Global Regulatory Monitor
Regulatory News, Week 3 · 2026/7

(QUALITY SYSTEM) Written procedures for the qualification and approval of suppliers of components were not adequately implemented.

Specifically, Your firm's SOP QA200-07.02 Vendor Audits effective date 8/19/2020, requires the performance of paper audits as part of supplier qualification. However, paper audits were not conducted for suppliers of components used in the manufacture of drug products. a. There was no documentation demonstrating that suppliers of components were evaluated and approved by the Quality Unit prior to use. b. For all component suppliers reviewed during the inspection, there was no documentation demonstrating evaluation and approval prior to use. c. No completed supplier questionnaires or audit documentation were available for review. d. There was no documentation establishing defined supplier responsibilities or quality expectations.

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

Specifically, A. Extrinsic biological particulates (mammalian hair) have continued to be identified in finished sterile drug products. However, investigations into these events have not been completed in a timely manner and do not demonstrate that the root cause has been adequately identified and corrected. From approximately 08/30/2025 to present, you have identified mammalian hair in finished units in at least(®) (4) batches, including three identified in 2026, representing a recurring contamination issue (approximately (b) (4)batches out of(b) (4) inspected in 2026). Probable root cause has been attributed to stopper components; however, this conclusion is based on an ongoing, aggregated trend investigation (REC 1093464), that was opened on 08/28/2025, and has not been substantiated through complete, batch specific investigations. All ©) @ deviations are currently open. You stated that closure of those deviations is pending completion of this trend investigation. Despite implementation of multiple corrective and preventative actions, you continue to observe mammalian hair in finished drug products.

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.

Specifically, A. Visual inspection methods have been implemented without adequately qualifying inspection sensitivity, defect detectability, or comparability between methods. For example: Your threshold (b) (4) ) studies failed to generate (b) (4) across the full visible range of defects and failed to establish (b) (4) based on defect size at which defects become reliably detectable. Without establishing (b) (4) supported by (b) (4) , you have not demonstrated that inspection sensitivity has been adequately qualified or that the visual inspection process is capable of consistently detecting and rejecting critical defects. Additionally, MVI studies were conducted using aggregated “particulate” defect categories that combined multiple particulate defect types (ex: glass, metal, rubber, fibers). Further, defect units were characterized by using broad size ranges rather than actual measured particle sizes, which

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

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

Aseptic processing areas are deficient regarding the system for monitoring environmental conditions, Specifically, Environmental monitoring is not always performed in response to interventions located and / or impacting critical surfaces.

Examples include but are not limited to: (b) (4) , tools to include (b) (4) (b) (4)

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

Specifically, You lack comprehensive trending analysis regarding your environmental monitoring program as well as your(b) (4) and (©) 4) decontamination (6) (4)) program. Both programs lack adequate spatial analysis such as intra and inter location requirements over justified periods.

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

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

Specifically, The (b) (4) Assembly Machine (Equipment ID# (6)(@)) is utilized to assemble and label sterile drug product (b) (4) into (b) (4) . The firm assembles and labels the sterile drug products (b) (4) © and(b) (4) on the (b) (4) assembly machine. The equipment performance qualification studies titled “(b) (4) Assembly Machine (System (b) (4)) Performance Qualification Protocol Summary Report-VL-087JUN21, VPQ-(b) (4) 00019-S- VL-087JUN21, Client (6) (4)™,” effective: 01/23/2023, “(b) (4) Assembly Machine (System (b) (4) Performance Qualification Protocol Summary Report-VL-087JUN21, Client(b) (4) (6) (4) Addendum 11, VPQ(By(4)illl-00019-S-VL-087JUN21-ADD1 1,” effective: 01/27/2026, and “(b) (4) Assembly and Labeling Machine (System (6) (4)) Performance Qualification Protocol, A- VPQ-00061-P,” effective: 04/08/2025, do not assess the assembly and labeling functionality as indicated in the production of(b) (4) and EMPLO YEE(S)

Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).

Your firm failed to perform operations within specifically defined areas of adequate size and to have separate or defined areas or such other control systems necessary to prevent contamination or mix-ups in aseptic processing areas. Your firm also failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile and that include validation of all aseptic and sterilization processes (21 CFR 211.42(c)(10) and 21 CFR 211.113(b)).

Your firm failed to use equipment in the manufacture, processing, packing, or holding of drug products that is of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance (21 CFR 211.63).

Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).

Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2)).

Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess, and your firm’s quality control unit did not review and approve those procedures, including any changes (21 CFR 211.100(a)).

Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).

Your firm failed to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products and the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated (21 CFR 211.22(a)).

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

. ; ; ONC) Specifically, testing and release of OO) Tablets do not include appropriate laboratory determination of satisfactory conformance to the impurities specifications. (4) Tablets are tested for Impurities by using analytical method (# Z TM 0252-02, Version: 02, Effective Date: 7/15/2019). As per this test procedure HPLC sample run time for impurities analysis is M@ However, when commercial release and stability data is processed for impurities analysis; integration of peaks is inhibited after m@ of run time. There is no assurance that any impurities eluting after m@ would be accounted for towards total impurities. Firm’s practice to inhibit integration of peaks at m@ is consistent during commercial release and stability testing of 0) Tablets. Since last inspection the site shipped m@ batches ofm@ OY) Tablets into the US market.

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

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

Specifically, the equipment used to manufactureg@ Tablets is not of appropriate design to facilitate its intended use, cleaning, and maintenance. On 12/9/2019the O® used @) step, room # w@ equipment inventory # 30125) to manufacture @ @ tablets for the US market was observed to have portion of the inside surface (potential product contact surface) scratched and dented. The impacted surface appeared to be unsmooth. After each use, gw are dismantled and removed out for cleaning. It was stated when these @@ of the equipment are removed for cleaning: surface scratching is hard to avoid due to the unique shape of the equipment O® @@ This is a shared equipment and is used to manufacture multiple drug products including gq oe Tablets etc.

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, production equipment such as »@ Machine w@ room # we equipment inventory # 35152) used to o@ is not appropriately cleaned to prevent contamination that would alter the safety, identity, strength, quality or purity of the drug products. For example; A. Some stains that appear to be m@ were observed on the tubings m@ ©) Similar m@ stains were also observed on other surfaces of the equipment. This equipment was tagged as clean and the cleaning was performed and verified on 12/5/2019. B. w@ that appeared to be m@ was observed on the floor of room # mw where w@ 0) Machine, @@ is housed. This room was tagged as clean and the cleaning was performed and verified on 12/5/2019. Review of the use logbook for m@ indicated the equipment was last time used to manufacture 4) Tablets (that are @@ on 12/5/2019. QUALITY SYSTEM

Written procedures are not followed for evaluations done at least annually and including provisions for a review of investigations conducted for each drug product.

Written records are not made of investigations into unexplained discrepancies the failure of a batch or any of its components to meet specifications.

Specifically, no risk analysis exists to determine the root cause ofthe potential genotoxic and suspected human carcinogenic we have been found in your tablets. For example: A. Your firm sources it’s API 4ay from pyPy manufacturers which are solely determined by the customer. This API is received at the firm with a Certificate of Analysis (COA) from the API manufacturer. In reviewing a total of@COA for 4, 4 wa > We observed that testing for ©@ are not done by the API manufacturerwe . nor is aNy4» analysis conducted by your firm. Since 2024 the firm has accepted @ batches,4» of to manufacturee)@ batches ofie bulk tablets of which mw bulk batches oa tablets) were shipped to the United States. Additionally, while reviewing the firm’s documents. it was revealed that the firm requires 1... impurity testing ofm APIs ; - . o@ . we While &a ils

Procedures designed to prevent microbiological contamination ofdrug products purporting to be sterile are not established, written, followed, or including adequate validation of the sterilization process.

Specifically, A. During the inspection, I (EL) watched videos ofairflow visualization studies (smoke studies) performed in Formulation Workshop ®®vial filling line in 01/2025. Workshop @nanufactures LLL a the U.S. market. The lack ofadequate smoke coverage, turbulent airflow, or poor aseptic practice were observed. Examples included but were not limited to

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

A. There is a lack of laboratory data integrity. Bacterial colony growth in media growth promotion test (GPT) is inaccurately recorded to show acceptance result. Specifically, On 04/20/2026, I conducted a walkthrough inspection of the QC Microbiology Laboratory located in Building,,4, I reviewed GPT result for ie Lot No. jw (Exp. wa aftera incubation (acceptance: colony growth < gy) Thegy@) is an indicator media used to detect the presence ofobjectionable microorganism 4 wm 'gy@ API, excipients, and FP for the U.S. market. I inspected Lot No. 6) for evidence of microbial growth. I did not see any cfu on tested 4), plates. My finding ofno

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

Specifically, A. Your firm does not have a test method to conduct testing for o@ Therefor the firm is unable to test for ow

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, A. Risk assessments RARF-20190222 and RARF-20180718-1, both dated September 26, 2020 are conducted to determine the root cause of the potential genotoxic and suspected human

Written records of investigation of a drug complaint do not include the follow-up.

Specifically, Since January 2023, your firm has received 939 complaints. Of the 939, only 8 (~0.852%) were deemed to be “serious” complaints, with the rest deemed “not serious”. Per SMP-011.19, “Customer Complaint Management Procedure”, serious complaints are any “complaint that may possibly result in a product recall, detention, field correction or product notice to Health Authorities because the product defect potentially represents a high patient safety risk, with regard to the following topics: Questions for the sterility of injection products, Reports a product mix-up, cross contamination, mislabeling and misbranding”. Per the written procedure, all other complaints are “not serious”, which do not specifically require risk assessment, investigation or follow up. During review, “not serious” complaints included foreign tablets found in sealed containers, chipped tablets, broken tablets, empty blisters, crushed tablets, numerous adverse events, dark spots on tablets, wrong color tablets, discolored tablets, Ge compressed into tablets, missing package inserts, rough surface condition of tablets, failed AQL sampling upon receipt of bulk (customers), torn and taped outer shopping b

Backup data is not assured as exact, complete and secure from alteration, erasure or loss through keeping hard copy or alternate systems.

