You stated for the lots of media

Laboratory records do not include a complete record of all data secured in the course of each test, including all graphs, charts and spectra from laboratory instrumentation, properly identified to show the specific component and drug product tested.

Specifically, your firm uses an internally developed software (b) (4) that creates master batch records and stores test results. You stated this software currently does not maintain previous revisions of master batch records for document management, nor is there a system in place to ensure that master batch records and analytical results are complete, unaltered and inclusive of all activities performed. Additionally, this software has not been validated to demonstrate its ability to ensure data accuracy and security. PRODUCTION SYSTEM

Each component is not added to the batch by one person and verified by a second person..

Specifically, I observed your production staffperform batching operations for the formulation of(B) (4) "Original" Lotion (b) (4) Lot®)@. On 05/29/18, a production operator combined Phasem an phase component mixture with phase (b) (4) phase component mixture and thereafter added a (b) (4) mixture and(b) (4) with (©) (4) These steps were documented as performed and verified per the batch record, however, there was no additional operator present performing the verification of these additions.

There are no written procedures for production and process controls designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess.

Specifically, your process validations for the production of(b) (4) products are inadequate in that they do not include an evaluation of the elements identified below: 1. A requirement for training prior to execution of the validation protocol. 2. Identification of failure modes and critical process steps 3. A method of assessment based on scientific principles 4. Pre-determined acceptance criteria that are specific, measurable and clearly defined (This is a repeat observation from the cGMP inspection performed 11/09/2015 — 11/19/2015)

Written procedures are not followed that describe the in-process controls and examinations to be conducted on appropriate samples of in-process materials of each batch.

Specifically, on 05/21/18, I observed your production staffperform in-process weight and torque checking during the filling of (Db) (4) Lotion, Lot ®)@). The batch record requires in-process testing to be performed (b) (4) . With the prior in-process test documented as occurring at 10:30am, the production staffproceeded to perform the next in-process interval at (b) (4) (b) (4) I observed the staff perform this check and document the time as (b) (4) . The staff changed the documentation to the correct time only after instruction from management following my inquiry. Additionally, your employees failed to initiate an investigation for

Appropriate written procedures, designed to prevent objectionable microorganisms in drug products not required to be sterile, are not established and followed.

Specifically, A) On 03/17/2026 multiple leaks and associated apparent filth were observed at the facility’s ©)@ (b) (4) systems. On this date you manufactured drug products including (b) (4) Capsules Lot (b) (4) ,(b) (4) Capsules Lots (b) (4) , and (b) (4) Capsules Lot (b) (4) . i) A water leak was observed at the (b) (4) within the (BD) (4) system supplying Building ® Standing water and apparent filth were observed on the floor directly under this leak. Firm personnel stated this leak was known prior to the inspection team’s observation, but could neither provide documentation adequately supporting this assertion nor describe the date this leak may have been detected ii) Another water leak was observed within the USP (b) (4) system supplying Building™® at a pipe coupling downstream ofthe(b) (4) . aeGNATURE

here is no written testing program designed to access the stability characteristic of USP grade (b) (4) and (b) (4) gases.

Specifically, our firm has not established a stability program, nor you have performed stability studies to assess the stability characteristics of USP grade (b) (4) (b) (4)(b) (4) . & (b) (4) (b) (4) as well as (b) (4) (b) (4) (b) (4), 8(b) (4) (b) (4) | Currently you have manufactured, released and distributed approximately lots from 12/01/2025.

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