Specifically, Non-sterile drug manufacturing, packaging and labeling operations are controlled by standalone Programmable Logic Controllers (PLC) accessed via multiple Human Machine Interfaces (HMI). These manufacturing, packaging and labelling processes include o@ oa hase which are all controlled by 4)a equipment however, none of the systems save data, can export data, and in many cases, critical process parameter data Oe etc.) cannot be saved and are not 4) documented elsewhere. This is a repeat observation from your firm’s 2025 FDA Inspection.

You do not have written procedures and process control procedures to ensure and document that all key process parameters are controlled and any deviations from the procedures are justified.

Specifically, The ©@® Non-Viable Particle Counters (NVPC) were not appropriately qualified. During qualification, the accuracy and completeness of the saved and printed audit trail data was not verified. Complete data including records of manual sample collection abortions, alarms and user log-ins were not accurate and complete, at the time the NVPCs were qualified. Furthermore, there

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

Specifically, A. Your firm was notified by your customer that)... batches ©) @ a mg tablets (Batches: O® exceeded the ju limit of not more thanga for ©®During the inspection we asked to review the batch manufacturing records for the batches. According to Technology Director, the firm’s role for the manufacturing of the 4 mg tablets is that of a contract manufacturer and the batch numbers that are provided are the customer’s batch numbers. Technology Director further stated that “they do not have any idea on how to track their batch numbers to the site”. When asked if this is the case for all customers that the firm contract manufactures for, the Quality Assurance Manager stated that all bulk batches manufactured for contract manufacture products cannot be traced back to the firm’s respective batches. The firm has a total of {4 bulk batch customers of whichw@ iS shipped to a United State customer. Since Zhejiang Huahai Pharmaceutical Co., Ltd. cannot trace back customer batch numbers there is no way of knowing of the traceability ofeach bulk batch manufactured product.

Equipment used during the m@ drug substance manufacturing operations occurring in the manufacturing building@@ _ at your facility are not adequately designed to ensure the prevention of contamination of equipment or product by environmental or processing conditions that would be expected to have an adverse effect on product quality.

Specifically, . ©) @) On September 13, 2025, during the step of the mw drug substance manufacturing process for batchm@ performed in building@@ roomm@ we observed a high level of condensation on the floor, on the m@ pipes, and on the m@ @@ tank containing the mw bag. The presence of condensation does not allow detection of leakage from the m@ bag.

Preventive maintenance procedure for equipment is inadequate.

Specifically, On September 15, 2025, during the discussion of the procedures related to preventive and routine maintenance, the head of quality indicated that document MNP-001, titled Preventive and Routine Maintenance, revision 10, effective March 18, 2025, describes the timing for preventive maintenance notification, preventive maintenance due date, and preventive maintenance due date extension. However, this information could not be found in document MNP-001 or in any other document.

Your disinfectant efficacy study is inadequate.

Specifically, Qualifications of o@ (report VLP-FR-8020) and@@ (report VLP-FR-8453) conducted on February 3, 2014 and December 11, 2023, respectively, were performed without the use of clean room isolates. According to Document QCP-091, Qualification and Evaluation of Antimicrobial Efficacy of Disinfectants, revision 3, effective date June 20, 2025, and version 0, effective date July 4, 2013, disinfectant efficacy studies should include at leastq@ most commonly detected and identified microorganisms in clean controlled production facilities.

Your environmental monitoring program is deficient.

Specifically, On September 17, 2025, during they drug substance filling operations for batch m@ occurring in the manufacturing buildings@ room@@ we observed the operator performing post- operation personnel monitoring. The fingerprint collection of the operator was not conducted properly (e.g., without rolling on the contact plate).

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

Specifically, You failed to perform a protocol-driven Performance Qualification (PQ) study for multiple equipment used during the production of o@ @) According to your Eguipment/System Impact Assessment Report (Document Number: IAR/SDEPS068/001-00 approved on 09/12/2023, IAR/SDEPS033-00 approved on 05/15/2023, IAR/SDEPS034-00 approved on 05/15/2023), the equipment are considered "Direct Impact" due to the reasons listed: A. we Equipment (ID No: »@ ) is an equipment that provides product identification information, which includes a lot number and expiration date. B. m@ _ Integrity Tester ID Nowm@ ) and @@ _ = Integrity Tester (ID No: w@ ) are equipment that impact the products safety, integrity, strength, purity, and quality and would impact the quality of the product if there is a malfunction to the equipment.

Specific identification tests are not conducted on components that have been accepted based on the supplier's report of analysis.

Specifically, . _: ne () (4) . Testing was not conducted for impurities, in the m@ 0) (Lot#e@ ) raw material prior to the production of the O® © mg/mL) exhibit/process validation batches: we

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

Specifically, A) The Quality Unit failed to approve appropriate finished and stability drug product specifications for oe mg/mL). According to the procedure titled “Quality

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, A) The sampling plan to visually inspectiN. mg/m), whieh is contained in wm bottle that does not allow for 100% visual inspection, is done via a o® _ testing method in which for visual inspection as per test procedure @ This sample size of is not representative of the batch, nor adequate to ensure that batches do not contain units with visible particulates. The batch sizes are: B) There are no alert and action limits established for the viable and non-viable environmental monitoring (i.e., air, surface, and personnel) for the Grade A-Grade D classified areas that are utilized to produce, fill, and package the drug, prot, lll ®t

Facility design and procedural controls for manufacturing drug substance intended for commercial distribution do not provide adequate assurance against microbial contamination and cross-contamination risks in the manufacturing suite at your Fujifilm Diosynth Biotechnologies USA Durham facility.

Specifically, A. Your firm has failed to establish a facility cleaning and sanitization program that effectively prevents microbial contamination in drug substance manufacturing areas and products. Despite the repeated isolation of spore-forming organisms including approximately 80 bacterial isolates and approximately 6 mold isolates from classified air spaces between January 2025 and the present and the rejection of at least batches due to contamination with these organisms since 2024, your firm continues drug substance manufacturing intended for sterile injectable production without determining root cause or implementing corrective and preventive actions. In several investigations launched for these recoveries, your firm's documented position that "there is no impact to process performance or product quality" is unacceptable and demonstrates a fundamental failure to recognize the serious contamination risks posed to sterile drug products. B. You do not perform routine monitoring of your ISO-5 conditions. Currently, environmental monitoring (EM) of these conditions is limited to major activities such as (Db) (4) , passaging of (b) (4), and bulk fill operations. You do not have EM

Your unexplained discrepancies associated with your processes are not thoroughly investigated.

Specifically, A. You opened several investigations after recovering mold in your processing rooms, supporting rooms, raw materials, and product in various stages of your process. From our review, we concluded the following were not thoroughly investigated: Event Reason for Investigation Mold Recovered Reason for Inadequate Number Investigation PR Filamentous mold recovery in Talaromyces rugulosus The root cause was not identified. 386943 (b) (4) Viral(b) (4) pool of Batch was released. © lot(b) (4) . PR Mold in (b) (4) viable air | Cladosporium allicinum/ No root cause was identified, and 327905 sites. cladosporioides/ cucumerinum/ no remediation was performed. herbarum/ macrocarpum/ phaenocomae/ ramotenellum PR Mold recovery in batch Aureobasidium melanogenum No root cause identified, 380876 (b) (4) during (b) (4) inadequate corrective actions. Post Hold. Batch was ultimately rejected. PR Mold recovery in batch Paenibacillus glucanolvticus/ No root cause identified, no 353881 (b) (4) during (b) (4) Purpureocillium lilacinum. identified impact to product or (b) (4). process, and inadequate corrective actions. Batch was ultimately rejected.

Your procedure for testing (b) (4) after use in your drug substance processing is inadequate in that in does not limit of times it could be tested.

Specifically, your written procedure for testing process (b) (4), SOP-01444, Use and (b) (4) Testing of Solution and (b) (4) Assemblies in the Manufacturing and Facilities, Version 22, has a limit of(©) (4) (b) (4) tests before contacting the area manager. Per this procedure, the area manager can approve additional (non-defined) (b) (4) _ testing. This procedure is inadequate to detect (1b) (4) failures.

You have not ensured your microbiological methods are suitable for your operations.

You have not performed a risk assessment or evaluation to determine if your current bioburden methods of testing for both total aerobic microbial counts (TAMC) and total yeast microbial counts (TYMC) using both ©) @) and (®) (4) media is suitable for recovering organisms that could potentially posea risk to patients in light of the spore forming isolates (bacteria and mold) routinely recovered in your facility. Per your Sr. Quality Director, your organization “does not have a tolerance for spore-formers” and further stated “mold is bad.” Your current process does not screen for specific organisms. Per your Sr. Scientist of Microbiology, there is no trigger to evaluate the capability of the methods once its approved for use. Digitally signed by _ ' Saundrea Saundrea A. KAYLA V.__ Digitally signed by A. Munroe Munroe-s SPRAGUE SACUE S Date: 2026.03.27 ~ ; ; S 1aess one S Date: 2026.03.27 13:57:23 -04'00'

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

Specifically, A) Your firm failed to thoroughly investigate Out of Limit (OOS) investigations that were initiated in response to personnel monitoring samples that exceeded the specifications for the controlled classified spaces, specifically Grade A and Grade B, which are utilized to produce" sterile drug products. The corrective and preventative actions instituted did not address the root cause of the persistent personnel monitoring recoveries to mitigate sterile drug product quality impact. There were approximately 189 personnel monitoring Out of Limit (OOL) investigations from 06/2023-03/2026; 80 of the investigations describe isolates that were classified as objectionable microorganisms. The following are some examples of the investigations which have inadequate corrective and preventative actions: Investigatio Initiation Sterile Summar Batch nNo. Date Drug y Released Product Date Deviation- 02/09/2024 (b) (4) Recover 04/05/2024 008745 ed gram negative objectio nable lot # (6) (4)- organis

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

Specifically, The facility procedure and work instruction that describes the cleaning and disinfecting of controlled classified spaces (i.e., Grade A-Grade D) are titled “Baltimore (BPII) Production Facility Cleaning” and “Baltimore (BPII) Production Facility Cleaning Work Instruction,” respectively. The firm produces "® sterile drug products in the facility controlled classified areas. The aseptic core facility cleaning is performed ona (b) (4) and (b) (4) basis. The procedure indicates for equipment, (b) (4) surfaces, and (B) (4) to be wiped with (b) (4) _ following a (b) (4) disinfectant (i.e., (DB) (4) and (b) (4) Solution) contact time; however, it is not effective in removing the disinfectant residue. During the walkthrough on 03/12/2024, we observed apparent disinfectant residue on the (b) (4) panels that encompasses the (b) (4) Vial Filler (Equipment ID # (b) (4) _ ), (b) (4) and a (b) (4) table located in the controlled classified areas.

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

Separate or defined areas to prevent contamination or mix-ups are deficient regarding the manufacturing and processing operations.

Specifically, A. There is a lack of assurance that your cleaning procedures for process equipment are effective in preventing cross contamination. For example, i. The initial qualification of the (b) (4) (Equipment No. (6) (4) _) with respect to cleaning verification (Protocol No. 20-1690-PQ), as well as the routine cleaning verification of the ©)@ (b) (4) (Equipment No. (b) (4) ; FRM No. 019668), are deficient. Specifically, for both (b) (4) —_, (b) (4) swab sampling is limited to the (Db) (4) only. No samples are collected from other relevant product-contact or adjacent internal surfaces, including the (b) (4) , doors, and (b) (4) . In addition, no rinse samples are collected. Accordingly, the cleaning verification program is inadequate and does not provide sufficient evidence to demonstrate that the cleaning procedure is effective. ii. The cleaning verification for HEPA ©) @) is limited to visual inspection. In addition, SOP 017803 v9.0 for ®® cleaning and sanitization is deficient because it lacks validation data and predefined acceptance criteria to demonstrate cleaning effectiveness. Specifically, the SOP does not reference studies showing removal of product residues or micro

Laboratory controls do not include the establishment of scientifically sound and appropriate

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

Specifically, A- Your firm lacks adequate assurance that critical equipment and systems used in the manufacture of

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

Specifically, a) Your firm failed to reject lot #(b) (4) of (b) (4) bottles after it was noted there were imperfections in the (b) (4) during incoming inspection of the lot. The lot was then used to fill Lot #(b) (4) of (6)(4) on (b) (4) and Lot #(b) (4) — of (b) (4) on (b) (4) . Lot #(b) (4) Lot #(b) (4) were distributed. Lot #(b) (4) was placed on stability (b) (4) and long term) and was out-of- specification for (b) (4) assay at the (b) (4) _ timepoint for (b) (4) stability. The long term stability study was not continued after the (b) (4) timepoint. Your firm has no documentation addressing the cessation of the long term stability study for this lot.

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

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 received out-of-specification (OOS) test results for the following stability lots and timepoints for (b) (4) ((b) (4)): e Lot #(b) (4) at (b) (4) ((b) (4) ) ¢ Lot#(b)(4) at (1b) (4) (6) (4) ) Your investigation into the OOS’s invalidated the test results based on the fact that the samples were tested more than 10 days and/or 6 weeks past the pull date. Your firm has no

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

Specifically, your firm failed to perform an adequate process validation for new products to ensure that the manufacturing process is in a state of control. No appropriate control strategy was established to guarantee the process consistently produces product that meets predetermined specifications before commercial distribution, including all stages of the process, new ingredients, and test methods. Your firm manufactured and released (b) (4) batches of (b) (4) (6) (4)) using only data from one batch, stating this constituted adequate process qualification for a new filling line. Also, your firm manufactured and released (b) (4) batches of (b) (4) ((b) (4)), stating the existing components and filling line support validation completion using only one batch. All (6) (4) batches were released for commercial distribution under a concurrent approach prior to collecting sufficient data for statistical analysis of process performance, including © (b) (4) lots (b) (4) distributed on (b) (4) , and ©) @ (b) (4) lots (b) (4) distributed on (b) (4) ;

Failure to reject any lot of drug product containers that did not meet the appropriate written specifications for identity, strength, quality, and purity.

Specifically, your firm failed to reject lot #(b) (4) of (b) (4) bottles after it was noted there were imperfections in the (b) (4) during incoming inspection of the lot. The lot was then used to fill Lot #(b) (4) —_— of (b) (4) on (b) (4) and Lot #(b) (4) _— off (b) (4) on (b) (4) . During filling of lot #(6) (4) _, leaking bottles were noted that were attributed to the imperfections found at the incoming inspection of the (6) (4) bottles.

Each component is not tested for conformity with all appropriate written specifications for purity, strength, and quality.

Specifically, Your firm failed to ensure that all required compendial tests for materials used in the manufacture of OTC drug products are performed in accordance with USP monographs. Your firm conducts testing using a contract laboratory on each component received to support the supplier's CoA, however, the testing does not always include all compendial tests, and acceptance criteria are not always aligned. Examples include, but are not limited to

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, a) The cleaning validation study protocol # QA.VA.106, performed for equipment used in batch formulation of@@ over the counter (OTC) drug products is deficient in that: i.No documentation of microbiological examination testing to demonstrate that the cleaning procedure effectively removes microbial contamination. ii. The cleaning validation protocol and report fails to document the specific drug product(s) utilized during the validation study. iii. There is no scientific justification for the omission of direct surface sampling. The sampling methodology relies exclusively on rinse sampling to evaluate cleaning effectiveness. iv.While the protocol references SOP # HOMA-DKJKQP for the cleaning procedure, the execution records fail to document the specific cleaning steps performed, and the identity of the cleaning agents used. v.There is no evaluation of solubility of all material used in the manufacture of drug products. For example, (b) (4), an active ingredient in the (b) (4) ((6) (4)) is only slightly soluble in water. b) Your firm uses (b) (4) Detergent for the cleaning of equipment used in batch formulation off) OTC drug products. Your firm has no documentation to

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

Specifically, you failed to perform re-qualification of your real time and (b) (4) stability chambers # (b) (4) respectively, after moving to your new suite #110 in August 2023.

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

Specifically, on 03/16/2026, | observed that your firm had not calibrated the in-line (6) (4) (b) (4) used to test (b) (4) in the manufacture of P@ OTC drug products. The calibration was due in May 2025.

Permitted variations in the amount of component necessary are not reasonable and not specified in the master production and control records.

Your master production and control records did not include a statement of action limits on radiochemical yield. Your master production and control records did not include complete special notations and precautions to be followed. Specifically, A.You did not include the recording and reconciliation of all inputs and outputs in your production batch records to demonstrate that your production process is in a state of control and that you can consistently produce predictable batch yield and quality. For example, the following batches have varied cyclotron irradiation times from (b) (4) ; varied cyclotron charge amount; cyclotron calculated radioactivity generated; and resulting ® radioactivity at Start of Synthesis (SOS); final product vial (FPV) radioactivity at end of synthesis (EOS); and assay concentration from (b) (4) .

Your batch production record did not include labeling.

Specifically, During the review of batch records we found inconsistencies with batch record product and shield/packaging labels. For example: PPQ batch records (b) (4) and batch (b) (4) contain a single product vial label with lot number, date, total activity, volume, and expiration date and time. Batch records (b) (4) contain a single vial label but this label is different from the” batches above as it only contains lot number, date, and expiry date and time, but not activity. Batch(b) (4) did not have any product labels.

You did not review production records to determine whether errors had occurred.

Specifically, A.Expired reagents and materials were used in the production of PET batches, including but not limited to the following: Batch Record (b) (4) was produced using ™® expired (b) (4) Lot expired 10/2025, and (Bb) (4) unit Lot (Bb) (4) expired 2025/09. This was not documented in the batch record as a deviation nor was it noted on the deviation log. Batch Record (b) (4) labeling discrepancies. Product vial label has expiry time of(D) (4) at (b) (4) label had expiry time(b) (4) Also, the incorrect @ activity @ EOS (b) (4) is the starting level however the label should have the level after the process was completed which was (1) (4) no documentation in the batch record as a deviation nor was it noted on the deviation log. Expired (9) (4)” (b) (4) Lot (b) (4) expired 2025-12-31 were used with no documentation in the

You did not establish and follow written quality assurance procedures.

Specifically, Your firm did not establish adequate environmental monitoring procedures to ensure that the ISO-S, ISO-7, and ISO-8 classified areas used to produce(B) (4) PET drugs are consistently made in safe environmental conditions. e Standard Operating Procedure DOC-417, Environmental Monitoring Policy, version 1.1, effective 11/18/2025, describes that environmental monitoring sampling and testing will be conducted after (©) @) (b) (4) and by third party vendor(b) (4) HEPA filter recertifications, and additionally () (4) even when there is not activity. (b) (4) EM has not been done over the past 2 years, from the period of 4/24/2024, when the

You did not have written production and process control procedures to ensure that any deviations from the procedures are justified.

Specifically, 2026-0217-1 - CAPA still open with outstanding work not completed and no additional comments of status or when it will be completed. Doc 131 Inventory Management SOP was supposed to be finalized by the end of February. As of this inspection it has not be completed and the CAPA has not been updated with current information Additionally, the Change Control Program 102 states that changes in operating procedures are not recorded as change controls but instead are listed under change Document Request Policy 111, but this practice is also used for implementation of new procedures. The nature of the change or policy and significance or risk assessment is not included the determination of whether a change control or a document change request is used. This decision between the two processes does not cover criticality or process changes.

You did not establish written procedures describing the identification of components.

Specifically, your procedure unique document # 132 entitled Materials Acceptance effective Feb 16, 2026, states you will use a unique unit control number to identify all incoming lots of components and if you received several shipments of the same product with the same lot number on the same day each shipment would get its own unique identifier. Your SOP does not address receiving the same product with the same lot number on a different day.

You lack personnel with the necessary training and experience to perform their assigned functions.

Specifically, The firm has begun to provide basic GMP training, however, the managers acknowledged lack of awareness of GMP documentation, the need for consistent production processes, and to establish in- house evaluations and validations of microbiological, cleaning, and other procedures. No validation studies were performed in-house for cleaning and disinfectant efficacy, environmental monitoring, microbial media incubation conditions, or other relevant procedures with scientific bases to support the reason for the procedures used. Training on standard operating procedures is not documented. A review of the training record for the assistant cyclotron operator to be cross-trained to perform QC testing lacked documentation and evaluative assessment of the understanding of the relevant standard operating procedures. Complete training records for all employees covering common or specific work activities was not available. For

You did not implement your sanitation monitoring and corrective action procedures.

Specifically, Your firm manufactures frozen ready-to-eat (RTE) ice cream, dairy and nondairy desserts (eg. ice cream cones, sandwiches, bars, and fruit bars). Your hazard analysis for “Round Top Drumsticks,|| @ dated 11/22/25 identified the hazards: “Pathogen Contamination: Listeria” and “Pathogen Contamination: Salmonella” from theIGA steps to the(Gy steps where RTE products are exposed to the environment and are handled by your employees. Recontamination with environmental pathogens is a foreseeable hazard at these steps requiring sanitation preventive controls. Your written sanitation procedures (eg. Pathogen Monitoring Program Procedure, Pathogen Monitoring Adaptation, Bakersfield Sanitation Procedure, line specific sanitation procedures, and Production Listeria Treatment Form (also called Listeria clean)) were not implemented to control Listeria contamination because your environmental monitoring records continue to show confirmed positive for L. monocytogenes in zonesff and throughout the production and auxiliary areas as summarized in the table below. Zone may be 1.5 feet away from exposed products (eg. (GAY (GM) cart) and Zone may be 6-7 feet away from exposed products.

Your written sanitation preventive control procedures were not appropriate to significantly minimize or prevent the hazard requiring a preventive control.

Procedures describing the handling of written and oral complaints related to drug products are deficiently written or followed.

Specifically, the quality unit failed to identify appropriate root causes and to implement corrections to reduce and adequately address the number of complaints for ©@® drug product, oa For example, Since 2024, the site received approximately 845 complaints related to9) drug product batches distributed to the US. The complaint review indicated significant number (approximately 50%) of the complaints were related toy) _ malfunction such as ae )(4) ©©® as follows

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

Specifically, in the video for airflow visualization studies ofthe aseptic _ filling line used to produce all drug products (VALQ - 8900 - L3-2b, performed on August 1 Sth, 2023), the qualification of the 9)4» @@ intervention to add unopened stopped bags showed that airflow from the 4, _ filling unit into the stopper loading station causes a void over the unopened stopper bags, preventing first-pass airflow from reaching the bags while the, 4» The stopper bags are not further disinfected before they are opened tO &

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

Specifically, requalification for employees performing 100% visual inspection for particulates on (uy Ba is performed ome after each employee has completed inspection of O@ despite the fact that the employees will inspect up to 4)» during 4«) There has been no initial or requalification afterg, 45 ) inspection to demonstrate that the employees can perform the operation adequately 9)

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

Specifically, the quality unit failed to ensure environmental monitoring trend reports are generated as required under SOP-0509, Trending of environmental monitoring data. For example,

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, Investigation of OOS result is inadequate. No root cause or probable root cause was identified. Your firm changed release acceptance/specification without re-validation of the manufacturing process and release drug products to commerce. Investigation for A/OOS/QC/2024/003 was initiated 11/11/2024 regarding OOS results for product (b) (4) for ®® (b) (4) , Batch # (B) (4) . The (Bb) (4) failed at 72,000 (specification is (b) (4) No root cause or probable root cause was identified. You change the (b) (4) release acceptance/specification to a minimum of (b) (4) _—without scientific justification or re-validation of the manufacturing process. Batch No. (b) (4) (Mfg. Date (b) (4) —_, Exp. Date (6) (4) ) in total units were released to the commerce.

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.

The accuracy of test methods have not been established.

Specifically, Your firm’s test method for microbial release of OTC non-sterile drug product is inadequate. You use the commercially available (b) (4) system to detect total aerobic microbial count (TAMC), total yeast & mold count (TYMC), and objectionable organisms release testing for your OTC non-sterile drug products. Only 9 out of ®* non- sterile drug products were validated using the (b) (4) system also, known as the (b) (4) (b) (4) . Review of the (b) (4) method validation revealed it to be inadequate.

Records were not maintained concurrently with the performance of each step.

Specifically, incubation times for the (b) (4) are not concurrently . (©) (6). ©)(7) . . 5 . documented. On 9/9/2025, technologist © was observed recording the incubation stop time (b) (4) the (b) (4) of incubation. When questioned, the technologist stated that the time recorded represented the (b) (4) rather than the (BD) (4) the plate (6b) (4) from the - . (©) (6). (0) : incubator. A second technologist, “™ confirmed that they were trained to document (b) (4) (b) (4) . This practice does not ensure accurate and contemporaneous recording of incubation stop times.

The quality program does not include the investigation and the documentation of HCT/P deviations relating to core CTGP requirements.

Specifically, approximately 21 failed test runs from June 2024 to present were reviewed and 18 appeared to be lacking details specific to the investigation, outcome, and actions taken. For example: a) (b) (4) Failed Run Report dated 4/5/2025 documents that the cause of fail is (b) (4) b) (b) (4) Failed Run Report dated 2/3/2025 documents that the cause of fail is (b) (4)

Records did not identify the person performing the work and were not detailed as necessary to provide a complete history of work performed.

Specifically, your batch checklist forms of various test records were missing information. For example: a) (b) (4) , dated 9/1/2024, did not contain the plate reading time and time out and time in information for the test kit. b) (b) (4) , dated 9/1/2024, did not contain the batch number, initial and date of the technologist performing the work, and time out and time in for the test kit. c) (b) (4) , dated 9/1/2024, did not contain the technologist who performed the _ (b) (4) and time out and time in for the test kit. d) (b) (4) , dated 9/9/2025, did not contain the stop time after incubating the samples. e) (b) (4) , dated

Records are not concurrently maintained with the performance of each significant step in the processing of each unit of blood and blood components so that all steps can be clearly traced.

Specifically, During the inspection on 01/09/2026, Plasma Processoi@® was observed with a plasma bottle rack containing processed plasma bottles that had not been placed into the freezer for initial freezing. Review of the bottles in the rack showed that five plasma bottles had exceeded your! (B) (4) processing window between collection machine removal and freezer placement, yet the (1D) (4) labels documented compliant freezer placement times. Labels affixed to four bottles indicated a freezer placement time of© and one bottle of 2): however, the time of observation was © @). The remaining plasma bottles in the rack were within your established (b) (4) processing window. The five plasma bottles affected: (b) (4), documented removal at ®). Documented placement into the freezer at (b) (4) (b) (4). documented removal at® @). Documented placement into the freezer at ©) @)_ (b) (4) , documented removal atf®) 4). Documented placement into the freezer at (b) (4). (b) (4), documented removal at (©) (4) Documented placement into the freezer at (b) (4). (b) (4) , documented removal at )@). Documented placement into the freezer at ®) @)_ Upon discovery, the bottles were segregated but had not

The summary of records for HCT/Ps from donors determined to be ineligible based on screening and released for limited use did not contain a statement noting the reason(s) for the ineligibility.

Specifically, you fail to state the reason (s) of ineligibility for the following directed donors: Donor initials or number Eligibility determination Donated Tissue Reason for ineligibility Ineligible 1/31/20 Semen Risk assessment (born or sexually intimate with someone from certain countries in Africa) Ineligible 2/13/20 Oocyte Risk assessment (born or sexually intimate with someone from certain countries in Africa) Ineligible 11/16/22 Oocyte Physical exam (body piercing – ); risk assessment (tattoo, body piercing – Ineligible 12/5/24 Semen Physical exam (history of sexually transmitted diseases); risk assessment (Men who have had sex with another man in the preceding 5 years) Ineligible 12/16/24 Semen Risk assessment (born or sexually intimate with someone from certain countries in Africa), positive HBV (core)

You did not establish and maintain procedures that address the accompanying records after the donor eligibility determination is complete of HCT/Ps.

Specifically, you fail to have procedures established that describe how to complete a summary of record and accompanying records. From 2/24/23 – 7/1/24, your summary of records were missing the statement that testing was performed by a Clinical Laboratory Improvement Amendments certified laboratory. I observed summary of records for directed semen and oocyte donors where the statement was missing. From 12/4/19 – 1/25/23, your summary of records were missing the results and interpretation of the Hepatitis B virus Nucleic Acid Test. I observed summary of records for semen and oocyte donors (anonymous and directed) where the results and interpretation of the HBV NAT testing were missing. Since 12/4/2019, you have determined donor eligibility and created summary of records for oocyte (directed and anonymous) donors and directed semen donors. From to current, you did and do not have established or maintained a procedure for the summary of record and accompanying records.

HCT/Ps from ineligible donors which were made available for limited use were not prominently labeled with a statement warning of communicable disease risks.

Specifically, semen, oocytes, or combined reproductive tissue from directed ineligible donors did not include the label “WARNING: Advise patient of communicable disease risks.”

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

Specifically, lA. Your Quality Unit failed to: a. Ensure the timely implementation of corrective and preventive actions for the observed dried and cracked: <Redacted B4> settle plates used for environmental monitoring and then incubated in a <Redacted B4> incubator. Please refer to OBSERVATION 1: . b. Conduct adequate root-cause analyses for the ongoing Environmental Monitoring (EM) and Personnel Monitoring (PM) excursions. The Quality unit also failed to perform effectiveness checks on the implemented corrective and preventive actions. as evident by persistent fungal and bacterial recoveries despite implementing corrective actions in the clean room areas. Please refer to OBSERVATlON 2 and OBSERVATION 3: . c Investigate the root cause of visual inspection failure during initial 100% inspection before proceeding to secondary/tertiary inspection of the filled syringes. Please refer to OBSERVATION 4: . d. Evaluate air flow patterns under dynamic conditions in all ISO 5 classified BSC cabinets in the clean room. Please refer to OBSERVATTON 3.

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

Specifically, 2A. Your firm's environmental monitoring program failed to prevent or adequately address repeated fungaJ (mold) contamination in ISO Class 7 and ISO Class 8 classified areas adjacent to ISO Class 5 Primary Engineering Controls. The environmental monitoring data collected between July 2025 and April 2026 document at least twenty-two (22) separate fungal excursion events across ISO 8 rooms (Rooms 4, 7, and 8) representing a recurring and unresolved pattern of mold contamination in the classified cleanroom environment supporting aseptic compounding operations. The following is the list of twenty-two (22) documented fungal contamination events in the clean room area

Production personnel were not practicing good sanitation and health habits.

Specifically, Your firm failed to establish and maintain adequate controls to prevent repeated objectionable microorganism recoveries during personnel monitoring (PM) activities in TSO Class 5, ISO Class 7, and ISO Class 8 classified areas. Environmental monitoring records document eleven (11) personnel monitoring excursion events involving bacterial contamination from personnel gowning samples (chest. forehead, forearm) and fingertip samples collected between April 2025 and February 2026. Multiple excursions involved objectionable gram-negative organisms. The assigned root causes were generally insufficient aseptic gowning technique, improper material transfer, cleaning or personnel movement The following is the list of eleven (11) documented contamination events: Investigation Date of Sampl e Operator Sample Type Room ISO Cl ass CFl Count Organism(s) I dentified Lot Impacted Units R ejected Root Cause EM-25-001 NCR-25-013 16 Apr 2025 <Redact ed B4> <Redacted B4> Chest Room 2 / ISO 7 15 CFU Corynebacterum segmentosum Actinomyces oris/naesiundi Staphyloccus epidermis Staphyloccus captis <Redacted B4> Ineffective aseptic echnique during gowning and personnel movement EM-25-002 NCR-2

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 conduct, or document, an investigation into the root cause of visual inspection failures prior to proceeding with secondary and/or tertiary inspections. A review of ophthalmic lot visual inspection records spanning from March 2025 through early 2026 identified forty-four (44) lots in which the firm proceeded directly to secondary inspection following a primary visual inspection failure which was characterized by major reject rates exceeding the <Redacted B4> acceptance limit and/or major defects found at the primary AQL stage. There was no documented investigation and root cause analysis into the source and cause of these recurring defect types prior to reinspection. In addition <Redacted B4> lots <Redacted B4> proceeded to tertiary inspection after secondary inspection also failed, again without a documented investigation. The predominant defect types identified were intrinsic particulate and product fill volume defects.

An MDR report was not submitted within 30 days ofreceiving 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, your firm has not reported apparent malfunctions for the device constituent part of your firm's combination drug and medical device product (Vonvendi). The combination product's primary mode of action relates to the biologic drug product (recombinant von Willebrand factor). The medical device constituent part (Mix2Vial) is used for reconstituting the lyophilized drug product. Medical Device Reports (MD Rs) were not submitted for the following complaints regarding "Incomnlete Diluent Transfer:' (i.e., incomplete transfer of diluent via the device): product code (product code (product code ; (product code (product code and (product code In addition, an MDR was not submitted for the following complaint regarding a "Defective Device": product code .

The batch production and control records are deficient in that they do not include the identity of major equipment and lines used.

Specifically, there was no identification of critical equipment throughout batch production records. For example, the batch production records for ADV ATE®, Drug Product Batch and its corresponding BAXJECT III®, Finished Drug Product (FDP) Batch failed to include identification of: A. B. C. (b) (4) *DATES OF INSPECTION 9/10/2025(Wed), 9/11/2025(Thu), 9/12/2025(Fri), 9/15/2025(Mon), 9/16/2025(Tue), 9/17/2025(Wed), 9/18/2025(Thu)

The phlebotomy site is not prepared by a method that gives maximum assurance of a sterile container of blood.

During observations of collection procedures, Specialists were individually observed preparing venipuncture sites for separate donors. The following deficiencies were observed: A. The venipuncture sites were prepared using and that are labeled as "Non-sterile Solution." B. After preparing the venipuncture sites with the and , the Specialists were observed placing directly onto the venipuncture sites while the solution was still drying. Additionally, on 8/28/2025, a Specialist was also observed preparing a donor's venipuncture site without utilizing as directed by the manufacturer. The manufacturer's instructions for use specify: "

Written standard operating procedures including all steps to be followed in the collection and processing of blood and blood components for allogeneic transfusion and further manufacturing purposes were not always established and maintained.

Specifically, A. Your firm does not have written procedures governing donor follow-up activities for donors who experienced adverse reactions during the donation process. B.Your firm’s current procedure titled, “Anti- Hepatitis C Virus System” (Version 1.0, Effective date: 1/19/2021), does not contain detailed instructions for performing testing operations. Instead, your procedure instructs personnel to reference the System Operations Manual.

Your facilities are not adequate to ensure the prevention of contamination of equipment or product by substances, personnel, or environmental conditions that could reasonably be expected to have an adverse effect on product quality.

Specifically, A. You failed to assess, investigate or perform corrective and preventable actions (CAPA) following the recovery of a highly pathogenic and objectionable microorganism from inside your ISO 5 PEC Hot Cell-8. Your hot cell is comprised of an enclosed ISO 8 space surrounding and supporting a centrally located (b) (4) _— airflow ISO-5 Primary Engineering Control (PEC). For example, a 1 Colony Forming Unit (1 CFU) of fungal was recovered in your (b) (4) active air sampling of your ISO 5 PEC Hot Cell- § On 2/7/2025. In addition, I Colony Forming unit of Aspergillus Hiratsukae shendaweii was recovered on 10/2/2024 and one colony forming unit (1 CFU) of Talaromyces delawarensis was recovered on 10/8/2024. You did not conduct an investigation further into the excursion of the ISO 5 PEC Hot Cell-#, implement corrective and preventable actions, nor did you identify the specie of the fungal organism recovered on 2/7/2025. Your SOP D0012135, “(b) (4) Environmental Monitoring for Fungal “Revision K, dated 10/31/2020, had details those recoveries of 1 CFU of fungal in the ISO 5 PEC Hot Cell- & is handled as an alert action which is inadequate as it fails to investigate recoveries of

Your process controls did not include control of in-process materials to ensure that the materials are controlled until required tests or other verification activities have been completed or necessary approvals are received and documented.

Specifically, you do not have an in-process check on the (b) (4) target material for radioactive content. This material is returned to you as reprocessed product from all your domestic sites for re-use in your PET drug product manufacturing processes. (b) (4) batch (b) (4) used (b) (4) part No (b) (4) Lot Number (b) (4) for its manufacturing process and was released by your Quality unit on August-20-2025.

The RDRC did not assure that the investigator utilized adequate instrumentation for the detection and measurement of the specific radionuclide.

Specifically, you failed to qualify your™® oven operating temperature range to ®° C. Your current Equipment Installation and Operational Qualification Report for (b) (4) dated December 22, 2023, was qualified between the temperature ranges of (6) (4) ° C to (6) (4) ° C to (b) (4) °C - (©)(4)°C. This does not support most analysis which requires °C oven temperature. *DATES OF INSPECTION 2/09/2026(Mon), 2/10/2026(Tue), 2/11/2026(Wed), 2/13/2026(Fri), 2/17/2026(Tue)

Drug product component testing is deficient in that at least one specific test to verify the identity of each component is not performed.

Specifically, a. Your firm uses deionized (DI) water to clean and sanitize equipment used for manufacturing bulk OTC drug products. Your firm failed to assure that water used in the cleaning of equipment used in pharmaceutical production was adequate for pharmaceutical production in that the water system does not have routine testing for microbial contamination, TOC (Total Organic Carbon), and conductivity. Your firm performed TOC and conductivity testing only during the limited timeframe of August 5, 2025, to August 13, 2025. Your firm failed to provide documentation demonstrating that DI water does not require routine TOC, conductivity, and microbial testing. b.According to your firm SOP, SOP number: SOP-119, SOP Title: Water Analysis (Ver. 01, effective 12/15/2020), Section 4.3, requires testing of city water and processed water (b) (4) During review of your firm water testing folder titled” Micro Water Results Current” revealed that there was there was inconsistency in microbial testing and no documentation for analytical testing (BD) (4) of the city water and in-house deionized water. c. Your firms SOP number: SOP-119, SOP Title: Water Analysis (Ver. 01, effective 12/15/2020),

Results of stability testing are not used in determining appropriate storage conditions and expiration dates.

Specifically, Your firm manufactures ™ bulk drug products, (b) (4) and distributes them to your customer 1n() (4) for filling and packaging. Your firm failed to perform active pharmaceutical ingredient (API) identity and strength testing on bulk products prior to release and distribution to your customer in (B) 4) Specifically, your firm manufactured and distributed below lots of(D) (4) pera ESSER | am |

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 quality unit failed to follow your firm’s SOP Number: SOP-128, SOP Title: Annual Product Review (APR) for OTC Drugs, Ver. 01 to conduct Annual Product Review (APR) for your firm’s bulk over the counter (OTC) drug products time frame 2022 — 2025 pera ESSER | am |

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, a. Your firm failed to establish cleaning validation to verify that current cleaning practices for oe shared equipment, that could prevent the cause of cross contamination. Your firm uses Tank and Tank’ ~~‘for compounding both drug products and cosmetics. Your firm’s batch records for OTC bulk products do not include the equipment IDs to identify which compounding tank was used to manufacture the OTC drug product. b. Your firm manufactures bulk drug products, (b) (4) , for your customer in (6) (4) for finished packaging. Your firm failed to provide documentation demonstrating that the manufacturing process has been validated or designed to assure drug product strength and quality.

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

Specifically, During review ofbatch records with Lot Numbers: (b) (4) your employees failed to follow your firms SOP, SOP number: SOP-102, SOP Title: Good Documentation Practices; version: 01 section 4.0 — Procedure to perform corrections on errors. Your firm’s batch record with batch number (®)(4) employee". corrected the "release#" for (b) (4) (b) (4) with his initials on the pre-weight/Work Order Picklist section but failed to add a

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

Specifically, a. According to your firm's SOP-103 "Employee Training Program," Section 4.3, all employees must complete (B) (4) refresher training by (Db) (4) However, your firm failed to provide CGMP training records for senior management, including the Production Director, CEO and COO since last inspection 2022. b. Additionally, your firm failed to review your employees' GMP training records. During review of the 2025 CGMP training folder, the GMP quizzes that your firm's employees completed on September 12, 2025, were incomplete and missing the "qualification determined by" signature and date fields. PRODUCTION SYSTEM

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

Specifically, Your firm manufactures ® bulk drug products, (b) (4)

Failure to ensure the study is conducted in accordance with the protocol and/or investigational plan.

Specifically, Review and evaluation of information regarding the safety of the drug used in study (©)(@) was a responsibility maintained by your firm and was not transferred to a third party. You did not ensure adequate oversight of the vendor responsible for serious adverse event (SAE) case review and reporting. This vendor made an error while updating permissions for user roles for the study which granted the blinded PV staff access to potentially unblinded safety information for subjects in this study. This access was granted in May 2023 to five blinded PV staff on the study at the time and lasted over 7 months until January 2024. Two blinded PV staff members at your firm accessed suspect adverse reaction reports for study (©)(4) quring this period, and did not report the access issue internally per quality procedures. You remained unaware of this access permissions issue until August 2024, and unaware of the full scope of the access permissions granted until November 2025. A corrective and preventive action (CAPA) plan was not initiated by your firm until January 2026. *DATES OF INSPECTION 3/09/2026(Mon), 3/10/2026(Tue), 3/11/2026(Wed), 3/12/2026(Thu), 3/13/2026(Fri), 3/16/2026

Your hazard analysis did not identify a hazard that required a preventive control.

Your hazard analysis did not identify the following hazards as requiring allergen, sanitation, or process preventive controls when one was needed: 1) undeclared allergens due to allergen cross-contact, 2) undeclared allergens due to incorrect labeling, 3) recontamination with environmental pathogens, and 4) metal. Allergen Controls Your firm manufactures products that contain several allergen ingredients, such as wheat, milk, soy, egg, peanut, sesame, and tree nut (walnut and almond). Not all finished products contain all seven major food allergens and there is no dedicated equipment for each allergen profile. Your written hazard analysis and food safety plan for ready-to-eat (RTE) ambient products dated 7-31-2024 did not determine the chemical hazard of (1) undeclared allergens due to allergen cross-contact requires a a preventive control at steps in the process where a control is required. Additionally, your hazard analysis identified the hazard of allergens as requiring an “Allergen Control — allergen labeling at packaging”, however, you did not implement an allergen preventive control for the chemical hazard of (2) undeclared allergens due to incorrect labeling at the appropria

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

Specifically, on 03/12/2025, 03/13/2025, and 03/17/2025 we observed the following during the inspection: e We observed a folded and wrinkled wad of(6)(4) covered in loose powder ingredient that was wedged in a crevice of one of the dough press machines between the food contact conveyor belt and the framing of the machine. This (6) (4) was in direct contact with the food contact surface of the conveyor belt. The (by (4) had approximately 20 apparent live beetle larvae and approximately 10 apparent live adult beetles in, on, and around it. There were apparent larvae trails in the loose powder ingredient on and adjacent to the food contact surfaces of the machine. There was powder residue in, on, and around the food contact surfaces of this dough press machine and the dough divider machine, which had been cleaned @)/@) nights prior, according to your (b) (4) . These machines are used in processing bread dough prior to the bake step. e Approximately 20 apparent rodent excreta pellets (REPs) and apparent nesting material inside the framing of the dedicated pastry oven located in the@@) corner of the filling room. RTE in-process products such as mini cream cheese cakes, were seen tempora

You did not clean your non-food contact surface in a manner and as frequently as necessary to protect against contamination.

Specifically, on 03/14/2025, we observed the fan used to cool RTE finished product after it exits the oven had brown residue on the (6)(4) blades and front metal grill, We observed this fan being used to cool RTE finished product on 03/12/2025, 03/13/2025, and 03/14/2025, including the RTE vanilla sponge cake, which was then used to make the vanilla sponge cake with lemon jam. Your Factory Supervisor stated that this fan is also used to cool RTE finished products such as Taiwan Toast and Large Walnut Cookie.

You did not clean and sanitize your utensils or equipment as frequently as necessary to protect against contamination of food.

Specifically, we observed the following during the inspection on 03/17/2025

You did not take a reasonable measure or precaution related to personnel practices.

Specifically, we observed the following during the inspection: -On 03/17/2025 during the dough mixing for Taiwan Toast, we observed a bucket of® ingredient stored directly on the production floor. An employee transferred the™® to the dough mixer and touched the bottom of the bucket that had been in direct contact with the floor. The employee transferred the mixed dough from the dough mixer into (b)(4)) totes by directly touching and moving the dough. The employee did not wash their hands. *DATES OF INSPECTION 3/11/2025(Tue), 3/12/2025(Wed), 3/13/2025(Thu), 3/14/2025(Fri), 3/17/2025(Mon), 3/19/2025(Wed), 3/20/2025(Thu), 3/24/2025(Mon), 3/26/2025(Wed) Breena L D’Ambrogi X Stetsses

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, 1.During the facility walk-through of the QA laboratory, the date and time settings on the desktop computer connected to your firm’s only HPLC system, which utilizes (b) (4) software to perform ingredient assay and impurity testing for all OTC drug products, were observed to be user-accessible and capable of being modified by laboratory personnel. No adequate controls were in place to restrict or prevent unauthorized changes to the system clock. The ability to alter system date and time settings creates a risk to the integrity, accuracy, and reliability of electronic data, including analytical test results and audit trail information generated by the chromatographic data system. 2.Your data acquisition software and workstations, the systems used for your chromatography instruments, have not been suitably qualified to ensure that the data generated for routine release of incoming and final drug products are maintained and free of manual manipulation or deletion. For example, your QA Supervisor demonstrated within your computer system the deletion of an unknown conditioning run acquired by the chromatography software, (b) (4) . (REPEAT OBSERVATION)

The written stability program for drug products does not include specific test methods.

Specifically, Your firm’s written stability procedure, SOP 2-0102, Revision 17, effective December 11, 2025, titled “Stability Program,” identifies required stability parameters, including bioburden, (b) (4) ; and concentration. However, the procedure fails to reference, specify, or link to the validated analytical test methods to be used for testing these attributes. The absence of defined and validated test methods within, or cross-referenced by, the stability program does not ensure that stability testing is performed using appropriate, validated procedures, and therefore does not provide adequate assurance of the reliability and accuracy of stability data generated to support product quality and expiry dating.

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, On 13 Jun 2025, the firm received a spontaneous consumer report (case 2025US009908) describing hospitalization following Yorvipath use. The firm's own triage, completed 16 Jun 2025, identified the case as serious (hospitalization), unexpected, and expedited. The firm subsequently classified case 2025US009908 as non-valid on the basis that no patient identifier was available. The firm's own case narrative documented a single patient's sequential 12-day clinical course including laboratory values, emergency care at a hospital, and inpatient treatment — meeting the threshold for an identifiable patient. No 15-day expedited report was submitted to FDA for case 2025US009908. Furthermore, internal firm correspondence dated 18 Jun 2025 confirms that the firm applied the same non-valid classification collectively to three additional adverse event reports from the same social media source, each previously identified by the firm's own operations team as individual patient adverse event reports, on the basis of absent reporter email address and patient details — without individual medical review of each case.

There are no written procedures for the surveillance, receipt, evaluation and reporting of post-marketing adverse experiences to FDA.

Specifically, No written procedures to ensure systematic surveillance, receipt, and reporting of post-marketing adverse experiences identified through social media monitoring to FDA for SKYTROFA and YORVIPATH.

Failure to ensure the study is conducted in accordance with the protocol and/or investigational plan.

Specifically, SubjectPP was enrolled into StudyTes on July 20, 2023 without the testing of the subject's viral hepatitis C serologic markers at screening, per Protocol Amendment 1.0, Section 6.12.6, Hepatitis B and C Eligibility Testing. The protocol's Exclusion Criterion #8b requires a confirmation of hepatitis C status prior to enrollment, however, Subjecta : hepatitis C testing was not performed until August 9, 2023, twenty days after Subject enrollment into the study and administration of investigational product. Subjecta: consent, required by country-specific laws, to ship the subject's fresh tumor biopsy was not obtained by the clinical site and as such, the subject's biopsy was never shipped to a central laboratory to confirm the pathology diagnosis of per Protocol Amendment 2.0, Section 6.9.1, Sample Collection Guidance. Subject s fresh tumor biopsy was collected on December 20, 2023, the subject was enrolled and administered the investigational product on January 2, *DATES OF INSPECTION 2/09/2026(Mon), 2/10/2026(Tue), 2/11/2026(Wed), 2/12/2026(Thu), 2/13/2026(Fi1), 2/17/2026(Tue)

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

Specifically, Your quality unit failed to provide adequate quality oversight, based on the numerous cGMP deficiencies found during the inspection. Examples of this include, but may not be limited to: 1. You failed to perform an adequate bulk hold time study for product held in the manufacturing tank and (b) (4) before being packaged. The hold time report documented an elapsed time from whena batch is blended until it is packaged in a tube. There is no documentation of a hold study of the product held in (b) (4) before it is packaged. 2. Your firm did not have documentation of a method validation or method verification performed by the contract laboratory of its modified version equivalency to USP <61> and USP <62>. 3. Since October 2024, there have been approximately " batches that have been shipped from your facility before they were released by the quality unit. This practice deviates from section 6.6.2.1 of your SOP QMS-213, Material Control, which requires quality release prior to shipment.

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, Finished product tests for the active ingredient are sampled from the manufacturing tank rather than from the final finished product package for the following products: 1. (b) (4) 2. (b) (4) 3. (b) (4) 4. (b) (4)

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

Specifically, Your firm failed to perform all identification tests required by the USP monograph for incoming raw materials. Since January 2024, your firm received (b) (4) lots of (b) (4) and” lots of (b) (4) , USP, on which full identification testing was not performed. These raw materials were used in the production of the OTC drug products (b) (4) and (b) (4) which were manufactured from January 2024 through January 2026."

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.

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: . . Digitally signed by

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

Such procedures shall include validation of all aseptic and sterilization processes. . . Digitally signed by

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

Specifically, A. The firm's environmental monitoring and personnel monitoring procedures are inadequate. For example: 1. Your firm failed to analyze raw Environmental Monitoring data for patterns (e.g., increasing CFUs) that indicate a loss of control in aseptic areas. Data trending is not performed and compiled (b) (4) in accordance with procedures SOP-00044 ("Environmental Monitoring," vl, effective 06/24/2025) and SOP-00191 ("(b) (4) Trending and Reporting"). 2. Environmental monitoring points are not scientifically justified or located in critical areas, failing to detect potential sources of contamination. No risk assessment study was performed to define sampling locations and frequencies of monitoring in ISO 5 and ISO7 areas. 3. The Formulation© Chamber and Dispensing ©) Chamber were qualified with ISO 5 classification during Installation and Operational Qualification for Suite ® and Suite (b) (4) ISO 5 (b) (4) . However, your environmental monitoring program monitors these two ® @)chambers as ISO 6 areas without adequate justification. Digitally signed by

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

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

Specifically, Your firm uses (b) (4) cleaning for (b) (4) ISO 5(b) (4) in Suite§ (Room (6) @)) and Suite& (Room (®)(4)) but has not established or validated a decontamination method (e.g., (Bb) (4) (b) (4) or (b) (4) ). The firm's Validation Master Plan (TD-00001, v4, effective 05/13/2025) requires Installation and Operational Qualification (IQ/OQ) for the (®) @) (b) (4) and(b) (4) , referencing change control PC-00089, which was initiated on 03/25/2025 for (6) (4) implementation in ISO 5 spaces. No progress has been made since initiation, and your firm has provided no explanation or justification for failing to implement a validated sterilization method for the (b) (4)

Your firm failed to provide adequate system for cleaning and disinfecting the room and equipment to produce aseptic condition.

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

Specifically, On 02/18/2026, I performed a review of your (b) (4) system used for the workflows and activities associated with preventive maintenance (PM) and calibration of equipment in the production and QC laboratory. The review revealeda total of Digitally signed by

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

Specifically, Operators performing 100% manual visual inspection of (b) (4) finished vials lack adequate training per SOP-00134 (Visual Inspection Guidelines, v3, effective 11/21/2025). While the SOP defines three defect classifications (Critical, Major, Minor) covering” total defect types including ®@ ®® glass container defects, (6) (4) container closure defects, and (b) (4) content defects (with inherent, extrinsic, and intrinsic particulates), the qualification test only includes particulate defects. Operators are not qualified to identify the full range of defects or differentiate between the three particulate types.

Laboratory records do not include complete records of any testing and standardization of laboratory reference standards.

Specifically, Your firm did not perform reference standard characterizations of the (b) (4) reference standard used in the final release testing of(D) (4) Your firm uses the reference standard (b) (4) : : Digitally signed by

Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality.

Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals. Specifically, 1. Your firm does not conduct identity testing of raw materials used in the production of(b) (4) (b) (4) | | | 2. Your firm does not conduct testing on conformity of containers and closures to ensure that the manufacturer’s results are valid and reliable, including sterility of these containers and closures. 3. Your firm has never performed supplier audits on any of the raw materials received at your facility.

Master production and control records lack a statement of theoretical yield including the maximum and minimum percentages of theoretical yield beyond which investigation is required.

Specifically, The master batch record for the products (b) (4) Solution for (B) (4) does not have theoretical yield specifications at (b) (4) stage of the dug product. *DATES OF INSPECTION: 01/28/2026 (Wed), 01/30/2026 (Fri), 02/02/2026 (Mon), 02/03/2026 (Tue), 02/05/2026 (Thu), 02/06/2026 (Fri), 02/13/2026 (Fri), 02/18/2026 (Wed), 02/24/2026 (Tue).

An investigation was not conducted in accordance with the investigational plan.

Specifically, Your study site failed to follow the protocol and pharmacy manual instructions with respect to proper dosage and administration of the investigational product (IP). A. The Pharmacy Manual utilized for both @)@) and O@ studies require| to be diluted to achievea final concentration range of 1.1mg/mL to 3.4mg/mL. 2 of 8 (25%) subjects enrolled into OA) and 3 of 11 (27%) subjects enrolled into Oe received at least one dose of that is above the allowed concentration levels: Subject Dose Concentration Study Number Number Administered to Subject mg/mL a | C101 B | C1D1 4.255 a | C1D8 4.255 B | C2D1 4.255 a | C1D8 3.885 a } cia | a } cist a } cist

Failure to prepare or maintain adequate and accurate case histories with respect to observations and data pertinent to the investigation.

Specifically, A. Modifications were made to IP preparation documentation for the dilution volume for ©) dosing. The original value would result in a dose concentration outside of the protocol-specified range of 1.1 mg/mL to 3.4 mg/mL. Many of these were not attributable to a person or date, as there was no initials or dates documented by the changes. Study Subject Apparent Original (4) oncentration arated )4) @)cip1 4.12 mg/mL |No C1D8° 4.12 mg/mL |No c2p1° 4.12 mg/mL |No

An investigation was not conducted in accordance with the signed statement of investigator.

Specifically, in each of two studies, and subjects were enrolled despite ineligibility due to not meeting all inclusion criteria or by meeting an exclusion criterion. Due to not meeting all of the screening criteria, the following subjects were not eligible to be enrolled in their respective studies as follows: Study Subject Number Screening Criteria # Screening Criteria Finding Exclusion 13 Patients with active Hepatitis B or Hepatitis C The subject was not tested for Hepatitis C at screening. Inclusion 2ai “***Patients who received taxane, gemcitabine, or other platinum agents in the (neo)adjuvant chemotherapy setting can be treated with the same class of chemotherapy (taxane or gemcitabine/carboplatin if • 12 months have elapsed between the completion of treatment with curative intent (eg, date of primary breast tumor surgery or date of last (neo) adjuvant chemotherapy administration, whichever occurred last) and first The subject received their last dose of docetaxel on 05/30/2023, and was diagnosed with metastatic triple-negative breast cancer on . (b) (4) (b) (4) (b) (4) (b) (4) (b) (4) (b) (4) (b) (6) (b) (6) Establishment Inspection Report FEI: 3022159116 Eduardo Patricio Y

Failure to prepare or maintain accurate case histories with respect to observations and data pertinent to the investigation.

Specifically, A. OO out ofo) enrolled, dosed, and completed subjects were missing data in the source document pertinent to the measurement(s) of their injection site reactions (ISRs) reported to the sponsor in the Electronic Data Capture (eDC) system. The following are the affected subjects: Subject number Data reported in the Electronic Data Capture (eDC)/electronic ase report form (eCRF) treatment A, Day 1 on Erythema - 20mm 6/22/2020 esSoe treatment A, Day 1 on Erythema - 20mm 6/22/2020 So || treatment B, Day 1 on Erythema - 5mm

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

Specifically, (b) (4) _ based non-sterile finished OTC drug products and the (b) (4) used in manufacturing OTC drug products, are not routinely tested for Burkholderia cepacia (B. cepacia). No documented investigations were conducted when B. cepacia was identified during (b) (4) testing of your (6) (4) _ system on the following dates: e July 3, 2024 ((b) (4) ) e November 4, 2024 ((b) (4) ) e September 3, 2025 ((b) (4) ) e September 8, 2025 ((b) (4) ) ¢ October 24, 2025 ((b) (4) ) The following OTC drug products were manufactured with (b) (4) _ on (b) (4) , and (b) (4) ; respectively, and distributed: e (b) (4) ., Bulk Lot 4 (6) (4) . Finished Good Lot #(b) (4) (Expiration: (b) (4) +) e (b) (4) , Bulk Lot #(b) (4) |. Finished Good Lot 4(b) (4) (Expiration: (b) (4) ) val 03/27/2026

There is a failure to thoroughly review any unexplained discrepancy, 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, 1) The stability results at "°C RH for two lots of(b) (4) demonstrated the following OOS results: Lot # Time Point Assay OOS Results Color/Appearance (Specification) OOS Result Specification Lot (b) (4) (b) (4) —: 2.44% Color: Gray (Spec: (Spec: (b) (4) %) (b) (4) ) (b) (4) : 5.74% Appearance: Soft (Spec: (b) (4) %) Stick/Cream (Spec: (b) (4) ) Lot (b) (4) (b) (4) (b) (4) —-: 2.67% Color: Gray (b) (4) : 6.20% Appearance: Cream (b) (4) 4.36% The investigation (Non-Conformance Report (NCR) # 24-093), initiated on 12/27/2024, for these OOS assay results and appearance failures stated that bulk retains and finished good retains were pulled from pilot to most recent batches and confirmed that all samples showed “minor to major signs of softening”. Despite physical degradation observed across multiple batches, only (©)@) lots of retain samples were submitted for © @ testing and no Assay testing was conducted on any of the retain samples that exhibited softening. 2) NCR # 24-032 was initiated on 04/01/2024 for failed microbial results for Total Aerobic Microbial Count (TAMC) and Total Yeast and Mold Count (TYMC) (Results: >57,000 CFU/g, Specification: TAMC: ©) @) CFU/g, TYMC

The suitability of all testing methods is not verified under actual conditions of use.

Specifically, Failure to ensure that the approved contract laboratory has performed method suitability of compendial methods USP <61> MICROBIOLOGICAL EXAMINATION OF NONSTERILE PRODUCTS: MICROBIAL ENUMERATION TESTS and USP <62> MICROBIOLOGICAL EXAMINATION OF NONSTERILE PRODUCTS: TESTS FOR SPECIFIED MICROORGANISMS, used for the testing of Total Aerobic Microbial Count (TAMC), Total Yeast and Mold Count (TYMC), and tests for specified microorganisms such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Salmonella, respectively. For example, no method suitability was conducted for (b) (4) OTC Drug Products which have a (b) (4) (b) (4) . (b) (4) in the formulation.

The written stability program for drug products does not include reliable, meaningful, and specific test methods.

Specifically, Failure to ensure that the approved contract laboratory, which conducts stability testing for (b) (4) (b) (4) OTC Drug Products, has performed validation of the in-house method for Assay tests and has conducted forced degradation studies to demonstrate the Assay method is stability indicating. ’ ~ 3/27/2026

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, 1) Electronic data stored within the (b) (4) computer used to operate the FTIR (b) (4) Software. used for identification testing of raw materials used in the manufacturing of OTC dug products, is not protected against possible deletion or modification. The raw data/spectra are saved on the (b) (4) after analysis; on 03/17/2026, we observed that the delete function on (b) (4) is not disabled, and we observed deleted spectra in the recycle bin. Additionally, the software does not have an audit trail to track the creation, modification, and deletion of data. 2) There is no assurance that all analytical data on the standalone (b) (4) pH meters, used to test raw materials, in-process samples, and finished OTC drug products are retained. On 03/17/2026, we observed a flashing error message on pH Meter # which stated “(b) (4) (b) (4). The data from the pH meters are not backed up. In addition, results from the two pH Meters (4 and #") are not printed out, and no second person verification is conducted at time of testing. Additionally, we observed that the “delete” option on the pH meters are not disabled. 3) The (b)(4) weigh balances (IDs: (b) (4) ), used to conduct (b) (4) m

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, 1) Changes to manufacturing processes were implemented without undergoing a revalidation to ensure its reproducibility. For example, Customer Concern Communication Report (CCCR # 24-013) was initiated on 02/22/2024 when the customer expressed concerns with bulk manufactured material (6) (4) (b) (4) having a grainy appearance. An evaluation of finished goods and bulk retains was conducted and it was determined that samples showed some variance of grainy appearance. Aftera reviewofthe validated process, a decision was made that a new process/re-phasing was necessary. The new phasing consisted of (b) (4) as opposed to the validated procedure which included the (b) (4) (b) (4) The change in manufacturing process was implemented on 04/26/2024 without a Change Control per SOP QA-002c “Change Control System” and without re- validation. The following batches of (6) (4) were manufactured and released after the change in manufacturing process: © Lot #(b) (4) Expiration: (b) (4) © Lot # (b) (4), Expiration: (b) (4) © Lot #(b) (4), Expiration: (b) (4) © Lot #(b) (4). Expiration: (b) (4) 2) The process validation (PV) for (b) (4) . Formula (b) (4) (Protocol No: PV-006- 2024, Appro

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, 1) Cleaning Validation (CV) conducted for(b)(4), Formula (b)(4) (Protocol No: PV-006-2024, Approved: 12/26/2024) is deficient for the following reasons: a. (6)(4) bulk batches (b)(4)7) were manufactured but only © were filled and assembled. Validation batch #(6)(4)) did not proceed to the filling and assembly stage; as a result, swab samples for detergent and API residue and microbial burden samples were not collected from product contact areas of the filling and assembly equipment for (®©)(@) batches in accordance with the firm’s procedure #VA-001a “Validation Master Plan” which requires CV to be conducted through (b) (4) product changeovers. b. During the CV, the following results from swab analyses which exceeded specification for residuals of actives (Specification: (6) (4) +) were received and no investigations were conducted: PV Batch No. Result (ppmiswab) (6)(4): 13.26 (yi): 48.08 (4): 12.31 (6)(4)_: 16.78 (b)(4): 16.83 (BI): 75.30 (b) (4): 28.17 YAY: 28.20 . . _— 03/27 26

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

Specifically, 1) No investigation was initiated when the contract testing laboratory did not perform species identification on two Colony Forming Units of Gram-negative rods recovered on 08/07/2023 from (b) (4) of the (b) (4) (b) (4) system. 2) Retain samples were not assessed in response to a Customer Concern Communication Report (CCCR # 23- 025) initiated on 10/04/2023 for (b) (4) , Formula: (b) (4) ; the customer ((b) (4) _) received complaints from clients of severe allergic reactions linked to lot numbers (6) (4) and (6) (4). The investigation failed to include a documented review of retain samples of the lots as required by SOP QA-034e “Customer Concern Communication (CCCR)” which states that preliminary investigations should include evaluations of retain samples. 3) No investigation was initiated to investigate low percentage yields for the following bulk batches of(b) (4) (b) (4) which were summarized as achieving the following yields in the Annual Product Review (APR) (Approved 04/23/2024): a. Batch (b) (4) (manufactured (b) (4) ) achieved a 94.11% yield b. Batch (b) (4) (manufactured (b) (4) ) achieved a 94.64% yield The APR states that the allowable theoretical yield for

An investigation was not conducted in accordance with the signed statement of investigator.

Specifically, Protocol version dated 8/25/22, section 9.3.1 Expedited Reporting Requirements for Adverse Events, requires grade 3 serious adverse events (SAE) not resulting in hospitalization greater than or equal to 24 hours, be reported to the National Cancer Institute (NCI) via CTEP-AERS no greater than 10 calendar days from awareness of the event. — ° (b) (6), (b) (7(C) . : ‘| Subject experienced an SAE on 8/27/22 to 9/7/22. The site became aware of the SAE on 9/13/22. The SAE was not reported via CTEP-AERS until 11/30/22. *DATES OF INSPECTION 2/10/2026(Tue), 2/11/2026( Wed), 2/12/2026(Thu), 2/17/2026(Tue), 2/18/2026(Wed), 2/23/2026(Mon), 2/26/2026(Thu), 2/27/2026(Fri), 3/02/2026(Mon), 3/03/2026(Tue)

You did not take corrective action that ensured affected product was not entered into commerce and the cause of the deviation was corrected.

Your facility imports Reduced Oxygen Packaging (ROP) refrigerated fresh fish from Japan, including products in. Your HACCP plan identifies Clostridium botulinum as a hazard for ROP products and establishes a critical limit ofQQG)(4AY during receiving to control this hazard. Your HACCP plan also establishes critical limits for refrigerated fresh fish products at temperature do not exceed GJ). Your written procedures require that suppliers be discontinued when [§(6)(4) placement issues are identified until the issue has been corrected. During the inspection conducted on 02/19-20/2026, a review of receiving records for seafood products revealed the following: 1. (QGP readings documented temperatures exceeding established critical limits during transport, yet products were accepted without adequate corrective actions or hazard evaluation 2. (GA were marked as "pass" despite documented temperature excursions above critical limits

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

Specifically, we observed the following in your warehouse, Building Pf, where M™™products such as rice, fortune cookies, flour, sugar, graham pie crust, sauces, etc. and containers, napkins, and lids for chain restaurants are stored. 1. Apparent gnawed holes ranging from 0.25 x 0.5 inch to 7.5 x 2 inch on nine bags, apparent rodent urine stains ranging from 0.25 x 0.25 to 3.5 x 1.5 inch on six bags, anda total of about 77 apparent rodent excreta pellets (AREPs) found on bags ofoeot packaged in (®)@) layer paper bag at aisle(GAY. 2. Apparent gnawed holes ranging from 1 x 0.5 inch to 2 x 1 inch on ten bags, apparent rodent urine stains ranging from 0.25 x 1 inch to 10x2 on 18 bags, and about 53 apparent rodent excreta pellets found on bags of KG) packaged in layer paper bag at aisle . At least 30 AREPs were also found under the bottom layer of bags of dusting flour. Additionally, we observed at least two apparent gnawed bags (out of four) of (IG) 4) PIII at least 10 apparent rodent excreta pellets, and a pile of gnawed packaging materials ona pallet at aisle(5/4 in your ambient warehouse Building Mf, where other products such as pallets of rice, peanuts, fortune cookies, etc. are sto

Your plant was not constructed to facilitate maintenance and sanitary operations.

Specifically, the following were observed: e A patched up dry wall with exposed holes ranging from 2x3 inches to 4x5 inches located between aisles PM and @@ in Building ff, where pallets of fortune cookies, teriyaki sauces, forks, containers, and etc. were stored along the dry wall. e A gap of about 1.5 inches wide and 6 ft. long on the panel of the roll up door [f, where(5) wooden pallets, which are organized outside in the yard between Building/ and|™ and then brought into Building /¥ after. *DATES OF INSPECTION 2/18/2026(Wed), 2/19/2026(Thu), 2/20/2026(Fri), 2/23/2026(Mon), 2/24/2026(Tue)

The separate or defined areas necessary to prevent contamination or mix-ups are deficient.

Specifically, Your laboratory has three problems that could contaminate testing: 1.The pass-through counter has no physical barrier, allowing contaminants to enter the lab from the office area. 2.A dog was seen in the office next to the lab. This violates your own procedure (SOP CA26150, Section 12.5), which prohibits animals in laboratory areas. Animal hair, dander, and microorganisms can easily move into the lab through the open pass-through. 3.The lab door opens straight to the outdoor environment, allowing airborne particles and contaminants to enter. The lab tests drug products, including OTC (b) (4) (Lot # (b) (4) ) and(b) (4) (Lot #(b) (4) ©. These uncontrolled environmental exposures could compromise your microbiological media preparation and test results.

Buildings used in the manufacture, processing, packing or holding of drug products are not maintained in a clean and sanitary condition.

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

Specifically, Your firm initiated Corrective and Preventive Action (CAPA) 501-01-2026 on January 15, 2026, after inconsistent results were observed during (DB) (4) balance performance qualification testing of laboratory balances. The investigation concluded that SOP CAS01 — Laboratory Balance OQ and PQ Procedures incorrectly implemented the repeatability requirements of USP <41>.

Written procedures are not 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 critical storage equipment including your (®) @) freezer, ID (DB) (4), which is used to store analytical samples provided by your customers. (DB) (4) preventative maintenance for - (©) (4) freezer, ID (b) (4). was not completed by the required due date of December 31, 2025. Your firm’s deviation, DEV-25-008-GA, postponed the required maintenance until April 30, 2026. To date, there have been multiple temperature excursions exceeding the acceptable limits (b) (4) with freezer (D) (4) reaching temperatures as high as -59.00°C for an excursion lasting over 55 minutes per Alarm Report from September 2025 — December 2025. Your firm has no scientific justification for the delay in the preventative maintenance or failing to replace or use working critical storage equipment for the storage of test samples.

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

Specifically, Your firm does not perform minimum verification testing to qualify the reference standards you use for testing of various drug products and raw materials for release, or for stability testing. Instead, according to SOP-000898, Reference Standards, Version 4, your firm relies on a review of the Certificate of Analysis of incoming lots to assess the quality of the reference standard. Examples are as follows: A. Your firm used(b) (4) Reference Standard (Lot (b) (4) supplied by (b) (4) received 04Jun2025) to conduct method transfer activities without performing verification testing to confirm the identity, quality, and suitability of the reference standard lot prior to use. According to your SOP SOP-000898 - Reference Standards, V4, section 5 your firm relies on the COA to verity the purity and identification of reference standards. Examples include, but are not limited to: e SGS-MT-09-25-29R, Method Transfer Reportfor the Determination of(1) (4) Concentration in (b) (4) by OM and Assay for (BY (4) in (b) (4) (Bb) (4) (November 03, 2025): Reference Standard Lot (Db) (4) was used throughout the method transfer study (Section 4.2, page 7; Section 6.3.1.1, page 43) without d